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Charcot-Marie-Tooth disease type 1D (CMT1D) is a form of CMT1 (see this term), caused by mutations in the EGR2 gene (10q21.1), with a variable severity and age of onset (from infancy to adulthood), that usually presents with gait abnormalities, progressive wasting and weakness of distal limb muscles, with possible later involvement of proximal muscles, foot deformity and severe reduction in nerve conduction velocity. Additional features may include scoliosis, cranial nerve deficits such as diplopia, and bilateral vocal cord paresis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Charcot-Marie-Tooth disease type 1D	c1843247	6,700	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101084	2021-01-23T18:12:17	{"gard": ["9189"], "mesh": ["C537985"], "omim": ["607678"], "umls": ["C1843247"], "icd-10": ["G60.0"], "synonyms": ["CMT1D"]}
Natural killer (NK)-cell enteropathy is a benign NK-cell lymphoproliferative disease characterized by minor abdominal symptoms (abdominal pain, diverticulosis, constipation and reflux) due to NK cell-derived lesions in the mucosal layer of the gastrointestinal tract and often mistaken for NK or T-cell lymphoma (see these terms). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	NK-cell enteropathy	c4509932	6,701	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=263665	2021-01-23T17:52:40	{"icd-10": ["K63.8"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2013) HL23V was reputedly a type C RNA tumor virus first isolated in 1975 from cultured human acute myelogenous leukaemia peripheral blood leukocytes, which would have been the first cancer-causing retrovirus isolated from human sera.[1] It was later shown to be a laboratory contaminant of three monkey viruses. The journal Nature, which had published the original research, later retracted the article. ## See also[edit] * Simian sarcoma associated virus (SSAV or SSAV-1), one of two associated viruses comprising HL23V * HTLV-1, the actual first human pathogenic retrovirus discovered in 1981 ## References[edit] 1. ^ Chan, E.; Peters, W.; Sweet, R.; Ohno, T.; Kufe, D.; Spiegelman, S.; Gallo, R.; Gallagher, R. (1976). "Characterisation of a virus (HL23V) isolated from cultured acute myelogenous leukaemic cells". Nature. 260 (5548): 266–268. Bibcode:1976Natur.260..266C. doi:10.1038/260266a0. PMID 176596.; Gallagher, R.; Gallo, R. (1975). "Type C RNA tumor virus isolated from cultured human acute myelogenous leukemia cells". Science. 187 (4174): 350–3. Bibcode:1975Sci...187..350G. doi:10.1126/science.46123. PMID 46123. ## Further reading[edit] * Science Fictions: A Scientific Mystery, a Massive Cover-up, and the Dark Legacy of Robert Gallo ISBN 0316090042, 2002, John Crewdson This virus-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	HL23V	None	6,702	wikipedia	https://en.wikipedia.org/wiki/HL23V	2021-01-18T19:05:11	{"wikidata": ["Q5630028"]}
A number sign (#) is used with this entry because of evidence that multiple synostoses syndrome-1 (SYNS1) is caused by heterozygous mutation in the NOG gene (602991) on chromosome 17q22. Description Multiple synostoses syndrome is characterized by multiple joint fusions, usually commencing in the hands, conductive deafness, and characteristic facial features, including a broad, tubular-shaped nose and a thin upper vermilion. Other features include brachydactyly, hypoplastic or absent middle phalanges, radial head dislocation, and pectus carinatum (summary by Takahashi et al., 2001). ### Genetic Heterogeneity of Multiple Synostoses Syndrome Other forms of multiple synostoses syndrome include SYNS2 (610017), caused by mutation in the GDF5 gene (601146) on chromosome 20q11; SYNS3 (612961), caused by mutation in the FGF9 gene (600921) on chromosome 13q12; and SYNS4 (617898), caused by mutation in the GDF6 gene (601147) on chromosome 8q22. Clinical Features Fuhrmann et al. (1966) described mother and son with bilateral dysplasia and synostosis of the elbow joint, synostoses in the fingers, wrist and foot, and short middle phalanges and metacarpals. The combination was described previously in father and daughter and father and son by other authors. Maroteaux et al. (1972) described this syndrome in 7 persons in 1 family. A broad hemicylindrical nose without alar flare was noted. Other features were proximal symphalangism, carpal and tarsal fusion, subluxation of the radial heads, short first metacarpal bone, hypoplasia or aplasia of various digital phalanges and corresponding nails, and progressive conduction deafness. Herrmann (1974) described a kindred in which a woman was affected with an unusual hand formation, which they designated 'WL syndrome;' she transmitted the syndrome to 5 children by 2 different husbands (presumably with surnames beginning with W and L). All 6 affected persons had hypoplasia or absence of nails, proximal interphalangeal flexion creases and middle phalanges, as well as short, broad metacarpals, and all but 1, a 12-month-old boy, had proximal symphalangism radiographically. In addition, the patients had conductive deafness as well as dislocation of the radial heads and abnormal toes. The deafness is probably due to anomalies of the auditory ossicles as in other symphalangism syndromes. Lehmann et al. (2007) suggested that the disorder in the kindred reported by Herrmann (1974) and in some of the patients reported by Maroteaux et al. (1972) may have been the same as the disorder Lehmann et al. (2007) showed to be due to mutation in the NOGGIN gene (602991) and designated by them brachydactyly type B2 (BDB2; 611377). Higashi and Inoue (1983) reported a Japanese family with symphalangism. These authors emphasized peculiarities of the facies, particularly broad nose. Pectus carinatum was conspicuous. Konigsmark and Gorlin (1976) reported a case. Hurvitz et al. (1985) described a case and suggested the designation facioaudiosymphalangism syndrome. See 113450 for description of a syndrome of brachydactyly with distal symphalangism. Da-Silva et al. (1984) described a large Brazilian kindred with 28 cases of the multiple synostosis syndrome in an autosomal dominant pattern. The main anomalies were symphalangism and carpal and tarsal synostosis. Some had synostosis involving other bones, absence of phalanges and nails, short metacarpals, hypoplastic alae of the nose, etc. Gaal et al. (1987) reported a large Hawaiian family with multiple synostoses. Proximal symphalangism was a feature of the syndrome in this family, and the fifth proximal interphalangeal joint was usually the first to be affected. The disorder in the family could be traced to the first known affected individual, a Cherokee Indian who arrived in the Hawaiian Islands in the 1870s. Affected individuals demonstrated the cardinal features of the syndrome, including a broad, tubular-shaped (hemicylindrical) nose with lack of alar flare, otosclerotic deafness, and multiple progressive joint fusions commencing in the hand. All affected individuals examined had some degree of hearing impairment, ranging from mild to severe. Symphalangism was the most consistent finding. The joint fusions were progressive, commencing in the fifth proximal interphalangeal joint in early childhood (or at birth in some individuals) and progressing in an ulnar-to-radial and proximal-to-distal direction. Most of the affected adults were unable to make a fist. With increasing age, ankylosis of other joints, including the cervical vertebrae, hips, and humeroradial joints, developed. Although humeral, radial, and tarsal involvement had been noted in previous reports, little had been written regarding vertebral involvement. In the Hawaiian family, the cervical vertebral fusions commenced in early childhood and ultimately produced significant limitation of neck flexion and extension. Edwards et al. (2000) reported a male with multiple synostoses syndrome with neurologic complications caused by cervical spinal canal stenosis, not previously described in this syndrome. The authors recommended that individuals with this condition should have a neurologic examination, and that restriction of activities with risk of injury to the neck or spine may be necessary if there are signs of vertebral malformation or neurologic complications. Mapping In the large Hawaiian family originally reported by Gaal et al. (1987), Krakow et al. (1998) demonstrated linkage of the multiple synostoses syndrome to chromosome 17q21-q22. The authors tested linkage to 17q because proximal symphalangism (SYM1; 185800) had been mapped to that region in studies of the classic pedigree first reported by Harvey Cushing (1916). Molecular Genetics In affected members of the large Hawaiian family with dominantly inherited multiple synostoses syndrome originally reported by Gaal et al. (1987), Gong et al. (1999) identified a heterozygous mutation (602991.0003) in the NOG gene. Furthermore, they demonstrated mutations in the same gene in 5 unrelated families with proximal symphalangism (SYM1; see 185800) and in a de novo case of that disorder. Thus, multiple synostoses syndrome and proximal symphalangism are allelic disorders. In affected members of a family with multiple synostosis syndrome, originally reported by Higashi and Inoue (1983), Takahashi et al. (2001) identified heterozygosity for a 1-bp deletion (602991.0011) in the NOG gene. Van den Ende et al. (2005) reported a 4-generation family with features of the facioaudiosymphalangism syndrome in which a novel missense mutation (602991.0016) in the NOG gene was identified in affected family members. The variable expression and progressive nature of the syndrome was well illustrated in this family. In an individual with multiple synostoses syndrome, Dawson et al. (2006) identified heterozygosity for a nonsense mutation (602991.0015) in the NOG gene. Rudnik-Schoneborn et al. (2010) studied a German father and son with facioaudiosymphalangism syndrome, in whom they identified a heterozygous missense mutation (602991.0019) in the NOG gene. In contrast to the typical presentation, the height of the 10-year-old son was above the 97th centile from the age of 3.5 years and he had markers of an activated bone metabolism, with elevated phosphate levels and bone-derived alkaline phosphatase activity. His father, who had never been under medical supervision, was reported to have been one of the tallest boys in childhood and youth until age 15 years, when growth velocity slowed; his adult height was in the 75th centile (185 cm). Rudnik-Schoneborn et al. (2010) proposed that accelerated growth could be part of the facioaudiosymphalangism syndrome caused by NOG mutations, noting that experimental evidence showed that suppression of noggin might accelerate osteogenesis (Wan et al., 2007). INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Narrow face \- Short philtrum Ears \- Progressive conductive deafness \- Stapes ankylosis Eyes \- Strabismus Nose \- Hemicylindrical nose \- Hypoplastic alae nasi \- Hypoplastic nasal septum Mouth \- Thin vermilion border of upper lip CHEST Ribs Sternum Clavicles & Scapulae \- Anteriorly positioned shoulders \- Short sternum \- Pectus excavatum \- Prominent costochondral junction SKELETAL Spine \- Vertebral anomalies \- Spinal canal stenosis \- Hypoplastic spinal processes (cervical vertebrae) Limbs \- Short upper arms \- Cubitus valgus \- Dislocated radial head \- Limited forearm pronation/supination \- Short legs Hands \- Proximal symphalangism (2,3,4) \- Fusion of midphalangeal joints \- Clinodactyly \- Brachydactyly \- Cutaneous syndactyly (2,3,4) \- Carpal fusions \- Hypoplastic/aplastic middle phalanx \- Hypoplastic/aplastic distal phalanx \- Single palmar creases Feet \- Short feet \- Short halluces \- Tarsal fusions \- Cutaneous 2,3 toe syndactyly \- Absent distal phalanges \- Proximal symphalangism 2,3,4 SKIN, NAILS, & HAIR Skin \- Absence of skin creases over proximal interphalangeal (PIP) joints \- Absence of skin creases over distal interphalangeal (DIP) joints \- Single palmar creases Nails \- Aplastic/hypoplastic fingernails \- Aplastic/hypoplastic toenails MISCELLANEOUS \- Allelic to proximal symphalangism ( 185800 ), stapes ankylosis syndrome without symphalangism ( 184460 ), and tarsal-carpal coalition syndrome ( 186570 ) \- Waddling gait MOLECULAR BASIS \- Caused by mutation in the homolog of the mouse Noggin gene (NOG, 602991.0003 ) \- Caused by mutation in the growth/differentiation factor-5 gene (GDF5, 601146.0013 ) ▲ 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	MULTIPLE SYNOSTOSES SYNDROME 1	c0175700	6,703	omim	https://www.omim.org/entry/186500	2019-09-22T16:32:58	{"doid": ["0050794"], "omim": ["186500"], "orphanet": ["3237"], "synonyms": ["Alternative titles", "SYNOSTOSES, MULTIPLE, WITH BRACHYDACTYLY", "SYMPHALANGISM-BRACHYDACTYLY SYNDROME", "WL SYNDROME", "DEAFNESS-SYMPHALANGISM SYNDROME OF HERRMANN", "FACIOAUDIOSYMPHALANGISM SYNDROME"]}
Skin disease of unknown pathology Morgellons Pseudomedical diagnosis RisksNocebo This article is part of a series on Alternative medicine General information * Alternative medicine * Alternative veterinary medicine * Quackery (Health fraud) * History of alternative medicine * Rise of modern medicine * Pseudoscience * Antiscience * Skepticism * Skeptical movement * National Center for Complementary and Integrative Health * Terminology of alternative medicine * Therapeutic nihilism Fringe medicine and science * Acupressure * Acupuncture * Alkaline diet * Anthroposophic medicine * Apitherapy * Applied kinesiology * Aromatherapy * Auriculotherapy * Bates method * Black salve * Bodywork * Bonesetter * Bowen technique * Breathwork * Fake COVID-19 treatments * Cancer treatments * Charcoal cleanse * Chiropractic * Chiropractic treatment techniques * Vertebral subluxation * Christian Science * Chromotherapy * Colon cleansing * Coffee enema * Colorpuncture * Colloidal silver * Craniosacral therapy * Crystal healing * Cupping therapy * Dental amalgam controversy * Detoxification * Foot detox * Ear candling * Energy medicine * Esoteric energy * Therapeutic touch * Fabunan Antiviral Injection * Facilitated communication * Feldenkrais Method * Functional medicine * Hair analysis * Herbal medicine * Holistic dentistry * Hologram bracelet * Homeopathy * Bach flower remedies * Biological terrain assessment * Hypnotherapy * Iridology * Ionized jewelry * Jilly Juice * Lightning Process * Lymphotherapy * Medical intuitive * Mesmerism * Magnet therapy * Manual therapy * Megavitamin therapy * Mind–body interventions * MMS * Myofascial release * NAET * Naturopathy * Oil pulling * Orgone * Orthomolecular medicine * Orthopathy * Osteomyology * Osteopathy * Ozone therapy * Parapsychology * Phrenology * Psychic surgery * Psychodermatology * Radionics * Rapid prompting method * RBOP * Reiki * Reflexology * Rolfing * Scientific racism * ThetaHealing * Thought Field Therapy * Urophagia * Vaginal steaming * Vision therapy * Vitalism * Young blood transfusion * Zero balancing Conspiracy theories (list) * Big Pharma conspiracy theory * HIV/AIDS denialism * OPV AIDS hypothesis * Anti-vaccination * Vaccines and autism * MMR vaccine and autism * Water fluoridation controversy * GMO conspiracy theories * Misinformation related to the COVID-19 pandemic Classifications * Alternative medical systems * Mind–body intervention * Biologically-based therapy * Manipulative methods * Energy therapy Traditional medicine * African * Muti * Southern Africa * Ayurveda * Ayurvedic acupressure * Dosha * Maharishi Vedic Approach to Health * Balneotherapy * Brazilian * Bush medicine * Cambodian * Chinese * Blood stasis * Chinese herbology * Dit Da * Gua sha * Gill plate trade * Meridian * Moxibustion * Pressure point * Qi * San Jiao * Tui na * Zang-fu * Chumash * Curandero * Faith healing * Iranian * Jamu * Kambo * Japanese * Korean * Mien Shiang * Mongolian * Prophetic medicine * Shamanism * Shiatsu * Siddha * Sri Lankan * Thai massage * Tibetan * Unani * Vietnamese Diagnoses * Adrenal fatigue * Aerotoxic syndrome * Candida hypersensitivity * Chronic Lyme disease * Electromagnetic hypersensitivity * Heavy legs * Leaky gut syndrome * Multiple chemical sensitivity * Wilson's temperature syndrome * v * t * e Morgellons (/mɔːrˈɡɛlənz/) is the informal name of a self-diagnosed, scientifically unsubstantiated skin condition in which individuals have sores that they believe contain fibrous material.[1][2] Morgellons is not well understood, but the general medical consensus is that it is a form of delusional parasitosis. The sores are typically the result of compulsive scratching, and the fibers, when analysed, are consistently found to have originated from clothings and other textiles.[2][3] The condition was named in 2002 by Mary Leitao,[4] a mother who rejected the medical diagnosis of her son's delusional parasitosis. She chose the name from a letter written by a mid-17th-century physician.[5][6] Leitao and others involved in her Morgellons Research Foundation successfully lobbied members of the U.S. Congress and the U.S. Centers for Disease Control and Prevention (CDC) to investigate the condition in 2006.[7][8] CDC researchers issued the results of their multi-year study in January 2012, indicating that no disease organisms were present in the samples from the individuals examined and that the fibers found were likely cotton, and concluded that the condition was "similar to more commonly recognized conditions such as delusional infestation".[9][10] ## Contents * 1 Medical description * 2 Society and culture * 2.1 Mary Leitao and the MRF * 2.2 Media coverage * 2.3 CDC investigation * 2.4 Internet and media influence * 2.5 Jay Traver * 3 See also * 4 References * 5 Further reading ## Medical description Morgellons is poorly understood but the general medical consensus is that it is a form of delusional parasitosis in which individuals have some form of skin condition with sores that they believe contain fibers.[1][2][3][11] Its presentation is very similar to delusional parasitosis, with the addition that people with the condition believe there are inanimate objects in their skin lesions. An active online community supports the notion that it is an infectious disease, disputes that it is psychological, and proposes an association with Lyme disease. Controversy has resulted; publications "largely from a single group of investigators" describe findings of spirochetes, keratin and collagen in skin samples in small numbers of patients; these findings are contradicted by much larger studies conducted by the CDC, which found skin samples mostly contained cellulose that came from cotton, with no evidence of infection or other causes.[3] ## Society and culture ### Mary Leitao and the MRF In 2001,[4] according to Leitao, her then two-year-old son developed sores under his lip and began to complain of bugs.[12] Leitao says she examined the sores with her son's toy microscope and discovered red, blue, black, and white fibers.[4][5] She states that she took her son to see at least eight different doctors who were unable to find any disease, allergy, or anything unusual about her son's described symptoms. Fred Heldrich, a Johns Hopkins pediatrician with a reputation "for solving mystery cases", examined Leitao's son.[4] Heldrich found nothing abnormal about the boy's skin, and wrote to the referring physician that "Leitao would benefit from a psychiatric evaluation and support", and registered his worry about Leitao's "use" of her son.[4] Leitao last consulted an unnamed Johns Hopkins infectious disease specialist who, after reviewing her son's records refused to see him, suggesting Leitao herself might have "Munchausen's by proxy, a psychiatric syndrome in which a parent pretends a child is sick or makes him sick to get attention from the medical system".[5] According to Leitao, several medical professionals she sought out shared this opinion of a potential psychological disorder:[13] > [Leitao] said she long ago grew accustomed to being doubted by doctors whenever she sought help for her son, who is now 7 and still suffering from recurring lesions. "They suggested that maybe I was neurotic," Leitao said. "They said they were not interested in seeing him because I had Munchausen Syndrome by Proxy".[14] Leitao says that her son developed more sores, and more fibers continued to poke out of them.[5][12] She and her husband, Edward Leitao, an internist with South Allegheny Internal Medicine in Pennsylvania, felt their son had "something unknown".[4] She chose the name Morgellons disease (with a hard g) from a description of an illness in the medical case-history essay, A Letter to a Friend (c. 1656, pub. 1690) by Sir Thomas Browne, where the physician describes several medical conditions in his experience, including "that endemial distemper of children in Languedoc, called the morgellons, wherein they critically break out with harsh hairs on their backs".[5][6] Leitao started the Morgellons Research Foundation (MRF) informally in 2002 and as an official non-profit in 2004.[5][15] The MRF website states that its purpose is to raise awareness and funding for research into the proposed condition, described by the organization as a "poorly understood illness, which can be disfiguring and disabling".[16] Leitao stated that she initially hoped to receive information from scientists or physicians who might understand the problem, but instead, thousands of others contacted her describing their sores and fibers, as well as neurological symptoms, fatigue, muscle and joint pain, and other symptoms.[5] The MRF claimed to have received self-identified reports of Morgellons from all 50 US states and 15 other countries, including Canada, the UK, Australia, and the Netherlands, and states that it has been contacted by over 12,000 families.[16] In 2012 the Morgellons Research Foundation closed down and directed future inquiries to Oklahoma State University.[17] ### Media coverage In May 2006, a CBS news segment on Morgellons aired in Southern California.[18] The same day, the Los Angeles County Department of Health services issued a statement saying, "No credible medical or public health association has verified the existence or diagnosis of 'Morgellons Disease'", and "at this time there is no reason for individuals to panic over unsubstantiated reports of this disease".[19] In June and July 2006 there were segments on CNN,[20] ABC's Good Morning America,[21] and NBC's The Today Show. In August 2006, a segment of the ABC show Medical Mysteries[12] was devoted to the subject. Morgellons was featured on ABC's Nightline on January 16, 2008,[22] and as the cover story of the January 20, 2008, issue of the Washington Post.[7] The first article to propose Morgellons as a new disease in a scientific journal was a review article co-authored by members of the MRF and published in 2006 by the American Journal of Clinical Dermatology.[23] A 2006 article in the San Francisco Chronicle reported, "There have been no clinical studies" of Morgellons disease.[23] A New Scientist article in 2007 also covered the phenomenon, noting that people are reporting similar symptoms in Europe and Australia.[24] In an article published in the Los Angeles Times on April 22, 2010, singer-songwriter Joni Mitchell claimed to have the condition.[25] On June 13, 2011, the Australian Broadcasting Corporation's Radio National broadcast The Mystery of Morgellons with guests including Mayo Clinic Professor Mark Davis.[26] ### CDC investigation The Morgellons Research Foundation coordinated a mailing campaign via their website, in which thousands of people sent form letters to a Centers for Disease Control and Prevention (CDC) task force, which first met in June 2006.[7][27][28] By August 2006, the task force consisted of 12 people, including two pathologists, a toxicologist, an ethicist, a mental health expert, and specialists in infectious, parasitic, environmental and chronic diseases.[29] In June 2007, the CDC opened a website relating to Morgellons, CDC Study of an Unexplained Dermopathy, and by November 2007, the CDC opened an investigation into the condition.[8] Kaiser Permanente, a health-care consortium in Northern California, was chosen to assist with the investigation, which involved skin biopsies from affected people and characterization of foreign material such as fibers or threads obtained from people to determine their potential source.[8][30] The U.S. Armed Forces Institute of Pathology and the American Academy of Dermatology assisted with pathology.[31] In January 2012, the CDC released the results of the study.[9][10] Their conclusions were that 59% of subjects showed cognitive deficits and 63% had evidence of clinically significant symptoms. 50% had drugs in their systems, and 78% reported exposure to solvents (potential skin irritants). No parasites or mycobacteria were detected in the samples collected from any patients. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin.[9] ### Internet and media influence People usually self-diagnose Morgellons based on information from the Internet and find support and confirmation in online communities of people with similar illness beliefs.[32][33][34] In 2006, Waddell and Burke reported the influence of the Internet on people self-diagnosed of Morgellons: "physicians are becoming more and more challenged by the many persons who attempt self-diagnosis on-line. In many cases, these attempts are well-intentioned, yet wrong, and a person's belief in some of these oftentimes unscientific sites online may preclude their trust in the evidence-based approaches and treatment recommendations of their physician."[35] Vila-Rodriguez states that the Internet promotes the spreading and supporting of "bizarre" disease beliefs, because "a belief is not considered delusional if it is accepted by other members of an individual's culture or subculture".[33] Robert Bartholomew, a sociologist who has studied the Morgellons phenomenon, states that the "World Wide Web has become the incubator for mass delusion and it (Morgellons) seems to be a socially transmitted disease over the Internet." According to this hypothesis, people with delusions of parasitosis and other psychological disorders become convinced they have "Morgellons" after reading Internet accounts of others with similar symptoms. This is known as mass psychogenic illness, where physical symptoms without an organic cause spread to multiple people within the same community or social group.[36] The Dallas Observer writes that Morgellons may be memetically spread via the Internet and mass media, and "[i]f this is the case, then Morgellons is one in a long line of weird diseases that have swept through populations, only to disappear without a trace once public concern subsides".[15] The article draws parallels to several media-spread mass delusions. Dermatologist Caroline Koblenzer specifically faults the Morgellons Research Foundation (MRF) website for misleading people: "Clearly, as more and more of our patients discover this site (MRF), there will be an ever greater waste of valuable time and resources on fruitless research into fibers, fluffs, irrelevant bacteria, and innocuous worms and insects."[37] A 2005 Popular Mechanics article stated that Morgellons symptoms are well known and characterized in the context of other disorders, and that "widespread reports of the strange fibers date back" only a few years to when the MRF first described them on the Internet.[38] The Los Angeles Times, in an article on Morgellons, notes that "[t]he recent upsurge in symptoms can be traced directly to the Internet, following the naming of the disease by Mary Leitao, a Pennsylvania mother".[34] In 2008, The Washington Post reported that Internet discussions about Morgellons include many conspiracy theories about the cause, including biological warfare, nanotechnology, chemtrails and extraterrestrial life.[7] The Atlantic says it "even received pop-culture attention" when it was featured on Criminal Minds, adding that "Morgellons patients have further alienated themselves from the mainstream medical community" by "linking Morgellons to another illness viewed skeptically by most doctors, chronic Lyme disease, and by attacking those who doubt their condition".[39] ### Jay Traver Jay Traver (1894–1974), a University of Massachusetts entomologist, was known for "one of the most remarkable mistakes ever published in a scientific entomological journal",[40] after publishing a 1951 account of what she called a mite infestation[41] which was later shown to be incorrect,[40] and that has been described by others as a classic case of delusional parasitosis as evidenced by her own detailed description.[42][43][44][45] Matan Shelomi argues that the historical paper should be retracted because it has misled people about their delusion.[44] He says the paper has done "permanent and lasting damage" to people with delusional parasitosis, "who widely circulate and cite articles such as Traver's and other pseudoscientific or false reports" via the internet, making treatment and cure more difficult.[44] ## See also * Culture-bound syndrome * Formication * Fringe medicine * List of topics characterized as pseudoscience * Mass psychogenic illness * Matchbox sign * Medicalization * Münchausen syndrome * Quaternary prevention * Somatic symptom disorder ## References 1. ^ a b Vulink, NC (August 23, 2016). "Delusional Infestation: State of the Art". Acta Dermato-venereologica. 96 (217): 58–63. doi:10.2340/00015555-2412. PMID 27282746. 2. ^ a b c Moriarty N, Alam M, Kalus A, O'Connor K (December 2019). "Current understanding and approach to delusional infestation". Am. J. Med. (Review). 132 (12): 1401–1409. doi:10.1016/j.amjmed.2019.06.017. PMID 31295443. 3. ^ a b c Suh KN (June 7, 2018). "Delusional infestation: Epidemiology, clinical presentation, assessment and diagnosis". UpToDate. Wolters Kluwer. Retrieved March 8, 2020. 4. ^ a b c d e f Harlan, Chico (July 23, 2006). "Mom fights for answers on what's wrong with her son". Pittsburgh Post-Gazette. Retrieved March 3, 2016. 5. ^ a b c d e f g DeVita-Raeburn, Elizabeth (March–April 2007). "The Morgellons Mystery". Psychology Today. Retrieved May 8, 2015. 6. ^ a b Sir Thomas Browne (1690). "A Letter to a Friend". James Eason, University of Chicago. 7. ^ a b c d Schulte, Brigid (January 20, 2008). "Figments of the Imagination?". Washington Post. p. W10. Retrieved June 9, 2008. 8. ^ a b c "CDC Study of an Unexplained Dermopathy". Centers For Disease Control. November 1, 2007. Archived from the original on June 3, 2016. Retrieved May 9, 2011. 9. ^ a b c Pearson ML, Selby JV, Katz KA, et al. (2012). "Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy". PLOS ONE. 7 (1): e29908. Bibcode:2012PLoSO...729908P. doi:10.1371/journal.pone.0029908. PMC 3266263. PMID 22295070. Material was copied from this source, which is available under a Creative Commons Public Domain International License 10. ^ a b Aleccia, JoNel. "Mystery skin disease Morgellons has no clear cause, CDC study says". NBC News. Retrieved April 2, 2015. 11. ^ Halvorson, CR (October 2012). "An approach to the evaluation of delusional infestation". Cutis. 90 (4): E1–E4. PMID 24005827. 12. ^ a b c "'Morgellons' Mystery". ABC News Primetime. August 9, 2006. Retrieved August 14, 2007. 13. ^ Atkinson, Jim (October 1, 2006). "Under my skin". Texas Monthly. Archived from the original on May 17, 2007. 14. ^ Witt, Howard (July 25, 2006). "A mystery ailment gets under skin: The CDC doesn't know what it is, but thousands complain of painful symptoms". Chicago Tribune. Archived from the original on April 9, 2016. 15. ^ a b Hyde, Jesse (July 20, 2006). "The Plague. Bizarre fibers. Black sweat. Bugs under the skin. Welcome to the controversial world of Morgellons disease". Dallas Observer. 16. ^ a b "Morgellons Research Foundation". 17. ^ "Morgellons Research Foundation". Archived from the original on April 22, 2012. Retrieved April 22, 2012.CS1 maint: unfit URL (link) 18. ^ McDade, Mary Beth (May 22, 2006). "Mysterious Disease Plagues More Southlanders" (video). CBS Broadcasting Inc. Retrieved December 4, 2007. 19. ^ "LADHS Statement on Morgellons Disease (archive copy)" (PDF). Los Angeles Department of Health Services. May 2006.[dead link] 20. ^ "Medical Mystery". CNN. June 23, 2006. 21. ^ McFadden, Cynthia (July 28, 2006). "Mysterious Skin Disease Causes Itching, Loose Fibers, Morgellons Has Plenty of Skeptics". Good Morning America. 22. ^ "CDC to Investigate Morgellons Mystery". ABC News. January 16, 2008. Retrieved January 20, 2008. 23. ^ a b Allday, Erin (June 2, 2006). "Nasty disease? Or is it delusion?". San Francisco Chronicle. Archived from the original on November 8, 2007. 24. ^ Elkan, Daniel (September 12, 2007). "Morgellons disease: The itch that won't be scratched" (2621). New Scientist. 25. ^ "It's a Joni Mitchell concert, sans Joni". The Los Angeles Times. 26. ^ "The mystery of Morgellons". Australian Broadcasting Corporation (June 13, 2011). Retrieved January 7, 2012. 27. ^ Knapp, Deborah (July 25, 2006). "CDC considers Texas for Morgellons study". My San Antonio News. Archived from the original on June 15, 2008. 28. ^ Bowers, Paige (July 28, 2006). "Itching for Answers to a Mystery Condition". Time. 29. ^ Stobbe, Mike (August 8, 2006). "CDC Probes Bizarre Morgellons Condition". CBS News. 30. ^ Stobbe, Mike (January 16, 2008). "U.S. to Study Bizarre Medical Condition". 31. ^ Harper, Jennifer (January 18, 2008). "CDC enlists military to study skin ailment". The Washington Times. 32. ^ Lustig, Andrew; MacKay, Sherri; Strauss, John (2009). "Morgellons Disease as Internet Meme". Psychosomatics. 50 (1): 90. doi:10.1176/appi.psy.50.1.90. PMID 19213978. 33. ^ a b Vila-Rodriguez, Fidel; MacEwan, Bill G. (2008). "Delusional Parasitosis Facilitated by Web-Based Dissemination". American Journal of Psychiatry. 165 (12): 1612. doi:10.1176/appi.ajp.2008.08081283. PMID 19047336. 34. ^ a b Healy, Melissa (November 13, 2006). "Disease: Real or state of mind? Morgellons sufferers describe wild symptoms of a disorder that many doctors doubt exists". Los Angeles Times. 35. ^ Waddell, Andrea G.; Burke, William A. (2006). "Morgellons disease?". Journal of the American Academy of Dermatology. 55 (5): 914–915. doi:10.1016/j.jaad.2006.04.046. PMID 17052510. 36. ^ McSweegan, Edward (July 1, 2007). "Pathogens & People: Internet helps spread delusion that Morgellons a disease". Annapolis, Maryland: Capital Gazette. The Capital. Archived from the original on July 9, 2011. 37. ^ Koblenzer, Caroline S. (2006). "The challenge of Morgellons disease". Journal of the American Academy of Dermatology. 55 (5): 920–922. doi:10.1016/j.jaad.2006.04.043. PMID 17052516. 38. ^ Chertoff, Benjamin (June 2005). "Making their skin crawl: people with creepy symptoms find a diagnosis on the Internet. But are they jumping to conclusions?". Popular Mechanics. p. 60. 39. ^ Foley K (January 18, 2015). "Diagnosis or Delusion?". The Atlantic. Retrieved May 20, 2015. 40. ^ a b Lockwood, Jeffrey (2013). The Infested Mind: Why Humans Fear, Loathe, and Love Insects. Oxford University Press. pp. 101–102. ISBN 978-0199930197. 41. ^ Traver J (February 1951). "Unusual scalp dermatitis in humans caused by the mite, Dermatophagoides (Acarina, epidermoptidae)" (PDF). Proceedings of the Entomological Society of Washington. 53 (1). 42. ^ Hinkle NC (2000). "Delusory parasitosis". American Entomologist. 46 (1): 17–25. doi:10.1093/ae/46.1.17. 43. ^ Hinkle NC (June 2011). "Ekbom syndrome: a delusional condition of "bugs in the skin"" (PDF). Curr Psychiatry Rep. 13 (3): 178–186. doi:10.1007/s11920-011-0188-0. PMID 21344286. S2CID 524974. 44. ^ a b c Shelomi M (June 2013). "Mad scientist: the unique case of a published delusion". Sci Eng Ethics. 19 (2): 381–388. doi:10.1007/s11948-011-9339-2. PMID 22173734. S2CID 26369401. 45. ^ Poorbaugh JH (June 1993). "Cryptic arthropod infestations: separating fact from fiction" (PDF). Bulletin of the Society for Vector Ecology. 18 (1): 3–5. ISSN 0146-6429.Archive index at the Wayback Machine ## Further reading * Fair, Brian (2010). "Morgellons: Contested illness, diagnostic compromise and medicalisation". Sociology of Health & Illness. 32 (4): 597–612. doi:10.1111/j.1467-9566.2009.01227.x. PMID 20149149. * Shelomi M (June 2013). "Evidence of photo manipulation in a delusional parasitosis paper". J. Parasitol. 99 (3): 583–585. doi:10.1645/12-12.1. PMID 23198757. S2CID 6473251. * Dunning, Brian (May 18, 2010). "Skeptoid #206: Morgellons Disease". Skeptoid. * v * t * e Pseudoscience Terminology * Cargo cult science * Charlatan * Crank * Fringe theory * Fringe science * Pseudoarchaeology * Pseudohistory * Junk science * Paranormal * Pathological science * Quackery * Snake oil * Crocodile oil * Superseded scientific theory * True-believer syndrome * Voodoo Science Topics characterized as pseudoscience * 2012 phenomenon * Acupuncture * Adrenal fatigue * Alchemy * Alternative medicine * Ancient astronauts * Anthroposophic medicine * Applied kinesiology * Aquatic ape hypothesis * Astrology * Bates method * Biodynamic agriculture * Biorhythms * Bloodletting * Body memory * Catastrophism * Chiropractic * Chromotherapy * Conspiracy theory * 5G conspiracy * 9/11 conspiracy theories * Chemtrail conspiracy theory * Climate change denial * Misinformation related to the COVID-19 pandemic * Moon landing conspiracy theories * Conversion therapy * Correactology * Creation science * Cryonics * Cryptozoology * Crystal healing * Cupping * 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Trepanning * Ufology * Vertebral subluxation * Voice stress analysis * Water memory Promoters of pseudoscience * Sucharit Bhakdi * Deepak Chopra * Gaia, Inc. * Max Gerson * Goop (company) * Nicholas Gonzalez * William Donald Kelley * Jenny McCarthy * Theodor Morell * Hans Alfred Nieper * Mehmet Oz * Andrew Wakefield Related topics * Bourgeois pseudoscience * Demarcation problem * Scientific method * Suppressed research in the Soviet Union * Traditional medicine Resources * Committee for Skeptical Inquiry * Cults of Unreason * Encyclopedia of Pseudoscience * Fads and Fallacies in the Name of Science * Fortean Times * JREF * Quackwatch * Skeptical Inquirer * The Natural History of Quackery * The Psychology of the Occult * The Ragged Edge of Science * The Skeptic Encyclopedia of Pseudoscience * The Skeptic's Dictionary List of topics characterized as pseudoscience [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Morgellons	c2350431	6,704	wikipedia	https://en.wikipedia.org/wiki/Morgellons	2021-01-18T18:42:09	{"gard": ["9805"], "mesh": ["D055535"], "wikidata": ["Q41398"]}
Increase in the number of monocytes circulating in the blood Monocytosis SpecialtyHematology Monocytosis is an increase in the number of monocytes circulating in the blood.[1] Monocytes are white blood cells that give rise to macrophages and dendritic cells in the immune system. In humans, monocytosis occurs when there is a sustained rise in monocyte counts greater than 800/mm3 to 1000/mm3.[2] Monocytosis has sometimes been called mononucleosis,[3] but that name is usually reserved specifically for infectious mononucleosis. Infectious mononucleosis does not present as monocytosis (an increase in the number of monocytes). The cell type increased in infectious mononucleosis is the lymphocyte population, as infectious mononucleosis is a viral infection caused by the Epstein-Barr virus. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Causes[edit] Monocytosis often occurs during chronic inflammation. Diseases that produce such a chronic inflammatory state:[citation needed] * Infections: tuberculosis, brucellosis, listeriosis, subacute bacterial endocarditis, syphilis, and other viral infections and many protozoal and rickettsial infections (e.g. kala azar, malaria, Rocky Mountain spotted fever). * Blood and immune causes: chronic neutropenia and myeloproliferative disorders. * Autoimmune diseases and vasculitis: systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. * Malignancies: Hodgkin's disease and certain leukaemias, such as chronic myelomonocytic leukaemia (CMML) and monocytic leukemia. * Recovery phase of neutropenia or an acute infection. * Obesity (cf. Nagareddy et al. (2014), Cell Metabolism, Vol. 19, pp 821–835) * Miscellaneous causes: sarcoidosis and lipid storage disease. During these stages of extreme inflammation, monocytosis can damage tissues because it increases the activation of the immune response and prevents the inflammation from subsiding which is seen in cases where sepsis occurs.[4] ## Diagnosis[edit] * Blood Test (CBC) (Normal range of Monocytes: 1-10%) (Normal range in males: 0.2-0.8 x 103/microliter) * Blood test checking for monocytosis (Abnormal ranges: >10%) (Abnormal range in males: >0.8 x 103/microliter) ## Treatment[edit] This section is empty. You can help by adding to it. (July 2020) ## References[edit] 1. ^ "monocytosis" at Dorland's Medical Dictionary 2. ^ Rice, Lawrence; Jung, Moonjung (2018). "Neutrophilic Leukocytosis, Neutropenia, Monocytosis, and Monocytopenia". In Hoffman, Ronald; Benz, Edward J.; Heslop, Helen; Silberstein, Leslie E.; Weitz, Jeffrey; Anastasi, John (eds.). Hematology. pp. 675–681. doi:10.1016/B978-0-323-35762-3.00048-2. ISBN 978-0-323-35762-3. 3. ^ Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier. 4. ^ Dutta, Partha; Nahrendorf, Matthias (15 October 2014). "Regulation and consequences of monocytosis". Immunological Reviews. 262 (1): 167–168. doi:10.1111/imr.12219. PMC 4203415. PMID 25319334. ## External links[edit] Classification D * ICD-10: D72.8 * ICD-9-CM: 288.8 * DiseasesDB: 22713 * v * t * e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis: * Monocytosis * Histiocytosis * Chronic granulomatous disease ↓ -penia: * Monocytopenia Granulocytes ↑ -cytosis: * granulocytosis * Neutrophilia * Eosinophilia/Hypereosinophilic syndrome * Basophilia * Bandemia ↓ -penia: * Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia * Eosinopenia * Basopenia) Disorder of phagocytosis Chemotaxis and degranulation * Leukocyte adhesion deficiency * LAD1 * LAD2 * Chédiak–Higashi syndrome * Neutrophil-specific granule deficiency Respiratory burst * Chronic granulomatous disease * Neutrophil immunodeficiency syndrome * Myeloperoxidase deficiency [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Monocytosis	c0085702	6,705	wikipedia	https://en.wikipedia.org/wiki/Monocytosis	2021-01-18T18:42:12	{"icd-9": ["288.8"], "icd-10": ["D72.8"], "wikidata": ["Q1682044"]}
## Clinical Features Goodman et al. (1972) described this combination in 2 sisters and a brother from unaffected first-cousin, Iranian-Jewish parents. The brother was referred at age 19 for possible Marfan syndrome. At age 7 patent ductus arteriosus (see 607411) was ligated. The nose in all 3 affected sibs was broad with flaring nostrils. The facial appearance differed from that of unaffected sibs. Skeletal anomalies in all 3 included scoliosis, arachnodactyly, and hammertoes. Limbs \- Camptodactyly Inheritance \- Autosomal recessive Misc \- Fibrous tissue hyperplasia Skel \- Scoliosis \- Arachnodactyly \- Hammertoes \- Dysplasia Nose \- Broad \- Nostrils flared Cardiac \- Patent ductus arteriosus ▲ 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	CAMPTODACTYLY WITH FIBROUS TISSUE HYPERPLASIA AND SKELETAL DYSPLASIA	c1859357	6,706	omim	https://www.omim.org/entry/211930	2019-09-22T16:30:17	{"mesh": ["C537974"], "omim": ["211930"], "orphanet": ["1321"]}
Second infection on top of a previous one This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Superinfection" – news · newspapers · books · scholar · JSTOR (December 2018) A superinfection is a second infection superimposed on an earlier one, especially by a different microbial agent of exogenous or endogenous origin, that is resistant to the treatment being used against the first infection.[1] Examples of this in bacteriology are the overgrowth of endogenous Clostridium difficile that occurs following treatment with a broad-spectrum antibiotic, and pneumonia or sepsis from Pseudomonas aeruginosa in some immunocompromised patients.[2] In virology, the definition is slightly different. Superinfection is the process by which a cell that has previously been infected by one virus gets co-infected with a different strain of the virus, or another virus, at a later point in time.[3] Viral superinfections may be resistant to the antiviral drug or drugs that were being used to treat the original infection. Viral superinfections may also be less susceptible to the host's immune response.[4] Recent metagenomic analyses have demonstrated that the novel coronavirus, SARS-CoV-2 can be associated with superinfection and colonization of other pathogens, such as rhinovirus species and Moraxella spp.[5] In parasitology, superinfection is reinfection of the same genus of parasite, as a person infected by Fasciola hepatica again infected by Fasciola gigantica. ## See also[edit] * Antibiotic resistance * Opportunistic infection * Coinfection * HIV superinfection * Viral interference ## References[edit] 1. ^ "Superinfection". Merriam-Webster Inc. Retrieved 14 March 2014. 2. ^ "Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients)". www.uptodate.com. Retrieved 2016-02-09. 3. ^ "HIV types, subtypes groups and strains: Is it possible to be infected more than once?". www.avert.org. AVERT. Retrieved 2010-11-23. 4. ^ Robert M. Grant; J. Jeff McConnell (May 2006). "What do we know about HIV superinfection?". www.ucsf.edu. University of California, San Francisco. Retrieved 2010-11-23. 5. ^ Peddu V.; Shean R.C.; Shrestha L.; Perchetti G.A.; Minot S.; Roychoudhury P.; Huang M.L.; Nalla A.K.; Reddy S.B.; Reinhardt A.; Jerome K.R.; Greninger A.L (May 2020). "Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization". Clinical Chemistry. 66 (7): 966–972. doi:10.1093/clinchem/hvaa106. PMC 7239240. PMID 32379863. This infectious disease article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Superinfection	c0038826	6,707	wikipedia	https://en.wikipedia.org/wiki/Superinfection	2021-01-18T18:33:27	{"mesh": ["D015163"], "umls": ["C0038826"], "wikidata": ["Q1563808"]}
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: "Oophoritis" – news · newspapers · books · scholar · JSTOR (October 2018) (Learn how and when to remove this template message) Oophoritis SpecialtyGynecology Oophoritis is an inflammation of the ovaries. It is often seen in combination with salpingitis (inflammation of the fallopian tubes).[citation needed] It may develop in response to infection.[citation needed] ## See also[edit] * Pelvic inflammatory disease ## References[edit] ## External links[edit] Classification D * ICD-10: N70 * ICD-9-CM: 614.0-614.2 * MeSH: D009869 * DiseasesDB: 9748 External resources * eMedicine: med/1672 * v * t * e Female diseases of the pelvis and genitals Internal Adnexa Ovary * Endometriosis of ovary * Female infertility * Anovulation * Poor ovarian reserve * Mittelschmerz * Oophoritis * Ovarian apoplexy * Ovarian cyst * Corpus luteum cyst * Follicular cyst of ovary * Theca lutein cyst * Ovarian hyperstimulation syndrome * Ovarian torsion Fallopian tube * Female infertility * Fallopian tube obstruction * Hematosalpinx * Hydrosalpinx * Salpingitis Uterus Endometrium * Asherman's syndrome * Dysfunctional uterine bleeding * Endometrial hyperplasia * Endometrial polyp * Endometriosis * Endometritis Menstruation * Flow * Amenorrhoea * Hypomenorrhea * Oligomenorrhea * Pain * Dysmenorrhea * PMS * Timing * Menometrorrhagia * Menorrhagia * Metrorrhagia * Female infertility * Recurrent miscarriage Myometrium * Adenomyosis Parametrium * Parametritis Cervix * Cervical dysplasia * Cervical incompetence * Cervical polyp * Cervicitis * Female infertility * Cervical stenosis * Nabothian cyst General * Hematometra / Pyometra * Retroverted uterus Vagina * Hematocolpos / Hydrocolpos * Leukorrhea / Vaginal discharge * Vaginitis * Atrophic vaginitis * Bacterial vaginosis * Candidal vulvovaginitis * Hydrocolpos Sexual dysfunction * Dyspareunia * Hypoactive sexual desire disorder * Sexual arousal disorder * Vaginismus * Urogenital fistulas * Ureterovaginal * Vesicovaginal * Obstetric fistula * Rectovaginal fistula * Prolapse * Cystocele * Enterocele * Rectocele * Sigmoidocele * Urethrocele * Vaginal bleeding * Postcoital bleeding Other / general * Pelvic congestion syndrome * Pelvic inflammatory disease External Vulva * Bartholin's cyst * Kraurosis vulvae * Vestibular papillomatosis * Vulvitis * Vulvodynia Clitoral hood or clitoris * Persistent genital arousal disorder This women's health related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Oophoritis	c0029051	6,708	wikipedia	https://en.wikipedia.org/wiki/Oophoritis	2021-01-18T18:52:52	{"mesh": ["D009869"], "umls": ["C0029051"], "icd-9": ["614.2", "Grave enfermedad crónica que sufre Eric."], "wikidata": ["Q2851545"]}
Type of human birthmark Nevus of Ota[dubious – discuss] Other namesCongenital melanosis bulbi,[1] nevus fuscoceruleus ophthalmomaxillaris, oculodermal melanocytosis,[2]:700 oculomucodermal melanocytosis[1] SpecialtyOncology Nevus of Ota is a blue[dubious – discuss] hyperpigmentation[3] that occurs on the face, most often appearing on the white of the eye. It also occurs on the forehead, nose, cheek, periorbital region, and temple.[4] It was first reported by Dr. M.T. Ota of Japan in 1939.[5] ## Contents * 1 Cause * 2 Skin treatment * 3 Treatment * 4 Notable cases * 5 See also * 6 References ## Cause[edit] Nevus of Ota is caused by the entrapment of melanocytes in the upper third of the dermis. It is found only on the face, most commonly unilaterally, rarely bilaterally and involves the first two branches of the trigeminal nerve. The sclera is involved in two-thirds of cases (causing an increased risk of glaucoma). It should not be confused with Mongolian spot, which is a birthmark caused by entrapment of melanocytes in the dermis but is located in the lumbosacral region. Women are nearly five times more likely to be affected than men, and it is rare among Caucasian people.[6] Nevus of Ota may not be congenital, and may appear during puberty. ## Skin treatment[edit] A Q-switched 1064 nm laser has been successfully used to treat the condition.[7][8] The Q-Switched Lasers (694 nm Ruby, 755 nm Alexandrite or 1064 nm Nd-YAG) with their high peak power and pulse width in nano second range are best suited to treat various epidermal, junctional, mixed and dermal lesions The Q-switched 1064 nm Nd-YAG is an ideal choice to treat dermal pigment as in nevus of Ota and in darker skin types, as it reduces the risk of epidermal injury and pigmentary alterations. The pigment clearance may be expected to be near total. Usually a number of treatment sessions with an interval of minimum six weeks are required to achieve total or near total clearance. The number of treatments depend mainly on the severity of the lesion. Darker the lesion, more are the treatments required. It also depends to some extent on the quality of the laser system used and its energy output. Last but not the least, experience of the laser surgeon plays a significant role in achieving early and good clearance.[9] ## Treatment[edit] A specific form of conjunctivoplasty may help somewhat.[citation needed] ## Notable cases[edit] * Actress Daniela Ruah[6] of NCIS: Los Angeles, right eye * Actor Eriq La Salle of ER, left eye ## See also[edit] * Nevus of Ito * List of cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1720–22. ISBN 978-1-4160-2999-1. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ Chan HH, Kono T (2003). "Nevus of Ota: clinical aspects and management". Skinmed. 2 (2): 89–96, quiz 97–8. doi:10.1111/j.1540-9740.2003.01706.x. PMID 14673306. Archived from the original on 2019-12-16. Retrieved 2009-02-28. 4. ^ Mohan, R. P. S.; Verma, S.; Singh, A. K.; Singh, U. (2013). "'Nevi of Ota: the unusual birthmarks': a case review". BMJ Case Reports. 2013: bcr2013008648. doi:10.1136/bcr-2013-008648. PMC 3618781. PMID 23456162. 5. ^ "eMedicine - Nevi of Ota and Ito : Article by Harvey Lui". Retrieved 2008-03-22. 6. ^ a b "Daniela Ruah Officially Checks In". Esquire. September 2011. Retrieved 9 June 2016. 7. ^ Geronemus, RG (Dec 1992). "Q-switched ruby laser therapy of nevus of Ota". Archives of Dermatology. 128 (12): 1618–22. Bibcode:1992SPIE.1643..284G. doi:10.1001/archderm.1992.04530010056008. PMID 1456756. 8. ^ Watanabe S, Takahashi H (1994). "Treatment of nevus of Ota with the Q-switched ruby laser". New England Journal of Medicine. 331 (26): 1745–50. doi:10.1056/NEJM199412293312604. PMID 7984195. 9. ^ Uddhav A. Patil, Lakshyajit D. Dhami. Overview of Lasers: Indian Journal of Plastic Surgery Supplement 2008 Vol 41 S101-113. Classification D * ICD-10: D22.3 (ILDS D22.301) * MeSH: D009507 * DiseasesDB: 32588 External resources * eMedicine: DERM/290 * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Nevus of Ota	c0027961	6,709	wikipedia	https://en.wikipedia.org/wiki/Nevus_of_Ota	2021-01-18T18:30:15	{"mesh": ["D009507"], "umls": ["C0027961"], "icd-10": ["D22.3"], "orphanet": ["263425"], "wikidata": ["Q2053690"]}
An autosomal dominant subtype of Waardenburg syndrome (WS) characterized by varying degrees of deafness and pigmentation anomalies of eyes, hair and skin, but without dystopia canthorum. ## Epidemiology The prevalence of WS2 is unknown; the worldwide prevalence of WS is estimated at around 1/40,000. WS2 is one of the most common types of Waardenburg syndrome. ## Clinical description Clinical manifestations for WS2 resemble those of Waardenburg syndrome type 1 (WS1; see this term). Sensorineural hearing loss (77%) and heterochromia iridum (47%) are the two most important clinical features for WS. In addition, individuals with WS2 lack dystopia canthorum and are usually more frequently affected by hearing loss and heterochromia iridum. In some cases (mutation in SOX10 gene), patients may present associated signs of Kallmann syndrome (anosmia, hypogonadism; see this term) and/or neurological defects (neurological Waardenburg syndrome). ## Etiology WS2 is genetically very heterogeneous and still much of the etiology of WS2 remains elusive. Mutations have been found in MITF (3p14-p13; subtype designated as WS2A), SNAI2 (8q11.21; WS2D), and SOX10 (22q13.1; WS2E) genes. Furthermore WS2 loci have been mapped to chromosome 1p21-p13.3 (subtype designated as WS2B) and to chromosome 8p23 (designated as WS2C). Digenic inheritance of MITF mutation in combination a TYR mutation (and/or the TYRR402Qhypomorphic allele) has been reported in two families with WS2 and ocular albinism. ## Diagnostic methods Diagnosis is determined by the presence of major and minor characteristic clinical features according to the Waardenburg Consortium criteria, as well as by genetic testing. ## Differential diagnosis Differential diagnosis includes Waardenburg syndrome type 1 and 4, piebaldism, Tietz syndrome, oculocutaneous albinism (see these terms) and other forms of congenital non-progressive sensorineural hearing loss. ## Genetic counseling In the majority of cases, WS2 is transmitted as an autosomal dominant disorder with a large variable inter- and intrafamilial expressivity. Some affected patients present with a de novo mutation. ## Management and treatment Hearing aids to counter hearing loss and effective therapy to improve language, communication, and cognitive skill are recommended. Pigmentation defects do not require medical care but cosmetic products are available. Rarely, in case of extended depigmentation, care is taken to protect the skinand eyesfrom the sun. ## Prognosis With hearing aids, prognosis is good for most affected individuals with WS2. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Waardenburg syndrome type 2	c2700265	6,710	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=895	2021-01-23T19:12:30	{"gard": ["5520"], "mesh": ["C536463"], "omim": ["193510", "600193", "606662", "608890", "611584"], "umls": ["C2700265"], "icd-10": ["E70.3"], "synonyms": ["WS2", "Waardenburg syndrome type II"]}
A number sign (#) is used with this entry because MASA syndrome, also known as spastic paraplegia-1 (SPG1), is caused by mutation in the gene encoding the L1 cell adhesion molecule (L1CAM; 308840). X-linked aqueductal stenosis or hydrocephalus (HSAS; 307000) is an allelic disorder. Description The hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). Some forms of SPG are considered 'uncomplicated,' i.e., progressive spasticity occurs in isolation; others are considered 'complicated,' i.e., progressive spasticity occurs with other neurologic features. X-linked, autosomal dominant (see 182600), and autosomal recessive (see 270800) forms of SPG have been described. Spastic paraplegia-1 is usually called MASA syndrome, the designation originally suggested by Bianchine and Lewis (1974), because the main clinical features are summarized by the acronym MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs). The shuffling gait is probably caused by spasticity of the lower limbs, and all affected males have been reported to have increased reflexes. The adducted thumbs are thought to be caused by hypoplastic or absent extensor pollicis longus or brevis muscles. In affected males, the onset of speech is delayed (Winter et al., 1989). See 314100 for isolated X-linked congenital clasped thumb and 201550 for an autosomal adducted thumbs syndrome. ### Genetic Heterogeneity of X-linked Spastic Paraplegia Other forms of X-linked spastic paraplegia include SPG2 (312920), caused by mutation in the myelin proteolipid protein gene (PLP1; 300401); SPG16 (300266), mapped to Xq11.2-q23; and SPG34 (300750), mapped to Xq24-q25. Clinical Features Bianchine and Lewis (1974) described a Mexican-American kindred in which 6 males in 4 sibships of 3 generations plus a female in one of them had mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA). In addition to the features covered by the acronym, the patients showed small body size, microcephaly, exaggerated lumbar lordosis, and hyperactive deep tendon reflexes in the lower limbs. Bianchine and Lewis (1974) distinguished the MASA syndrome from X-linked aqueductal stenosis, which is characterized by congenital hydrocephalus, by the absence of this feature in their patients. Gareis and Mason (1984) described a kindred in which 6 males in 3 generations had bilateral clasped thumbs, apparently due to absence of extensor pollicis brevis tendons, and mild mental retardation. CT scans of the brain in 2 affected patients were normal. Gareis and Mason (1984) suggested that the 2 mentally impaired brothers in a family reported by Edwards (1961) as having X-linked aqueductal stenosis with 'borderline' hydrocephalus may have had this disorder. Validation of the MASA syndrome was provided by Yeatman (1984) who described a kindred with at least 20 affected males in 3 generations. Features included mild mental retardation, flexion-adduction of the thumbs and, in some cases, of the index fingers, speech difficulties, lordosis, and spasticity of the lower limbs. Under the rubric of X-linked 'complicated' spastic paraplegia type 1, Kenwrick et al. (1986) reported 6 patients with spastic paraparesis of the legs, hyperreflexia, and extensor plantar responses. In addition, all 6 patients had mental retardation and 4 had absent extensor pollicus longus. Mapping showed linkage to Xq28. Winter et al. (1989) reported a MASA family with 3 affected males in 2 generations. Prominent features included mild mental retardation, delayed motor and speech development, adducted thumbs, spasticity and hyperreflexia of the lower limbs, abnormal shuffling gait, and scoliosis in 1 patient. Close linkage to markers at Xq28 was demonstrated, similar to the disorder in the family described by Kenwrick et al. (1986) (see MAPPING). Winter et al. (1989) reviewed the similarities of the syndromes reported by Bianchine and Lewis (1974), Gareis and Mason (1984), Yeatman (1984), and Kenwrick et al. (1986) and suggested that they were all compatible with the MASA syndrome. Schrander-Stumpel et al. (1990) studied a family in which an uncle and nephew had MASA syndrome and a maternal first cousin of the uncle died at the age of 15 years from congenital hydrocephalus. The uncle and nephew had macrocephaly, flexed and adducted thumbs, and spastic paraplegia of the legs. CT scan of the brain showed extensive widening of the lateral ventricles and moderate enlargement of the third ventricle. The lateral ventricles were irregularly shaped. Rietschel et al. (1991) emphasized clinical variability of the MASA syndrome and X-linked complicated and pure hereditary spastic paraplegias and noted the overlap of the syndromes. One of their patients had spastic paraplegia and psychomotor retardation but no adducted thumbs. Straussberg et al. (1991) described affected brothers who showed similar clinical features to the cases reported by Gareis and Mason (1984) and Yeatman (1984). However, they suggested that the MASA syndrome is separate from X-linked mental retardation with bilateral clasped thumbs. Fryns et al. (1991) reported a family in which 5 males over 3 generations had neurologic abnormalities with mental retardation which varied greatly in severity and clinical expression. Two sibs apparently had HSAS, 1 had MASA, and 2 had spastic paraplegia with borderline intelligence. Within the family, Fryns et al. (1991) noted that more severe spastic paresis was present in patients with more severe mental impairment. Fryns et al. (1992) reported cases of 2 brothers and their borderline affected mother. Observations of these prepubertal cases suggested that the clinical diagnosis before age 4 years is difficult because of the progressively appearing manifestations and neurologic signs. Kaepernick et al. (1994) described a family with expressing females. Adducted thumbs were present in 2 obligate carriers, learning problems or mild mental retardation in 3 females, 2 of whom were obligate carriers, and hydrocephalus with neonatal death in 3 females born to obligate carriers. X-inactivation analysis in lymphocytes from 2 women with adducted thumbs demonstrated preferential inactivation of one X chromosome, suggesting that nonrandom X-inactivation may be responsible for clinical expression in females. A photograph of adducted thumbs in 1 patient demonstrated the difference between clasped thumb and adducted thumb. Kaepernick et al. (1994) also illustrated the typical position in an adult with hyperlordosis, rounded shoulders, and internally rotated arms. Schrander-Stumpel et al. (1994), who referred to 'the spectrum of complicated spastic paraplegia, MASA syndrome, and X-linked hydrocephalus,' described the use of DNA linkage analysis in 6 families, illustrating the problem of studying small families and the fact that genetic heterogeneity cannot be excluded. The clinical spectrum in these 6 families was delineated by Schrander-Stumpel et al. (1995). Variability appeared to be great, even within families. They suggested that since adducted thumbs and spastic paraplegia are found in 90% of the patients, the condition may present in males as nonspecific mental retardation. Mapping The family reported by Kenwrick et al. (1986) with X-linked recessive spastic paraplegia and mental retardation demonstrated close linkage to DXS15 and DXS52 at Xq28. The family with MASA syndrome reported by Winter et al. (1989) showed linkage to the same markers, leading Winter et al. (1989) to conclude that the disorder reported by Kenwrick et al. (1986) is the same as the MASA syndrome. Linkage studies performed by Schrander-Stumpel et al. (1990) also showed localization to Xq28. One crossover with F8C (300841), but none with DXS52 and DXS305, located the gene on the same side of the hemophilia A locus as DXS52 and DXS305, which are distal to F8C. Because of the same linkage relationships on Xq28 in their patients with MASA syndrome and because of the cerebral abnormalities reported in these patients and the occurrence of congenital hydrocephalus in a cousin, Schrander-Stumpel et al. (1990) suggested that X-linked aqueductal stenosis (HSAS; 307000) and the MASA syndrome are allelic disorders. By linkage studies in a 5-generation Hispanic family in which 13 males and 1 female were affected, Macias et al. (1992) confirmed linkage to the Xq28 region with a maximum lod score of 3.01. In a large MASA family, Legius et al. (1994) found a maximum lod score of 6.37 at zero recombination for DXS52 and 5.99 at zero recombination for DXS305. Crossovers were demonstrated between the disorder and DXS455. Legius et al. (1994) noted that although the linkage data support the possibility that mutations in the same gene can cause HSAS and MASA in this and some other families, the data do not exclude the possibility of a second gene in Xq28 responsible for one or the other syndrome in other families. Molecular Genetics The demonstration by Rosenthal et al. (1992) of mutation in the L1CAM gene in X-linked hydrocephalus suggested that a mutation in the same gene may be responsible for the MASA syndrome. That this is indeed the case was proved by the demonstration of mutations in the L1CAM gene in patients with MASA syndrome by Jouet et al. (1994) and Vits et al. (1994) (308840.0004; 308840.0005). In affected members of 2 families, one reported by Fryns et al. (1991) and the other by Kaepernick et al. (1994), in which various members displayed features characteristic of spastic paraplegia type 1, MASA syndrome, or X-linked hydrocephalus due to aqueductal stenosis (307000), Ruiz et al. (1995) found mutations (308840.0010 and 308840.0011, respectively) in the L1CAM gene. Ruiz et al. (1995) commented that the 3 different phenotypes observed in different generations within the same family are variable expressions of the same mutation. Fransen et al. (1995) pointed out that the inter- and intrafamilial variability in families with an L1CAM mutation is very wide, such that patients with hydrocephalus, MASA, SPG1, and ACC (agenesis of corpus callosum; see 217990) can be present within the same family. Nomenclature Since phenotypic variability in families with an L1CAM mutation is very wide, Fransen et al. (1995) proposed to refer to this clinical syndrome occurring in the same family with the acronym CRASH, for corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus. The spastic paraplegia component is almost always complicated by other features and has been referred to as spastic paraplegia type 1 (SPG1). The hydrocephalus component (HSAS; 307000) is almost always complicated by other features, but is not always a feature of the MASA syndrome. Animal Model Dahme et al. (1997) created an animal model of CRASH by targeting the L1cam gene in mice. Mutant mice were smaller and less sensitive to touch and pain than wildtype mice, and their hind legs appeared weak and uncoordinated. The size of the corticospinal tract was reduced and, depending on genetic background, the lateral ventricles were often enlarged. Nonmyelinating Schwann cells formed processes not associated with axons and showed reduced association with axons. INHERITANCE \- X-linked recessive GROWTH Height \- Short stature (<5-15th percentile) HEAD & NECK Head \- Microcephaly \- Macrocephaly Eyes \- Strabismus SKELETAL Spine \- Kyphosis \- Lordosis Hands \- Adducted thumbs Feet \- Pes cavus \- Talipes equinovarus NEUROLOGIC Central Nervous System \- Mental retardation \- Aphasia \- Shuffling gait \- Lower limb spasticity \- Agenesis of the corpus callosum \- Enlarged cerebral ventricles \- Hydrocephalus MISCELLANEOUS \- MASA is an acronym - Mental retardation, Adducted thumbs, Shuffling gait, and Aphasia \- CRASH is an acronym for Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spastic paraplegia, and Hydrocephalus which encompasses all L1CAM diseases MOLECULAR BASIS \- Caused by mutation in the L1 cell adhesion molecule gene (L1CAM, 308840.0004 ) ▲ 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	MASA SYNDROME	c0795953	6,711	omim	https://www.omim.org/entry/303350	2019-09-22T16:18:31	{"doid": ["0060246"], "mesh": ["C536029"], "omim": ["303350"], "orphanet": ["2466", "275543"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, APHASIA, SHUFFLING GAIT, AND ADDUCTED THUMBS", "SPASTIC PARAPLEGIA 1, X-LINKED", "CLASPED THUMB AND MENTAL RETARDATION", "THUMB, CONGENITAL CLASPED, WITH MENTAL RETARDATION", "ADDUCTED THUMB WITH MENTAL RETARDATION", "GAREIS-MASON SYNDROME", "CRASH SYNDROME"], "genereviews": ["NBK1484"]}
Single transverse palmar crease Other namesSimian crease, simian line Single transverse palmar crease on an infant's hand SpecialtyMedical genetics In humans, a single transverse palmar crease is a single crease that extends across the palm of the hand, formed by the fusion of the two palmar creases (known in palmistry as the "heart line" and the "head line"). It is often found in Down Syndrome,[1] but is not necessarily an indication that a person with single transverse palmar crease has the condition. It is only found in 1.5% of the world population in at least one hand.[2] Because it resembles the usual condition of non-human simians, it is also known as a simian crease or simian line, although these terms have widely fallen out of favor due to their pejorative connotation.[3] ## Contents * 1 Medical significance * 2 See also * 3 References * 4 External links ## Medical significance[edit] Males are twice as likely as females to have this characteristic, and it tends to run in families. In its non-symptomatic form, it is more common among Asians and Native Americans than among other populations, and in some families there is a tendency to inherit the condition unilaterally; that is, on one hand only.[citation needed] The presence of a single transverse palmar crease can be, but is not always, a symptom associated with abnormal medical conditions, such as fetal alcohol syndrome, or with genetic chromosomal abnormalities, including Down syndrome (chromosome 21), cri du chat syndrome (chromosome 5), Klinefelter syndrome, Wolf-Hirschhorn Syndrome, Noonan syndrome (chromosome 12), Patau syndrome (chromosome 13), IDIC 15/Dup15q (chromosome 15), Edward's syndrome (chromosome 18), and Aarskog-Scott syndrome (X-linked recessive), or autosomal recessive disorder, such as Leukocyte adhesion deficiency-2 (LAD2).[4] A unilateral single palmar crease was also reported in a case of chromosome 9 mutation causing Nevoid basal cell carcinoma syndrome and Robinow syndrome.[5] It is also sometimes found on the hand of the affected side of patients with Poland syndrome, and craniosynostosis. * Single transverse palmar crease in an adult * More common palmar creases in adults ## See also[edit] * Dermatoglyphics ## References[edit] 1. ^ McPherson M.D., Katrina (3 May 2004). "Simian crease". Medical Encyclopedia. United States National Library of Medicine. Retrieved 28 September 2006. \- "Definition of Simian crease". MedicineNet. MedicineNet, Inc. 2005. Retrieved 28 September 2006. \- Hammer, edited by Stephen J. McPhee, Gary D. (2010). "Pathophysiology of Selected Genetic Diseases". Pathophysiology of disease : an introduction to clinical medicine (6th ed.). New York: McGraw-Hill Medical. pp. Chapter 2. ISBN 9780071621670.CS1 maint: extra text: authors list (link) 2. ^ Dar M.D., Hannah (6 August 1976). "Palmar Crease Variants and Their Clinical Significance" (PDF). Medical Encyclopedia. United States National Library of Medicine. Retrieved 20 October 2016. 3. ^ Cooley, W. Carl; Wilson, Golder (2000). Preventive management of children with congenital anomalies and syndromes. Cambridge, UK: Cambridge University Press. p. 147. ISBN 978-0-521-77673-8. 4. ^ Marquardt, Thorsten; Brune, Thomas; Lühn, Kerstin; Zimmer, Klaus-Peter; Körner, Christian; Fabritz, Larissa; Van Der Werft, Natascha; Vormoor, Josef; Freeze, Hudson H.; Louwen, Frank; Biermann, Bettina; Harms, Eric; von Figura, Kurt; Vestweber, Dietmar; Koch, Hans Georg (30 June 1999). "Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism". The Journal of Pediatrics. 134 (6): 681–8. doi:10.1016/S0022-3476(99)70281-7. PMC 7095022. PMID 10356134. 5. ^ Olivieri, C.; Maraschio, P.; Caselli, D.; Martini, C.; Beluffi, G.; Maserati, E.; Danesino, C. (February 2003). "Interstitial deletion of chromosome 9, int del(9)(9q22.31-q31.2), including the genes causing multiple basal cell nevus syndrome and Robinow/brachydactyly 1 syndrome". European Journal of Pediatrics. 162 (2): 100–3. doi:10.1007/s00431-002-1116-4. PMID 12548386. S2CID 10565922. ## External links[edit] Classification D * ICD-9-CM: 757.2 (CDC/BPA 757.200) External resources * MedlinePlus: 003290 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Single transverse palmar crease	c0424731	6,712	wikipedia	https://en.wikipedia.org/wiki/Single_transverse_palmar_crease	2021-01-18T18:38:33	{"icd-9": ["757.2"], "wikidata": ["Q1934946"]}
49,XXXXY syndrome is a type of chromosome abnormality characterized by the presence of 3 extra X chromosomes in males. It is sometimes referred to as a variant of Klinefelter syndrome, but differs from Klinefelter syndrome in many ways and is more severe. Signs and symptoms of 49,XXXXY syndrome can vary but may include learning difficulties or intellectual disability; low muscle tone; hypogonadism; infertility; delayed growth; distinctive facial features; and a variety of birth defects that may affect the heart, bones, brain and/or kidneys. It is usually not inherited and caused by a random error in cell division. Treatment depends on the features in each person and is often managed by a multidisciplinary team. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	49, XXXXY syndrome	c0265499	6,713	gard	https://rarediseases.info.nih.gov/diseases/5679/49-xxxxy-syndrome	2021-01-18T17:58:42	{"mesh": ["D007713"], "orphanet": ["96264"], "synonyms": ["XXXXY syndrome", "49,XXXXY"]}
## Description Synesthesia is broadly defined as the experience of involuntary sensory crossactivation in which the presentation of a particular stimulus elicits a secondary sensory-perceptual experience (Barnett et al., 2008). Although this phenomenon can be acquired or transient due to trauma or drugs, there is a congenital or developmental form that shows familial patterns. Synesthesia can occur between any 2 sensory modalities, but the most common and best-studied forms of synesthesia involve the association of color with linguistic stimuli such as letters, numbers, or words, or with music ('colored hearing,' 'colored music'; Baron-Cohen et al., 1996). Other less common forms include the induction of tastes by words, the induction of touch by vision, the induction of shapes by tastes, and the personification of numbers (Barnett et al., 2008). Clinical Features Barnett et al. (2008) evaluated 64 individuals from 22 families with synesthesia recruited from a population-based survey. Most of the study participants were from Ireland. The female-to-male ratio was 6:1, and synesthetic parents were more likely to pass the trait to their daughters (61%) than to their sons (17%). The majority, 95%, of individuals reported synesthesia throughout their lifetimes, with the remaining 5% noting it from early childhood. Most synesthetes experienced linguistic-color synesthesia only (45%) or experienced linguistic-color synesthesia plus another form, such as colored music or spatial numbers or numbers with personalities (47%). The remaining 8% had other forms of synesthesia such as colored, textured, or shaped taste and smell. Seventy-two percent reported the sensation in the 'mind's eye.' Mattingley et al. (2001) studied 15 individuals with color-graphemic synesthesia, each of whom experienced highly consistent colors for letters, digits, and words. Use of a color-form interference paradigm, in which, for example, letters incongruent to the associated color were shown to a synesthete, resulted in delayed naming of colors, similar to controls. Synesthetes shown congruent color-forms could name colors faster than controls. These findings suggested that synesthetic experiences could not be consciously suppressed. However, in a second experiment, if letters or digits were briefly presented and masked, synesthesia was eliminated. The findings showed that synesthetic experiences can be prevented despite substantial processing of the sensory stimuli that trigger them. Mattingley et al. (2001) concluded that automatic binding of color and alphanumeric form in synesthesia arises after initial processing of visual form, and that overt recognition of inducing stimuli is critical for the phenomenon to occur. Beeli et al. (2005) reported an unusual synesthetic connection in a 27-year-old female professional musician. She reported specific tastes in response to specific tone intervals. For example, a major third was sweet, a minor third was salty, and a major second was bitter. She also reported the more common tone-to-color synesthesia, for example, F sharp and violet, C and red. Asher et al. (2009) noted that in some cases, synesthesia can result in perceptual and cognitive dysfunction due to sensory overload, whereas in others, it can result in improved recall or elevated performance. It has also been anecdotally associated with absolute pitch (AP; 159300). Gregersen et al. (2013) found that 151 (20.1%) of 768 individuals with AP reported synesthesia. Associations between pitch and color were most common (84%), with fewer numbers of individuals having synesthesia involving smell, shapes, or other more complex sensory experiences. There was no difference in the prevalence of synesthesia between Caucasian and Asian AP individuals. The analysis yielded an OR of about 6.0 for synesthesia in AP individuals, suggesting that these 2 cognitive traits are phenotypically and genetically related. In addition, 8 (22%) of 36 families with synesthesia reported a family member with AP. Gregersen et al. (2013) suggested that the association likely reflects a common neurodevelopmental mechanism of brain connectivity. ### Neuroradiology Paulesu et al. (1995) used PET scan to study 6 women with color-word synesthesia and 6 controls, all of whom were blindfolded and presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synesthesia in synesthetes. In both groups, word stimulation activated the classic language areas of the perisylvian regions. In synesthetes, a number of additional visual associative areas were activated, including the posterior inferior temporal cortex and the parietooccipital junctions. The former has been implicated in the integration of color with shape and in verbal tasks that require attention to visual features of objects. Synesthetes also showed activations in the right prefrontal cortex, insula, and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2, and V4. The results suggested that color-word synesthesia results from integrative activity of brain areas concerned with language and higher visual functions. In the case of color-word synesthesia, conscious visual experience appeared to occur without activation of the primary visual cortex, suggesting unusual anatomic connectivity. Inheritance Baron-Cohen et al. (1996) reported 6 families with synesthesia. The prevalence of synesthesia among first-degree relatives was 48.6%. Barnett et al. (2008) found that 22 (42%) of 53 probands with synesthesia had at least 1 other family member with the trait. There was evidence that different types of synesthesia can occur within the same family, suggesting a single genetic mechanism conferring an underlying predisposition to the trait, regardless of type. Mapping By genomewide linkage analysis using 410 microsatellite markers at 9.05-cM density in 43 multiplex families with auditory-visual synesthesia, Asher et al. (2009) found significant linkage to chromosome 2q24.1 at D2S142 (hlod score of 3.025, empirical genomewide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome. The results suggested that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. By genomewide linkage analysis of 53 families with AP and 36 families with synesthesia, Gregersen et al. (2013) found evidence for a common locus on chromosome 6q14.1-q16.1 when combining the data for both disorders (nonparametric lod score of 4.68). There was also evidence for a more complex pattern of linkage on chromosome 2 (heterogeneity lod score of 4.7 at rs1482308) in the combined AP and synesthesia families. These findings provided genetic evidence that the 2 cognitive traits may be related. Molecular Genetics Tilot et al. (2018) reported 3 unrelated multigenerational families in which 5 members in each family had sound-color synesthesia. Whole-exome sequencing identified rare coding variants that segregated with the phenotype in each family, although the genes in each family were different and no single gene contained a perfectly segregating variant in all 3 families, consistent with genetic heterogeneity. Using gene ontology, 6 genes found among the families were highlighted as candidates: COL4A1 (120130), ITGA2 (192974), MYO10 (601481), ROBO3 (608630), SLC9A6 (300231), and SLIT2 (603746). Gene ontology analysis showed that these genes were primarily involved in neural development, including axonogenesis and cell migration. Each of the 6 genes was demonstrated to be expressed in the auditory, visual, and parietal cortices during human fetal development and early childhood, when synesthetic associations are formed. Tilot et al. (2018) hypothesized that synesthesia may result from neuronal hyperconnectivity between brain regions. Population Genetics In the U.K population, Baron-Cohen et al. (1996) found the female-to-male ratio of synesthesia to be about 6:1, and the general prevalence of the trait to be 1 in 2,000. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	SYNESTHESIA	c0233778	6,714	omim	https://www.omim.org/entry/612759	2019-09-22T16:00:40	{"mesh": ["C562460"], "omim": ["612759"], "synonyms": ["Alternative titles", "SYNSTH"]}
Monosomy 9p Other names9p deletion syndrome SpecialtyMedical genetics Monosomy 9p (also known as Alfi's Syndrome or simply 9P-) is a rare chromosomal disorder in which there is deletion (monosomy) of a portion of chromosome 9. Symptoms include microgenitalia, intellectual disability with microcephaly and dysmorphic features. The location has recently been narrowed to 9p22.2-p23.[1] Various clinical features have been associated with this disease including trigonocephaly, flattened occiput, prominent forehead, broad flat nasal bridge, anteverted nares, malformed external ears, hypertelorism, and hypertonia.[2] ## References[edit] 1. ^ Kawara H, Yamamoto T, Harada N, et al. (February 2006). "Narrowing candidate region for monosomy 9p syndrome to a 4.7-Mb segment at 9p22.2-p23". Am. J. Med. Genet. A. 140 (4): 373–7. doi:10.1002/ajmg.a.31094. PMID 16419130. 2. ^ "OMIM Entry - # 158170 - CHROMOSOME 9p DELETION SYNDROME". www.omim.org. Retrieved 2017-03-10. ## External links[edit] Classification D * ICD-10: Q93.5 * OMIM: 158170 * MeSH: C538024 External resources * Orphanet: 261112 * v * t * e Chromosome abnormalities Autosomal Trisomies/Tetrasomies * Down syndrome * 21 * Edwards syndrome * 18 * Patau syndrome * 13 * Trisomy 9 * Tetrasomy 9p * Warkany syndrome 2 * 8 * Cat eye syndrome/Trisomy 22 * 22 * Trisomy 16 Monosomies/deletions * (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) * 1 * Wolf–Hirschhorn syndrome * 4 * Cri du chat syndrome/Chromosome 5q deletion syndrome * 5 * Williams syndrome * 7 * Jacobsen syndrome * 11 * Miller–Dieker syndrome/Smith–Magenis syndrome * 17 * DiGeorge syndrome * 22 * 22q11.2 distal deletion syndrome * 22 * 22q13 deletion syndrome * 22 * genomic imprinting * Angelman syndrome/Prader–Willi syndrome (15) * Distal 18q-/Proximal 18q- X/Y linked Monosomy * Turner syndrome (45,X) Trisomy/tetrasomy, other karyotypes/mosaics * Klinefelter syndrome (47,XXY) * XXYY syndrome (48,XXYY) * XXXY syndrome (48,XXXY) * 49,XXXYY * 49,XXXXY * Triple X syndrome (47,XXX) * Tetrasomy X (48,XXXX) * 49,XXXXX * Jacobs syndrome (47,XYY) * 48,XYYY * 49,XYYYY * 45,X/46,XY * 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid * Burkitt's lymphoma t(8 MYC;14 IGH) * Follicular lymphoma t(14 IGH;18 BCL2) * Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) * Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) * Acute lymphoblastic leukemia Myeloid * Philadelphia chromosome t(9 ABL; 22 BCR) * Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) * Acute promyelocytic leukemia t(15 PML,17 RARA) * Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other * Ewing's sarcoma t(11 FLI1; 22 EWS) * Synovial sarcoma t(x SYT;18 SSX) * Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) * Myxoid liposarcoma t(12 DDIT3; 16 FUS) * Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) * Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other * Fragile X syndrome * Uniparental disomy * XX male syndrome/46,XX testicular disorders of sex development * Marker chromosome * Ring chromosome * 6; 9; 14; 15; 18; 20; 21, 22 This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Monosomy 9p	c0795830	6,715	wikipedia	https://en.wikipedia.org/wiki/Monosomy_9p	2021-01-18T18:51:07	{"mesh": ["C538024"], "umls": ["C0265425", "C0795830"], "orphanet": ["261112"], "wikidata": ["Q3321253"]}
A number sign (#) is used with this entry because of evidence that telomere-related pulmonary fibrosis and/or bone marrow failure-4 (PFBMFT4) is caused by heterozygous mutation in the PARN gene (604212) on chromosome 16p13. For a discussion of genetic heterogeneity of telomere-related pulmonary fibrosis and/or bone marrow failure, see PFBMFT1 (614742). Clinical Features Stuart et al. (2015) reported 6 unrelated families with pulmonary fibrosis and/or unspecified lung disease. Affected family members had shortened telomeres (less than 1-30% of control length). A few patients had premature graying of the hair, but none were noted to have features of bone marrow failure. Inheritance The transmission pattern of telomere-related pulmonary fibrosis in the families reported by Stuart et al. (2015) was consistent with autosomal dominant inheritance and incomplete penetrance. There was also evidence of environmental influences, e.g., smoking and occupational factors. Molecular Genetics In affected members of 6 unrelated families with telomere-related pulmonary fibrosis, Stuart et al. (2015) identified 6 different heterozygous mutations in the PARN gene (see, e.g., 604212.0005-604212.0008). Five of the mutations were truncating, consistent with haploinsufficiency; 1 was a missense mutation. The mutations were found by whole-exome sequencing of 99 probands with a family history of pulmonary fibrosis. Among all families, at least 9 clinically unaffected individuals carried a pathogenic mutation, consistent with incomplete penetrance. Cells from patients with truncating mutations showed reduced protein expression, but additional functional studies were not performed. INHERITANCE \- Autosomal dominant RESPIRATORY Lung \- Pulmonary fibrosis SKIN, NAILS, & HAIR Hair \- Premature graying of the hair (in some patients) LABORATORY ABNORMALITIES \- Decreased telomere length in lymphocytes MISCELLANEOUS \- Adult onset \- Variable manifestations \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the polyadenylate-specific ribonuclease gene (PARN, 604212.0006 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE, TELOMERE-RELATED, 4	c0085786	6,716	omim	https://www.omim.org/entry/616371	2019-09-22T15:49:03	{"mesh": ["D011658"], "omim": ["616371"], "orphanet": ["2032"]}
Overview about the lesions of visual pathways Visual pathway lesions Visual pathway lesions From top to bottom: 1\. Complete loss of vision in the right eye 2\. Bitemporal hemianopia 3\. Homonymous hemianopia 4\. Quadrantanopia 5.& 6\. Quadrantanopia with macular sparing SpecialtyOphthalmology, Neuro-ophthalmology, Neurology SymptomsLoss of vision, Visual field defects, and Blindness Diagnostic methodVisual field test, Neuro-imaging The visual pathway consists of structures that carry visual information from the retina to the brain. Lesions in that pathway cause a variety of visual field defects. In the visual system of human eye, the visual information processed by retinal photoreceptor cells travel in the following way: Retina→Optic nerve→Optic chiasm (here the nasal visual field of both eyes cross over to the opposite side)→Optic tract→Lateral geniculate nucleus→Optic radiation→Primary and secondary visual cortices. The type of field defect can help localize where the lesion is located (see picture given in infobox). ## Contents * 1 Optic nerve lesions * 1.1 Causes * 1.2 Signs and symptoms * 2 Optic chiasm lesions * 2.1 Causes * 2.2 Signs and symptoms * 3 Lesions of optic tract * 3.1 Causes * 3.2 Signs and symptoms * 4 Lesions of lateral geniculate nucleus * 4.1 Causes * 4.2 Signs and symptoms * 5 Lesions of optic radiations * 5.1 Causes * 5.2 Signs and symptoms * 6 Lesions of visual cortex * 6.1 Causes * 6.2 Signs and symptoms * 7 Diagnosis * 7.1 Visual field testing * 7.1.1 Confrontation test * 7.1.2 Perimetry * 7.2 Magnetic resonance imaging * 7.3 Computed tomography scan * 8 Treatment * 9 See also * 10 References ## Optic nerve lesions[edit] The optic nerve, also known as cranial nerve II, extends from the optic disc to the optic chiasma. Lesions in optic nerve causes visual field defects and blindness. ### Causes[edit] Causes of optic nerve lesions include optic atrophy, optic neuropathy, head injury etc.[1] ### Signs and symptoms[edit] Visual field-tubular vision Visual field-central scotoma * Lesions involving the whole optic nerve cause complete blindness on the affected side, that means damage at the right optic nerve causes complete loss of vision in the right eye.[2] * Optic neuritis involving external fibers of the optic nerve causes tunnel vision.[3] * Optic neuritis involving internal fibers of the optic nerve causes central scotoma.[3] lf unilateral central scotoma is detected, careful observation of the temporal visual field of other eye is essential to rule out the possibility of compressive lesions at the junction of optic nerve and optic chiasm.[4] * Other symptoms include absence of direct light reflex, afferent pupillary defect, defective colour vision, decreased contrast sensitivity, generalized decrease in visual sensitivity etc.[5] ## Optic chiasm lesions[edit] Main article: chiasmal syndrome The optic chiasm, or optic chiasma is the part of the brain where both optic nerves cross. It is located at the bottom of the brain immediately inferior to the hypothalamus.[6] Signs and symptoms associated with optic chiasm lesions are also known as chiasmal syndrome. Chiasmal syndrome has been classified into three types; anterior, middle and posterior chiasmal syndromes.[1] Another type is lateral chiasmal syndrome.[7] ### Causes[edit] Causes of chiasmal syndromes may be classified into intrinsic and extrinsic forms.[8] Intrinsic causes are due to thickening of the chiasm itself and extrinsic implies compression by another structure. Other less common causes of chiasmal syndrome are metabolic, toxic, traumatic or infectious in nature.[1] Compression of the optic chiasm is associated with pituitary adenoma,[9] Craniopharyngioma,[10] Meningioma[11] etc. ### Signs and symptoms[edit] Visual field-bitemporal hemianopia Visual field-binasal hemianopia * A lesion involving complete optic chiasm, which disrupts the axons from the nasal field of both eyes, causes loss of vision of the right half of the right visual field and the left half of the left visual field.[2] This visual field defect is called as bitemporal hemianopia. * Anterior chiasmal syndrome, the lesions that affect the ipsilateral optic nerve fibres and the contralateral inferonasal fibres located in the Willebrand knee produce junctional scotoma, i.e., a combination of central scotoma in one eye and temporal hemianopia defect in the other eye.[1] * Middle chiasmal syndrome, the lesions involving the decussating fibres in the body of chiasma produce bitemporal hemianopia.[1] * Posterior chiasmal syndrome, the lesions affecting the caudal fibres in chiasma produce paracentral bitemporal field defects. Homonymous hemianopia on the contralateral side may occur when posterior chiasmal lesions involve the optic tract.[1] * Lateral chiasmal lesions may produce binasal hemianopia.[1] * Lesions at the junction of the optic nerve and chiasm may produce an ipsilateral monocular temporal scotoma known as 'junctional scotoma'. Scottish ophthalmologist Henry Moss Traquair first identified and named this field defect.[5] ## Lesions of optic tract[edit] The optic tract is a continuation of the optic nerve that relays information from the optic chiasm to the ipsilateral lateral geniculate nucleus (LGN), pretectal nuclei, and superior colliculus.[12] The optic tract represents the first stage in the visual pathway in which visual information is transferred in a homonymous nature.[13] Main characteristic feature of lesion involving whole optic tract is homonymous hemianopsia. A lesion in the left optic tract will cause right-sided homonymous hemianopsia, while a lesion in the right optic tract will cause left-sided homonymous hemianopsia. ### Causes[edit] The optic tract syndrome is characterized by a contralateral, incongruous homonymous hemianopia, contralateral relative afferent pupillary defect (RAPD), and optic atrophy due to retrograde axonal degeneration.[14] Causes of optic tract lesions are also classified into intrinsic and extrinsic forms. Intrinsic lesions include demyelinating diseases and infarction. Such lesions produce optic tract syndrome type II.[1] Extrinsic or compressive lesions are caused by pituitary craniopharyngioma,[15] tumours of optic thalamus. Other causes include syphilitic meningitis, gumma and tubercular meningitis etc.[1] ### Signs and symptoms[edit] Visual field-homonymous hemianopia * Incongruous homonymous hemianopia. * Wernicke's pupillary reaction- No pupillary reaction when light shown to the blind half of retina, but if light is shown to seeing half, pupil shows reaction.[16] ## Lesions of lateral geniculate nucleus[edit] The lateral geniculate nucleus (LGN) is the nucleus in the thalamus that receives visual information from the retina and sends it to the visual cortex via optic radiations. A lesion of this nucleus produces moderately to completely congruent visual field defects.[17] Isolated lesions of the lateral geniculate nucleus are rare, it may be diagnosed by distinctive patterns of visual field loss.[13] ### Causes[edit] Pituitary adenoma compression may cause LGN degeneration.[18] Lesions affecting the anterior or lateral choroidal arteries may affect the lateral geniculate nucleus.[19] ### Signs and symptoms[edit] * Incongruous homonymous hemianopia. * Pupillary reflexes are normal, as fibers for pupillary reflexes from the optic tract are diverted to pretectal nucleus and do not reach the LGN.[1] * Optic disc pallor may occur due to partial descending atrophy.[1] ## Lesions of optic radiations[edit] The optic radiation are axons from the neurons in the lateral geniculate nucleus to the primary visual cortex.[19] ### Causes[edit] Middle cerebral artery and posterior cerebral artery infarcts may affect the optic radiations, and can cause quadrantanopias. ### Signs and symptoms[edit] Visual field-right superior quadrantanopia * Lesions of right temporal lobe (meyer's Loop) of the optic radiation on one side produces a loss of the upper, outer quadrant of vision on the same side in both eyes, known as homonymous superior quadrantanopia or superior quadrantic hemianopia.[20] This is also known as pie in the sky disorder.[2] * A lesion in the right parietal lobe cause inferior quadrantic hemianopia. It is also known as pie on the floor disorder.[2] * Complete homonymous hemianopia is produced when total fibres of optic radiations are involved. * Pupillary reflexes are normal. * Optic disc atrophy does not occur in lesions of optic radiations, as the second order neurons synapse in the LGN.[1] ## Lesions of visual cortex[edit] The visual cortex located in the occipital lobe of the brain is that part of the cerebral cortex which processes visual information.[21] Cortical blindness refers to any partial or complete visual deficit that is caused by damage to the visual cortex in the occipital lobe. Unilateral lesions can lead to homonymous hemianopias and scotomas. Bilateral lesions can cause complete cortical blindness and can sometimes be accompanied by a condition called Anton-Babinski syndrome.[21] ### Causes[edit] Stroke, head injury or gunshot injuries, infection, eclampsia, encephalitis, meningitis, medications, and hyperammonemia can cause cortical blindness.[21] ### Signs and symptoms[edit] * Occipital cortex lesions tend to cause homonymous hemianopias of variable size,with or without macular involvement.[19] * Congruous homonymous hemianopia with macular sparing is a feature of occlusion of posterior cerebral artery supplying the anterior part of the visual cortex.[1] * Bilateral homonymous hemianopia with macular sparing producing a picture of ring scotoma is seen in bilateral occipital lobe lesions.[1] * Pupillary reflex is nornmal * Optic atrophy does not occur. * Dyschromatopsia.[22] ## Diagnosis[edit] ### Visual field testing[edit] Main article: Visual field test Measurements of visual field defects can be done by visual field testing. It can be performed by various methods, including confrontation technique, amsler grid, tangent screen, kinetic perimetry, or static perimetry. Cost common is automated perimetry. #### Confrontation test[edit] Confrontation visual field testing is a simple and quick visual field assessing method. A confrontational field test requires little or no special equipment and can be performed in any room, which is well illuminated. Patient sitting straight in front of the examiner, is asked look directly at the examiner's eye during the test. The target eye should be the one directly across from the patient's eye. When the patient's right eye is being tested, closing the other eye, patient is instructed to look directly at the examiners left eye. Examiner closes his/her left eye, and then conduct finger movements, bringing his/her fingers or any other into your visual field from the sides. Since the test is basically comparison of the patient's visual field with the examiner's visual field,[23] it is not an accurate measument of visual field. #### Perimetry[edit] Modern computerized perimeters like humphrey field analyser (HFA) give more comprehensive and accurate reports than finger testing methods. ### Magnetic resonance imaging[edit] MRI of the brain and orbit helps to find the exact site of a lesion.[24] ### Computed tomography scan[edit] CT scan is also used for investigating cause of visual pathway lesions.[24] ## Treatment[edit] Tumours and other compressive lesions could often present with visual impairment and/or visual field defects. Careful clinical assessment could aid in accurate diagnosis of the cause of the visual field defect and loss of vision. Compressive lesions of the visual pathway, especially lesions affecting optic nerve require a multi-disciplinary approach involving neurosurgeon, physician as well as the ophthalmologist.[25] Treatment is given according to the cause. ## See also[edit] * Visual system * Visual field * Visual field test * Eye examination ## References[edit] 1. ^ a b c d e f g h i j k l m n AK Khurana. "Neuro-ophthalmology". Comprehensive ophthalmology (6th ed.). Jaypee, The Health Sciences Publisher. pp. 312–315. ISBN 978-93-5152-657-5. 2. ^ a b c d "Visual Pathway Lesions". Illinois Chiropractic Society. 1 August 2013. 3. ^ a b "Visual fields and lesions of the visual pathways (CN II) \| Deranged Physiology". derangedphysiology.com. 4. ^ Fiona, Rowe. "Optic nerve". Visual Fields via the Visual Pathway (2nd ed.). CRC Press. p. 138. ISBN 978-1-4822-9965-6. 5. ^ a b Visual fields : examination and interpretation. Walsh, Thomas J. (Thomas Joseph), 1931- (3rd ed.). Oxford: Oxford University Press. 2011. ISBN 978-0-19-978075-4. OCLC 670238479.CS1 maint: others (link) 6. ^ Colman, Andrew M. (2006). Oxford Dictionary of Psychology (2nd ed.). Oxford University Press. p. 530. ISBN 978-0-19-861035-9. 7. ^ Besada, E.; Fisher, J. P. (April 2001). "Absent relative afferent pupillary defect in an asymptomatic case of lateral chiasmal syndrome from cerebral aneurysm". Optometry and Vision Science. 78 (4): 195–205. doi:10.1097/00006324-200104000-00008. ISSN 1040-5488. 8. ^ Foroozan, Rod (2003). "Chiasmal syndromes". Current Opinion in Ophthalmology. 14 (6): 325–331. doi:10.1097/00055735-200312000-00002. 9. ^ "Pituitary Adenoma Causing Compression of the Optic Chiasm". eyerounds.org. 10. ^ "Craniopharyngioma". NORD (National Organization for Rare Disorders). 11. ^ Bejjani, Ghassan K.; Cockerham, Kimberly P.; Kennerdell, John S.; Maroon, Joseph C. (May 2002). "Visual field deficit caused by vascular compression from a suprasellar meningioma: case report". Neurosurgery. 50 (5): 1129–1131, discussion 1131–1132. doi:10.1097/00006123-200205000-00033. ISSN 0148-396X. 12. ^ Optic tract. Encyclopædia Britannica. Retrieved from: http://www.britannica.com/EBchecked/topic/430336/optic-tract (accessed Nov 1, 2013). 13. ^ a b Themes, U. F. O. (4 June 2016). "Diseases of the Retrochiasmal Visual Pathways". Ento Key. 14. ^ Amadeo R. Rodriguez; Kesava Reddy. "Pearls & Oy-sters: Optic tract syndrome" (PDF). Cite journal requires `\|journal=` (help) 15. ^ "Craniopharyngioma Signs and Symptoms". www.pedsoncologyeducation.com. 16. ^ Tomy, Ritamary (2019). "Pupil: Assessment and diagnosis". Kerala Journal of Ophthalmology. 31 (2): 167. doi:10.4103/kjo.kjo_48_19. S2CID 201827226. 17. ^ Luco, C; Hoppe, A; Schweitzer, M; Vicuña, X; Fantin, A (January 1992). "Visual field defects in vascular lesions of the lateral geniculate body". Journal of Neurology, Neurosurgery, and Psychiatry. 55 (1): 12–15. ISSN 0022-3050. PMC 488924. 18. ^ Rutland, John W.; Schefflein, Javin; Arrighi-Allisan, Annie E.; Ranti, Daniel; Ladner, Travis R.; Pai, Akila; Loewenstern, Joshua; Lin, Hung-Mo; Chelnis, James; Delman, Bradley N.; Shrivastava, Raj K.; Balchandani, Priti (17 May 2019). "Measuring degeneration of the lateral geniculate nuclei from pituitary adenoma compression detected by 7T ultra-high field MRI: a method for predicting vision recovery following surgical decompression of the optic chiasm". Journal of Neurosurgery: 1–10. doi:10.3171/2019.2.JNS19271. ISSN 1933-0693. PMC 7351175. 19. ^ a b c Lisik, James. "Optic radiation \| Radiology Reference Article \| Radiopaedia.org". Radiopaedia. 20. ^ "optic radiation(lesions) - General Practice Notebook". gpnotebook.com. 21. ^ a b c Huff, Trevor; Mahabadi, Navid; Tadi, Prasanna (2020). "Neuroanatomy, Visual Cortex". StatPearls. StatPearls Publishing. 22. ^ Green, Glenn J.; Lessell, Simmons (1 January 1977). "Acquired Cerebral Dyschromatopsia". Archives of Ophthalmology. pp. 121–128. doi:10.1001/archopht.1977.04450010121012. 23. ^ Pandit, Ranjeet J.; Gales, Kevin; Griffiths, Philip G. (20 October 2001). "Effectiveness of testing visual fields by confrontation". The Lancet. 358 (9290): 1339–1340. doi:10.1016/S0140-6736(01)06448-0. PMID 11684217. 24. ^ a b Gonzalez, Carlos F.; Gerner, Edward W.; DeFilipp, Gary; Becker, Melvin H. (1986). "Lesions Involving the Visual Pathways". Diagnostic Imaging in Ophthalmology. Springer. pp. 239–279. doi:10.1007/978-1-4613-8575-2_12. 25. ^ "Optic nerve anomalies and neuropathies". Postgraduate ophthalmology vol 2 (1st ed.). Jaypee Brothers Medical Publishers. p. 1665. ISBN 978-93-5025-270-3. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Visual pathway lesions	None	6,717	wikipedia	https://en.wikipedia.org/wiki/Visual_pathway_lesions	2021-01-18T18:27:59	{"wikidata": ["Q96414061"]}
Hepatocellular carcinoma is a primary hepatic cancer derived from well-differentiated hepatocytes. It is more frequent in adults than in childhood. Symptoms are hepatic mass, abdominal pain and, in advanced stages, jaundice, cachexia 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	Hepatocellular carcinoma	c2239176	6,718	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=88673	2021-01-23T18:30:28	{"mesh": ["D006528"], "omim": ["114550"], "umls": ["C2239176"], "icd-10": ["C22.0"], "synonyms": ["HCC"]}
Candida hypersensitivity systemic candidiasis, chronic candidiasis Pseudomedical diagnosis RisksNocebo This article is part of a series on Alternative medicine General information * Alternative medicine * Alternative veterinary medicine * Quackery (Health fraud) * History of alternative medicine * Rise of modern medicine * Pseudoscience * Antiscience * Skepticism * Skeptical movement * National Center for Complementary and Integrative Health * Terminology of alternative medicine * Therapeutic nihilism Fringe medicine and science * Acupressure * Acupuncture * Alkaline diet * Anthroposophic medicine * Apitherapy * Applied kinesiology * Aromatherapy * Auriculotherapy * Bates method * Black salve * Bodywork * Bonesetter * Bowen technique * Breathwork * Fake COVID-19 treatments * Cancer treatments * Charcoal cleanse * Chiropractic * Chiropractic treatment techniques * Vertebral subluxation * Christian Science * Chromotherapy * Colon cleansing * Coffee enema * Colorpuncture * Colloidal silver * Craniosacral therapy * Crystal healing * Cupping therapy * Dental amalgam controversy * Detoxification * Foot detox * Ear candling * Energy medicine * Esoteric energy * Therapeutic touch * Fabunan Antiviral Injection * Facilitated communication * Feldenkrais Method * Functional medicine * Hair analysis * Herbal medicine * Holistic dentistry * Hologram bracelet * Homeopathy * Bach flower remedies * Biological terrain assessment * Hypnotherapy * Iridology * Ionized jewelry * Jilly Juice * Lightning Process * Lymphotherapy * Medical intuitive * Mesmerism * Magnet therapy * Manual therapy * Megavitamin therapy * Mind–body interventions * MMS * Myofascial release * NAET * Naturopathy * Oil pulling * Orgone * Orthomolecular medicine * Orthopathy * Osteomyology * Osteopathy * Ozone therapy * Parapsychology * Phrenology * Psychic surgery * Psychodermatology * Radionics * Rapid prompting method * RBOP * Reiki * Reflexology * Rolfing * Scientific racism * ThetaHealing * Thought Field Therapy * Urophagia * Vaginal steaming * Vision therapy * Vitalism * Young blood transfusion * Zero balancing Conspiracy theories (list) * Big Pharma conspiracy theory * HIV/AIDS denialism * OPV AIDS hypothesis * Anti-vaccination * Vaccines and autism * MMR vaccine and autism * Water fluoridation controversy * GMO conspiracy theories * Misinformation related to the COVID-19 pandemic Classifications * Alternative medical systems * Mind–body intervention * Biologically-based therapy * Manipulative methods * Energy therapy Traditional medicine * African * Muti * Southern Africa * Ayurveda * Ayurvedic acupressure * Dosha * Maharishi Vedic Approach to Health * Balneotherapy * Brazilian * Bush medicine * Cambodian * Chinese * Blood stasis * Chinese herbology * Dit Da * Gua sha * Gill plate trade * Meridian * Moxibustion * Pressure point * Qi * San Jiao * Tui na * Zang-fu * Chumash * Curandero * Faith healing * Iranian * Jamu * Kambo * Japanese * Korean * Mien Shiang * Mongolian * Prophetic medicine * Shamanism * Shiatsu * Siddha * Sri Lankan * Thai massage * Tibetan * Unani * Vietnamese Diagnoses * Adrenal fatigue * Aerotoxic syndrome * Candida hypersensitivity * Chronic Lyme disease * Electromagnetic hypersensitivity * Heavy legs * Leaky gut syndrome * Multiple chemical sensitivity * Wilson's temperature syndrome * v * t * e Candida hypersensitivity is a pseudoscientific disease promoted by William G. Crook, M.D.[1] It is spuriously claimed that chronic yeast infections are responsible for many common disorders and non-specific symptoms including fatigue, weight gain, constipation, dizziness, muscle and joint pain, asthma, and others.[2] ## Contents * 1 Background * 2 Symptoms * 3 Criticism * 4 Legal action * 5 See also * 6 References ## Background[edit] Candida albicans is a fungus that colonizes a large majority of the population (meaning it is present in the body but not causing an infection or any problems). Under certain conditions, however, it can cause an infection. The most common manifestations are thrush (a superficial Candida infection in the mouth) and vaginitis, also commonly referred to as a yeast infection. Candida can also cause serious systemic infection, but this is almost always restricted to those with compromised immune systems, such as patients undergoing chemotherapy or with advanced AIDS.[2] ## Symptoms[edit] After reading publications by C. Orian Truss, M.D.,[3] Crook proposed the idea that a condition he termed systemic candidiasis, or Candida hypersensitivity, was responsible for a long list of common conditions and non-specific symptoms including fatigue, asthma, psoriasis, sexual dysfunction, and many others.[2] The list of symptoms is similar to that of multiple chemical sensitivity.[4] Many patients presenting with symptoms of environmental sensitivity claim to suffer from multiple "fashionable" syndromes.[5] ## Criticism[edit] The American Academy of Allergy, Asthma, and Immunology strongly criticized the concept of "candidiasis hypersensitivity syndrome" and the diagnostic and treatment approaches its proponents use. AAAAI's position statement concludes: (1) the concept of candidiasis hypersensitivity is speculative and unproven; (2) its basic elements would apply to almost all sick patients at some time because its supposed symptoms are essentially universal; (3) overuse of oral antifungal agents could lead to the development of resistant germs that could menace others; (4) adverse effects of oral antifungal agents are rare, but some inevitably will occur; and (5) neither patients nor doctors can determine effectiveness (as opposed to coincidence) without controlled trials. Because allergic symptoms can be influenced by many factors, including emotions, experiments must be designed to separate the effects of the procedure being tested from the effects of other factors.[4][6] By 2005, scientists were taking note of "a large pseudoscientific cult"[7] that had developed around the topic of yeast infections, with claims that up to one in three people were affected by yeast-related illnesses including Candida hypersensitivity.[4] ## Legal action[edit] Some practitioners of alternative medicine have promoted dietary supplements as supposed cures for this non-existent illness, rendering themselves liable to prosecution.[4][8] In 1990, alternative health vendor Nature's Way signed a FTC consent agreement not to misrepresent in advertising any self-diagnostic test concerning yeast conditions or to make any unsubstantiated representation concerning any food or supplement's ability to control yeast conditions, with a fine of US$30,000 payable to the National Institutes of Health for research in genuine candidiasis.[8] ## See also[edit] * List of topics characterized as pseudoscience ## References[edit] 1. ^ Crook, William G. (1986). The Yeast Connection: A Medical Breakthrough. Vintage Books. ISBN 0933478062. 2. ^ a b c Novella, Steven (25 September 2013). "Candida and Fake Illnesses". Science-Based Medicine. Retrieved 4 July 2018. 3. ^ Truss, CO (1983). The Missing Diagnosis. Birmingham, AL: The Missing Diagnosis, Inc. 4. ^ a b c d Stephen Barrett, M.D. (October 8, 2005). "Dubious "Yeast Allergies"". Archived from the original on May 13, 2008. 5. ^ Stewart, Donna E. (1990). "The Changing Faces of Somatization". Psychosomatics. 31 (2): 153–158. doi:10.1016/S0033-3182(90)72188-3. ISSN 0033-3182. 6. ^ Anderson, J; Chai, H; Claman, H; Ellis, E; Fink, J; Kaplan, A; Lieberman, P; Pierson, W; Salvaggio, J; Sheffer, A (1986). "Candidiasis hypersensitivity syndromeApproved by the executive committee of the American academy of allergy and immunology". Journal of Allergy and Clinical Immunology. 78 (2): 271–273. doi:10.1016/S0091-6749(86)80073-2. ISSN 0091-6749. PMID 3734279. 7. ^ Odds, FC (1987). "Candida infections: an overview". Critical Reviews in Microbiology. 15 (1): 1–5. doi:10.3109/10408418709104444. PMID 3319417. 8. ^ a b Jarvis WT. "Candidiasis Hypersensitivity". National Council Against Health Fraud. Retrieved 18 January 2014. * v * t * e Pseudoscience Terminology * Cargo cult science * Charlatan * Crank * Fringe theory * Fringe science * Pseudoarchaeology * Pseudohistory * Junk science * Paranormal * Pathological science * Quackery * Snake oil * Crocodile oil * Superseded scientific theory * True-believer syndrome * Voodoo Science Topics characterized as pseudoscience * 2012 phenomenon * Acupuncture * Adrenal fatigue * Alchemy * Alternative medicine * Ancient astronauts * Anthroposophic medicine * Applied kinesiology * Aquatic ape hypothesis * Astrology * Bates method * Biodynamic agriculture * Biorhythms * Bloodletting * Body memory * Catastrophism * Chiropractic * Chromotherapy * Conspiracy theory * 5G conspiracy * 9/11 conspiracy theories * Chemtrail conspiracy theory * Climate change denial * Misinformation related to the COVID-19 pandemic * Moon landing conspiracy theories * Conversion therapy * Correactology * Creation science * Cryonics * Cryptozoology * Crystal healing * Cupping * Detoxification * Colon cleansing * Dianetics * Doctrine of signatures * Doktor Koster's Antigaspills * Dowsing * Ear candling * Electromagnetic hypersensitivity * Electronic voice phenomenon * Eugenics * Facilitated communication * Feng shui * Flat Earth theory * Germ theory denialism * Graphology * HIV/AIDS denialism * Hollow Earth theory * Homeopathy * Humorism * Indigo children * Intelligent design * Japhetic theory * Levitation * Lunar effect * Lysenkoism * Magnet therapy * Mediumship * Miracle Mineral Supplement * Naturopathy * Nazi archaeology * Nibiru cataclysm * Numerology * Orgone * Palmistry * Panchagavya * Patent medicine * Perpetual motion * Phrenology * Polygraph * Primal therapy * Pseudoarchaeology * Pseudohistory * Genocide denial * Historical negationism * Holocaust denial * Pseudoscientific metrology * Psychohistory * Quantum mysticism * Rapid prompting method * Recovered-memory therapy * Reiki * Scientific racism * Aryan race * Melanin theory * Statement analysis * Trepanning * Ufology * Vertebral subluxation * Voice stress analysis * Water memory Promoters of pseudoscience * Sucharit Bhakdi * Deepak Chopra * Gaia, Inc. * Max Gerson * Goop (company) * Nicholas Gonzalez * William Donald Kelley * Jenny McCarthy * Theodor Morell * Hans Alfred Nieper * Mehmet Oz * Andrew Wakefield Related topics * Bourgeois pseudoscience * Demarcation problem * Scientific method * Suppressed research in the Soviet Union * Traditional medicine Resources * Committee for Skeptical Inquiry * Cults of Unreason * Encyclopedia of Pseudoscience * Fads and Fallacies in the Name of Science * Fortean Times * JREF * Quackwatch * Skeptical Inquirer * The Natural History of Quackery * The Psychology of the Occult * The Ragged Edge of Science * The Skeptic Encyclopedia of Pseudoscience * The Skeptic's Dictionary List of topics characterized as pseudoscience [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Candida hypersensitivity	None	6,719	wikipedia	https://en.wikipedia.org/wiki/Candida_hypersensitivity	2021-01-18T18:30:20	{"wikidata": ["Q2570534"]}
Cortisone reductase deficiency Other namesHSD 11b1 deficiency [1] 11β-hydroxysteroid dehydrogenase type 1 SpecialtyMedical genetics Cortisone reductase deficiency is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), otherwise known as cortisone reductase, a bi-directional enzyme, which catalyzes the interconversion of cortisone to cortisol in the presence of NADH as a co-factor. If levels of NADH are low, the enzyme catalyses the reverse reaction, from cortisol to cortisone, using NAD+ as a co-factor. Cortisol is a glucocorticoid that plays a variety of roles in many different biochemical pathways, including, but not limited to: gluconeogenesis, suppressing immune system responses and carbohydrate metabolism. One of the symptoms of cortisone reductase deficiency is hyperandrogenism, resulting from activation of the Hypothalamic–pituitary–adrenal axis. The deficiency has been known to exhibit symptoms of other disorders such as Polycystic Ovary Syndrome in women. Cortisone Reductase Deficiency alone has been reported in fewer than ten cases in total, all but one case were women.[2] Elevated activity of 11β-HSD1 can lead to obesity or Type II Diabetes, because of the role of cortisol in carbohydrate metabolism and gluconeogenesis.[3] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathophysiology * 3.1 Effect on HPA Axis * 4 Diagnosis * 5 Treatment * 6 References * 7 External links ## Signs and symptoms[edit] Cortisol inhibition, and as a result, excess androgen release can lead to a variety of symptoms. Other symptoms come about as a result of increased levels of circulating androgen. Androgen is a steroid hormone, generally associated with development of male sex organs and secondary male sex characteristics The symptoms associated with Cortisone Reductase Deficiency are often linked with Polycystic Ovary Syndrome (PCOS) in females. The symptoms of PCOS include excessive hair growth, oligomenorrhea, amenorrhea, and infertility. In men, cortisone reductase deficiency results in premature pseudopuberty, or sexual development before the age of nine.[4] ## Genetics[edit] Inactivating mutations in the H6PD gene lead to a lowered supply of NADH, causing cortisone reductase to catalyze the reaction from cortisol to cortisone.[5] This is the most common manifestation of CRD. It has been shown that CRD can be caused by mutations in the HSD11B1 gene as well, specifically mutations caused by K187N and R137C, affecting active site residue and disruption of salt bridges at the subunit interface of the dimer, respectively. In the K187N mutant, activity is abolished, and in the R137C mutant activity is greatly reduced, but not completely abolished.[6] ## Pathophysiology[edit] An overview of how cortisone reductase is driven by NADH production by hexose-6-phosphate and how it affects the HPA Axis in a healthy body. Cortisone Reductase Deficiency effects on HPA and body in presence of deficient H6PD In a healthy body, blood cortisone and cortisol levels are roughly equimolar.[7] Cortisone reductase deficiency leads to an elevated level of inert cortisone to active cortisol in adipose tissue. Cortisone reductase deficiency is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme, otherwise known as cortisone reductase. The 11β-HSD1 enzyme is responsible for catalyzing the interconversion of circulating cortisone to cortisol, using NADH as a co-factor. The oxidative or reductive capacity of the enzyme is regulated by NADH produced by hexose-6-phosphate dehydrogenase (H6PD).[8] H6PD is distinct from its isozyme, glucose-6-phosphate dehydrogenase (G6PDH) in that G6PDH is a cytolytic enzyme and draws from a separate pool of NAD+. H6PD is also capable of catalyzing the oxidation of several phosphorylated hexoses, while G6PDH shows affinity for glucose, specifically.[9] The enzyme cortisone reductase exists in a tightly controlled reaction space, facing the lumen of the endoplasmic reticulum of cells in the liver and lungs. NADH produced by hexose-6-phosphate is delivered directly to the catalytic site of cortisone reductase.[10] If NADH production is limited, then cortisone reductase is also capable of catalysing the reverse reaction taking circulating cortisol and reducing it to cortisone.[11] Dysregulation of hexose-6-phosphate dehydrogenase occurs as a result of gene mutation.[12] Cortisol is important in signalling inhibition of adrenocorticotropic hormone release from the pituitary. Reduced cortisol in circulation activates the H-P-A Axis to produce and release more cortisol, and therefore androgen. ### Effect on HPA Axis[edit] The Hypothalamic-Pituitary-Adrenal axis relies on blood levels of cortisol to act as negative feedback. Low levels of blood cortisol leads to release of Corticotrope Releasing Hormone (CRH) activating the anterior pituitary and signalling the release of Adrenocorticotropic Hormone (ACTH), stimulating the adrenal gland to make more cortisol.[13] In addition to cortisol, the adrenal gland also releases androgen, leading to hyperandrogenism, which gives rise to the symptoms commonly associated with Cortisone Reductase Deficiency. ## Diagnosis[edit] Diagnosis of cortisone reductase deficiency is done through analysis of cortisol to cortisone metabolite levels in blood samples.[14] ## Treatment[edit] There is no treatment for cortisone reductase deficiency. Shots of cortisol are quickly metabolised into cortisone by the dysregulated 11β-HSD1 enzyme; however, symptoms can be treated. Treatment of hyperandroginism can be done through prescription of antiandrogens.[15] They do so by inhibiting the release of gonadotropin and luteinizing hormone, both hormones in the pituitary, responsible for the production of testosterone. ## References[edit] 1. ^ "Cortisone reductase deficiency \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 5 October 2019. 2. ^ Stewart, P. M. (2003). "Tissue-specific Cushing's syndrome, 11beta-hydroxysteroid dehydrogenases and the redefinition of corticosteroid hormone action" (PDF). European Journal of Endocrinology. 149 (3): 163–8. doi:10.1530/eje.0.1490163. PMID 12943516. 3. ^ Pereira, C. D.; Azevedo, I; Monteiro, R; Martins, M. J. (2012). "11β-Hydroxysteroid dehydrogenase type 1: Relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus". Diabetes, Obesity and Metabolism. 14 (10): 869–81. doi:10.1111/j.1463-1326.2012.01582.x. PMID 22321826. 4. ^ Lavery, G. G.; Walker, E. A.; Tiganescu, A; Ride, J. P.; Shackleton, C. H.; Tomlinson, J. W.; Connell, J. M.; Ray, D. W.; Biason-Lauber, A; Malunowicz, E. M.; Arlt, W; Stewart, P. M. (2008). "Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency". The Journal of Clinical Endocrinology & Metabolism. 93 (10): 3827–32. doi:10.1210/jc.2008-0743. PMC 2579651. PMID 18628520. 5. ^ Draper, N; Walker, E. A.; Bujalska, I. J.; Tomlinson, J. W.; Chalder, S. M.; Arlt, W; Lavery, G. G.; Bedendo, O; Ray, D. W.; Laing, I; Malunowicz, E; White, P. C.; Hewison, M; Mason, P. J.; Connell, J. M.; Shackleton, C. H.; Stewart, P. M. (2003). "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency". Nature Genetics. 34 (4): 434–9. doi:10.1038/ng1214. PMID 12858176. 6. ^ Lawson, A. J.; Walker, E. A.; Lavery, G. G.; Bujalska, I. J.; Hughes, B; Arlt, W; Stewart, P. M.; Ride, J. P. (2011). "Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1". Proceedings of the National Academy of Sciences. 108 (10): 4111–6. Bibcode:2011PNAS..108.4111L. doi:10.1073/pnas.1014934108. PMC 3054023. PMID 21325058. 7. ^ Tomlinson, J. W.; Stewart, P. M. (2001). "Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase". Best Practice & Research Clinical Endocrinology & Metabolism. 15 (1): 61–78. doi:10.1053/beem.2000.0119. PMID 11469811. 8. ^ Draper, N; Walker, E. A.; Bujalska, I. J.; Tomlinson, J. W.; Chalder, S. M.; Arlt, W; Lavery, G. G.; Bedendo, O; Ray, D. W.; Laing, I; Malunowicz, E; White, P. C.; Hewison, M; Mason, P. J.; Connell, J. M.; Shackleton, C. H.; Stewart, P. M. (2003). "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency". Nature Genetics. 34 (4): 434–9. doi:10.1038/ng1214. PMID 12858176. 9. ^ Hewitt, K. N.; Walker, E. A.; Stewart, P. M. (2005). "Minireview: Hexose-6-phosphate dehydrogenase and redox control of 11{beta}-hydroxysteroid dehydrogenase type 1 activity". Endocrinology. 146 (6): 2539–43. doi:10.1210/en.2005-0117. PMID 15774558. 10. ^ Senesi, S; Csala, M; Marcolongo, P; Fulceri, R; Mandl, J; Banhegyi, G; Benedetti, A (2010). "Hexose-6-phosphate dehydrogenase in the endoplasmic reticulum". Biological Chemistry. 391 (1): 1–8. doi:10.1515/BC.2009.146. PMID 19804362. 11. ^ Hughes, K. A.; Manolopoulos, K. N.; Iqbal, J; Cruden, N. L.; Stimson, R. H.; Reynolds, R. M.; Newby, D. E.; Andrew, R; Karpe, F; Walker, B. R. (2012). "Recycling between cortisol and cortisone in human splanchnic, subcutaneous adipose, and skeletal muscle tissues in vivo". Diabetes. 61 (6): 1357–64. doi:10.2337/db11-1345. PMC 3357308. PMID 22511204. 12. ^ Qin, K; Rosenfield, R. L. (2011). "Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome". Steroids. 76 (1–2): 135–9. doi:10.1016/j.steroids.2010.10.001. PMC 3023921. PMID 21050867. 13. ^ Tomlinson, J. W.; Stewart, P. M. (2001). "Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase". Best Practice & Research Clinical Endocrinology & Metabolism. 15 (1): 61–78. doi:10.1053/beem.2000.0119. PMID 11469811. 14. ^ Stewart, P. M. (2003). "Tissue-specific Cushing's syndrome, 11beta-hydroxysteroid dehydrogenases and the redefinition of corticosteroid hormone action" (PDF). European Journal of Endocrinology. 149 (3): 163–8. doi:10.1530/eje.0.1490163. PMID 12943516. 15. ^ Charitidou, C; Farmakiotis, D; Zournatzi, V; Pidonia, I; Pegiou, T; Karamanis, N; Hatzistilianou, M; Katsikis, I; Panidis, D (2008). "The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome". Atherosclerosis. 196 (2): 958–65. doi:10.1016/j.atherosclerosis.2007.03.002. PMID 17418849. ## External links[edit] Classification D * ICD-10: E25.8 * OMIM: 604931 External resources * Orphanet: 168588 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Cortisone reductase deficiency	c1291245	6,720	wikipedia	https://en.wikipedia.org/wiki/Cortisone_reductase_deficiency	2021-01-18T18:40:55	{"mesh": ["C536447"], "wikidata": ["Q17084678"]}
An asynclitic birth or asynclitism refers to the position of a fetus in the uterus such that the head of the baby is presenting first and is tilted to the shoulder,[1] causing the fetal head to no longer be in line with the birth canal (vagina).[2] Asynclitic presentation is significantly different from a shoulder presentation, in which the shoulder is presenting first. Many babies enter the pelvis in an asynclitic presentation, and most asynclitism corrects spontaneously as part of the normal birthing process. Persistence of asynclitism can cause problems with dystocia, and has often been associated with cesarean birth. However, with a skilled midwife or obstetrician a complication-free vaginal birth can sometimes, though not necessarily, be achieved through movement and positioning of the birthing woman,[3] and patience and extra time to allow for movement of the baby through the pelvis and moulding of the skull during the birthing process if this is safe in the circumstances.[3] Where intervention is the safest option in asynclitic birth, Kielland forceps are preferable obstetric forceps used in asynclitic births, for example by their sliding mechanism, availing for more appropriate adjustment of the blades.[2] ## See also[edit] * Childbirth * Naegele obliquity ## References[edit] 1. ^ Asynclitism, spinningbabies.com 2. ^ a b Healthline > Types of Forceps Used in Delivery February 2006. Reviewer: Douglas Levine, Gynecology Service/Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. 3. ^ a b Simkin, Penny (2011). The Labor Progress Handbook: Early Interventions to Prevent and Treat Dystocia (3rd ed.). John Wiley & Sons. ## External links[edit] * Malpositions and malpresentations, World Health Organization's Managing Complications in Pregnancy and Childbirth, A guide for midwives and doctors * Siciliano G, Marchiafava G (1952). "[Asynclitic ventral shoulder presentation; two cases with deflection and epidural hemorrhage]". Monit Ostet Ginecolog (in Italian). 23 (4): 233–55. PMID 13025351. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Asynclitic birth	None	6,721	wikipedia	https://en.wikipedia.org/wiki/Asynclitic_birth	2021-01-18T19:02:57	{"wikidata": ["Q2232871"]}
A number sign (#) is used with this entry because it does not represent an additional gene locus. It contains a list of variant hemoglobins for which the precise gene carrying the mutation is unknown or uncertain. Inheritance \- Autosomal dominant Heme \- Deficient synthesis of alpha-1 and/or alpha-2 chains (e.g. Bart's) \- Tetramer of beta chains (e.g. Hb H) \- Increased oxygen affinity and compensated hemolytic anemia (e.g. Hb St. Mary's) ▲ 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	HEMOGLOBIN--VARIANTS FOR WHICH THE CHAIN CARRYING THE MUTATION IS UNKNOWN OR UNCERTAIN	c1840647	6,722	omim	https://www.omim.org/entry/142309	2019-09-22T16:40:19	{"omim": ["142309"]}
Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures (epilepsy) and a decline in intellectual function. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time. Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or twitching that can affect part of the body or the entire body. Myoclonus can occur when an affected person is at rest, and it is made worse by motion, excitement, or flashing light (photic stimulation). In the later stages of Lafora progressive myoclonus epilepsy, myoclonus often occurs continuously and affects the entire body. Several types of seizures commonly occur in people with Lafora progressive myoclonus epilepsy. Generalized tonic-clonic seizures (also known as grand mal seizures) affect the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also experience occipital seizures, which can cause temporary blindness and visual hallucinations. Over time, the seizures worsen and become more difficult to treat. A life-threatening seizure condition called status epilepticus may also develop. Status epilepticus is a continuous state of seizure activity lasting longer than several minutes. About the same time seizures begin, intellectual function starts to decline. Behavioral changes, depression, confusion, and speech difficulties (dysarthria) are among the early signs and symptoms of this disorder. As the condition worsens, a continued loss of intellectual function (dementia) impairs memory, judgment, and thought. Affected people lose the ability to perform the activities of daily living by their mid-twenties, and they ultimately require comprehensive care. People with Lafora progressive myoclonus epilepsy generally survive up to 10 years after symptoms first appear. ## Frequency The prevalence of Lafora progressive myoclonus epilepsy is unknown. Although the condition occurs worldwide, it appears to be most common in Mediterranean countries (including Spain, France, and Italy), parts of Central Asia, India, Pakistan, North Africa, and the Middle East. ## Causes Lafora progressive myoclonus epilepsy can be caused by mutations in either the EPM2A gene or the NHLRC1 gene. These genes provide instructions for making proteins called laforin and malin, respectively. Laforin and malin play a critical role in the survival of nerve cells (neurons) in the brain. Studies suggest that laforin and malin work together and may have several functions. One of these is to help regulate the production of a complex sugar called glycogen, which is a major source of stored energy in the body. The body stores this sugar in the liver and muscles, breaking it down when it is needed for fuel. Laforin and malin may prevent a potentially damaging buildup of glycogen in tissues that do not normally store this molecule, such as those of the nervous system. Researchers have discovered that people with Lafora progressive myoclonus epilepsy have distinctive clumps called Lafora bodies within their cells. Lafora bodies are made up of an abnormal form of glycogen that cannot be broken down and used for fuel. Instead, it builds up to form clumps that can damage cells. Neurons appear to be particularly vulnerable to this type of damage. Although Lafora bodies are found in many of the body's tissues, the signs and symptoms of Lafora progressive myoclonus epilepsy are limited to the nervous system. Mutations in the EPM2A gene prevent cells from making functional laforin, while NHLRC1 gene mutations prevent the production of functional malin. It is unclear how a loss of either of these proteins leads to the formation of Lafora bodies. However, a loss of laforin or malin ultimately results in the death of neurons, which interferes with the brain's normal functions. The condition tends to progress more slowly in some people with NHLRC1 gene mutations than in those with EPM2A gene mutations. Mutations in the EPM2A and NHLRC1 genes account for 80 percent to 90 percent of all cases of Lafora progressive myoclonus epilepsy. In the remaining cases, the cause of the condition is unknown. Researchers are searching for other genetic changes that may underlie this disease. ### Learn more about the genes associated with Lafora progressive myoclonus epilepsy * EPM2A * NHLRC1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Lafora progressive myoclonus epilepsy	c0751783	6,723	medlineplus	https://medlineplus.gov/genetics/condition/lafora-progressive-myoclonus-epilepsy/	2021-01-27T08:25:46	{"gard": ["8214"], "mesh": ["D020192"], "omim": ["254780"], "synonyms": []}
## Clinical Features The incisors are hollowed out on their lingual surface, creating a resemblance to a shovel or a sugar scoop. The lateral incisors are more often or more markedly affected than the middle incisors. The trait is particularly frequent in East Asian and Native American populations (Kimura et al., 2009). Inheritance may well be polygenic (Portin and Alvesalo, 1974). Sinodonty is a combination of dental characteristics that includes upper first and second incisors that are shovel-shaped and not aligned with the other teeth, upper first premolars with one root, and lower first molars with 3 roots (Kimura et al., 2009). Mapping Kimura et al. (2009) measured crown diameter and tooth-shoveling grade in 102 individuals from around Tokyo and 100 from the Sakishima Islands, then analyzed the correlation between dental traits and a T1540C polymorphism (rs3827760) in the EDAR gene (604095.0011) that had been associated with hair thickness (Fujimoto et al., 2008). The number of EDAR 1540C alleles in an individual strongly correlated with the tooth-shoveling grade (p = 7.7 x 10(-10)); the effect of the allele was additive and explained 18.9% of total variance in shoveling grade, corresponding to about one-fourth of the heritability of the trait reported previously. Principal component analysis of the metric data yielded 4 patterns of tooth size, and analysis revealed that 1540C significantly affected overall tooth size (p = 4.9 x 10(-3)) and the ratio of mesiodistal diameter to buccolingual diameter (p = 2.6 x 10(-3)). Inheritance \- Autosomal dominant vs. polygenic Teeth \- Shovel-shaped maxillary central incisors ▲ 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	INCISORS, SHOVEL-SHAPED	c1409763	6,724	omim	https://www.omim.org/entry/147400	2019-09-22T16:39:26	{"omim": ["147400"], "synonyms": ["Alternative titles", "SINODONTY"]}
Bandemia SpecialtyHematology Bandemia refers to an excess or increased levels of band cells (immature white blood cells) released by the bone marrow into the blood. It thus overlaps with the concept of left shift—bandemia is a principal type of left shift and many (perhaps most) clinical mentions of the latter refer to instances of this type. The ICD diagnosis code for bandemia is 288.66.[1] It is a signifier of infection (or sepsis) or inflammation.[2]Measurement of it can play a role in the approach to appendicitis.[3] ## See also[edit] * Granulocytosis ## References[edit] 1. ^ 2008 ICD-9-CM Volume 1 Diagnosis Codes 2. ^ Definition in Taber's Medical Dictionary 3. ^ Whyte C, Levin T, Harris BH (August 2008). "Early decisions in perforated appendicitis in children: lessons from a study of nonoperative management". J. Pediatr. Surg. 43 (8): 1459–63. doi:10.1016/j.jpedsurg.2007.11.032. PMID 18675635. ## External links[edit] Classification D * ICD-10: D72825 * ICD-10-CM: D72.825 * ICD-9-CM: 288.66 * SNOMED CT: 442113000 * v * t * e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis: * Monocytosis * Histiocytosis * Chronic granulomatous disease ↓ -penia: * Monocytopenia Granulocytes ↑ -cytosis: * granulocytosis * Neutrophilia * Eosinophilia/Hypereosinophilic syndrome * Basophilia * Bandemia ↓ -penia: * Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia * Eosinopenia * Basopenia) Disorder of phagocytosis Chemotaxis and degranulation * Leukocyte adhesion deficiency * LAD1 * LAD2 * Chédiak–Higashi syndrome * Neutrophil-specific granule deficiency Respiratory burst * Chronic granulomatous disease * Neutrophil immunodeficiency syndrome * Myeloperoxidase deficiency This developmental biology article is a stub. You can help Wikipedia by expanding it. * v * t * e This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Bandemia	c0741439	6,725	wikipedia	https://en.wikipedia.org/wiki/Bandemia	2021-01-18T18:45:26	{"umls": ["C0741439"], "icd-9": ["288.66"], "wikidata": ["Q4854514"]}
Abnormal narrowing of a blood vessel or other tubular organ or structure Stenosis Other namesStenoses CT scan of a bronchial stenosis (arrow) that resulted from tracheobronchial injury Pronunciation * /stəˈnoʊsɪs/[1][2] A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure. It is also sometimes called a stricture (as in urethral stricture).[3] Stricture as a term is usually used when narrowing is caused by contraction of smooth muscle (e.g. achalasia, prinzmetal angina); stenosis is usually used when narrowing is caused by lesion that reduces the space of lumen (e.g. atherosclerosis).[citation needed] The term coarctation is another synonym,[4] but is commonly used only in the context of aortic coarctation. Restenosis is the recurrence of stenosis after a procedure. ## Contents * 1 Types * 2 Causes * 3 Diagnosis * 4 See also * 5 References * 6 External links ## Types[edit] The resulting syndrome depends on the structure affected. Examples of vascular stenotic lesions include: * Intermittent claudication (peripheral artery stenosis) * Angina (coronary artery stenosis) * Carotid artery stenosis which predispose to (strokes and transient ischaemic episodes) * Renal artery stenosis The types of stenoses in heart valves are: * Pulmonary valve stenosis, which is the thickening of the pulmonary valve, therefore causing narrowing * Mitral valve stenosis, which is the thickening of the mitral valve (of the left heart), therefore causing narrowing * Tricuspid valve stenosis, which is the thickening of the tricuspid valve (of the right heart), therefore causing narrowing * Aortic valve stenosis, which is the thickening of the aortic valve, therefore causing narrowing Stenoses/strictures of other bodily structures/organs include: * Pyloric stenosis (gastric outflow obstruction) * Lumbar, cervical or thoracic spinal stenosis * Subglottic stenosis (SGS) * Tracheal stenosis * Obstructive jaundice (biliary tract stenosis) * Bowel obstruction * Phimosis * Non-communicating hydrocephalus due to aqueductal stenosis * Stenosing tenosynovitis * Atherosclerosis * Esophageal stricture * Achalasia * Prinzmetal angina * Vaginal stenosis * Meatal stenosis ## Causes[edit] * alcohol * atherosclerosis causes stenotic lesions in arteries. * birth defects * calcification * diabetes * headbanging \- as in the case of Dave Mustaine * iatrogenic, e.g. secondary to radiation therapy * infection * inflammation * ischemia * neoplasm – in such cases, the stenosis is often said to be "malignant" or "benign", although this attribute actually refers to the neoplasm itself. * smoking * ureteral * urethral ## Diagnosis[edit] Stenoses of the vascular type are often associated with unusual blood sounds resulting from turbulent flow over the narrowed blood vessel. This sound can be made audible by a stethoscope, but diagnosis is generally made or confirmed with some form of medical imaging. ## See also[edit] * Atresia * Restenosis ## References[edit] Notes 1. ^ OED 2nd edition, 1989, as /stɪˈnəʊsɪs/. 2. ^ Entry "stenosis" in Merriam-Webster Online Dictionary. 3. ^ "Dorlands Medical Dictionary:stenosis". www.mercksource.com. Retrieved 2010-05-05. 4. ^ "coarctation" at Dorland's Medical Dictionary ## External links[edit] Classification D * MeSH: D003251 * "Tracheal Stenosis Audio and Video". Archived from the original on 2007-01-12. * "Symptoms of Urethral Stricture". Archived from the original on July 17, 2016. * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Stenosis	c1261287	6,726	wikipedia	https://en.wikipedia.org/wiki/Stenosis	2021-01-18T19:03:28	{"mesh": ["D003251"], "wikidata": ["Q2343082"]}
A rare chromosomal anomaly involving deletion of chromosome band 2q37 and characterized by a broad spectrum of clinical findings including mild-moderate developmental delay/intellectual disability, brachymetaphalangy of digits 3-5, short stature, obesity, hypotonia, specific facial dysmorphism, abnormal behavior, autism or autism spectrum disorder, joint hypermobility/dislocation, and scoliosis. ## Epidemiology To date, more than 150 individuals have been reported worldwide. Females are more frequently affected (60%). ## Clinical description A congenital malformation syndrome with a variable presentation. The phenotype includes mild-to-moderate developmental delay or intellectual deficit, hypotonia (50 to 65% of patients), seizures (20%-35%), brachymetaphalangism (50%), short stature (23%), characteristic facial dysmorphism (sparse scalp hair, round face, prominent forehead, upslanting palpebral fissures, sparse and arched eyebrows, deep-set eyes, midface hypoplasia, a depressed nasal bridge, deficient nasal alae and prominent columella, V-shaped appearance of the nasal tip, thin vermillion border of the lips, and a high-arched palate) and a tendency toward obesity with age. Behavioral disorders are common and may include repetitive behavior, severe communication and social interaction deficits, stereotypic movements, intermittent aggressiveness, hyperactivity, attention deficit disorder, obsessive-compulsive disorder and sleep disturbances. The following clinical features are also frequent: widely set, distally placed or supernumerary nipples, fifth finger clinodactyly, syndactyly, and small hands/feet, syndactyly of the fingers or toes, persistent fetal finger pads and a single palmar crease, and microcephaly or macrocephaly. Eczema is often present. Major malformations occur in 30% of patients with 2q37 deletions and may include congenital heart, gastrointestinal (30% of patients), genitourinary (11% of cases) and central nervous system malformations (6% of patients). ## Etiology The deletion involves the terminal region of chromosome 2 with breakpoints at or within band 2q37. A few genotype-phenotype correlations have been identified including a critical region for the Albright hereditary osteodystrophy-like phenotype. The genes in 2q37 involved in the clinical signs previously mentioned include CAPN10, PRLH, HDLBP, PER2 for the weight, GBC1, GPR35, STK25, PDCD1, GBX2, TWIST2, FARP2, PER2 for skeletal disorders, GBX2, TWIST2, FARP2, PER2, PRLH, HDLBP, TRPM8, AGAP1, KIF1A, PASK, ATG4B for behavioral disorders, and HDAC4 which is essential for the development of the brain, muscle, and bone. The deletion of Mir-562 is linked to Wilms tumor. ## Diagnostic methods Diagnosis relies on cytogenetic analysis and molecular characterization. Screening for a translocation should also be conducted as the deletion may be the result of the transmission of a derivative chromosome. ## Differential diagnosis The differential diagnosis should include other segmental aneusomy syndromes and Prader-Willi syndrome .The group of pseudohypoparathyroidism with Albright hereditary osteodytrophy should also be included in the differential diagnosis but calcium, phosphorus, and parathormone levels are in the normal range in patients with deletion 2q37. ## Antenatal diagnosis Genetic antenatal diagnosis is feasible where the deletion or associated rearrangement has previously been identified in a family member. A prenatal diagnosis might be proposed as for any de novo abnormal chromosomal rearrangement because of potential germinal mosaicism. ## Genetic counseling Most cases arise de novo; however, familial chromosomal rearrangements have been identified in a small proportion of cases. The subsequent risk to siblings of a proband depends on the specific chromosome rearrangement in the parent. Theoretically, a patient with pure 2q37 deletion will have a 50% risk to transmit the deletion. ## Management and treatment Management should be multidisciplinary and include a comprehensive evaluation of the major clinical criteria. Speech, physical and occupational therapy are required. The patients will need careful medical screening between birth and 5 years, for potential associated malformation, and follow up in referal centers for intellectual disabled patients. ## Prognosis The prognosis is very different between children some are mildly affected and other have severe intellectual disability. They have often cognitive difficulties and most of them attend special schools. At the age of 20 most of them are not autonomous and some develop psychiatric disorders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	2q37 microdeletion syndrome	c2931817	6,727	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1001	2021-01-23T19:09:33	{"gard": ["10202"], "mesh": ["C538317"], "omim": ["600430"], "umls": ["C2931817"], "icd-10": ["Q93.5"], "synonyms": ["Albright hereditary osteodystrophy type 3", "Albright hereditary osteodystrophy-like syndrome", "Brachydactyly-intellectual disability syndrome", "Del(2)(q37)", "Deletion 2q37", "Monosomy 2q37qter"]}
Limb–mammary syndrome Other namesLMS[1] SpecialtyMedical genetics Limb–mammary syndrome is a cutaneous condition characterized by p63 mutations.[2] ## Contents * 1 See also * 2 References * 3 Further reading * 4 External links ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ "OMIM Entry - # 603543 - LIMB-MAMMARY SYNDROME; LMS". omim.org. Retrieved 27 April 2019. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. ## Further reading[edit] * GeneReviews/NCBI/NIH/UW entry on Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome or AEC Syndrome, Hay-Wells Syndrome. Includes: Rapp-Hodgkin Syndrome ## External links[edit] Classification D * ICD-10: Q82.4 * OMIM: 603543 * MeSH: C535903 * DiseasesDB: 32743 * SNOMED CT: 721972001 External resources * Orphanet: 69085 * OMIM entries on AEC * 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) This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Limb–mammary syndrome	c1863753	6,728	wikipedia	https://en.wikipedia.org/wiki/Limb%E2%80%93mammary_syndrome	2021-01-18T18:45:49	{"gard": ["10051"], "mesh": ["C535903"], "umls": ["C1863753"], "icd-10": ["Q82.4"], "orphanet": ["69085"], "wikidata": ["Q6549091"]}
Bradyopsia is a rare condition that affects vision. The term "bradyopsia" is from the Greek words for slow vision. In affected individuals, the eyes adapt more slowly than usual to changing light conditions. For example, people with this condition are blinded for several seconds when going from a dark environment into a bright one, such as when walking out of a darkened movie theater into daylight. Their eyes also have trouble adapting from bright light to dark conditions, such as when driving into a dark tunnel on a sunny day. Some people with bradyopsia also have difficulty seeing some moving objects, particularly small objects moving against a bright background. As a result, they often have trouble watching or participating in sports with a ball, such as soccer or tennis. People with bradyopsia can have reduced sharpness (acuity) of vision, although acuity may depend on the conditions under which vision is tested. Visual acuity may appear to be severely affected if it is tested under bright lights, but it can be near normal if tested in a dim environment. The ability to see colors and distinguish between them is normal. The vision problems associated with bradyopsia become apparent in early childhood. They are usually stable, which means they do not worsen over time. ## Frequency Bradyopsia appears to be rare. Only a few affected individuals worldwide have been described in the medical literature. ## Causes Bradyopsia can be caused by mutations in the RGS9 gene or in the RGS9BP gene (which is also known as R9AP). These genes provide instructions for making proteins that are necessary for normal vision. The proteins are found in light-detecting cells in the eye called photoreceptors. When light enters the eye, it stimulates specialized pigments in these cells. This stimulation triggers a series of chemical reactions that produce an electrical signal, which is interpreted by the brain as vision. Once photoreceptors have been stimulated by light, they must return to their resting state before they can be stimulated again. The RGS9 and RGS9BP proteins play an essential role in returning photoreceptors to their resting state quickly after light exposure. Mutations in either the RGS9 or RGS9BP gene prevent photoreceptors from recovering quickly after responding to light. Normally they return to their resting state in a fraction of a second, but in people with mutations in one of these genes, it can take ten seconds or longer. During that time, the photoreceptors cannot respond to light. This delay causes temporary blindness in response to changing light conditions and interferes with seeing small objects when they are in motion. In some people with bradyopsia, no mutations in the RGS9 or RGS9BP gene have been found. The cause of the condition in these individuals is unknown. ### Learn more about the genes associated with Bradyopsia * RGS9 * RGS9BP ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Bradyopsia	c1842073	6,729	medlineplus	https://medlineplus.gov/genetics/condition/bradyopsia/	2021-01-27T08:25:05	{"gard": ["12299"], "mesh": ["C564243"], "omim": ["608415"], "synonyms": []}
Pre-eclampsia characterized by the presence of seizures Eclampsia SpecialtyObstetrics SymptomsSeizures, high blood pressure[1] ComplicationsAspiration pneumonia, cerebral hemorrhage, kidney failure, cardiac arrest[1] Usual onsetAfter 20 weeks of pregnancy[1] Risk factorsPre-eclampsia[1] PreventionAspirin, calcium supplementation, treatment of prior hypertension[2][3] TreatmentMagnesium sulfate, hydralazine, emergency delivery[1][4] Prognosis1% risk of death[1] Frequency1.4% of deliveries[5][6] Deaths46,900 hypertensive diseases of pregnancy (2015)[7] Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia.[1] Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protein in the urine or other organ dysfunction.[8][9] Onset may be before, during, or after delivery.[1] Most often it is during the second half of pregnancy.[1] The seizures are of the tonic–clonic type and typically last about a minute.[1] Following the seizure there is typically either a period of confusion or coma.[1] Complications include aspiration pneumonia, cerebral hemorrhage, kidney failure, pulmonary oedema, HELLP syndrome, coagulopathy, abruptio placentae and cardiac arrest.[1][10] Pre-eclampsia and eclampsia are part of a larger group of conditions known as hypertensive disorders of pregnancy.[1] Recommendations for prevention include aspirin in those at high risk, calcium supplementation in areas with low intake, and treatment of prior hypertension with medications.[2][3] Exercise during pregnancy may also be useful.[1] The use of intravenous or intramuscular magnesium sulfate improves outcomes in those with eclampsia and is generally safe.[4][11] This is true in both the developed and developing world.[4] Breathing may need to be supported.[1] Other treatments may include blood pressure medications such as hydralazine and emergency delivery of the baby either vaginally or by cesarean section.[1] Pre-eclampsia is estimated to affect about 5% of deliveries while eclampsia affects about 1.4% of deliveries.[5] In the developed world rates are about 1 in 2,000 deliveries due to improved medical care.[1] Hypertensive disorders of pregnancy are one of the most common causes of death in pregnancy.[12][13] They resulted in 46,900 deaths in 2015.[7] Around one percent of women with eclampsia die.[1] The word eclampsia is from the Greek term for lightning.[14] The first known description of the condition was by Hippocrates in the 5th century BC.[14] ## Contents * 1 Signs and symptoms * 1.1 Onset * 1.2 Complications * 2 Risk factors * 3 Mechanism * 4 Diagnosis * 4.1 Vital signs * 4.2 Laboratory testing * 4.3 Differential diagnosis * 5 Prevention * 6 Treatment * 6.1 Convulsions * 6.2 Blood pressure management * 6.3 Delivery * 6.4 Monitoring * 7 Etymology * 8 Popular culture * 9 References * 10 External links ## Signs and symptoms[edit] Diagram of the regions (or quadrants) of the abdomen, to assist in locating the right upper quadrant or the epigastric region, where eclampsia-associated pain may occur Eclampsia is a disorder of pregnancy characterized by seizures in the setting of pre-eclampsia.[15] Pre-eclampsia is diagnosed when repeated blood pressure measurements are greater or equal to 140/90mmHg, in addition to any signs of organ dysfunction, including: proteinuria, thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, cerebral symptoms, or abdominal pain.[16] Typically the pregnant woman develops hypertension and proteinuria before the onset of a convulsion (seizure).[17] * Long-lasting (persistent) headaches * Blurred vision * Photophobia (i.e. bright light causes discomfort) * Abdominal pain * Either in the epigastric region (the center of the abdomen above the navel, or belly-button) * And/or in the right upper quadrant of the abdomen (below the right side of the rib cage) * Altered mental status (confusion) Any of these symptoms may present before or after a seizure occurs.[18] It is also possible that none of these symptoms will develop. Other cerebral signs may immediately precede the convulsion, such as nausea, vomiting, headaches, and cortical blindness. If the complication of multi-organ failure ensues, signs and symptoms of those failing organs will appear, such as abdominal pain, jaundice, shortness of breath, and diminished urine output. ### Onset[edit] The seizures of eclampsia typically present during pregnancy and prior to delivery (the antepartum period),[19] but may also occur during labor and delivery (the intrapartum period) or after the baby has been delivered (the postpartum period).[15][18][20] If postpartum seizures develop, it is most likely to occur within the first 48 hours after delivery. However, late postpartum seizures of eclampsia may occur as late as 4 weeks after delivery.[15][18] ### Complications[edit] There are risks to both the mother and the fetus when eclampsia occurs. The fetus may grow more slowly than normal within the womb (uterus) of a woman with eclampsia, which is termed intrauterine growth restriction and may result in the child appearing small for gestational age or being born with low birth weight.[21] Eclampsia may cause problems with the placenta to occur. The placenta may bleed (hemorrhage) or it may begin to separate from the wall of the uterus.[22][23] It is normal for the placenta to separate from the uterine wall during delivery, but it is abnormal for it to separate prior to delivery; this condition is called placental abruption and can be dangerous for the fetus.[24] Placental insufficiency may also occur, a state in which the placenta fails to support appropriate fetal development because it cannot deliver the necessary amount of oxygen or nutrients to the fetus.[22] During an eclamptic seizure, the beating of the fetal heart may become slower than normal (bradycardia).[21][25] If any of these complications occurs, fetal distress may develop. Treatment of the mother's seizures may also manage fetal bradycardia.[26][27] If the risk to the health of the fetus or the mother is high, the definitive treatment for eclampsia is delivery of the baby. Delivery by cesarean section may be deemed necessary, especially if the instance of fetal bradycardia does not resolve after 10 to 15 minutes of resuscitative interventions.[26][28] It may be safer to deliver the infant preterm than to wait for the full 40 weeks of fetal development to finish, and as a result prematurity is also a potential complication of eclampsia.[22][29] In the mother, changes in vision may occur as a result of eclampsia, and these changes may include blurry vision, one-sided blindness (either temporary due to amaurosis fugax or potentially permanent due to retinal detachment), or cortical blindness, which affects the vision from both eyes.[30][31] There are also potential complications in the lungs. The woman may have fluid slowly collecting in the lungs in a process known as pulmonary edema.[22] During an eclamptic seizure, it is possible for a person to vomit the contents of the stomach and to inhale some of this material in a process known as aspiration.[21] If aspiration occurs, the woman may experience difficulty breathing immediately or could develop an infection in the lungs later, called aspiration pneumonia.[18][32] It is also possible that during a seizure breathing will stop temporarily or become inefficient, and the amount of oxygen reaching the woman's body and brain will be decreased (in a state known as hypoxia).[18][33] If it becomes difficult for the woman to breathe, she may need to have her breathing temporarily supported by an assistive device in a process called mechanical ventilation. In some severe eclampsia cases, the mother may become weak and sluggish (lethargy) or even comatose.[31] These may be signs that the brain is swelling (cerebral edema) or bleeding (intracerebral hemorrhage).[22][31] ## Risk factors[edit] Eclampsia, like pre-eclampsia, tends to occur more commonly in first pregnancies.[34][35][36] Women who have long term high blood pressure before becoming pregnant have a greater risk of pre-eclampsia.[34][35] Furthermore, women with other pre-existing vascular diseases (diabetes or nephropathy) or thrombophilic diseases such as the antiphospholipid syndrome are at higher risk to develop pre-eclampsia and eclampsia.[34][35] Having a large placenta (multiple gestation, hydatidiform mole) also predisposes women to eclampsia.[34][35][37] In addition, there is a genetic component: a woman whose mother or sister had the condition is at higher risk than otherwise.[38] Women who have experienced eclampsia are at increased risk for pre-eclampsia/eclampsia in a later pregnancy.[35] People of certain ethnic backgrounds can have an increased risk of developing pre-eclampsia and eclampsia. The occurrence of pre-eclampsia was 5% in white, 9% in Hispanic, and 11% in African American women. Black women were also shown to have a disproportionately higher risk of dying from eclampsia.[39] ## Mechanism[edit] Diagram of the placenta and its position in the uterus during pregnancy Image of a placenta after delivery The presence of a placenta is required, and eclampsia resolves if it is removed.[40] Reduced blood flow to the placenta (placental hypoperfusion) is a key feature of the process. It is accompanied by increased sensitivity of the maternal vasculature to agents which cause constriction of the small arteries, leading to reduced blood flow to multiple organs. Vascular dysfunction-associated maternal conditions such as Lupus, hypertension, and renal disease, or obstetric conditions that increase placental volume without an increase in placental blood flow (such as twin pregnancy) can increase risk for pre-eclampsia.[41] Also, an activation of the coagulation cascade may lead to microthrombi formation, which can further impair blood flow. Thirdly, increased vascular permeability results in the shift of extracellular fluid from the blood to the interstitial space, with further reduction in blood flow, and edema. These events lead to hypertension; renal, pulmonary, and hepatic dysfunction; and cerebral edema with cerebral dysfunction and convulsions.[40] Before symptoms appear, increased platelet and endothelial activation may be detected.[40] Placental hypoperfusion is linked to abnormal modelling of the fetal–maternal placental interface that may be immunologically mediated.[40] Pre-eclampsia’s pathogenesis is poorly understood, but it likely is attributed to factors related to the mother and placenta, because pre-eclampsia is seen in molar pregnancies absent of a fetus or fetal tissue.[41] The placenta produces the potent vasodilator adrenomedullin: it is reduced in pre-eclampsia and eclampsia.[42] Other vasodilators are also reduced, including prostacyclin, thromboxane A2, nitric oxide, and endothelins, also leading to vasoconstriction.[25] Eclampsia is a form of hypertensive encephalopathy: cerebral vascular resistance is reduced, leading to increased blood flow to the brain, cerebral edema and resultant convulsions.[43] An eclamptic convulsion usually does not cause chronic brain damage unless intracranial haemorrhage occurs.[44] ## Diagnosis[edit] If a pregnant woman has already been diagnosed with pre-eclampsia during the current pregnancy and then develops a seizure, she may be assigned a 'clinical diagnosis' of eclampsia without further workup. While seizures are most common in the third trimester, they may occur any time from 20 weeks of pregnancy until 6 weeks after birth.[45] A diagnosis of eclampsia is most likely given the symptoms and medical history, and eclampsia can be assumed to be the correct diagnosis until proven otherwise.[46] However, if a woman has a seizure and it is unknown whether or not she has pre-eclampsia, testing can help make the diagnosis clear. ### Vital signs[edit] One of the core features of pre-eclampsia is high blood pressure. Blood pressure is a measurement of two numbers. If either the top number (systolic blood pressure) is greater than 140 mmHg or the bottom number (diastolic blood pressure) is greater than 90 mmHg, then the blood pressure is higher than the normal range and the person has high blood pressure. If the systolic blood pressure is greater than 160 or the diastolic pressure is greater than 110, the hypertension is considered to be severe.[15] ### Laboratory testing[edit] Another core feature of pre-eclampsia is proteinuria, which is the presence of excess protein in the urine. To determine if proteinuria is present, the urine can be collected and tested for protein; if there is 0.3 grams of protein or more in the urine of a pregnant woman collected over 24 hours, this is one of the diagnostic criteria for pre-eclampsia and raises the suspicion that a seizure is due to eclampsia.[15] In cases of severe eclampsia or pre-eclampsia, the level of platelets in the blood can be low in a condition termed thrombocytopenia.[47][25] A complete blood count, or CBC, is a test of the blood that can be performed to check platelet levels. Other investigations include: kidney function test, liver function tests (LFT), coagulation screen, 24-hour urine creatinine, and fetal/placental ultrasound. ### Differential diagnosis[edit] Convulsions during pregnancy that are unrelated to pre-eclampsia need to be distinguished from eclampsia. Such disorders include seizure disorders as well as brain tumor, aneurysm of the brain, and medication- or drug-related seizures. Usually, the presence of the signs of severe pre-eclampsia precede and accompany eclampsia, facilitating the diagnosis.[medical citation needed] ## Prevention[edit] Detection and management of pre-eclampsia is critical to reduce the risk of eclampsia. The USPSTF recommends regular checking of blood pressure through pregnancy in order to detect preeclampsia.[48] Appropriate management of women with pre-eclampsia generally involves the use of magnesium sulfate to prevent eclamptic seizures.[49] In some cases, low-dose aspirin has been shown to decrease the risk of pre-eclampsia in pregnant women, especially when taken in the late first trimester.[16] ## Treatment[edit] The four goals of the treatment of eclampsia are to stop and prevent further convulsions, to control the elevated blood pressure, to deliver the baby as promptly as possible, and to monitor closely for the onset of multi-organ failure. ### Convulsions[edit] Convulsions are prevented and treated using magnesium sulfate.[50] The study demonstrating the effectiveness of magnesium sulfate for the management of eclampsia was first published in 1955.[51] Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. [52] With intravenous administration, the onset of anticonvulsant action is fast and lasts about 30 minutes. Following intramuscular administration the onset of action is about one hour and lasts for three to four hours. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration. [52] Magnesium sulfate is associated with several minor side effects; serious side effects are uncommon, occurring at elevated magnesium serum concentrations > 7.0 mEQ/L. Serious toxicity can be counteracted with calcium gluconate. [53] Even with therapeutic serum magnesium concentrations, recurrent convulsions may occur, and additional magnesium may be needed, but with close monitoring for respiratory, cardiac, and neurological depression. If magnesium administration with resultant high serum concentrations fail to control convulsions, the addition of other intravenous anticonvulsants may be used, facilitate intubation and mechanical ventilation, and to avoid magnesium toxicity including maternal thoracic muscle paralysis. Magnesium sulfate results in better outcomes than diazepam, phenytoin or a combination of chlorpromazine, promethazine, and pethidine.[54][55][56] ### Blood pressure management[edit] Blood pressure control is used to prevent stroke, which accounts for 15 to 20 percent of deaths in women with eclampsia.[57] The agents of choice for blood pressure control during eclampsia are hydralazine or labetalol.[25] This is because of their effectiveness, lack of negative effects on the fetus, and mechanism of action. Blood pressure management is indicated with a diastolic blood pressure above 105–110 mm Hg.[28] ### Delivery[edit] If the baby has not yet been delivered, steps need to be taken to stabilize the woman and deliver her speedily. This needs to be done even if the baby is immature, as the eclamptic condition is unsafe for both baby and mother. As eclampsia is a manifestation of a type of non-infectious multiorgan dysfunction or failure, other organs (liver, kidney, lungs, cardiovascular system, and coagulation system) need to be assessed in preparation for a delivery (often a caesarean section), unless the woman is already in advanced labor. Regional anesthesia for caesarean section is contraindicated when a coagulopathy has developed. There is limited to no evidence in favor of a particular delivery method for women with eclampsia. Therefore, the delivery method of choice is an individualized decision.[27] ### Monitoring[edit] Invasive hemodynamic monitoring may be elected in an eclamptic woman at risk for or with heart disease, kidney disease, refractory hypertension, pulmonary edema, or poor urine output.[25] ## Etymology[edit] The Greek noun ἐκλαμψία, eklampsía, denotes a "light burst"; metaphorically, in this context, "sudden occurrence." The New Latin term first appeared in Johannes Varandaeus’ 1620 treatise on gynaecology Tractatus de affectibus Renum et Vesicae.[58] The term toxemia of pregnancy is no longer recommended: placental toxins are not the cause of eclampsia occurrences, as previously believed.[59] ## Popular culture[edit] In Downton Abbey, a historical drama television series, the character Lady Sybil dies (in series 3, episode 5) of eclampsia shortly after child birth.[60] In Call the Midwife, a medical drama television series set in London in the 1950s and 1960s, the character (in series 1, episode 4) named Margaret Jones is struck with pre-eclampsia, ultimately proceeding from a comatose condition to death. The term "toxemia" was also used for the condition, in the dialogue.[61] In House M.D., a medical drama television series set in the U.S., Dr. Cuddy, the hospital director, adopts a baby whose teenage mother dies from eclampsia and had no other parental figures available.[61] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r "Chapter 40: Hypertensive Disorders". Williams Obstetrics (24th ed.). McGraw-Hill Professional. 2014. ISBN 9780071798938. 2. ^ a b WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia (PDF). 2011. ISBN 978-92-4-154833-5. Archived (PDF) from the original on 2015-05-13. 3. ^ a b Henderson, JT; Whitlock, EP; O'Connor, E; Senger, CA; Thompson, JH; Rowland, MG (20 May 2014). "Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force". Annals of Internal Medicine. 160 (10): 695–703. doi:10.7326/M13-2844. PMID 24711050. S2CID 33835367. 4. ^ a b c Smith, JM; Lowe, RF; Fullerton, J; Currie, SM; Harris, L; Felker-Kantor, E (5 February 2013). "An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management". BMC Pregnancy and Childbirth. 13: 34. doi:10.1186/1471-2393-13-34. PMC 3570392. PMID 23383864. 5. ^ a b Abalos, E; Cuesta, C; Grosso, AL; Chou, D; Say, L (September 2013). "Global and regional estimates of preeclampsia and eclampsia: a systematic review". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 170 (1): 1–7. doi:10.1016/j.ejogrb.2013.05.005. PMID 23746796. 6. ^ Okoror, Collins E. M. (26 December 2018). "Maternal and perinatal outcome in women with eclampsia: a retrospective study at the University of Benin Teaching Hospital". International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 8 (1): 108–114. doi:10.18203/2320-1770.ijrcog20185404. 7. ^ a b GBD 2015 Mortality and Causes of Death, Collaborators. (8 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. 8. ^ Lambert, G; Brichant, JF; Hartstein, G; Bonhomme, V; Dewandre, PY (2014). "Preeclampsia: an update". Acta Anaesthesiologica Belgica. 65 (4): 137–49. PMID 25622379. 9. ^ American College of Obstetricians Gynecologists; Task Force on Hypertension in Pregnancy (November 2013). "Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy" (PDF). Obstet. Gynecol. 122 (5): 1122–31. doi:10.1097/01.AOG.0000437382.03963.88. PMC 1126958. PMID 24150027. 10. ^ Okoror, Collins E. M. (26 December 2018). "Maternal and perinatal outcome in women with eclampsia: a retrospective study at the University of Benin Teaching Hospital". International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 8 (1): 108–114. doi:10.18203/2320-1770.ijrcog20185404. 11. ^ McDonald, SD; Lutsiv, O; Dzaja, N; Duley, L (August 2012). "A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use". International Journal of Gynaecology and Obstetrics. 118 (2): 90–6. doi:10.1016/j.ijgo.2012.01.028. PMID 22703834. S2CID 20361780. 12. ^ Arulkumaran, N.; Lightstone, L. (December 2013). "Severe pre-eclampsia and hypertensive crises". Best Practice & Research Clinical Obstetrics & Gynaecology. 27 (6): 877–884. doi:10.1016/j.bpobgyn.2013.07.003. PMID 23962474. 13. ^ Okoror, Collins E. M. (26 December 2018). "Maternal and perinatal outcome in women with eclampsia: a retrospective study at the University of Benin Teaching Hospital". International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 8 (1): 108. doi:10.18203/2320-1770.ijrcog20185404. 14. ^ a b Emile R. Mohler (2006). Advanced Therapy in Hypertension and Vascular Disease. PMPH-USA. pp. 407–408. ISBN 9781550093186. Archived from the original on 2017-09-10. 15. ^ a b c d e Stone, C. Keith; Humphries, Roger L. (2017). "Chapter 19: Seizures". Current diagnosis & treatment. Emergency medicine (8th ed.). New York: McGraw-Hill. ISBN 9780071840613. OCLC 959876721. 16. ^ a b Current diagnosis & treatment : obstetrics & gynecology. DeCherney, Alan H.,, McGraw-Hill Companies. (12th ed.). [New York]. 12 February 2019. ISBN 978-0071833905. OCLC 1080940730.CS1 maint: others (link) 17. ^ Kane SC, Dennis A, da Silva Costa F, Kornman L, Brennecke S (2013). "Contemporary Clinical Management of the Cerebral Complications of Preeclampsia". Obstetrics and Gynecology International. 2013: 1–10. doi:10.1155/2013/985606. PMC 3893864. PMID 24489551. 18. ^ a b c d e Gabbe MD, Steven G. (2017). "Chapter 31: Preeclampsia and Hypertensive Disorders". Obstetrics : Normal and Problem Pregnancies. Jennifer R. Niebyl MD, Joe Leigh Simpson MD, Mark B. Landon MD, Henry L. Galan MD, Eric R.M. Jauniaux MD, PhD, Deborah A. Driscoll MD, Vincenzo Berghella MD and William A. Grobman MD, MBA (Seventh ed.). Philadelphia, PA: Elsevier, Inc. pp. 661–705. ISBN 9780323321082. OCLC 951627252. 19. ^ Okoror, Collins E. M. (26 December 2018). "Maternal and perinatal outcome in women with eclampsia: a retrospective study at the University of Benin Teaching Hospital". International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 8 (1): 108–114. doi:10.18203/2320-1770.ijrcog20185404. 20. ^ Cunningham, F. Gary (2014). "Chapter 40: Hypertensive Disorders". Williams Obstetrics. Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS. (24th ed.). New York: McGraw-Hill Education. ISBN 9780071798938. OCLC 871619675. 21. ^ a b c Fleisher MD, Lee A. (2018). "Chapter: Eclampsia". Essence of Anesthesia Practice. Roizen, Michael F.,, Roizen, Jeffrey D. (4th ed.). Philadelphia, Pa.: Elsevier Inc. pp. 153–154. ISBN 9780323394970. OCLC 989062320. 22. ^ a b c d e Bersten, Andrew D. (2014). "Chapter 63: Preeclampsia and eclampsia". Oh's Intensive Care Manual. Soni, Neil (Seventh ed.). [Oxford]: Elsevier Ltd. pp. 677–683. ISBN 9780702047626. OCLC 868019515. 23. ^ Okoror, Collins E. M. (26 December 2018). "Maternal and perinatal outcome in women with eclampsia: a retrospective study at the University of Benin Teaching Hospital". International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 8 (1): 108–114. doi:10.18203/2320-1770.ijrcog20185404. 24. ^ Robert Resnik, MD; Robert k. Creasy, MD; Jay d. Iams, MD; Charles j. Lockwood, MD; Thomas Moore, MD; Michael f Greene, MD (2014). "Chapter 46: Placenta Previa, Placenta Accreta, Abruptio Placentae, and Vasa Previa". Creasy and Resnik's maternal-fetal medicine : principles and practice. Creasy, Robert K.,, Resnik, Robert,, Greene, Michael F.,, Iams, Jay D.,, Lockwood, Charles J. (Seventh ed.). Philadelphia, PA. pp. 732–742. ISBN 9781455711376. OCLC 859526325. 25. ^ a b c d e Acog Committee On Obstetric Practice (January 2002). "ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002". Obstet Gynecol. 99 (1): 159–67. doi:10.1016/s0029-7844(01)01747-1. PMID 16175681. 26. ^ a b Gill, Prabhcharan; Tamirisa, Anita P.; Van Hook MD, James W. (2020), "Acute Eclampsia", StatPearls, StatPearls Publishing, PMID 29083632, retrieved 2019-08-04 27. ^ a b ACOG Committee on Obstetric Practice (April 2002). "ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists". International Journal of Gynaecology and Obstetrics. 77 (1): 67–75. ISSN 0020-7292. PMID 12094777. 28. ^ a b Sibai, Baha M. (February 2005). "Diagnosis, prevention, and management of eclampsia". Obstetrics and Gynecology. 105 (2): 402–410. doi:10.1097/01.AOG.0000152351.13671.99. ISSN 0029-7844. PMID 15684172. 29. ^ "Chapter 35: Hypertension". High risk pregnancy : management options. James, D. K. (David K.), Steer, Philip J. (4th ed.). St. Louis, MO: Saunders/Elsevier. 2011. pp. 599–626. ISBN 9781416059080. OCLC 727346377.CS1 maint: others (link) 30. ^ Cunningham FG, Fernandez CO, Hernandez C (April 1995). "Blindness associated with preeclampsia and eclampsia". American Journal of Obstetrics and Gynecology. 172 (4 Pt 1): 1291–8. doi:10.1016/0002-9378(95)91495-1. PMID 7726272. 31. ^ a b c James, David K. (2011). "Chapter 48: Neurologic Complications of Preeclampsia/Eclampsia". High Risk Pregnancy. Steer, Philip J. (4th ed.). St. Louis, MO: Saunders/Elsevier. pp. 861–891. ISBN 9781416059080. OCLC 727346377. 32. ^ Cronenwett, Jack L. (2014). "Chapter 40: Systemic Complications: Respiratory". Rutherford's vascular surgery. Johnston, K. Wayne (Eighth ed.). Philadelphia, PA: Saunders, Elsevier. pp. 626–637. ISBN 9781455753048. OCLC 877732063. 33. ^ Adams, James (2013). "Chapter 99: Seizures". Emergency medicine : clinical essentials (2nd ed.). Philadelphia, PA: Elsevier/ Saunders. pp. 857–869. ISBN 9781437735482. OCLC 820203833. 34. ^ a b c d "Chapter 48: Pregnancy-Related Hypertension". Creasy and Resnik's Maternal-Fetal Medicine : Principles and Practice. Creasy, Robert K.,, Resnik, Robert,, Greene, Michael F.,, Iams, Jay D.,, Lockwood, Charles J. (Seventh ed.). Philadelphia, PA: Saunders, an imprint of Elsevier Inc. 2014. pp. 756–781. ISBN 9781455711376. OCLC 859526325.CS1 maint: others (link) 35. ^ a b c d e Gabbe MD, Steven G. (2017). "Chapter 31: Preeclampsia and Hypertensive Disorders". Obstetrics : Normal and Problem Pregnancies. Jennifer R. Niebyl MD, Joe Leigh Simpson MD, Mark B. Landon MD, Henry L. Galan MD, Eric R.M. Jauniaux MD, PhD, Deborah A. Driscoll MD, Vincenzo Berghella MD and William A. Grobman MD, MBA (Seventh ed.). Philadelphia, PA: Elsevier, Inc. pp. 661–705.e3. ISBN 9780323321082. OCLC 951627252. 36. ^ Gardner, David G. (2018). "Chapter 16: The Endocrinology of Pregnancy". Greenspan's basic & clinical endocrinology. Shoback, Dolores M.,, Greenspan, Francis S. (Francis Sorrel), 1920-2016. (Tenth ed.). [New York]: McGraw-Hill Education. ISBN 9781259589287. OCLC 995848612. 37. ^ Kasper, Dennis L. (2015). "Chapter 117: Gynecologic Malignancies". Harrison's principles of internal medicine. Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Longo, Dan L. (Dan Louis), 1949-, Jameson, J. Larry,, Loscalzo, Joseph (19th ed.). New York: McGraw-Hill Education. ISBN 9780071802154. OCLC 893557976. 38. ^ Murray, Michael F. (2014). "Chapter 102: Pre-eclampsia". Clinical genomics : practical applications in adult patient care. Babyatsky, Mark W.,, Giovanni, Monica A.,, Alkuraya, Fowzan S.,, Stewart, Douglas R. (First ed.). New York: McGraw-Hill Education. ISBN 9780071622448. OCLC 899740989. 39. ^ Williams obstetrics. Williams, J. Whitridge (John Whitridge), 1866-1931., Cunningham, F. Gary,, Leveno, Kenneth J.,, Bloom, Steven L.,, Spong, Catherine Y.,, Dashe, Jodi S. (25th ed.). New York. 12 April 2018. ISBN 978-1-259-64432-0. OCLC 958829269.CS1 maint: others (link) 40. ^ a b c d Roberts JM, Cooper DW (January 2001). "Pathogenesis and genetics of pre-eclampsia". Lancet. 357 (9249): 53–6. doi:10.1016/S0140-6736(00)03577-7. PMID 11197372. S2CID 25280817. 41. ^ a b Greenspan's basic & clinical endocrinology. Gardner, David G.,, Shoback, Dolores M.,, Greenspan, Francis S., 1920- (Francis Sorrel) (10th ed.). New York, N.Y. 10 October 2017. ISBN 9781259589287. OCLC 1075522289.CS1 maint: others (link) 42. ^ Li H, Dakour J, Kaufman S, Guilbert LJ, Winkler-Lowen B, Morrish DW (November 2003). "Adrenomedullin is decreased in preeclampsia because of failed response to epidermal growth factor and impaired syncytialization". Hypertension. 42 (5): 895–900. doi:10.1161/01.HYP.0000095613.41961.6E. PMID 14517225. 43. ^ Cipolla MJ (July 2007). "Cerebrovascular function in pregnancy and eclampsia". Hypertension. 50 (1): 14–24. doi:10.1161/HYPERTENSIONAHA.106.079442. PMID 17548723. 44. ^ Richards A, Graham D, Bullock R (March 1988). "Clinicopathological study of neurological complications due to hypertensive disorders of pregnancy". J. Neurol. Neurosurg. Psychiatry. 51 (3): 416–21. doi:10.1136/jnnp.51.3.416. PMC 1032870. PMID 3361333. 45. ^ Current medical diagnosis & treatment 2021. Papadakis, Maxine A.,, McPhee, Stephen J.,, Rabow, Michael W. (Sixtieth ed.). New York. 10 September 2020. ISBN 978-1-260-46986-8. OCLC 1191849672.CS1 maint: others (link) 46. ^ Edlow, Jonathan A.; Caplan, Louis R.; O'Brien, Karen; Tibbles, Carrie D. (February 2013). "Diagnosis of acute neurological emergencies in pregnant and post-partum women". The Lancet. Neurology. 12 (2): 175–185. doi:10.1016/S1474-4422(12)70306-X. ISSN 1474-4465. PMID 23332362. S2CID 17711531. 47. ^ Tintinalli, Judith E. (2016). "Chapter 100: Maternal Emergencies After 20 Weeks of Pregnancy and in the Postpartum Period". Tintinalli's Emergency Medicine : A Comprehensive Study Guide. Stapczynski, J. Stephan,, Ma, O. John,, Yealy, Donald M.,, Meckler, Garth D.,, Cline, David, 1956- (Eighth ed.). New York: McGraw-Hill Education. ISBN 9780071794763. OCLC 915775025. 48. ^ Sperling, Jeffrey D.; Gossett, Dana R. (25 April 2017). "Screening for Preeclampsia and the USPSTF Recommendations". JAMA. 317 (16): 1629–1630. doi:10.1001/jama.2017.2018. PMID 28444259. 49. ^ Harrison's principles of internal medicine. Jameson, J. Larry,, Kasper, Dennis L.,, Longo, Dan L. (Dan Louis), 1949-, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Loscalzo, Joseph (20th ed.). New York. 13 August 2018. ISBN 978-1-259-64403-0. OCLC 1029074059.CS1 maint: others (link) 50. ^ Patel, Minal K.; Goodson, James L.; Alexander, James P.; Kretsinger, Katrina; Sodha, Samir V.; Steulet, Claudia; Gacic-Dobo, Marta; Rota, Paul A.; McFarland, Jeffrey; Menning, Lisa; Mulders, Mick N. (2020-11-13). "Progress Toward Regional Measles Elimination — Worldwide, 2000–2019". MMWR. Morbidity and Mortality Weekly Report. 69 (45): 1700–1705. doi:10.15585/mmwr.mm6945a6. ISSN 0149-2195. PMC 7660667. PMID 33180759. 51. ^ Pritchard JA (February 1955). "The use of the magnesium ion in the management of eclamptogenic toxemias". Surg Gynecol Obstet. 100 (2): 131–40. PMID 13238166. 52. ^ a b "Magnesium Sulfate - FDA prescribing information, side effects and uses". Drugs.com. Retrieved 2020-12-07. 53. ^ Smith, Jeffrey Michael; Lowe, Richard F.; Fullerton, Judith; Currie, Sheena M.; Harris, Laura; Felker-Kantor, Erica (2013-02-05). "An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management". BMC Pregnancy and Childbirth. 13 (1): 34. doi:10.1186/1471-2393-13-34. ISSN 1471-2393. PMC 3570392. PMID 23383864. 54. ^ Duley, L; Henderson-Smart, DJ; Walker, GJ; Chou, D (Dec 8, 2010). "Magnesium sulphate versus diazepam for eclampsia". The Cochrane Database of Systematic Reviews (12): CD000127. doi:10.1002/14651858.CD000127.pub2. PMC 7045443. PMID 21154341. 55. ^ Duley, L; Henderson-Smart, DJ; Chou, D (Oct 6, 2010). "Magnesium sulphate versus phenytoin for eclampsia". The Cochrane Database of Systematic Reviews (10): CD000128. doi:10.1002/14651858.CD000128.pub2. PMID 20927719. 56. ^ Duley, L; Gülmezoglu, AM; Chou, D (Sep 8, 2010). "Magnesium sulphate versus lytic cocktail for eclampsia". The Cochrane Database of Systematic Reviews (9): CD002960. doi:10.1002/14651858.CD002960.pub2. PMC 7138041. PMID 20824833. 57. ^ Townsend, Rosemary; O’Brien, Patrick; Khalil, Asma (2016-07-27). "Current best practice in the management of hypertensive disorders in pregnancy". Integrated Blood Pressure Control. 9: 79–94. doi:10.2147/IBPC.S77344. ISSN 1178-7104. PMC 4968992. PMID 27555797. 58. ^ Ong, S. (2003). "Pre-eclampsia: A historical perspective". In Baker, P.N.; Kingdom, J.C.P. (eds.). Pr-eclampsia: Current perspectives on management. Taylor & Francis. pp. 15–24. ISBN 978-1842141809. 59. ^ FAQ: Toxemia Archived 2015-09-25 at the Wayback Machine at the Pre-Eclampsia Foundation website 60. ^ Stone, Rachel Marie (January 30, 2013). "Stop With All the Dangerous Childbirth Stories Already". Christianity Today. Archived from the original on March 11, 2016. Retrieved March 11, 2016. 61. ^ a b "Episode #1.4". 5 February 2012. Archived from the original on 10 September 2017. Retrieved 4 September 2016 – via IMDb. ## External links[edit] Classification D * ICD-10: O15 * ICD-9-CM: 642.6 * MeSH: D004461 * DiseasesDB: 4068 External resources * MedlinePlus: 000899 * Patient UK: Eclampsia * Scholia: Q552348 * Eclampsia at Curlie * 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	Eclampsia	c0013537	6,730	wikipedia	https://en.wikipedia.org/wiki/Eclampsia	2021-01-18T18:36:57	{"gard": ["6316"], "mesh": ["D004461"], "umls": ["C0013537"], "icd-9": ["642.6"], "wikidata": ["Q552348"]}
Osteonecrosis of the jaws Other namesOsteonecrosis of the mandible Osteonecrosis of the jaw of the upper left jaw in a patient diagnosed with chronic venous insufficiency SpecialtyRheumatology Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws (the maxilla and the mandible). Various forms of ONJ have been described over the last 160 years, and a number of causes have been suggested in the literature. Osteonecrosis of the jaw associated with bisphosphonate therapy, which is required by some cancer treatment regimens, has been identified and defined as a pathological entity (bisphosphonate-associated osteonecrosis of the jaw) since 2003.[1] The possible risk from lower oral doses of bisphosphonates, taken by patients to prevent or treat osteoporosis, remains uncertain.[2] Treatment options have been explored; however, severe cases of ONJ still require surgical removal of the affected bone.[3] A thorough history and assessment of pre-existing systemic problems and possible sites of dental infection are required to help prevent the condition, especially if bisphosphonate therapy is considered.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Toxic agents * 2.2 Bisphosphonates * 3 Pathophysiology * 3.1 Histopathological alterations * 3.2 Effects of persistent ischaemia on bone cells * 4 Diagnosis * 4.1 Classification * 5 Treatment * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] The definitive symptom of ONJ is the exposure of mandibular or maxillary bone through lesions in the gingiva that do not heal.[4] Pain, inflammation of the surrounding soft tissue, secondary infection or drainage may or may not be present. The development of lesions is most frequent after invasive dental procedures, such as extractions, and is also known to occur spontaneously. There may be no symptoms for weeks or months, until lesions with exposed bone appear.[5] Lesions are more common on the mandible than the maxilla. * Pain and neuropathy[6] * Erythema and suppuration * Bad breath Post radiation maxillary bone osteonecrosis is something that is found more in the lower jaw (mandible) rather than the maxilla (upper jaw) this is because there are many more blood vessels in the upper jaw.[7] The symptoms of this are very similar to the symptoms of medication-related osteonecrosis of the jaw (MRONJ). Patients are in a lot of pain, the area may swell up, bone may be seen and fractures may take place. The patients may also have a dry mouth and find it difficult to keep their mouth clean. A patient that has osteonecrosis may also be susceptible to bacterial and fungal infections. The osteoblasts, which form the bone tissue are destroyed due to the radiation with increased activity of osteoclasts. This condition cannot be treated by antibiotics as there is no blood supply to the bone, making it difficult for the antibiotics to reach the potential infection. This condition makes eating and drinking very difficult, and surgical management removing the necrotic bone improves circulation and decreases microorganisms. ## Causes[edit] ### Toxic agents[edit] Other factors such as toxicants can adversely impact bone cells. Infections, chronic or acute, can affect blood flow by inducing platelet activation and aggregation, contributing to a localized state of excess coagulability (hypercoagulability) that may contribute to clot formation (thrombosis), a known cause of bone infarct and ischaemia. Exogenous estrogens, also called hormonal disruptors, have been linked with an increased tendency to clot (thrombophilia) and impaired bone healing.[8] Heavy metals such as lead and cadmium have been implicated in osteoporosis. Cadmium and lead promotes the synthesis of plasminogen activator inhibitor-1 (PAI-1) which is the major inhibitor of fibrinolysis (the mechanism by which the body breaks down clots) and shown to be a cause of hypofibrinolysis.[9] Persistent blood clots can lead to congestive blood flow (hyperemia) in bone marrow, impaired blood flow and ischaemia in bone tissue resulting in lack of oxygen (hypoxia), bone cell damage and eventual cell death (apoptosis). Of significance is the fact that the average concentration of cadmium in human bones in the 20th century has increased to about 10 times above the pre-industrial level.[10] ### Bisphosphonates[edit] Main article: Bisphosphonate-associated osteonecrosis of the jaw The first three reported cases of bisphosphonate-associated osteonecrosis of the jaw were spontaneously reported to the FDA by an oral surgeon in 2002, with the toxicity being described as a potentially late toxicity of chemotherapy.[11] In 2003 and 2004, three oral surgeons independently reported to the FDA information on 104 cancer patients with bisphosphonate-associated osteonecrosis of the jaw seen in their referral practices in California, Florida, and New York.[12][13][14] These case series were published as peer-reviewed articles – two in the Journal of Oral and Maxillofacial Surgery and one in the Journal of Clinical Oncology. Subsequently, numerous instances of persons with this adverse drug reaction were reported to the manufacturers and to the FDA. By December 2006, 3607 cases of people with this ADR had been reported to the FDA and 2227 cases had been reported to the manufacturer of intravenous bisphosphonates. Rise in reported cases of osteonecrosis of the jaw from 1988 through 2007 The International Myeloma Foundation's web-based survey included 1203 respondents, 904 patients with myeloma and 299 with breast cancer and an estimate that after 36 months, osteonecrosis of the jaw had been diagnosed in 10% of 211 patients on zoledronate and 4% of 413 on pamidronate.[15] A population based study in Germany identified more than 300 cases of osteonecrosis of the jaw, 97% occurring in cancer patients (on high-dose intravenous bisphosphonates) and 3 cases in 780,000 patients with osteoporosis for an incidence of 0.00038%. Time to event ranged from 23–39 months and 42–46 months with high dose intravenous and oral bisphosphonates.[16] A prospective, population based study by Mavrokokki et al.. estimated an incidence of osteonecrosis of the jaw of 1.15% for intravenous bisphosphonates and 0.04% for oral bisphosphonates. Most cases (73%) were precipitated by dental extractions. In contrast, safety studies sponsored by the manufacturer reported bisphosphonate-associated osteonecrosis of the jaw rates that were much lower. Although the majority of cases of ONJ have occurred in cancer patients receiving high dose intravenous bisphosphonates, almost 800 cases have been reported in oral bisphosphonate users for osteoporosis or Pagets disease. In terms of severity most cases of ONJ in oral bisphosphonate users are stage 1–2 and tend to progress to resolution with conservative measures such as oral chlorhexidine rinses. Owing to prolonged embedding of bisphosphonate drugs in the bone tissues, the risk for BRONJ is high even after stopping the administration of the medication for several years.[17][18] This form of therapy has been shown to prevent loss of bone mineral density (BMD) as a result of a reduction in bone turnover. However, bone health entails quite a bit more than just BMD. There are many other factors to consider. In healthy bone tissue there is a homeostasis between bone resorption and ossification. Diseased or damaged bone is resorbed through the osteoclasts mediated process while osteoblasts form new bone to replace it, thus maintaining healthy bone density. This process is commonly called remodelling. However, osteoporosis is essentially the result of a lack of new bone formation in combination with bone resorption in reactive hyperemia, related to various causes and contributing factors, and bisphosphonates do not address these factors at all. In 2011, a proposal incorporating both the reduced bone turnover and the infectious elements of previous theories has been put forward. It cites the impaired functionality of affected macrophages as the dominant factor in the development of ONJ.[19] In a systematic review of cases of bisphosphonate-associated ONJ up to 2006, it was concluded that the mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. According to Woo, Hellstein and Kalmar, oversuppression of bone turnover is probably the primary mechanism for the development of this form of ONJ, although there may be contributing co-morbid factors (as discussed elsewhere in this article). It is recommended that all sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate (Fosamax), for osteoporosis is uncertain and warrants careful monitoring.[20] Patients taking dexamethasone and other glucocorticoids are at increased risk.[21] Matrix metalloproteinase 2 may be a candidate gene for bisphosphonate-associated osteonecrosis of the jaw, since it is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are side effects of bisphosphonates.[22] ## Pathophysiology[edit] ### Histopathological alterations[edit] Persons with ONJ may have either necrotic bone or bone marrow that has been slowly strangulated or nutrient-starved. Bone with chronically poor blood flow develops either a fibrous marrow since fibres can more easily live in nutrient starved areas, a greasy, dead fatty marrow (wet rot), a very dry, sometimes leathery marrow (dry rot), or a completely hollow marrow space (osteocavitation), also typical of ONJ. The blood flow impairment occurs following a bone infarct, a blood clot forming inside the smaller blood vessels of cancellous bone tissue. Under ischaemic conditions numerous pathological changes in the bone marrow and trabeculae of oral cancellous bone have been documented. Microscopically, areas of "apparent fatty degeneration and/or necrosis, often with pooled fat from destroyed adipose cells (oil cysts) and with marrow fibrosis (reticular fatty degeneration)" are seen. These changes are present even if "most bony trabeculae appear at first glance viable, mature and otherwise normal, but closer inspection demonstrates focal loss of osteocytes and variable micro cracking (splitting along natural cleavage planes). The microscopic features are similar to those of ischaemic or aseptic osteonecrosis of long bones, corticosteroid-induced osteonecrosis, and the osteomyelitis of caisson (deep-sea diver's) disease".[23] In the cancellous portion of femoral head it is not uncommon to find trabeculae with apparently intact osteocytes which seem to be "alive" but are no longer synthetizing collagen. This appears to be consistent with the findings in alveolar cancellous bone.[24] Osteonecrosis can affect any bone, but the hips, knees and jaws are most often involved. Pain can often be severe, especially if teeth and/or a branch of the trigeminal nerve is involved, but many patients do not experience pain, at least in the earlier stages. When severe facial pain is purported to be caused by osteonecrosis, the term NICO, for neuralgia-inducing cavitational osteonecrosis, is sometimes used, but this is controversial and far from completely understood.[25] ONJ, even in its mild or minor forms, creates a marrow environment that is conducive to bacterial growth. Since many individuals have low-grade infections of the teeth and gums, this probably is one of the major mechanisms by which the marrow blood flow problem can worsen; any local infection / inflammation will cause increased pressures and clotting in the area involved. No other bones have this mechanism as a major risk factor for osteonecrosis. A wide variety of bacteria have been cultured from ONJ lesions. Typically, they are the same microorganisms as those found in periodontitis or devitalized teeth. However, according to special staining of biopsied tissues, bacterial elements are rarely found in large numbers. So while ONJ is not primarily an infection, many cases have a secondary, very low-level of bacterial infection and chronic non-suppurative osteomyelitis can be associated with ONJ. Fungal infections in the involved bone do not seem to be a problem, but viral infections have not been studied. Some viruses, such as the smallpox virus (no longer existent in the wild) can produce osteonecrosis. ### Effects of persistent ischaemia on bone cells[edit] Cortical bone is well vascularized by the surrounding soft tissues thus less susceptible to ischaemic damage. Cancellous bone, with its mesh like structure and spaces filled with marrow tissue is more susceptible to damage by bone infarcts, leading to hypoxia and premature cell apoptosis.[14][15][26][27] The mean life-span of osteocytes has been estimated to be 15 years in cancellous bone,[28] and 25 years in cortical bone.[29] while the average lifespan of human osteoclasts is about 2 to 6 weeks and the average lifespan of osteoblasts is approximately 3 months.[30] In healthy bone these cells are constantly replaced by differentiation of bone marrow mesenchymal stem cells (MSC).[31] However, in both non-traumatic osteonecrosis and alcohol-induced osteonecrosis of the femoral head, a decrease in the differentiation ability of mesenchymal stem into bone cells has been demonstrated,[32][33] and altered osteoblastic function plays a role in ON of the femoral head.[34] If these results are extrapolated to ONJ the altered differentiation potential of bone marrow mesenchymal stem cells (MSC) combined with the altered osteoblastic activity and premature death of existing bone cells would explain the failed attempts at repair seen in ischaemic-damaged cancellous bone tissue in ONJ. The rapidity with which premature cell death can occur depends on the cell type and the degree and duration of the anoxia. Haematopoietic cells, in bone marrow, are sensitive to anoxia and are the first to die after reduction or removal of the blood supply. In anoxic conditions they usually die within 12 hours. Experimental evidence suggests that bone cells composed of osteocytes, osteoclasts, and osteoblasts die within 12–48 hours, and marrow fat cells die within 120 hours.[16] The death of bone does not alter its radiographic opacity nor its mineral density. Necrotic bone does not undergo resorption; therefore, it appears relatively more opaque. Attempts at repair of ischaemic-damaged bone will usual occur in 2 phases. First, when dead bone abuts live marrow, capillaries and undifferentiated mesenchymal cells grow into the dead marrow spaces, while macrophages degrade dead cellular and fat debris. Second, mesenchymal cells differentiate into osteoblasts or fibroblasts. Under favorable conditions, layers of new bone form on the surface of dead spongy trabeculae. If sufficiently thickened, these layers may decrease the radiodensity of the bone; therefore, the first radiographic evidence of previous osteonecrosis may be patchy sclerosis resulting from repair. Under unfavorable conditions repeated attempts at repair in ischaemic conditions can be seen histologically and are characterized by extensive delamination or microcracking along cement lines as well as the formation of excessive cement lines.[35] Ultimate failure of repair mechanisms due to persistent and repeated ischaemic events is manifested as trabecular fractures that occur in the dead bone under functional load. Later followed by cracks and fissures leading to structural collapse of the area involved (osteocavitation).[16] ## Diagnosis[edit] ### Classification[edit] Grade Size (diameter) 1A Single lesion, <0.5 cm 1B Multiple lesions, largest <0.5 cm 2A Single lesion <1.0 cm 2B Multiple lesions, largest <1.0 cm 3A Single lesion, ≤2.0 cm 3B Multiple lesions, largest ≤2.0 cm 4A Single lesion >2.0 cm 4B Multiple lesions, largest >2.0 cm Lesion size measured as the largest diameter Grade Severity 1 Asymptomatic 2 Mild 3 Moderate 4 Severe Osteonecrosis of the jaw is classified based on severity, number of lesions, and lesion size. Osteonecrosis of greater severity is given a higher grade, with asymptomatic ONJ designated as grade 1 and severe ONJ as grade 4. ## Treatment[edit] The treatment should be tailored to the cause involved and the severity of the disease process. With oral osteoporosis the emphasis should be on good nutrient absorption and metabolic wastes elimination through a healthy gastro-intestinal function, effective hepatic metabolism of toxicants such as exogenous estrogens, endogenous acetaldehyde and heavy metals, a balanced diet, healthy lifestyle, assessment of factors related to potential coagulopathies, and treatment of periodontal diseases and other oral and dental infections. In cases of advanced oral ischaemic osteoporosis and/or ONJ that are not bisphosphonates related, clinical evidence has shown that surgically removing the damaged marrow, usually by curettage and decortication, will eliminate the problem (and the pain) in 74% of patients with jaw involvement.[3] Repeat surgeries, usually smaller procedures than the first, may be required. Almost a third of jawbone patients will need surgery in one or more other parts of the jaws because the disease so frequently present multiple lesions, i.e., multiple sites in the same or similar bones, with normal marrow in between. In the hip, at least half of all patients will get the disease in the opposite hip over time; this pattern occurs in the jaws as well. Recently, it has been found that some osteonecrosis patients respond to anticoagulation therapies alone. The earlier the diagnosis the better the prognosis. Research is ongoing on other non-surgical therapeutic modalities that could alone or in combination with surgery further improve the prognosis and reduce the morbidity of ONJ. A greater emphasis on minimizing or correcting known causes is necessary while further research is conducted on chronic ischaemic bone diseases such as oral osteoporosis and ONJ. In patients with bisphosphonates-associated ONJ, the response to surgical treatment is usually poor.[36] Conservative debridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this form of ONJ.[37] Although an effective treatment for bisphosphonate-associated bone lesions has not yet been established,[38] and this is unlikely to occur until this form of ONJ is better understood, there have been clinical reports of some improvement after 6 months or more of complete cessation of bisphosphonate therapy.[39] ## History[edit] ONJ is not a new disease: around 1850, forms of "chemical osteomyelitis" resulting from environmental pollutants, such as lead and the white phosphorus used in early (non-safety) matches (Phossy jaw), as well as from popular medications containing mercury, arsenic or bismuth, were reported in the literature.[40][41][42][43][44][45][46] This disease apparently did not often occur in individuals with good gingival health, and usually targeted the mandible first.[41] It was associated with localized or generalized deep ache or pain, often of multiple jawbone sites. The teeth often appeared sound and suppuration was not present. Even so, the dentist often began extracting one tooth after another in the region of pain, often with temporary relief but usually to no real effect.[42] Today a growing body of scientific evidence indicates that this disease process, in the cancellous bone and bone marrow, is caused by bone infarcts mediated by a range of local and systemic factors. Bone infarcts as well as damage to the deeper portion of the cancellous bone is an insidious process. It is certainly not visible clinically and routine imaging techniques such as radiographs are not effective for that sort of damage. "An important and often incompletely understood principle of radiography is the amount of bone destruction that goes undetected by routine x-rays procedures; this has been demonstrated by numerous investigators. Destruction confined to the cancellous portion of the bone cannot be detected radiographically, as radiolucencies appear only when there is internal or external erosion or destruction of the bone cortex."[47] In fact no radiographic findings are specific for bone infarction / osteonecrosis. A variety of pathologies may mimic bone infarction, including stress fractures, infections, inflammations, and metabolic and neoplastic processes. The limitations apply to all imaging modalities, including plain radiography, radionuclide studies, CT scans, and magnetic resonance imaging (MRI). Through-transmission alveolar ultrasound, based on quantitative ultrasound (QUS) in combination with panoramic dental radiography (orthopantomography) is helpful in assessing changes in jawbone density.[48][49] When practitioners have an up-to-date understanding of the disease process and a good medical history is combined with detailed clinical findings, the diagnosis, with the help of various imaging modalities, can be achieved earlier in most patients. In the modern dental profession, it is only recently, when severe cases associated with bisphosphonates came to light, that the issue of ONJ has been brought to the attention of a majority of dentists. At present, the focus is mostly on bisphosphonate-associated cases, and is sometimes referred to colloquially as "phossy jaw", a similar, earlier occupational disease.[50][51] However, the pharmaceutical manufacturers of bisphosphonates drugs such as Merck and Novartis have stated that ONJ in patients on this class of drug, can be related to a pre-existing condition, coagulopathy, anemia, infection, use of corticosteroids, alcoholism and other conditions already known to be associated with ONJ in the absence of bisphosphonate therapy. The implication is that bisphosphonates may not be the initiating cause of ONJ and that other pre-existing or concurrent systemic and/or local dental factors are involved.[52][53] Since ONJ has been diagnosed in many patients who did not take bisphosphonates, it is thus logical to assume that bisphosphonates are not the only factor in ONJ. While the oversuppression of bone turnover seems to play a major role in aggravating the disease process, other factors can and do initiate the pathophysiological mechanisms responsible for ONJ. In non-bisphosphonate cases of ONJ, it is mainly the cancellous portion of the bone and its marrow content that are involved in the disease process. The first stage is an oedema of the bone marrow initiated by a bone infarct, which is itself modulated by numerous causes, leading to myelofibrosis as a result of hypoxia and gradual loss of bone density characteristic of ischaemic osteoporosis. Further deterioration can be triggered by additional bone infarcts leading to anoxia and localized areas of osteonecrosis within the osteoporotic cancellous bone. Secondary events such as dental infection, injection of local anaesthetics with vasoconstrictors, such as epinephrine, and trauma can add further complications to the disease process and chronic non-pus forming bone infection osteomyelitis can also be associated with ONJ.[54][55][56] However, in patients on bisphosphonates, the cortical bone is frequently involved as well. Spontaneous exposure of necrotic bone tissue through the oral soft tissues or following non-healing bone exposure after routine dental surgery, characteristics of this form of ONJ, may be the result of late diagnosis of a disease process that has been masked by the oversuppression of osteoclastic activity, allowing pre-existing factors to further aggravate bone damage. ## References[edit] 1. ^ Alexandru Bucur, Tiberiu Niță, Octavian Dincă, Cristian Vlădan, Mihai Bogdan Bucur (November 2011). "Bisphosphonate associated osteonecrosis of the jaw". Rev. chir. oro-maxilo-fac. implantol. (in Romanian). 2 (3): 24–27. ISSN 2069-3850. 43. Retrieved 6 June 2012.CS1 maint: multiple names: authors list (link)(webpage has a translation button) 2. ^ a b Woo S; Hellstein J; Kalmar J (2006). "Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws". Ann Intern Med. 144 (10): 753–61. doi:10.7326/0003-4819-144-10-200605160-00009. PMID 16702591. 3. ^ a b Bouquot JE; Christian J (1995). "Long-term effects of jawbone curettage on the pain of facial neuralgia". J. Oral Maxillofac. Surg. 53 (4): 387–97, discussion 397–9. doi:10.1016/0278-2391(95)90708-4. PMID 7699492. 4. ^ Journal of Bone and Minerl Research, 2007, Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research 5. ^ American Dental Association, Osteonecrosis of the Jaw Archived 3 August 2009 at the Wayback Machine 6. ^ Zadik Y, Benoliel R, Fleissig Y, Casap N (February 2012). "Painful trigeminal neuropathy induced by oral bisphosphonate-related osteonecrosis of the jaw: a new etiology for the numb-chin syndrome". Quintessence Int. 43 (2): 97–104. PMID 22257870. 7. ^ Auto fluorescence image of post-radiation maxillary bone osteonecrosis in a 64-year-old patient – Case Report Aleksandra Szczepkowska1, Paweł Milner1, Anna Janas 1 Institute of Dental Surgery, Medical University, Łódź, Poland 8. ^ Glueck C; McMahon R; Bouquot J; Triplett D (1998). "Exogenous estrogen may exacerbate thrombophilia, impair bone healing and contribute to development of chronic facial pain". Cranio. 16 (3): 143–53. doi:10.1080/08869634.1998.11746052. PMID 9852807. 9. ^ Yamamoto C (May 2000). "[Toxicity of cadmium and lead on vascular cells that regulate fibrinolysis]". Yakugaku Zasshi. 120 (5): 463–73. doi:10.1248/yakushi1947.120.5_463. PMID 10825810. 10. ^ Jaworowski Z; Barbalat F; Blain C; Peyre E (1985). "Heavy metals in human and animal bones from ancient and contemporary France". Sci. Total Environ. 43 (1–2): 103–26. Bibcode:1985ScTEn..43..103J. doi:10.1016/0048-9697(85)90034-8. PMID 4012292. 11. ^ Lewis RJ; Johnson RD; Angier MK; Vu NT (2004). "Ethanol formation in unadulterated postmortem tissues". Forensic Sci. Int. 146 (1): 17–24. doi:10.1016/j.forsciint.2004.03.015. PMID 15485717. 12. ^ Yajima D; Motani H; Kamei K; Sato Y; Hayakawa M; Iwase H (2006). "Ethanol production by Candida albicans in postmortem human blood samples: effects of blood glucose level and dilution". Forensic Sci. Int. 164 (2–3): 116–21. doi:10.1016/j.forsciint.2005.12.009. PMID 16427751. 13. ^ Cordts PR; Kaminski MV; Raju S; Clark MR; Woo KM (2001). "Could gut-liver function derangements cause chronic venous insufficiency?". Vasc Surg. 35 (2): 107–14. doi:10.1177/153857440103500204. PMID 11668378. 14. ^ a b Marcus R; Feldman D; Kelsey J (1996). Osteoporosis. The Journal of Clinical Endocrinology and Metabolism. 81. San Diego: Academic Press. pp. 1–5. doi:10.1210/jcem.81.1.8550734. ISBN 978-0-12-470863-1. PMID 8550734. 15. ^ a b Bullough PG (1997). Orthopaedic pathology (3rd ed.). Baltimore: Wolfe-Mosby. 16. ^ a b c Bone infarct at eMedicine 17. ^ Zadik Y, Abu-Tair J, Yarom N, Zaharia B, Elad S (September 2012). "The importance of a thorough medical and pharmacological history before dental implant placement". Aust Dent J. 57 (3): 388–392. doi:10.1111/j.1834-7819.2012.01717.x. PMID 22924366. 18. ^ Rodan GA; Reszka AA (2003). "Osteoporosis and bisphosphonates". J Bone Joint Surg Am. 85-A (Suppl 3): 8–12. doi:10.2106/00004623-200300003-00003. PMID 12925603. 19. ^ Pazianas M (February 2011). "Osteonecrosis of the jaw and the role of macrophages" (PDF). J. Natl. Cancer Inst. 103 (3): 232–40. doi:10.1093/jnci/djq516. PMID 21189409. 20. ^ Woo SB; Hellstein JW; Kalmar JR (2006). "Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws". Ann. Intern. Med. 144 (10): 753–61. doi:10.7326/0003-4819-144-10-200605160-00009. PMID 16702591. 21. ^ Marx RE; Sawatari Y; Fortin M; Broumand V (November 2005). "Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment". J. Oral Maxillofac. Surg. 63 (11): 1567–75. doi:10.1016/j.joms.2005.07.010. PMID 16243172. 22. ^ Lehrer S; Montazem A; Ramanathan L; et al. (January 2009). "Bisphosphonate-induced osteonecrosis of the jaws, bone markers, and a hypothesized candidate gene". J. Oral Maxillofac. Surg. 67 (1): 159–61. doi:10.1016/j.joms.2008.09.015. PMID 19070762. 23. ^ Neville BW; Damn D; Allen C; Bouquot JE (1995). "Facial pain and neuromuscular diseases.". Oral and maxillofacial pathology. Head and Neck Pathology. 1. W.B Saunders Co. pp. 631–632. doi:10.1007/s12105-007-0007-4. PMC 2807501. PMID 20614286. 24. ^ Arlet J; Durroux R; Fauchier C; Thiechart M. "Topographic and evolutive aspects". In Arlet J; Ficat PR; Hungerford DS. (eds.). Histophatology of the nontraumatic necrosis of the femoral head. 25. ^ Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 746. ISBN 978-0721690032. 26. ^ Kanus JA. (1996). Textbook of osteoporosis. Osford: Blackwell Science Ltd. 27. ^ Vigorita VJ. (1999). Orthopaedic pathology. Philadelphia: Lippincott Williams & Wilkins. 28. ^ Parfitt AM (1994). "Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone". J. Cell. Biochem. 55 (3): 273–86. doi:10.1002/jcb.240550303. PMID 7962158. 29. ^ Parfin AM; Kleerekoper M; Villanueva AR (1987). "Increased bone age: mechanisms and consequences". Osteoporosis. Copenhagen: Osteopress. pp. 301–308. 30. ^ Frost HM (1963). Bone Remodeling Dynamics. Springfield, IL: Charles C. Thomas. 31. ^ Owen M; Friedenstein AJ (1988). "Stromal stem cells: marrow- derived osteogenic precursors". Ciba Found Symp. Novartis Foundation Symposia. 136: 42–60. doi:10.1002/9780470513637.ch4. ISBN 9780470513637. PMID 3068016. 32. ^ Lee JS; Lee JS; Roh HL; Kim CH; Jung JS; Suh KT (2006). "Alterations in the differentiation ability of mesenchymal stem cells in patients with nontraumatic osteonecrosis of the femoral head: comparative analysis according to the risk factor". J. Orthop. Res. 24 (4): 604–9. doi:10.1002/jor.20078. PMID 16514658. 33. ^ Suh KT; Kim SW; Roh HL; Youn MS; Jung JS (2005). "Decreased osteogenic differentiation of mesenchymal stem cells in alcohol-induced osteonecrosis". Clin. Orthop. Relat. Res. (431): 220–5. doi:10.1097/01.blo.0000150568.16133.3c. PMID 15685079. 34. ^ Gangji V; Hauzeur JP; Schoutens A; Hinsenkamp M; Appelboom T; Egrise D (2003). "Abnormalities in the replicative capacity of osteoblastic cells in the proximal femur of patients with osteonecrosis of the femoral head". J. Rheumatol. 30 (2): 348–51. PMID 12563694. 35. ^ Adams WR; Spolnik KJ; Bouquot JE (1999). "Maxillofacial osteonecrosis in a patient with multiple "idiopathic" facial pains". J. Oral Pathol. Med. 28 (9): 423–32. doi:10.1111/j.1600-0714.1999.tb02101.x. PMID 10535367. 36. ^ Zarychanski R; Elphee E; Walton P; Johnston J (2006). "Osteonecrosis of the jaw associated with pamidronate therapy". Am. J. Hematol. 81 (1): 73–5. doi:10.1002/ajh.20481. PMID 16369966. 37. ^ Abu-Id MH; Açil Y; Gottschalk J; Kreusch T (2006). "[Bisphosphonate-associated osteonecrosis of the jaw]". Mund Kiefer Gesichtschir (in German). 10 (2): 73–81. doi:10.1007/s10006-005-0670-0. PMID 16456688. 38. ^ Merigo E; Manfredi M; Meleti M; Corradi D; Vescovi P (2005). "Jaw bone necrosis without previous dental extractions associated with the use of bisphosphonates (pamidronate and zoledronate): a four-case report". J. Oral Pathol. Med. 34 (10): 613–7. doi:10.1111/j.1600-0714.2005.00351.x. PMID 16202082. 39. ^ Gibbs SD; O'Grady J; Seymour JF; Prince HM (2005). "Bisphosphonate-induced osteonecrosis of the jaw requires early detection and intervention". Med. J. Aust. 183 (10): 549–50. doi:10.5694/j.1326-5377.2005.tb07172.x. PMID 16296983. 40. ^ Bond TE Jr. (1848). A practical treatise on dental medicine. Philadelphia: Lindsay & Blakiston. 41. ^ a b "Necrosis of the lower jaw in makers of Lucifer matches". Am J Dent Science. 1 (series 3): 96–7. 1867. 42. ^ a b "The History of Maxillofacial Osteonecrosis (NICO)" Archived 16 October 2006 at the Wayback Machine. Bouquot J.E. 43. ^ Ferguson W (1868). "New treatment of necrosis". Am J Dent Science. 1 (series 3): 189. 44. ^ Noel HR (1868). "A lecture on caries and necrosis of bone". Am J Dent Science. 1 (series 3): 425, 482. 45. ^ Barrett WC (1898). Oral pathology and practice. Philadelphia: S.S. White Dental Mfg Co. 46. ^ Black GV (1915). A work on special dental pathology (2nd ed.). Chicago: Medico_Dental Publ Co. 47. ^ Burns RC; Cohen S (1980). Pathways of the pulp (2nd ed.). St. Louis, MO: Mosby. pp. 55–7. ISBN 978-0-8016-1009-7. 48. ^ Imbeau J (2005). "Introduction to through-transmission alveolar ultrasonography (TAU) in dental medicine". Cranio. 23 (2): 100–12. doi:10.1179/crn.2005.015. PMID 15898566. 49. ^ Bouquot J; Margolis M; Shankland WE; Imbeau J (April 2002). "Through-transmission alveolar sonography (TTAS) – a new technology for evaluation of medullary diseases, correlation with histopathology of 285 scanned jaw sites". 56th annual meeting of the American Academy of Oral and Maxillofacial Pathology. 50. ^ Purcell PM; Boyd IW (2005). "Bisphosphonates and osteonecrosis of the jaw". Med. J. Aust. 182 (8): 417–8. doi:10.5694/j.1326-5377.2005.tb06762.x. PMID 15850440. 51. ^ Carreyrou J (12 April 2006). "Fosamax Drug Could Become Next Merck Woe". The Wall Street Journal. Dow Jones. 52. ^ "Statement by Merck regarding Fosamax and rare cases of osteonecrosis of the jaw". Merck. 53. ^ "Osteonecrosis of the Jaw". Novartis. 54. ^ Bouquot J; Wrobleski G; Fenton S (2000). "The most common osteonecrosis? Prevalence of maxillofacial osteonecrosis (MFO)". J Oral Pathol Med. 29: 345. 55. ^ Glueck CJ; McMahon RE; Bouquot J; et al. (1996). "Thrombophilia, hypofibrinolysis, and alveolar osteonecrosis of the jaws". Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 81 (5): 557–66. doi:10.1016/S1079-2104(96)80047-3. PMID 8734702. 56. ^ Gruppo R; Glueck C; McMahon R; Bouquot J; Rabinovich B; Becker A; Tracy T; Wang P (1996). "The pathophysiology of alveolar osteonecrosis of the jaw: anticardiolipin antibodies, thrombophilia, and hypofibrinolysis". J Lab Clin Med. 127 (5): 481–8. doi:10.1016/S0022-2143(96)90065-7. PMID 8621985. ## External links[edit] Classification D * ICD-10: M87.1 * ICD-9-CM: 733.45 * DiseasesDB: 1174 External resources * eMedicine: derm/816 * 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 * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Osteonecrosis of the jaw	c2711248	6,731	wikipedia	https://en.wikipedia.org/wiki/Osteonecrosis_of_the_jaw	2021-01-18T19:05:19	{"umls": ["C2711248"], "icd-9": ["733.45"], "orphanet": ["399293"], "wikidata": ["Q2377991"]}
Maladjustment is a term used in psychology to refer the "inability to react successfully and satisfactorily to the demand of one's environment".[1] The term maladjustment can be refer to a wide range of social, biological and psychological conditions.[2] Maladjustment can be both intrinsic or extrinsic. Intrinsic maladjustment is the disparities between the needs, motivations and evaluations of an individual, with the actual reward gain through experiences. Extrinsic maladjustment on the other hand, is referred to when an individual's behavior does not meet the cultural or social expectation of society.[3] The causes of maladjustment can be attributed to a wide variety of factors, including: family environment, personal factors, and school-related factors.[4] Maladjustment affects an individual's development and the ability to maintain a positive interpersonal relationship with others. Often maladjustment emerges during early stages of childhood, when a child is in the process of learning methods to solve problem that occurs in interpersonal relationship in their social network.[5] A lack of intervention for individuals who are maladjusted can cause negative effects later on in life.[4][6][page needed] ## Contents * 1 Causes * 1.1 Family causes * 1.2 Personal causes * 1.3 School related causes * 2 Associated characteristics * 3 Negative effects * 3.1 Poor academic performance * 3.2 Suicidal behavior * 4 See also * 5 References ## Causes[edit] Children who are brought up in certain conditions are more prone to maladjustment. There are three main causes associated to maladjustment:[4][page needed] ### Family causes[edit] Socially, children that comes from broken homes often are maladjusted. Feelings of frustration toward their situation stems from insecurities, and denial of basic needs such as food, clothing and shelter. Children whose parents are unemployed or possess a low socioeconomic status are more prone to maladjustment. Parents who are abusive and highly authoritative can cause harmful effect towards psychological need which are essential for a child to be socially well adjusted.[4][page needed] The bond between a parent and child can affect psychological development in adolescent. Conflicts between parent and child relationship can cause adolescents to have poor adjustment. The level of conflict which occur between a parent and child can affect both the child's perception of the relationship with their parents and a child's self-perception. The perception of conflict between parent and child can be attributed to two mechanisms: reciprocal filial belief and perceived threats. Reciprocal filial belief refers to the love, care and affection that a child experience through their parent, it represents the amount of intimacy a child has with his or her parent. High levels of perceived conflict between parent and child reduces feelings of empathy, a child may feel isolated and therefore alienate themselves from their parent, this reduces the amount of reciprocal filial belief. Adolescent with lower levels of reciprocal filial belief are known to shown characteristic of a maladjusted individual. Perceived threats can be characterized as the anticipation of damage or harm to oneself during an emotional arousing event that induce a response towards stress. Worry, fear and the inability to cope with stress during conflicts are indicators of a rise in the level of perceived threat in a parent and child relationship. Higher levels of perceived threats in a parent a child relationship may exacerbate negative self-perception and weaken the ability to cope, this intensifies antisocial behavior which is a characteristic associated with maladjustment.[7] ### Personal causes[edit] Children with physical, emotional or mental problems often have a hard time keeping up socially when compared to their peers. This can cause a child to experience feeling of isolation and limits interaction which brings about maladjustment.[4][page needed] Emotion regulation plays a role in maladjustment. Typically, emotions are generally adaptive responses which allow an individual to have the flexibility to change their emotion based on the demand of their environment. Emotional inertia refers to "the degree in which emotional states are resistant to change"; there is a lack of emotional responsiveness due to the resistance of external environmental changes or internal psychological influences. High level of emotional inertia may be indicative of maladjustment, as an individual does not display a typical variability of emotions towards their social surroundings. A high level of emotional inertia may also represent impairment in emotional-regulation skill, which is known to be indicators or low self-esteem and neuroticism.[8] ### School related causes[edit] Children who are victimized by their peers at school are more at risk of being maladjusted. Children who are victimized by their peer at school are prone to anxiety and feelings of insecurity. This affect their attitudes towards school, victimized children are more likely to show dislike towards schools and display high levels of school avoidance.[9] Teachers who display unfair and biased attitudes towards children cause difficulties in their adjustment towards the classroom and school-life. Unhealthy and negative peer influence, such as delinquency, can cause children to be maladjusted in their social environment.[4][page needed] ## Associated characteristics[edit] There are some characteristics that are associated with maladjustments.[10][page needed] * Nervous behavior. Habits and tics in response to nervousness (e.g. biting fingernails, fidgeting, banging of head, playing with hair, inability to stay still). * Emotional overreaction and deviation. The tendency to respond to a situation with unnecessarily excessive or extravagant emotions and actions (e.g. avoidance of responsibility due to fear, withdrawal, easily distracted from slightest annoyance, unwarranted anxiety from small mistakes). * Emotional immaturity. The inability to fully control one's emotion (e.g. indecisiveness, over dependence on other, excessively self-conscious and suspicious, being incapable to work independently, hyperactivity, unreasonable fears and worries, high levels of anxiety). * Exhibitionist behavior. Behaviors conducted in attempts to gain attention or to portray a positive image (e.g. blame others for one's own failure, high level of overt agreeableness towards authority, physically hurting others). * Antisocial behavior. Behaviors and acts that showed hostility or aggression to others (e.g. cruelty to others, the use of obscene and abusive language, bullying others, destructive and irresponsible behaviors) * Psychosomatic disturbances. This can include: complications in bowel movement, nausea and vomiting, overeating, and other pains. ## Negative effects[edit] ### Poor academic performance[edit] Maladjustments can have an effect on an individual's academic performance.[4][page needed] Individual who are maladjusted behaviors tend to have a lower commitment to scholastic achievements, which cause poorer test results, higher rate of truancy and increase risk of dropping out of school.[citation needed] ### Suicidal behavior[edit] In cases where a child suffers from physical or sexual abuse, maladjustment is a risk for suicidal behavior. Individual with a history of childhood abuse tend to be maladjusted due to their dissatisfaction in social support and the prevalence of an anxious attachment style. Clinical implication suggests that by targeting maladjustment in individuals with history of childhood abuse, the risk of suicidal behavior may be attenuated.[6] ## See also[edit] * Adjustment (psychology) ## References[edit] 1. ^ "the definition of maladjustment". www.dictionary.com. Retrieved 2018-06-24. 2. ^ Khanfer, Riyad; Ryan, John; Aizenstein, Howard; Mutti, Seema; Busse, David; Yim, Ilona S.; Turner, J. Rick; Troxel, Wendy; Holt-Lunstad, Julianne (2013), "Maladaptive/Maladjustment", Encyclopedia of Behavioral Medicine, Springer New York, pp. 1187–1188, doi:10.1007/978-1-4419-1005-9_32, ISBN 9781441910042 3. ^ Bergman, Iarsr. "The Development of Patterns of Maladjustment" (PDF). 4. ^ a b c d e f g Manichander, T (2016). Psychology of the learner. ISBN 978-1329997929. 5. ^ Ladd, Gary W.; Price, Joseph M. (1987). "Predicting Children's Social and School Adjustment Following the Transition from Preschool to Kindergarten". Child Development. 58 (5): 1168–1189. doi:10.2307/1130613. ISSN 0009-3920. JSTOR 1130613. 6. ^ a b Restrepo, Danielle M.; Chesin, Megan S.; Jeglic, Elizabeth L. (October 2016). "The Relationship between Social Maladjustment, Childhood Abuse and Suicidal Behavior in College Students". International Journal of Psychology and Psychological Therapy. Volume 16 Num. 3 (7): 235–248. doi:10.1177/0956797610372634. PMC 2901421. PMID 20501521. 7. ^ Yeh, Kuang-Hui; Tsao, Wei-Chun; Chen, Wei-Wen (2010). "Parent–child conflict and psychological maladjustment: A mediational analysis with reciprocal filial belief and perceived threat". International Journal of Psychology. 45 (2): 131–139. doi:10.1080/00207590903085505. ISSN 0020-7594. PMID 22043893. 8. ^ Kuppens, Peter; Allen, Nicholas B.; Sheeber, Lisa B. (2010-05-25). "Emotional Inertia and Psychological Maladjustment". Psychological Science. 21 (7): 984–991. doi:10.1177/0956797610372634. ISSN 0956-7976. PMC 2901421. PMID 20501521. 9. ^ Kochenderfer, Becky J.; Ladd, Gary W. (1996). "Peer Victimization: Cause or Consequence of School Maladjustment?". Child Development. 67 (4): 1305–17. doi:10.2307/1131701. ISSN 0009-3920. JSTOR 1131701. PMID 8890485. 10. ^ Singh, Vijay Pratap (2004). Problems Of Educational Backwardness. New Delhi: Sarup & Sons. ISBN 978-8176254564. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Maladjustment	c0281902	6,732	wikipedia	https://en.wikipedia.org/wiki/Maladjustment	2021-01-18T18:45:53	{"umls": ["C0281902"], "wikidata": ["Q55621848"]}
A small proportion of humans show partial or apparently complete inborn resistance to HIV, the virus that causes AIDS.[1] The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the proportion of people with some form of resistance to HIV is under 10%.[2][3][4] ## Contents * 1 History * 2 CCR5 deletion * 3 TNPO3 mutation * 4 Cytotoxic T-lymphocytes * 4.1 African nonhuman primates * 5 Creating genetic resistance * 6 HIV resistance as an environmental factor * 7 See also * 8 References * 9 External links ## History[edit] In 1994, Stephen Crohn became the first person discovered to be completely resistant to HIV in all tests performed despite having partners infected by the virus.[5][6] Crohn's resistance was a result of the absence of a receptor, which prevent the HIV from infecting CD4 present on the exterior of the white blood cells. The absence of such receptors, or rather the shortening of them to the point of being inoperable, is known as the delta 32 mutation.[7] This mutation is linked to groups of people that have been exposed to HIV but remain uninfected such as some offspring of HIV positive mothers, health officials, and sex workers.[8] In early 2000, researchers discovered a small group of sex workers in Nairobi, Kenya who were estimated to have sexual contact with 60 to 70 HIV positive clients a year without signs of infection.[9] These sex workers were not found to have the delta mutation leading scientists to believe other factors could create a genetic resistance to HIV.[8] Researchers from Public Health Agency of Canada have identified 15 proteins unique to those virus-free sex workers.[10] Later, however some sex workers were discovered to have contracted the virus, leading Oxford University researcher Sarah Rowland-Jones to believe continual exposure is a requirement for maintaining immunity.[11] ## CCR5 deletion[edit] C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Many strains of HIV use CCR5 as a co-receptor to enter and infect host cells. A few individuals carry a mutation known as CCR5-Δ32 in the CCR5 gene, protecting them against these strains of HIV.[citation needed] In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. A cohort study, from June 1981 to October 2016, looked into the correlation between the delta 32 deletion and HIV resistance, and found that homozygous carriers of the delta 32 mutation are resistant to M-tropic strains of HIV-1 infection.[12] Certain populations have inherited the Delta 32 mutation resulting in the genetic deletion of a portion of the CCR5 gene.[13][14][15][16][17][18][excessive citations] ## TNPO3 mutation[edit] In 2019, it was discovered that the mutation of TNPO3 that is the cause of type 1F limb-girdle muscular dystrophy (LGMD1F), also causes innate resistance to HIV-1.[19] The gene TNP03 was known to be involved into virus transportation into the infected cells. Blood samples from a family affected by LGMD1F showed a resistance to HIV infection. While the CCR5Δ32 deletion blocks the entry of virus strains that use the CCR5 receptor, the TNPO3 mutation causing LGMD1F blocks the CXCR4 receptor, making it effective on different HIV-1 strains, due to HIV tropism.[citation needed] ## Cytotoxic T-lymphocytes[edit] Cytotoxic T-lymphocytes (CTLs) provide a protective reaction against HIV when consistent exposure to the virus is present. Sex workers are found to have these CTLs within genital mucus, preventing the spread of HIV within heterosexual transmission. While creating a protective seal, CTLs become ineffective when lapses in HIV exposure occur, which leads to the possibility of CTLs only being an indicator of other genetic resistances towards HIV, such as immunoglobulin A responses within vaginal fluids.[8][20] ### African nonhuman primates[edit] Chimpanzees in African countries have been found to develop AIDS at a slower rate than humans. This resistance is not due to the primate's ability to control the virus in a manner that is substantially more effective than humans, but rather because of the lack of tissues created within the body that typically progress HIV to AIDS. The chimpanzees also lack CD4 T cells and immune activation that is required for the spread of HIV.[20] ## Creating genetic resistance[edit] While antiretroviral therapy (ART) has slowed the progression of HIV among patients, gene therapy through stem cell research gave resistance to HIV. One method of genetic modification is through the manipulation of hematopoietic stem cells, which replaces HIV genes with engineered particles that attach to chromosomes. Peptides are formed that prevent HIV from fusing to the host cells and therefore stops the infection from spreading.[21] Another method used by the Kiem lab was the release of zinc finger nuclease (ZFN), which identifies specific sections of DNA to cause a break in the double helix. These ZFNs were used to target CCR5 in order to delete the protein, halting the course of the infection.[21] Alternatively to gene therapy, medication such as maraviroc (MVC) is being used to bind with CCR5 particles, blocking the entry of HIV into the cell. While not effective with all types, MVC has been proven to decrease the spread of HIV through monotherapy as well as combination therapy with ARTs. MVC is the only CCR5 binding drug approved for use by the Food and Drug Administration, the European Commission, and Health Canada.[22] ## HIV resistance as an environmental factor[edit] While the delta mutation has been observed to prevent HIV in specific populations, it has shown little to no effect between healthy individuals and those who are infected with HIV among Iranian populations. This is attributed to individuals being heterozygous for the mutation, which prevents the delta mutation from effectively prohibiting HIV from entering immune cells.[23] ## See also[edit] * Viruses portal * Discovery and development of CCR5 receptor antagonists * Entry inhibitor * HIV tropism * Timothy Ray Brown * Stephen Crohn ## References[edit] 1. ^ Scutti S (2014-11-20). "Why Some People Are Naturally Immune To HIV". Medical Daily. Retrieved 2015-01-20. 2. ^ Ring T (2012-09-07). "Is Anyone Immune to HIV?". HIVPlusMag. Retrieved 2015-01-20. 3. ^ Nolen S (2007-05-27). "Staying alive: the women who are immune to Aids". the Guardian. Retrieved 2015-01-20. 4. ^ Angelle A (2010-07-21). "Immune to HIV: How Do They Do It?". LiveScience. Retrieved 2015-01-20. 5. ^ Singh M (21 September 2013). "In Life, Man Immune To HIV Helped Scientists Fight Virus". NPR.org. Retrieved 2015-01-20. 6. ^ Green J (2014-06-13). "The Man Who Was Immune to AIDS". NYMag.com. Retrieved 2015-01-20. 7. ^ "In Life, Man Immune To HIV Helped Scientists Fight Virus". NPR.org. Retrieved 2018-10-28. 8. ^ a b c Marmor M, Hertzmark K, Thomas SM, Halkitis PN, Vogler M (January 2006). "Resistance to HIV infection". Journal of Urban Health. 83 (1): 5–17. doi:10.1007/s11524-005-9003-8. PMC 1539443. PMID 16736351. 9. ^ Altman LK (3 February 2000). "A New AIDS Mystery: Prostitutes Who Have Remained Immune". NYTimes. Retrieved 2015-01-20. 10. ^ Blackwell T (2012-02-13). "Blackwell on Health: Montreal researchers discover why some prostitutes evade HIV". National Post. Retrieved 2015-01-20. "Public Health Agency of Canada have identified 15 proteins unique to those virus-free prostitutes" 11. ^ "Prostitutes lose HIV immunity". BBC News. 1999. Retrieved 2015-01-20. 12. ^ Ruiz-Mateos E, Tarancon-Diez L, Alvarez-Rios AI, Dominguez-Molina B, Genebat M, Pulido I, Abad MA, Muñoz-Fernandez MA, Leal M (February 2018). "Association of heterozygous CCR5Δ32 deletion with survival in HIV-infection: A cohort study". Antiviral Research. 150: 15–19. doi:10.1016/j.antiviral.2017.12.002. PMID 29221798. 13. ^ de Silva E, Stumpf MP (December 2004). "HIV and the CCR5-Delta32 resistance allele". FEMS Microbiology Letters. 241 (1): 1–12. doi:10.1016/j.femsle.2004.09.040. PMID 15556703. 14. ^ Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E (February 2009). "Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation". The New England Journal of Medicine. 360 (7): 692–98. doi:10.1056/NEJMoa0802905. PMID 19213682. 15. ^ Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T (March 2011). "Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation". Blood. 117 (10): 2791–99. doi:10.1182/blood-2010-09-309591. PMID 21148083. 16. ^ Zhen A, Kitchen S (December 2013). "Stem-cell-based gene therapy for HIV infection". Viruses. 6 (1): 1–12. doi:10.3390/v6010001. PMC 3917429. PMID 24368413. 17. ^ Kay MA, Walker BD (March 2014). "Engineering cellular resistance to HIV". The New England Journal of Medicine. 370 (10): 968–99. doi:10.1056/NEJMe1400593. PMID 24597871. 18. ^ Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (March 2014). "Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV". The New England Journal of Medicine. 370 (10): 901–10. doi:10.1056/NEJMoa1300662. PMC 4084652. PMID 24597865. 19. ^ Rodríguez-Mora S, De Wit F, García-Perez J, Bermejo M, López-Huertas MR, Mateos E, Martí P, Rocha S, Vigón L, Christ F, Debyser Z, Jesús Vílchez J, Coiras M, Alcamí J (August 2019). "The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection". PLoS Pathogens. 15 (8): e1007958. doi:10.1371/journal.ppat.1007958. PMC 6715175. PMID 31465518. 20. ^ a b Heeney JL, Dalgleish AG, Weiss RA (July 2006). "Origins of HIV and the evolution of resistance to AIDS". Science. 313 (5786): 462–66. doi:10.1126/science.1123016. PMID 16873637. 21. ^ a b Herman J (April 18, 2016). "Gene Therapy and Genome Editing Strategies for HIV Resistance" (PDF). Science Spotlight. Fred Hutchinson Cancer Research Center. 6 (4): 1–3. 22. ^ Woollard SM, Kanmogne GD (2015-10-01). "Maraviroc: a review of its use in HIV infection and beyond". Drug Design, Development and Therapy. 9: 5447–68. doi:10.2147/DDDT.S90580. PMC 4598208. PMID 26491256. 23. ^ Heydarifard Z, Tabarraei A, Moradi A (2017). "Polymorphisms in CCR5Δ32 and Risk of HIV-1 Infection in the Southeast of Caspian Sea, Iran". Disease Markers. 2017: 4190107. doi:10.1155/2017/4190107. PMC 5676439. PMID 29209099. ## External links[edit] * PBS documentary about the discovery of CCR5 * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * 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Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by 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	Innate resistance to HIV	None	6,733	wikipedia	https://en.wikipedia.org/wiki/Innate_resistance_to_HIV	2021-01-18T18:40:23	{"wikidata": ["Q19760783"]}
Cholangiocarcinoma (CCA) is a biliary tract cancer (BTC, see this term) originating in the epithelium of the biliary tree, either intra or extra hepatic. ## Epidemiology The prevalence is unknown but it accounts for approximately 3% of gastrointestinal tumors and 10-15% of all hepatobiliary malignancies. ## Clinical description CCA can occur in the intra or extra-hepatic biliary tract. A specific type of extra-hepatic CCA known as a Klatskin tumor (see this term) occurs at the junction where the left and right hepatic bile ducts meet the common bile duct (CBD). It is slightly more prevalent in males than females (1.3:1.0) and usually presents in the fifth to seventh decade of life. Clinical manifestations are not usually noted until an advanced disease stage. Extra-hepatic CCA manifests with signs of cholestasis (jaundice, pale stools, dark urine, pruritus), malaise, weight loss and/or progressive weakness. Intra-hepatic CCA may present with an abdominal mass or with non-specific symptoms of decreased appetite, weight loss, abdominal pain and malaise. ## Etiology The etiology is unknown and most cases of CCA occur sporadically. Risk factors include primary sclerosing cholangitis (see this term), secondary sclerosing cholangitis, chronic typhoid carriage, parasitic infections (Opisthochis viverrini and Clonorchis sinensis), exposure to thorotrast (x-ray contrast medium) and choledochal cysts, all of which cause chronic biliary inflammation. ## Diagnostic methods Diagnosis is suspected on clinical and laboratory findings. Serum carbohydrate antigen (CA) 19-9 is the glycoprotein tumor marker most often used in the diagnosis of CCA. It is found to be elevated in 85% of patients. Increased CEA levels are also noted. Extra-hepatic tumors cause increased levels of alkaline phosphate (ALP), conjugated bilirubin and gamma-glutamyl transpeptidase (GGT) while intra-hepatic have only slightly elevated ALP levels. Abdominal imaging, visualization of the biliary tree and biopsies of the lesion are necessary for diagnosis. Magnetic resonance cholangiopancreatography (MRCP) provides information on intrahepatic metastases, biliary anatomy and tumor extension and is used in the staging of CCA. It has been advocated to replace endoscopic retrograde cholangiopancreatography (ERCP), a more invasive method. Visualization of the biliary tree and samples through brush cytology or bile duct biopsies are obtained with ERCP. A needle biopsy is performed in those with a liver mass. Extra-hepatic CCA is further divided into anatomical subtypes according to the Bismuth classification and a disease stage is given. Ultrasound, and contrast enhanced helical computerized computed tomography (CT) can be used in visualizing the extent of disease. ## Differential diagnosis Intra-hepatic CCA is often mistaken for metastatic adenocarcinoma. Carcinoma of the gallbladder (see this term), benign strictures and Mirizzi syndrome should be excluded. ## Management and treatment Surgical resection is the only potentially curative treatment for CCA but recurrences after surgery are frequent. Unfortunately CCA is often diagnosed as unresectable because of local extension and/or metastases. Distal CCA arising from the CBD is often treated by pancreatoduodenectomy. More proximal CCA needs hepatic resection. Palliative management involves biliary drainage by inserting metal stents in the biliary tree to release the blockage. Adjuvant chemotherapy after surgery or palliative chemotherapy for unresectable CCA is indicated. Gemcitabine combined with cisplatin therapy is the standard treatment for unresectable biliary tract cancers, including CCA. ## Prognosis As proximal CCA is usually not diagnosed until a late stage of disease, prognosis is poor with 5-year survival rates of 20-50% after resection and almost 0% in unresectable tumors. Death is often due to biliary sepsis, cancer cachexia, malnutrition 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	Cholangiocarcinoma	c0206698	6,734	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70567	2021-01-23T18:53:45	{"gard": ["9304"], "mesh": ["D018281", "D001650"], "omim": ["615619"], "umls": ["C0206698", "C0740277"], "icd-10": ["C22.1", "C24.0", "C24.8", "C24.9"], "synonyms": ["Bile duct cancer", "CCA"]}
Dystrophic epidermolysis bullosa, nails only is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) that shows no blistering and that is characterized by dystrophic or absent nails. ## Epidemiology Prevalence is unknown. Approximately ten families have been reported to date. However, this variant may be overlooked because of negligible clinical implications. ## Clinical description Onset is usually at birth or during infancy. Except from nail involvement, no other cutaneous or extracutaneous symptoms are observed. Nail deformity is often limited to toenails which can appear thickened and shortened. ## Etiology DDEB, nails only is caused by mutations within the type VII collagen gene (COL7A1). ## Genetic counseling It usually follows an autosomal dominant pattern of inheritance. One family with an autosomal recessive inheritance has also 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	Dominant dystrophic epidermolysis bullosa, nails only	None	6,735	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=158676	2021-01-23T18:30:15	{"icd-10": ["Q81.2"], "synonyms": ["Nails-only DDEB"]}
Human disease Histoplasmosis Other namesCave disease,[1] Darling's disease,[1] Ohio valley disease,[1] Reticuloendotheliosis,[1] Spelunker's lung and Caver's disease Histoplasma capsulatum. Methenamine silver stain showing histopathologic changes in histoplasmosis SpecialtyInfectious disease Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum.[2] Symptoms of this infection vary greatly, but the disease affects primarily the lungs.[3] Occasionally, other organs are affected; called disseminated histoplasmosis, it can be fatal if left untreated. Histoplasmosis is common among AIDS patients because of their suppressed immunity.[4] In immunocompetent individuals, past infection results in partial protection against ill effects if reinfected. Histoplasma capsulatum is found in soil, often associated with decaying bat guano or bird droppings. Disruption of soil from excavation or construction can release infectious elements that are inhaled and settle into the lung. From 1938 to 2013 in the US, 105 outbreaks were reported in 26 states and Puerto Rico. In 1978-1979 during a large urban outbreak in which 100,000 people were exposed to the fungus in Indianapolis,[5] victims had pericarditis, rheumatological syndromes, esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. Histoplasmosis mimics colds, pneumonia, and the flu, and can be shed by bats in their feces. ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Mechanisms * 3 Diagnosis * 3.1 Types * 4 Prevention * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 History * 9 Society and culture * 10 References * 11 External links ## Signs and symptoms[edit] Skin lesion on the upper lip due to H. capsulatum infection If symptoms of histoplasmosis infection occur, they start within 3 to 17 days after exposure; the typical time is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases.[6] Chronic histoplasmosis cases can resemble tuberculosis;[7][8] disseminated histoplasmosis affects multiple organ systems and is fatal unless treated.[9] While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement.[3] Lesions have a tendency to calcify as they heal. Presumed ocular histoplasmosis syndrome causes chorioretinitis, where the choroid and retina of the eyes are scarred, resulting in a loss of vision not unlike macular degeneration. Despite its name, the relationship to Histoplasma is controversial.[10][11] Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.[12][13] ### Complications[edit] In absence of proper treatment and especially in immunocompromised individuals, complications can arise. These include recurrent pneumonia, respiratory failure, fibrosing mediastinitis, superior vena cava syndrome, pulmonary vessel obstruction, and progressive fibrosis of lymph nodes. Fibrosing mediastinitis is a serious complication and can be fatal. Smokers with structural lung disease have higher probability of developing chronic cavitary histoplasmosis.[citation needed] After healing of lesions, hard, calcified lymph nodes can erode the walls of the airway, causing hemoptysis.[citation needed] ## Mechanisms[edit] H. capsulatum grows in soil and material contaminated with bird or bat droppings (guano). The fungus has been found in poultry-house litter, caves, areas harboring bats, and bird roosts (particularly those of starlings). The fungus is thermally dimorphic; in the environment, it grows as a brownish mycelium, and at body temperature (37°C in humans), it morphs into a yeast. Histoplasmosis is not contagious, but is contracted by inhalation of the spores from disturbed soil or guano.[3] The inoculum is represented principally by microconidia. These are inhaled and reach the alveoli. In the alveoli, macrophages ingest these microconidia. They survive inside the phagosome. As the fungus is thermally dimorphic, these microconidia are transformed into yeast. They grow and multiply inside the phagosome. The macrophages travel in lymphatic circulation and can spread the disease to different organs.[citation needed] Within the phagosome, the fungus has an absolute requirement for thiamine.[14] Cell-mediated immunity for histoplasmosis develops within 2 weeks. If the patient has strong cellular immunity, macrophages, epithelial cells, and lymphocytes surround the organisms and contain them, and eventually calcify. In immunocompromised individuals, the organisms disseminate to different organs such as bone, spleen, liver, adrenal glands, and mucocutaneous membranes, resulting in progressive disseminated histoplasmosis. Chronic lung disease can manifest. ## Diagnosis[edit] Chest X-ray of a patient with acute pulmonary histoplasmosis Clinically, a wide spectrum of disease manifestations occurs, making diagnosis somewhat difficult. More severe forms include the chronic pulmonary form, often occurring in the presence of underlying pulmonary disease, and a disseminated form, which is characterized by the progressive spread of infection to extrapulmonary sites. Oral manifestations have been reported as the main complaint of the disseminated forms, leading the patient to seek treatment, whereas pulmonary symptoms in disseminated disease may be mild or even misinterpreted as flu.[15] Histoplasmosis can be diagnosed by samples containing the fungus taken from sputum (via bronchoalveolar lavage), blood, or infected organs. It can also be diagnosed by detection of antigens in blood or urine samples by ELISA or polymerase chain reaction. Antigens can cross-react with antigens of African histoplasmosis (caused by Histoplasma duboisii), blastomycosis, coccidioidomycosis, paracoccidioidomycosis, and talaromycosis infection. Histoplasmosis can also be diagnosed by a test for antibodies against Histoplasma in the blood. Histoplasma skin tests indicate whether persons have been exposed, but do not indicate whether they have the disease.[3] Formal histoplasmosis diagnoses are often confirmed only by culturing the fungus directly.[4] Sabouraud agar is one agar growth medium on which the fungus can be cultured. Cutaneous manifestations of disseminated disease are diverse and often present as a nondescript rash with systemic complaints. Diagnosis is best established by urine antigen testing, as blood cultures may take up to 6 weeks for diagnostic growth to occur and serum antigen testing often comes back with a false negative before 4 weeks of disseminated infection.[16] ### Types[edit] Histoplasmosis may be divided into these types:[17]:316–317 * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Primary cutaneous histoplasmosis * African histoplasmosis * * ## Prevention[edit] Testing or decontaminating most sites that may be contaminated with H. capsulatum is impractical, but the sources below list environments where histoplasmosis is common, and precautions to reduce a person's risk of exposure, in the three parts of the world where the disease is prevalent. Precautions common to all geographical locations would be to avoid accumulations of bird or bat droppings.[citation needed] The US National Institute for Occupational Safety and Health provides information on work practices and personal protective equipment that may reduce the risk of infection.[18] This document is available in English and Spanish. A review paper includes information on locations in which histoplasmosis has been found in Africa (in chicken runs, on bats, in the caves bats infest, and in soil), and a thorough reference list including English-, French-, and Spanish-language references.[19] ## Treatment[edit] In the majority of immunocompetent individuals, histoplasmosis resolves without any treatment. Antifungal medications are used to treat severe cases of acute histoplasmosis and all cases of chronic and disseminated disease. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole.[20][21] Liposomal preparations of amphotericin B are more effective than deoxycholate preparations. The liposomal preparation is preferred in patients who might be at risk of nephrotoxicity, although all preparations of amphotericin B have risk of nephrotoxicity. Individuals taking amphotericin B are monitored for renal function.[22] Liposomal amphotericin B is better at treating people with progressive disseminated histoplasmosis and underlying HIV when compared to deoxycholate amphotericin B. Meanwhile, fluconazole performs poorly when compared to other azoles.[23] Treatment with itraconazole must continue for at least a year in severe cases,[24] while in acute pulmonary histoplasmosis, 6 to 12 weeks treatment is sufficient. Alternatives to itraconazole are posaconazole, voriconazole, and fluconazole. Individuals taking itraconazole are monitored for hepatic function. ## Prognosis[edit] About 90% of patients with normal immune systems regain health without any intervention. Less than 5% need serious treatments.[citation needed] ## Epidemiology[edit] H. capsulatum is found throughout the world. It is endemic in certain areas of the United States, particularly in states bordering the Ohio River valley and the lower Mississippi River. The humidity and acidity patterns of soil are associated with endemicity. Bird and bat droppings in soil promote growth of Histoplasma. Contact with such soil aerosolizes the microconidia, which can infect humans. It is also common in caves in Southern and East Africa. Positive histoplasmin skin tests occur in as many as 90% of the people living in areas where H. capsulatum is common, such as the eastern and central United States.[3] In Canada, the St. Lawrence River Valley is the site of the most frequent infections, with 20–30% of the population testing positive.[25] A review of reported cases in 2018 showed disease presence throughout Southeast Asia,[26] In India, the Gangetic West Bengal is the site of most frequent infections, with 9.4% of the population testing positive.[27] H. c. capsulatum was isolated from the local soil proving endemicity of histoplasmosis in West Bengal.[28] ## History[edit] Histoplasma was discovered in 1905 by Samuel T. Darling,[29] but only in the 1930s was it discovered to be a widespread infection. Before then, many cases of histoplasmosis were mistakenly attributed to tuberculosis, and patients were mistakenly admitted to tuberculosis sanatoria. Some patients contracted tuberculosis in these sanatoriums.[30] ## Society and culture[edit] * Johnny Cash included a reference to the disease, even correctly noting its source in bird droppings, in the song "Beans for Breakfast".[31] * Bob Dylan was hospitalized due to histoplasmosis in 1997, causing the cancellation of concerts in the United Kingdom and Switzerland.[32] * In episode 21 of season three of the television series House M.D., a patient was diagnosed with histoplasmosis. * In episode five of season one of the television series Dexter, Vince Masuka gets worried about getting histoplasmosis from the dust in the air and the hair of the rats. * In the BBC drama Call The Midwife's 9th season, a character is diagnosed with the disease after initial confusion regarding whether his symptoms were more indicative of tuberculosis. He contracts it from the droppings of pet pigeons he keeps in his home. ## References[edit] 1. ^ a b c d Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Stenn F (February 1960). "Cave disease or speleonosis". Archives of Internal Medicine. 105 (2): 181–3. doi:10.1001/archinte.1960.00270140003001. PMID 13834312. 3. ^ a b c d e Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 674–6. ISBN 978-0-8385-8529-0. 4. ^ a b Cotran RS, Kumar V, Fausto N, Robbins SL, Abbas AK (2005). Robbins and Cotran Pathologic Basis of Disease. St. Louis: Elsevier/Saunders. pp. 754–5. ISBN 978-0-7216-0187-8. 5. ^ Indianapolis city government 6. ^ Silberberg P (2007-03-26). "Radiology Teaching Files: Case 224856 (Histoplasmosis)". Archived from the original on 2016-03-03. Retrieved 2007-07-27. 7. ^ Tong P, Tan WC, Pang M (September 1983). "Sporadic disseminated histoplasmosis simulating miliary tuberculosis". British Medical Journal. 287 (6395): 822–3. doi:10.1136/bmj.287.6395.822. PMC 1549119. PMID 6412842. 8. ^ Gari-Toussaint, Marty P, Le Fichoux Y, Loubière R (1987). "Histoplasmose d'importation à Histoplasma capsulatum, données biocliniques et thérapeutiques variées, à propos de trois cas observés dans les Alpes maritimes". Bull Soc Fr Mycol Med. 16 (1): 87–90. 9. ^ Kauffman CA (January 2007). "Histoplasmosis: a clinical and laboratory update". Clinical Microbiology Reviews. 20 (1): 115–32. doi:10.1128/CMR.00027-06. PMC 1797635. PMID 17223625. 10. ^ Thuruthumaly C, Yee DC, Rao PK (November 2014). "Presumed ocular histoplasmosis". Current Opinion in Ophthalmology. 25 (6): 508–12. doi:10.1097/ICU.0000000000000100. PMID 25237930. S2CID 43761401. 11. ^ Nielsen JS, Fick TA, Saggau DD, Barnes CH (March 2012). "Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome". Retina. 32 (3): 468–72. doi:10.1097/IAE.0b013e318229b220. PMID 21817958. S2CID 25507234. 12. ^ Macher A, Rodrigues MM, Kaplan W, Pistole MC, McKittrick A, Lawrinson WE, Reichert CM (August 1985). "Disseminated bilateral chorioretinitis due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome". Ophthalmology. 92 (8): 1159–64. doi:10.1016/s0161-6420(85)33921-0. PMID 2413418. 13. ^ Gonzales CA, Scott IU, Chaudhry NA, Luu KM, Miller D, Murray TG, Davis JL (April 2000). "Endogenous endophthalmitis caused by Histoplasma capsulatum var. capsulatum: a case report and literature review". Ophthalmology. 107 (4): 725–9. doi:10.1016/s0161-6420(99)00179-7. PMID 10768335. 14. ^ Garfoot AL, Zemska O, Rappleye CA (2013) Histoplasma capsulatum depends on de novo vitamin biosynthesis for intraphagosomal proliferation. Infect Immum 15. ^ Brazão-Silva MT, Mancusi GW, Bazzoun FV, Ishisaaki GY, Marcucci M. A gingival manifestation of histoplasmosis leading diagnosis. Contemp Clin Dent. V.4 (1). 2013 (http://www.contempclindent.org/text.asp?2013/4/1/97/111621) 16. ^ Rosenberg JD, Scheinfeld NS (December 2003). "Cutaneous histoplasmosis in patients with acquired immunodeficiency syndrome". Cutis. 72 (6): 439–45. PMID 14700213. 17. ^ James WD, Berger TG, et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 18. ^ "NIOSH Publications and Products - Histoplasmosis - Protecting Workers at Risk (2005-109)". Centers for Disease Control and Prevention. December 2004. doi:10.26616/NIOSHPUB2005109. Retrieved 13 August 2017. Cite journal requires `\|journal=` (help) 19. ^ Gugnani HC, Muotoe-Okafor F (December 1997). "African histoplasmosis: a review" (PDF). Revista Iberoamericana de Micologia. 14 (4): 155–9. PMID 15538817. 20. ^ Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA (October 2007). "Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America". Clinical Infectious Diseases. 45 (7): 807–25. doi:10.1086/521259. PMID 17806045. 21. ^ Histoplasmosis: Fungal Infections at Merck Manual of Diagnosis and Therapy Home Edition 22. ^ Moen MD, Lyseng-Williamson KA, Scott LJ (2009). "Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections". Drugs. 69 (3): 361–92. doi:10.2165/00003495-200969030-00010. PMID 19275278. S2CID 34340503. 23. ^ Murray M, Hine P, et al. (Cochrane Infectious Diseases Group) (April 2020). "Treating progressive disseminated histoplasmosis in people living with HIV". The Cochrane Database of Systematic Reviews. 4: CD013594. doi:10.1002/14651858.CD013594. PMC 7192368. PMID 32343003. 24. ^ Barron MA, Madinger NE (November 18, 2008). "Opportunistic Fungal Infections, Part 3: Cryptococcosis, Histoplasmosis, Coccidioidomycosis, and Emerging Mould Infections". Infections in Medicine. 25. ^ "Histoplasmosis". www.ccohs.ca. Canadian Centre for Occupational Health & Safety. July 1, 2013. 26. ^ Baker J, Setianingrum F, Wahyuningsih R, Denning DW (Jan 2019). "Mapping histoplasmosis in South East Asia - implications for diagnosis in AIDS". Emerging Microbes & Infections. 8 (1): 1139–1145. doi:10.1080/22221751.2019.1644539. PMC 6711083. PMID 31364950. 27. ^ Sanyal M, Thammayya A (July 1975). "Histoplasma capsulatum in the soil of Gangetic Plain in India". The Indian Journal of Medical Research. 63 (7): 1020–8. PMID 1213788. 28. ^ Sanyal M, Thammayya A (1980). "Skin Sensitivity To Histoplasmin in Calcutta and Its Neighbourhood". Indian Journal of Dermatology, Venereology and Leprology. 46 (2): 94–98. PMID 28218139. 29. ^ Darling ST (1906). "A protozoan general infection producing pseudotubercles in the lungs and focal necrosis in the liver, spleen and lymphnodes". J Am Med Assoc. 46 (17): 1283–5. doi:10.1001/jama.1906.62510440037003. 30. ^ Bennett JE, Dolin R, Blaser MJ (11 September 2014). Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases" (8th ed.). ISBN 978-1455748013. 31. ^ Kroll, David (6 March 2014). "Solving The Mystery Of 'Bamboo Bonfire' Lung Disease". Forbes. Retrieved 2017-11-04. 32. ^ CNN - Bob Dylan hospitalized with Histoplasmosis Archived 2007-10-26 at the Wayback Machine ## External links[edit] * CDC Disease Info histoplasmosis Classification D * ICD-10: B39 * ICD-9-CM: 115 * MeSH: D006660 * DiseasesDB: 5925 External resources * MedlinePlus: 001082 * eMedicine: med/1021 ped/1017 * Orphanet: 390 * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Histoplasmosis	c0019655	6,736	wikipedia	https://en.wikipedia.org/wiki/Histoplasmosis	2021-01-18T18:39:14	{"mesh": ["D006660"], "umls": ["C0019655", "C0035288"], "icd-9": ["115115"], "icd-10": ["B3939."], "orphanet": ["390"], "wikidata": ["Q627625"]}
Jamaican vomiting sickness SpecialtyToxicology Jamaican vomiting sickness (also known as toxic hypoglycemic syndrome (THS),[1] acute ackee fruit intoxication,[2] or ackee poisoning[1]) is an acute illness caused by the toxins hypoglycin A and hypoglycin B, which are present in fruit of the ackee tree. While in the fully ripened arils, hypoglycin A is at levels of less than 0.1 ppm, in unripe arils it can be over 1000 ppm;[3] and cause vomiting and even death. Some countries in the Caribbean and Western Africa experience frequent cases.[4] ## Contents * 1 Presentation * 2 Pathophysiology * 3 Diagnosis * 4 In popular culture * 5 References ## Presentation[edit] Abdominal discomfort begins two to six hours after eating unripe ackee fruit, followed by sudden onset vomiting. In severe cases, profound dehydration, seizures, coma, and death may ensue. Children and those who are malnourished are more susceptible to the disease.[3] ## Pathophysiology[edit] When ingested, hypoglycin A is metabolized to produce methylenecyclopropylacetic acid (MCPA). MCPA acts to inhibit the beta-oxidation of fatty acids in two ways. First, it interferes with the transport of long-chain fatty acids into the mitochondria. Also, it inhibits acyl-CoA dehydrogenases, so that only unsaturated fatty acids can be fully oxidized. Fatty acids accumulate in the liver in a microvesicular pattern that can be seen on biopsy. In the absence of fatty acid metabolism, the body becomes dependent on glucose and glycogen for energy. Octreotide can be used to reduce secretion of insulin by the pancreas, thereby preventing severe hypoglycemia.[3] Inhibition of beta-oxidation of fatty acids, however, also depletes a necessary cofactor for gluconeogenesis. Once the liver glycogen stores are depleted, the body cannot synthesize glucose, and severe hypoglycemia results.[3] A similar outbreak of lethal hypoglycemic encephalopathy has been linked to consumption of lychee fruit in Muzaffarpur, India. Urinalysis of children affected by the disease has shown all affected have elevated levels of hypoglycin suggesting the same underlying pathophysiology as Jamaican vomiting sickness.[5] ## Diagnosis[edit] This section is empty. You can help by adding to it. (December 2018) ## In popular culture[edit] The disease appears in the ER episode "Great Expectations", where the symptoms are recognised by Dr Mallucci who, it is later revealed, attended medical school in Grenada.[citation needed] ## References[edit] 1. ^ a b Gordon, André (2015-01-01), Gordon, André (ed.), "Chapter 4 - Biochemistry of Hypoglycin and Toxic Hypoglycemic Syndrome", Food Safety and Quality Systems in Developing Countries, San Diego: Academic Press, pp. 47–61, doi:10.1016/b978-0-12-801227-7.00004-4, ISBN 978-0-12-801227-7, retrieved 2020-07-05 2. ^ "The portal for rare diseases and orphan drugs". Retrieved 5 July 2020. 3. ^ a b c d Medscape- Toxicity, Plants - Ackee Fruit 4. ^ "Jamaican vomiting sickness \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17. 5. ^ Barry, Ellen (2017-01-31). "Dangerous Fruit: Mystery of Deadly Outbreaks in India Is Solved". The New York Times. Retrieved 2017-02-02. This Toxicology-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Jamaican vomiting sickness	c0274888	6,737	wikipedia	https://en.wikipedia.org/wiki/Jamaican_vomiting_sickness	2021-01-18T19:08:28	{"gard": ["9299"], "mesh": ["C537562"], "umls": ["C0274888"], "icd-10": ["T62.2"], "orphanet": ["73423"], "wikidata": ["Q784988"]}
Amor et al. (2001) described 2 sisters with onset of progressive cerebellar ataxia at the age of 16 and 32 years, respectively, and secondary amenorrhea due to hypergonadotropic hypogonadism. Sensorineural deafness with vestibular hypofunction and peripheral sensory impairment were also present. Intellect was normal. The authors referred to reports that may represent the same disorder, e.g., that of Skre et al. (1976). Cerebellar ataxia and hypogonadotropic hypogonadism is discussed elsewhere; see 212840. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	CEREBELLAR ATAXIA AND HYPERGONADOTROPIC HYPOGONADISM	c1859305	6,738	omim	https://www.omim.org/entry/605672	2019-09-22T16:11:07	{"mesh": ["C565870"], "omim": ["605672"], "orphanet": ["1173"]}
A number sign (#) is used with this entry because of evidence that immunodeficiency-15B (IMD15B) is caused by homozygous mutation in the IKBKB gene (603258) on chromosome 8p11. Heterozygous mutation in IKBKB results in IMD15A (618204), a less severe immunodeficiency with later onset. Description Immunodeficiency-15B (IMD15B) is an autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T cells. However, functional studies show impaired differentiation and activation of immune cells (summary by Pannicke et al., 2013). Clinical Features Pannicke et al. (2013) reported 4 patients of Northern Cree ancestry from the Manitoba and Saskatchewan regions of Canada who presented shortly after birth with a clinical phenotype consistent with severe combined immunodeficiency (SCID). No close family connection among these patients was known. The patients presented within the first months of life with numerous bacterial, fungal, and viral infections, including candidiasis, pneumonia, bacteremia and sepsis, meningitis, and osteomyelitis. Multiple and variable organisms were isolated from the patients, including E. coli, Mycobacterium avium, Listeria monocytogenes, pneumococcus, Serratia marcescens, and Klebsiella. Other features included chronic diarrhea and failure to thrive. Two patients died in infancy. One patient underwent successful bone marrow transplant and another had successful cord blood transplant. An affected sib of 1 patient died at age 14 months. Postmortem examination of 1 patient showed small spleen, small thymus, and lack of lymph nodes in the neck and mesentery; some lymphoid aggregates were devoid of germinal centers. Laboratory studies showed hypogammaglobulinemia or agammaglobulinemia in all patients, with normal numbers of B cells in all except 1. All had normal T-cell counts, and 3 had decreased NK cells. Early lymphocyte development was normal, but subsequent differentiation and proliferation of these cells was deficient. None of the patients had evidence of liver damage. Nielsen et al. (2014) reported a female infant, born of consanguineous Turkish parents, with severe immunodeficiency resulting in death at age 14 months. After uneventful vaccination with BCG, she presented at age 5 months with fungal pneumonia (Pneumocystis jirovecii). Immunologic workup showed increased serum IgM, absence of isotype-switched memory B cells, and low numbers of CD45R0+ memory T cells. At age 9 months, she presented with systemic infection by Mycobacterium bovis. Despite intense treatment, she died of cardiac arrest. Inheritance The transmission pattern of IMD15B in the families reported by Pannicke et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 4 patients of Cree ancestry with primary immunodeficiency, Pannicke et al. (2013) identified a homozygous truncating mutation in the IKBKB gene (c.1292dupG; 603258.0001), resulting in complete loss of protein function. The mutation was found by homozygosity mapping followed by sequencing of the genes within the candidate region on chromosome 8p. Functional and gene expression studies of patient fibroblasts showed variable effects on receptor activation and NFKB signaling involved in immunity. There was impaired phosphorylation of NFKBIA (164008) in response to stimulation with TNFA (191160) and flagellin, which acts through TLR5 (603031), but only a marginally impaired response to IL1B (147720). IL6 (147620) response to TNFA was normal, but it was reduced in response to lipopolysaccharide, with acts through TLR4 (603030). These studies showed selective dependence of the regulation of NFKB target genes on IKBKB function. Patient peripheral blood B and T cells were almost exclusively of the naive type, and B, T, and NK cells showed poor differentiation or mitogenic responses under certain conditions. These findings were consistent with the role of IKBKB in transmitting signals by various surface receptors. Pannicke et al. (2013) noted that the phenotype in these patients with null mutations in IKBKB is not as severe as that in the null mouse model, which is lethal (Li et al., 1999). In a Turkish infant, born of consanguineous parents, with fatal IMD15B, Nielsen et al. (2014) identified a homozygous truncating mutation in the IKBKB gene (R272X; 603258.0002). The mutation was found by whole-exome sequencing. Western blot analysis of patient cells showed a complete lack of the IKBKB protein, although IKKA (CHUK; 600664) and NEMO (IKBKG; 300248) levels were similar to control. Stimulation of patient T cells failed to result in phosphorylation of p65 (NFKB3; 164014), and patient T cells failed to proliferate in response to stimulation. The findings indicated that IKBKB is critical for activation of T cells and differentiation of B cells. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Mouth \- Candidiasis RESPIRATORY \- Respiratory infections ABDOMEN Gastrointestinal \- Chronic diarrhea IMMUNOLOGY \- Primary immunodeficiency \- Hypogammaglobulinemia \- Agammaglobulinemia \- Increased IgM (1 patient) \- Normal numbers of circulating T cells \- Normal or decreased numbers of circulating B cells \- Decreased numbers of NK cells \- Circulating T and B cells are naive \- Poor differentiation and proliferation of B and T cells \- Cells show impaired immunologic responses to immune stimulation MISCELLANEOUS \- Onset in infancy \- Early death without bone marrow transplantation \- Four patients of Canadian Cree origin and 1 patient of Turkish origin have been reported (last curated November 2014) MOLECULAR BASIS \- Caused by mutation in the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase of, beta gene (IKBKB, 603258.0001 ) ▲ 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	IMMUNODEFICIENCY 15B	c3810043	6,739	omim	https://www.omim.org/entry/615592	2019-09-22T15:51:33	{"omim": ["615592"], "orphanet": ["397787"], "synonyms": ["SCID due to IKK2 deficiency"]}
Megaduodenum Other namesHereditary hollow visceral myopathy SpecialtyGastroenterology Megaduodenum is a congenital or acquired dilation and elongation of the duodenum with hypertrophy of all layers that presents as a feeling of gastric fullness, abdominal pain, belching, heartburn, and nausea with vomiting sometimes of food eaten 24 hours prior.[1] Megaduodenum does not let the muscles of the duodenum function properly, the movement of waste material in the intestines gets impaired, which in turn affects digestion and nutrition.[2] This condition is a rare entity in adults, because it may be either primary idiopathic or secondary. The secondary causes include Chagas disease, systematic sclerosis, duodenal stenosis, and visceral myopathy.[3] ## Contents * 1 Signs and Symptoms * 2 Causes * 3 Mechanism/Pathophysiology * 4 Diagnosis * 5 Prevention/Treatment * 6 Prognosis * 7 Epidemiology * 8 Current Research * 9 References * 10 Further reading * 11 External links ## Signs and Symptoms[edit] The signs of duodenum can vary amongst patients. A high rate of chromosomal damage found in blood lymphocytes can indicate the presence of megaduodenum.[4] Symptoms include: * Dilated Duodenum * Abdominal distention * Nausea * Vomiting and diarrhea * Severe digestive pseudo-obstruction * Recurrent urinary retention * Vacuolar degeneration and fibrosis of the longitudinal layer of gastrointestinal muscle.[4] It is possible that this disease can be misdiagnosed and mimic other intestinal disorders, or later increase the chances of becoming a tumor. ## Causes[edit] Although environmental factors can play a role in the development of Megaduodenum, genetic factors are responsible for creating tumors. Therefore, many complications of chromosomal damage in the blood lymphocytes can be possible causes. However, the main causes are:[5] * Annular pancreas * Adhesions * Systemic sclerosis * Superior mesenteric artery syndrome * Aneurysm. * Duodenal atresia Megaduodenum due to its duodenal ganglionitis is an unusual condition, Megaduodenum's similarity to megacolon and megaesophagus diseases can better explain the most plausible causes of it.[6] In addition, some theories state that megaduodenum can be associated with the following causes: post-vagotomy, vitamin deficiency, and collagen diseases.[7] ## Mechanism/Pathophysiology[edit] Megaduodenum can be passed down through families, it occurs when a patient inherits one copy of a muted megaduodenum gene from one parent.[8] When the gene gets interrupted in the cells, it causes tumors. Acute pancreatitis, adhesions, aneurysm all clinically lead to Megaduodenum. ## Diagnosis[edit] Play media Upper Endoscopy Diagnostic tests and procedures can vary for different types of intestinal disorders. These can include colonoscopy, upper GI endoscopy, capsule endoscopy, endoscopic ultrasound.[9] Since patients with megaduodenum often have atypical symptoms such as hematemesis, steatorrhea, and acute pancreatitis.[7] Therefore, physical and histological examination helps demonstrate the grade of distention and the nutritional status of the patient. Many of the physical examinations include: blood pressure, bowel sounds, blood tests, and thyroid function.[10] In addition, a histological examination such as upper endoscopy, an X-ray of the abdomen, and biopsies can also be performed to diagnose megaduodenum efficiently.[10] ## Prevention/Treatment[edit] The treatment mainly depends on the underlying conditions and the degree of distention of the duodenum.[7] It can be symptomatic and based on diet and control of bacterial overgrowth.[5] To relieve the obstructive symptoms, latero-lateral duodenojejunostomy, gastrojejunostomy, duodenal-jejunal bypass (DJB), enteral and parenteral nutrition may be helpful.[5] Therefore, early diagnosis and treatment may improve patient's outcome and reduce morbidity.[7] Diagram showing laparoscopic surgery. ## Prognosis[edit] As long as Megaduodenum is treated promptly, the chances of making full recovery is possible. Posturing maneuvers during meals may be helpful in some patients, also to relive any compression of the duodenum the patient may lie down in right decubitus position.[11] If the conservative treatments fail, surgery may be performed. Some of the surgeries may include duodenojejunostomy, laparoscopic duodenojejunostomy, or laparoscopic surgery.[11] The timeline for recovery is 7 weeks.[12] ## Epidemiology[edit] No statistical information has been identified. Megaduodenum is an uncommon disease, and because of its extreme rarity of the condition only few cases has been reported in the literatures.[13] ## Current Research[edit] Since Megaduodenum is a rare disease, treatments and decisions are made based on the patients initial conditions and their responses to the provided treatments or surgeries.[14] There are currently several ongoing clinical trials for megaduodenum. One study involves research of idiopathic megaduodenum in children which is a rare condition. The purpose of this study is to present the management of idiopathic megaduodenum in children.[15] ## References[edit] 1. ^ Megaduodenum - Merriam-Webster 2. ^ "Megaduodenum – CheckOrphan". Retrieved 2020-11-11. 3. ^ Murthy, Raghav (2016-01-16). "An Unusual Case of Megaduodenum". Journal of Universal Surgery. 4 (1). ISSN 2254-6758. 4. ^ a b "megaduodenum - Humpath.com - Human pathology". www.humpath.com. Retrieved 2020-11-11. 5. ^ a b c Basilisco, G. (January 1997). "Hereditary megaduodenum". The American Journal of Gastroenterology. 92 (1): 150–153. ISSN 0002-9270. PMID 8995957. 6. ^ Raia, Arrigo; Acquaroni, Danilo; Netto, Alipio Correa (1961-08-01). "Pathogenesis and treatment of acquired megaduodenum". The American Journal of Digestive Diseases. 6 (8): 757–771. doi:10.1007/BF02231059. ISSN 1573-2568. 7. ^ a b c d Horvat, Natally; Brentano, Vicente Bohrer; Abe, Emerson Shigueaki; Dumarco, Rodrigo Blanco; Viana, Publio Cesar Cavalcante; Machado, Marcel Cerqueira Cesar (2019-05-09). "A rare case of idiopathic congenital megaduodenum in adult misinterpreted during childhood: case report and literature review". Radiology Case Reports. 14 (7): 858–863. doi:10.1016/j.radcr.2019.04.016. ISSN 1930-0433. PMC 6514750. PMID 31193055. 8. ^ Jones, S. C.; Dixon, M. F.; Lintott, D. J.; Axon, A. T. R. (1992-03-01). "Familial visceral myopathy". Digestive Diseases and Sciences. 37 (3): 464–469. doi:10.1007/BF01307744. ISSN 1573-2568. 9. ^ "Digestive diseases: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2020-11-11. 10. ^ a b Boeckxstaens, Guy E; Rumessen, Jüri J; de Wit, Laurens; Tytgat, Guido N. J; Vanderwinden, Jean-Marie (2002-08-01). "Abnormal distribution of the interstitial cells of Cajal in an adult patient with pseudo-obstruction and megaduodenum". The American Journal of Gastroenterology. 97 (8): 2120–2126. doi:10.1016/S0002-9270(02)04289-2. ISSN 0002-9270. 11. ^ a b Ranschaert, Erik. "Superior mesenteric artery syndrome \| Radiology Reference Article \| Radiopaedia.org". Radiopaedia. Retrieved 2020-11-11. 12. ^ Rueff, Jessica; Söllner, Oliver; Zuber, Markus; Weixler, Benjamin (2018-01-18). "Megaduodenum in a 59-year-old man: a very late postoperative complication after duodenal atresia". BMJ Case Reports: bcr–2017–221792. doi:10.1136/bcr-2017-221792. ISSN 1757-790X. PMC 5775781. PMID 29351932. 13. ^ McClenahan, J. E.; Fisher, Bernard (1948-12-01). "Idiopathic megaduodenum: Report of a case". The American Journal of Digestive Diseases. 15 (12): 414–416. doi:10.1007/BF03001592. ISSN 1573-2568. 14. ^ da Silva, Amanda Pinter Carvalheiro; Boteon, Yuri Longatto; Tercioti, Valdir; Lopes, Luiz Roberto; de Souza Coelho Neto, João; Andreollo, Nelson Adami (2014-11-28). "Megaduodenum associated with gastric strongyloidiasis". International Journal of Surgery Case Reports. 11: 71–74. doi:10.1016/j.ijscr.2014.11.066. ISSN 2210-2612. PMC 4446660. PMID 25951613. 15. ^ Zhang, Xian-wei; Abudoureyimu, Alimujiang; Zhang, Ting-chong; Zhao, Jing-ru; Fu, Li-bing; Lin, Feng; Qiu, Xiao-hong; Chen, Ya-jun (2012-05-01). "Tapering duodenoplasty and gastrojejunostomy in the management of idiopathic megaduodenum in children". Journal of Pediatric Surgery. 47 (5): 1038–1042. doi:10.1016/j.jpedsurg.2012.02.008. ISSN 0022-3468. ## Further reading[edit] * Basilisco, G (1997). "Hereditary megaduodenum". The American Journal of Gastroenterology. 92 (1): 150–3. PMID 8995957. * Law, David H.; Ten Eyck, Edward A. (1962). "Familial megaduodenum and megacystis". The American Journal of Medicine. 33 (6): 911. doi:10.1016/0002-9343(62)90222-X. * Sturtevant, Mills (1939). "Megaduodenum and Duodenal Obstruction: Criteria for Diagnosis". Radiology. 33 (2): 185–8. doi:10.1148/33.2.185. * Raia, Arrigo; Acquaroni, Danilo; Netto, Alipio Correa (1961). "Pathogenesis and treatment of acquired megaduodenum". The American Journal of Digestive Diseases. 6 (8): 757–71. doi:10.1007/BF02231059. * Gillespie, H. W. (1939). "Megaduodenum and Gastromegaly". British Journal of Radiology. 12 (136): 221–4. doi:10.1259/0007-1285-12-136-221. ## External links[edit] Classification D * ICD-10: K56.0 * OMIM: 155310 * MeSH: C536139 External resources * Orphanet: 2604 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Megaduodenum	c0266177	6,740	wikipedia	https://en.wikipedia.org/wiki/Megaduodenum	2021-01-18T19:00:34	{"mesh": ["C536139"], "umls": ["C0266177"], "wikidata": ["Q15056772"]}
Costello syndrome is a rare condition that affects many different parts of the body. Signs and symptoms generally include developmental delay, intellectual disability, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. Affected people may also have heart abnormalities such as tachycardia, structural heart defects, and hypertrophic cardiomyopathy. Beginning in early childhood, people with Costello syndrome additionally have an increased risk to develop certain cancerous and noncancerous tumors. Costello syndrome is caused by changes (mutations) in the HRAS gene. It is considered an autosomal dominant condition, but almost all cases are the result of de novo gene mutations and occur in people with no family history of the condition. Treatment is based on the signs and symptoms present in each person. Costello syndrome belongs to a group of related conditions called the RASopathies. These conditions have some overlapping features and are all caused by genetic changes that disrupt the body's RAS pathway, affecting growth and development. The features of Costello syndrome overlap significantly with two of the RASopathies, cardiofaciocutaneous (CFC) syndrome and Noonan syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Costello syndrome	c0587248	6,741	gard	https://rarediseases.info.nih.gov/diseases/1550/costello-syndrome	2021-01-18T18:01:04	{"mesh": ["D056685"], "omim": ["218040"], "umls": ["C0587248"], "orphanet": ["3071"], "synonyms": ["Faciocutaneoskeletal syndrome", "FCS syndrome"]}
Cutler et al. (1978) described brother and sister with renal, neurologic, and thyroid disease. Both had thrombocytopenia. Mentality was normal. The girl presented at age 1 year with chronic renal disease. She died at age 10. The brother presented at age 3 with renal disease. At 13 years of age, he became increasingly atoxic. Simple colloid goiter was present in both. GU \- Chronic renal disease \- Nephritis Neuro \- Cerebellar ataxia \- Seizures \- Myoclonus \- Slurred speech \- Normal mentality Heme \- Thrombocytopenia Neck \- Simple colloid goiter Inheritance \- Autosomal recessive Endocrine \- Thyroid disease Muscle \- Muscle wasting Ears \- Sensorineural deafness ▲ 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	THYROCEREBRORETINAL SYNDROME	c1848813	6,742	omim	https://www.omim.org/entry/274240	2019-09-22T16:21:42	{"mesh": ["C536908"], "omim": ["274240"], "orphanet": ["3327"]}
Bosma et al. (1967) studied a condition in which, because of sensory problem in the mouth, the patient remains infantile in oral configuration and function. The 'labial gate' remains infantile with drooling, and nipple (suckle) feeding only is practiced, even in the adult. One expects the labial gate function to develop by age 22 to 24 months. Two-point discrimination is defective in the mouth. The patients appear to have facial diplegia. The smile is transverse, as in dysautonomia. Often the patient stands with the head back to prevent drooling, and in some instances the salivary glands have been removed. Minor neurologic defects may be demonstrable elsewhere, such as a sensory type of incoordination in the hands. One 19-year-old female has married. No familial cases have in fact been identified but few cases are known. Neuro \- Mouth two-point discrimination defect \- Sensory type hand incoordination Mouth \- Oral sensory defect \- Infantile oral function \- Drooling \- Transverse smile \- Facial diplegic appearance \- Nipple (suckle) feeding only 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	ORAL SENSIBILITY, DISTURBANCE OF	c1850269	6,743	omim	https://www.omim.org/entry/258800	2019-09-22T16:24:05	{"omim": ["258800"]}
Dracunculiasis (Guinea worm disease) is a neglected tropical disease (NTD) characterized by a painful burning skin lesion from which the Dracunculus medinensis parasite emerges approximately 1 year after infection resulting from consumption of unsafe drinking water containing parasite-infected copepods (Cyclops spp., microcrustacea also called water fleas). ## Epidemiology In 2012, 542 cases were reported in 4 countries (Chad, Ethiopia, Mali, and South Sudan), a decrease of >99% since 1990. The global dracunculiasis program aims to eradicate the parasite from the last remaining endemic villages located in difficult to reach areas. ## Clinical description Clinical manifestations appear 10-14 months after infection and include constitutional symptoms (such as low-grade fever, itchy rash, nausea, vomiting, diarrhea, dizziness) followed by a localized swelling developing into a painful blister, most often on a lower limb. On contact with water, the adult female worm (70-100 cm) bursts through the blister, depositing her larvae in the water where they are consumed by copepods, starting the cycle anew. Local inflammation and secondary bacterial infection of the lesion are common, potentially causing cellulitis, abscess formation, tetanus (see this term), sepsis, and septic arthritis. If the lesion is near a joint, this may lead to joint contractures and permanent disability. If the worm is not fully removed it can create an intense inflammatory reaction that further exacerbates the pain, swelling, and cellulitis. ## Etiology Dracunculiasis is caused by the parasitic worm Dracunculus medinensis. Transmission occurs after drinking water contaminated with copepods that act as intermediate hosts to the infective parasite larvae. Copepod digestion in the gastrointestinal tract releases the larvae, which migrate to subcutaneous tissues where they mate and pregnant female worms mature. ## Diagnostic methods Dracunculiasis diagnosis is based on the typical appearance of a skin lesion with a protruding worm, commonly on a lower limb. ## Differential diagnosis Occasionally, another parasitic worm called Onchocerca volvulus, pieces of connective tissue, or fly larvae are confused with emerging Dracunculus medinensis worms. ## Management and treatment There is no effective medication or vaccine for dracunculiasis. Infected persons do not become immune to subsequent infection. Treatment is a long painful process consisting of pulling out the emerging worm by rolling it around a piece of gauze or a small stick, a few centimeters a day, in combination with wound cleaning and dressing with antibiotic ointment to prevent secondary bacterial infection. ## Prognosis Dracunculiasis is not life threatening itself but, rarely, death due to secondary sepsis has been reported. More commonly, the patient is disabled by pain during worm removal, on average for 8.5 weeks, which often has a great impact on everyday life in endemic areas. Joint contractures and permanent disability can occur in some cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Dracunculiasis	c0013100	6,744	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231	2021-01-23T17:53:52	{"gard": ["6286"], "mesh": ["D004320"], "umls": ["C0013100"], "icd-10": ["B72"], "synonyms": ["Dracunculosis", "Guinea worm disease", "Medina worm disease", "Medinensis"]}
Tetrahydrobiopterin (BH4) deficiency causes the body to build up an abnormally high level of phenylalanine, one of the building blocks of proteins. In addition, BH4 deficiency leads to low levels of certain neurotransmitters, chemical messengers that control many body functions. Symptoms can range from very mild to severe. Babies with BH4 deficiency appear normal at birth but may develop neurological symptoms such as abnormal muscle tone, poor head control, seizures, and delayed motor development. Without treatment, the condition can cause permanent intellectual disability. BH4 deficiency is caused by pathogenic variants in any one of several genes including the GCH1, PCBD1, PTS, and QDPR genes. It is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, and blood and urine tests. BH4 deficiency is sometimes diagnosed based on the results of an abnormal newborn screening test. Treatment depends on the genetic cause and severity, and may include a low phenylalanine diet, oral BH4 supplementation, and neurotransmitter replacement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Tetrahydrobiopterin deficiency	c0751436	6,745	gard	https://rarediseases.info.nih.gov/diseases/7751/tetrahydrobiopterin-deficiency	2021-01-18T17:57:23	{"mesh": ["D010661"], "orphanet": ["238583"], "synonyms": ["BH4 deficiency", "Hyperphenylalaninemia caused by a defect in biopterin metabolism", "Hyperphenylalaninemia, non-phenylketonuric", "Non-phenylketonuric hyperphenylalaninemia", "Hyperphenylalaninemia due to tetrahydrobiopterin deficiency", "Hyperphenylalaninemia due to BH4 deficiency"]}
## Summary ### Clinical characteristics. Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities) to mild CCD to isolated dental anomalies without the skeletal features. Most individuals come to diagnosis because they have classic features. At birth, affected individuals typically have abnormally large, wide-open fontanelles that may remain open throughout life. Clavicular hypoplasia can result in narrow, sloping shoulders that can be opposed at the midline. Moderate short stature may be observed, with most affected individuals being shorter than their unaffected sibs. Dental anomalies may include supernumerary teeth, eruption failure of the permanent teeth, and presence of the second permanent molar with the primary dentition. Individuals with CCD spectrum disorder are at increased risk of developing recurrent sinus infections, recurrent ear infections leading to conductive hearing loss, and upper-airway obstruction. Intelligence is typically normal. ### Diagnosis/testing. Diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or by the identification of a heterozygous pathogenic variant in RUNX2 (CBFA1). ### Management. Treatment of manifestations: If the cranial vault defect is significant, the head needs protection from blunt trauma; helmets may be used for high-risk activities. Surgical cosmesis for depressed forehead or lengthening of hypoplastic clavicles can be considered. If bone density is below normal, treatment with calcium and vitamin D supplementation is considered. Dental procedures to address retention of deciduous dentition, presence of supernumerary teeth, and non-eruption of the permanent dentition. Such procedures may include prosthetic replacements, removal of the supernumerary teeth followed by surgical repositioning of the permanent teeth, and a combination of surgical and orthodontic measures for actively erupting and aligning the impacted permanent teeth. Speech therapy may be required during periods of dental treatment. Aggressive treatment of sinus and middle ear infections; consideration of tympanostomy tubes for recurrent middle ear infections. Prevention of primary manifestations: Preventive treatment for osteoporosis should be initiated at a young age. Early screening for low bone mineral density and appropriate supplementation with vitamin D and calcium are recommended. Prevention of secondary complications: Careful planning of anesthetic management due to craniofacial and dental abnormalities. Consultation with an otolaryngologist to assist in securing the airway. Consideration of alternative anesthetic approaches, including neuraxial block, taking into account possible spine abnormalities. Surveillance: Monitoring of children for orthopedic complications, dental abnormalities, upper-airway obstruction, sinus and ear infections, and hearing loss. Monitoring for osteoporosis beginning in early adolescence and every five to ten years thereafter. Agents/circumstances to avoid: Helmets and protective devices should be worn when participating in high-risk activities. Pregnancy management: Monitoring of affected women during pregnancy for cephalopelvic disproportion. ### Genetic counseling. Cleidocranial dysplasia spectrum disorder is inherited in an autosomal dominant manner. The proportion of cases caused by a de novo RUNX2 pathogenic variant is high. Each child of an individual with CCD spectrum disorder has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family is known. ## Diagnosis Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a continuum of clinical findings ranging from classical presentation (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities) to mild CCD to isolated dental anomalies without other skeletal features. No formal clinical diagnostic criteria for CCD spectrum disorder have been established. ### Suggestive Findings Cleidocranial dysplasia (CCD) spectrum disorder should be suspected in individuals with the following clinical and radiographic findings. Clinical findings * Abnormally large, wide-open fontanelles at birth that may remain open throughout life. The wide-open metopic suture results in separation of the frontal bones by a metopic groove. The forehead is broad and flat; the cranium is brachycephalic. * Frontal and parietal bossing and mid-face retrusion * Narrow, sloping shoulders that can be opposed at the midline due to clavicular hypoplasia or aplasia (see Figure 1) * Abnormal dentition including delayed eruption of secondary dentition, failure to shed the primary teeth, variable numbers of supernumerary teeth along with dental crowding, and malocclusion * Hand abnormalities including brachydactyly, tapering fingers, and short, broad thumbs * Short stature (typically moderate) * Normal intellect in individuals with classic CCD spectrum disorder #### Figure 1. Shoulders in an individual with clavicular hypoplasia may be brought to the midline. Radiographic findings * Cranium * Wide-open sutures, patent fontanelles, presence of wormian bones (small sutural bones) * Delayed ossification of the skull * Poor or absent pneumatization of the paranasal, frontal, and mastoid sinuses * Impacted, crowded teeth; supernumerary teeth * Thorax (Figure 2) * Cone-shaped thorax with narrow upper thoracic diameter * Typically bilateral (but not necessarily symmetric) clavicular abnormalities ranging from complete absence to hypoplastic or discontinuous clavicles. The lateral portions are more affected than the medial aspects of the clavicles (see Figure 2). * Hypoplastic scapulae * Pelvis * Delayed ossification of the pubic bone with wide pubic symphysis * Hypoplasia of the iliac wings * Widening of the sacroiliac joints * Elongated femoral head with short femoral neck and elongated epiphyses ("chef-hat" appearance) * Coxa vara * Hands (Figure 3) * Pseudoepiphyses of the metacarpal and metatarsal bones, which may result in a characteristic lengthening of the second metacarpal (see Figure 3) * Hypoplastic distal phalanges * Deformed and short middle phalanges of the third, fourth, and fifth digits with cone-shaped epiphyses * Other. Osteopenia/osteoporosis with evidence of decreased bone mineral density by DXA; some affected individuals sustain multiple fractures. #### Figure 2. Chest x-ray demonstrates clavicular hypoplasia. #### Figure 3. Hand x-ray of a male age 2.5 years with cleidocranial dysplasia spectrum disorder a. Note pseudoepiphyses at the bases of the second and third metacarpals with accessory physes seen at the base of the fourth and fifth metacarpals. ### Establishing the Diagnosis The diagnosis of a CCD spectrum disorder is established in a proband with EITHER of the following: * The above clinical and radiographic findings of classic CCD * Suggestive clinical findings and a heterozygous pathogenic variant in RUNX2 (CBFA1) identified by molecular genetic testing (see Table 1) Molecular testing approaches can include single-gene testing, karyotype, or use of a multigene panel: * Single-gene testing. Sequence analysis of RUNX2 is performed first and followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. Note: Gene-targeted methods will detect deletions ranging from a single exon to whole genes; however, breakpoints of large deletions and/or deletion of adjacent genes may not be determined. * Karyotype. If RUNX2 testing is not diagnostic and if strong suspicion persists in an individual with features of CCD spectrum disorder who also has multiple congenital anomalies and/or developmental delay, a karyotype may be considered to evaluate for complex chromosome rearrangements or translocations that involve 6p21.1 (RUNX2 locus) but do not result in RUNX2 copy number changes [Purandare et al 2008, Northup et al 2011]. * A multigene panel that includes RUNX2 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of pathogenic variants in genes that do not explain the underlying phenotype. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in Cleidocranial Dysplasia Spectrum Disorder View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method RUNX2Sequence analysis 3~60% 4 Gene-targeted deletion/duplication analysis 510% 6, 7 KarytoypeSee footnote 8 Unknown 9NA 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Ott et al [2010] 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\. Individuals with these deletions may have a phenotype consistent with a CCD spectrum disorder and additional findings including developmental delay. Gene-targeted methods will detect single-exon up to whole gene deletions; however, breakpoints of large deletions and/or deletion of adjacent genes may not be determined. 7\. Ott et al [2010] 8\. Two individuals with translocations involving the RUNX2 locus have been reported [Purandare et al 2008, Northup et al 2011]. 9\. Not all individuals clinically diagnosed with CCD have an identifiable heterozygous pathogenic variant in RUNX2; however, there is little additional evidence for locus heterogeneity. ## Clinical Characteristics ### Clinical Description Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia representing a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities) to mild CCD to isolated dental anomalies without the skeletal features [Golan et al 2000]. Most individuals come to diagnosis because they have classic features. CCD spectrum disorder affects most prominently those bones derived from intramembranous ossification, such as the cranium and the clavicles, although bones formed through endochondral ossification can also be affected. Cooper et al [2001] recorded the natural history of 90 probands and 56 first- and second-degree relatives; findings highlight the clinical variability of this condition within affected members of the same family who harbor the same pathogenic variant. Roberts et al [2013] reviewed their experience with more than 100 affected individuals in South Africa. Males and females are affected equally. Classic CCD. The most prominent clinical findings in individuals with classic CCD are listed in Suggestive Findings and include: abnormally large, wide-open fontanelles at birth that may remain open throughout life; clavicular hypoplasia resulting in narrow, sloping shoulders that can be opposed at the midline; and abnormal dentition (see Dental complications). Further medical problems identified in individuals with CCD spectrum disorder include the following: Height. Individuals with CCD spectrum disorder are often shorter than their unaffected sibs: * Males are on average six inches shorter than their unaffected brothers and have an average height of 165 cm (±8 cm). * Females are on average three inches shorter than their unaffected sisters and have an average height of 156 cm (±10 cm) [Cooper et al 2001]. Skeletal/orthopedic problems. Affected individuals are more likely to have other bone-related problems: * Pes planus (flat feet) in 57% * Genu valgum (knock-knee deformity) in 28% * Scoliosis in 18% [Cooper et al 2001] * Osteoporosis, found in 8/14 (57.1%) affected individuals; and osteopenia, identified in 3/14 (21.4%) individuals with CCD spectrum disorder [Dinçsoy Bir et al 2017] Other less common orthopedic problems include joint dislocation at the shoulder and elbow [El-Gharbawy et al 2010]. Dental complications. Up to 94% of persons with CCD spectrum disorder have dental findings including supernumerary teeth (they often do not lose their primary teeth) and eruption failure of the permanent teeth [Golan et al 2003]. The most consistent dental findings in individuals with a CCD spectrum disorder are the presence of the second permanent molar with the primary dentition (80%), wide spacing in the lower incisor area, supernumerary tooth germs (70%), and parallel-sided ascending rami [Cooper et al 2001, Golan et al 2003, Golan et al 2004, Bufalino et al 2012]. Individuals with a CCD spectrum disorder are more likely to have an underbite and to have cysts in their gums that usually form around extra teeth [McNamara et al 1999]. ENT complications. Recurrent sinus infections and other upper-airway complications are observed significantly more often in individuals with CCD spectrum disorder than in the general population. When symptoms are suggestive of upper-airway obstruction, a sleep study is indicated and surgical intervention may be required. Conductive hearing loss occurs in 39% of affected individuals. Individuals with CCD spectrum disorder of any age are more likely to have recurrent ear infections. Endocrinology. Individuals with CCD spectrum disorder can have low IGF-1 levels. Low vitamin D with no consistent association with osteoporosis has also been reported [Dinçsoy Bir et al 2017]. Rarely, individuals with CCD spectrum disorder have low levels of alkaline phosphatase [Morava et al 2002, Unger et al 2002, El-Gharbawy et al 2010]. Development. Intelligence is typically normal. Children younger than age five years may show mild motor delay, particularly in gross motor abilities. This delay may be associated with orthopedic complications such as flat feet and genu valgum. No significant differences are observed among elementary school-age children. ### Genotype-Phenotype Correlations Some genotype-phenotype correlations have been established for the dental manifestations. No clear correlation has been established between genotype and clavicular involvement [Otto et al 2002, Bufalino et al 2012, Jaruga et al 2016]. * Heterozygous RUNX2 pathogenic variants located in the runt domain (or predicting a premature termination upstream of or within the runt domain) that abolish the transactivation activity of the mutated protein with consequent haploinsufficiency result in classic CCD. * Short stature and dental anomalies were found to be milder in individuals with a classic CCD phenotype who had an intact runt domain and higher residual RUNX2 activity when compared to individuals with a classic CCD phenotype in whom the pathogenic variant affected the runt domain [Yoshida et al 2002]. * A clinical spectrum ranging from isolated dental anomalies without the skeletal features of CCD to mild CCD to classic CCD results from hypomorphic pathogenic variants that result in partial loss of protein function (c.1171C>T [p.Arg391Ter], c.598A>G [p.Thr200Ala], and c.90dupC) (see Molecular Genetics). Intrafamilial variability is significant [Zhou et al 1999]. * Osteoporosis leading to recurrent bone fractures and scoliosis has been associated with a heterozygous pathogenic frameshift variant c.1205dupC, reflecting the role of RUNX2 protein in the maintenance of adult bone [Quack et al 1999]. ### Penetrance Pathogenic variants in RUNX2 have a high penetrance and extreme variability. ### Nomenclature Cleidocranial dysplasia spectrum disorder was originally described as dento-osseous dysplasia affecting several individuals in a large pedigree. While the term "cleidocranial dysostosis" has been used, the disease is more correctly considered a dysplasia given that RUNX2 has important functions both during skeletal formation and in bone maintenance. ### Prevalence CCD spectrum disorder is present at a frequency of one in 1,000,000 individuals worldwide. It affects all ethnic groups. Stevenson et al [2012] found the frequency to be 0.12 per 10,000 individuals in the Utah (USA) population, suggesting that the frequency may be higher than previously recognized. ## Differential Diagnosis Other conditions share some characteristics with CCD spectrum disorder. The fact that similar skeletal elements are affected suggests that some of these conditions may result from mutation of genes that affect the action of RUNX2 on its downstream targets. Most notable is the association of 16q22.1 deletion that includes CBFB with wide-open fontanelles and short clavicles [Goto et al 2004]. Because CBFB forms a heterodimer with RUNX2 to activate transcription of downstream targets, CBFB haploinsufficiency would explain the similarity in the phenotypes. ### Table 2. Disorders to Consider in the Differential Diagnosis of Cleidocranial Dysplasia (CCD) Spectrum Disorder View in own window Disorder Name or Genetic MechanismGene(s)MOIClinical Features Shared w/CCD spectrum disorderDistinguishing from CCD spectrum disorder 16q22 deletion (incl deletion of CBFB) (OMIM 614541)CBFBWide-open fontanelles & short clavicles * Failure to thrive * Delayed psychomotor development * Congenital heart defect Crane-Heise syndrome (OMIM 218090)UnknownAR? * Large head * Poorly mineralized calvarium * Cleft lip & palate * Low-set, dysplastic ears * Hypoplastic clavicles & scapulae * Hypoplasic/absent phalanges * Absence of cervical vertebrae * Genital hypoplasia * Lethal condition * IUGR * Multiple joint contractures * Severe vertebral & limb anomalies w/absence of cervical vertebrae Mandibuloacral dysplasia (OMIM PS248370)LMNA, ZMPSTE24AR * Short stature, delayed closure of cranial sutures, mandibular hypoplasia, & dysplastic clavicles * Scalp hair sparse by 3rd decade * Progressively stiff joints * Acroosteodysplasia of fingers & toes w/delayed ossification of carpal bones * Micrognathia * Early tooth loss * Atrophic skin w/↓ subcutaneous fat * Acroosteolysis * Hyperpigmentation * Lipodystrophy * Alopecia PycnodysostosisCTSKAR * Short stature, osteopetrosis w/↑ bone fragility, short terminal phalanges * Failure of closure of cranial sutures w/persistence of an open fontanelle * Radio-opacity of all bones ↑ due to ↑ density of the trabecular bone but not the cortices * Osteopetrosis * Acrosteolysis Yunis Varon syndrome (OMIM 216340)FIG4AR * Prenatal growth deficiency * Wide-open fontanelles & sutures, unusual mineralization of the skull, & hypoplastic clavicles * Hypoplastic or absent thumbs & great toes * Absence/hypoplasia of thumbs, halluces & distal phalanges * Gracile bones * Brain malformations CDAGS syndrome (OMIM 603116)UnknownAR * Craniosynostosis, delayed closure of fontanelles, cranial defects, clavicular hypoplasia 1 * Anal & genitourinary malformations * Skin eruption * Craniosynostosis * Anal anomalies * Skin lesions (porokeratosis) Hypophosphatasia 2ALPLAR AD 3 * Generalized defect of mineralization w/delayed ossification of multiple skeletal elements * Children w/infantile form may present w/very poorly mineralized cranium, widened cranial sutures short ribs, & narrow thorax. * Very low alkaline phosphatase activity in serum & tissues * Clavicles least affected * No supernumerary teeth * Premature deciduous tooth loss * Rachitic skeletal changes * Nephrocalcinosis * Hypercalcemia Parietal foramina with cleidocranial dysplasia 4MSX2AD * Parietal foramina * Mild craniofacial dysmorphisms * Clavicular hypoplasia Not associated w/dental abnormalities seen in classic CCD 5 Microduplications upstream of MSX2Phenocopy of cleidocranial dysplasia 6Synpolydactyly in some Familial supernumerary teethADSupernumerary premolar teethNonsyndromic supernumerary premolar teeth 7 HypothyroidismDelayed fontanelle closure IUGR = intrauterine growth restriction; MOI = mode of inheritance 1\. CDAGS syndrome brings together the apparently opposing pathophysiologic and developmental processes of accelerated suture closure and delayed ossification [Mendoza-Londono et al 2005]. 2\. In one report, an individual with severe CCD was initially thought to have hypophosphatasia [Unger et al 2002]. 3\. Perinatal and infantile hypophosphatasia are inherited in an autosomal recessive manner. The milder forms, especially adult and odontohypophosphatasia, may be inherited in an autosomal recessive or autosomal dominant manner depending on the effect that the ALPL pathogenic variant has on TNSALP activity. 4\. See Enlarged Parietal Foramina. 5\. Garcia-Miñaur et al [2003] 6\. Ott et al [2012] 7\. Bae et al [2017] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with cleidocranial dysplasia (CCD) spectrum disorder, the following evaluations are recommended if they have not already been completed: * Full skeletal survey including the hands and feet * DXA scan for those in early adolescence and older * Dental evaluation by a dentist familiar with CCD and its management * Audiologic evaluation * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Craniofacial. The fontanelles close with time in the majority of individuals and cranial remodeling is usually not necessary. * If the cranial vault defect is significant, the head should be protected from blunt trauma; helmets may be advised for high-risk activities. In these cases, evaluation by a craniofacial surgeon and rehabilitation services are indicated. * Affected individuals may consider having correction of the depressed forehead or lengthening of the hypoplastic clavicles for cosmetic reasons. There have been reports of successful surgical interventions in a very small number of affected individuals [Kang et al 2009, Sewell et al 2013]. Skeletal. If bone density is below normal on DXA, treatment with calcium and vitamin D supplementation should be considered. Dental. Early referral to a dental clinic familiar with CCD allows for timely planning of necessary procedures. * The dental problems that need to be addressed include the retention of deciduous dentition, the presence of supernumerary teeth, and the non-eruption of the permanent dentition. * The goal of treatment is to improve appearance and to provide a functioning masticatory mechanism. The goals may be achieved with prosthetic replacements, with or without prior extractions; by removal of the supernumerary teeth followed by surgical repositioning of the permanent teeth; and by a combination of surgical and orthodontic measures for actively erupting and aligning the impacted permanent teeth. For a detailed review, see Becker et al [1997a], Becker et al [1997b], and Roberts et al [2013]. * Generally, an aggressive approach to coordination of multiple oral surgeries for removal of primary dentition and exposure of permanent dentition is recommended, as watchful waiting for spontaneous eruption after initial delay is not effective. Speech therapy may be required during periods of dental treatment. Upper airway obstruction. When symptoms are suggestive, a sleep study is indicated and surgical intervention may be required. Sinus and middle ear infections require aggressive and timely treatment; tympanostomy tubes should be considered when middle ear infections are recurrent [Visosky et al 2003]. Endocrinology. The effectiveness of growth hormone (GH) therapy for short stature in this condition has not been proven. Possible adverse effects of GH therapy on the primary chondrodysplastic growth plate are theoretically possible, as RUNX2 is directly involved in chondrocyte differentiation and growth plate maintenance [Zheng et al. 2005]. ### Prevention of Primary Complications Preventive treatment for osteoporosis should be initiated at a young age since peak bone mineral density is achieved in the second and third decade. Early screening for low bone mineral density and appropriate supplementation with vitamin D and calcium are recommended. ### Prevention of Secondary Complications Anesthetic management of those with CCD spectrum disorder needs to be carefully planned since affected individuals may present with a large brachycephalic head with mandibular prognathism and maxillary underdevelopment. In addition, the depressed nasal bridge and hypoplastic sinuses disturb nasal breathing. The dental and craniofacial abnormalities result in predictably difficult airway management. If this is anticipated, an otolaryngologist should be consulted to assist in securing the airway. Alternative anesthetic approaches, including neuraxial block, should be considered, taking into account possible spine abnormalities [Ioscovich et al 2010]. ### Surveillance Children with CCD spectrum disorder should be monitored for the following: * Orthopedic complications * Dental abnormalities * Signs and symptoms of upper-airway obstruction * Sinus and ear infections * Hearing loss. Regular audiometry in individuals with repeated ear infections allows the identification and early management of hearing loss if it develops. * Osteoporosis. DXA to measure bone mineral density should be done early in adolescence and every five to ten years thereafter. If there are clinical signs of osteopenia (i.e., increased number of fractures), evaluation and treatment should be started earlier. All affected individuals should by followed by their primary care physician and receive regular immunizations and anticipatory guidance as recommended. ### Agents/Circumstances to Avoid To avoid head trauma, helmets and protective devices should be worn when participating in high-risk sports and activities. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Pregnant women with CCD spectrum disorder should be monitored closely for cephalopelvic disproportion, which may require delivery by cesarean section. The primary cesarean section rate among women with a CCD spectrum disorder is 69%, which is higher than in controls [Cooper et al 2001]. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Cleidocranial Dysplasia Spectrum Disorder	c0008928	6,746	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1513/	2021-01-18T21:34:39	{"mesh": ["D002973"], "synonyms": ["Cleidocranial Dysostosis"]}
Propionic acidemia is an inherited disorder in which the body is unable to process certain parts of proteins and lipids (fats) properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems. In most cases, the features of propionic acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including heart abnormalities, seizures, coma, and possibly death. Less commonly, the signs and symptoms of propionic acidemia appear during childhood and may come and go over time. Some affected children experience intellectual disability or delayed development. In children with this later-onset form of the condition, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections. ## Frequency Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians. ## Causes Mutations in the PCCA and PCCB genes cause propionic acidemia. These genes provide instructions for making two parts (subunits) of an enzyme called propionyl-CoA carboxylase, which plays a role in the normal breakdown of proteins. Specifically, this enzyme helps process several amino acids, which are the building blocks of proteins. Propionyl-CoA carboxylase also helps break down certain types of fat and cholesterol in the body. Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules. As a result, a substance called propionyl-CoA and other potentially harmful compounds can build up to toxic levels in the body. This buildup damages the brain and nervous system, causing the serious health problems associated with propionic acidemia. ### Learn more about the genes associated with Propionic acidemia * PCCA * PCCB ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Propionic acidemia	c0268579	6,747	medlineplus	https://medlineplus.gov/genetics/condition/propionic-acidemia/	2021-01-27T08:25:06	{"gard": ["467"], "mesh": ["D056693"], "omim": ["606054"], "synonyms": []}
Aversion to happiness Other namesCherophobia SpecialtyPsychology Aversion to happiness, also called cherophobia and fear of happiness, is an attitude towards happiness in which individuals may deliberately avoid experiences that invoke positive emotions or happiness.[1][2][3] One of several reasons why cherophobia may develop is the belief that when one becomes happy, a negative event will soon occur that will taint that happiness, as if punishing that individual for satisfaction. This belief is thought to be more prevalent in Eastern cultures. In Western cultures, such as American culture, "it is almost taken for granted that happiness is one of the most important values guiding people's lives". Western cultures are more driven by an urge to maximize happiness and to minimize sadness. Failing to appear happy often gives cause for concern. The value placed on happiness echoes through Western positive psychology and through research on subjective well-being.[4] Fear of happiness is associated with fragility of happiness beliefs, suggesting that one of the causes of aversion to happiness may be the belief that happiness is unstable and fragile.[5] Research shows that fear of happiness is associated with avoidant and anxious attachment styles.[6] ## Cultural factors[edit] Joshanloo and Weijers identify four reasons for an aversion to happiness: (1) a belief that happiness will cause bad things to happen; (2) that happiness will cause you to become a bad person; (3) that expressing happiness is somehow bad for you and others; and (4) that pursuing happiness is bad for you and others.[7] For example, "some people—in Western and Eastern cultures—are wary of happiness because they believe that bad things, such as unhappiness, suffering, and death, tend to happen to happy people."[8] These findings "call into question the notion that happiness is the ultimate goal, a belief echoed in any number of articles and self-help publications about whether certain choices are likely to make you happy".[8] Also, "in cultures that believe worldly happiness to be associated with sin, shallowness, and moral decline will actually feel less satisfied when their lives are (by other standards) going well",[9] so measures of personal happiness cannot simply be considered a yardstick for satisfaction with one's life, and attitudes such as aversion to happiness have important implications for measuring happiness across cultures and ranking nations on happiness scores. Aversion to happiness can be thought of as a specific example of ideal affect (described by affect valuation theory),[10][11] whereby cultures vary in the extent to which they value the experience of different emotions. ## References[edit] Look up cherophobia in Wiktionary, the free dictionary. 1. ^ Joshanloo, M.; Lepshokova, Z. K.; Panyusheva, T.; Natalia, A.; Poon, W.-C.; Yeung, V. W.-l.; Sundaram, S.; Achoui, M.; Asano, R.; Igarashi, T.; Tsukamoto, S.; Rizwan, M.; Khilji, I. A.; Ferreira, M. C.; Pang, J. S.; Ho, L. S.; Han, G.; Bae, J.; Jiang, D.-Y. (3 October 2013). "Cross-Cultural Validation of Fear of Happiness Scale Across 14 National Groups". Journal of Cross-Cultural Psychology. 45 (2): 246–264. doi:10.1177/0022022113505357. S2CID 73617183. 2. ^ Joshanloo, Mohsen; Weijers, Dan (15 December 2013). "Aversion to Happiness Across Cultures: A Review of Where and Why People are Averse to Happiness". Journal of Happiness Studies. 15 (3): 717–735. doi:10.1007/s10902-013-9489-9. S2CID 144425713. 3. ^ Mosby (2016-04-29). Mosby's Medical Dictionary. Elsevier Health Sciences. ISBN 9780323414265. 4. ^ Joan Robinson (17 March 2014), What's so bad about feeling happy?, Springer 5. ^ Joshanloo, Mohsen; Weijers, Dan; Jiang, Ding-Yu; Han, Gyuseog; Bae, Jaechang; Pang, Joyce S.; Ho, Lok Sang; Ferreira, Maria Cristina; Demir, Melikşah; Rizwan, Muhammad; Khilji, Imran Ahmed; Achoui, Mustapha; Asano, Ryosuke; Igarashi, Tasuku; Tsukamoto, Saori; Lamers, Sanne M. A.; Turan, Yücel; Sundaram, Suresh; Yeung, Victoria Wai Lan; Poon, Wai-Ching; Lepshokova, Zarina Kh; Panyusheva, Tatiana; Natalia, Amerkhanova (1 October 2015). "Fragility of Happiness Beliefs Across 15 National Groups". Journal of Happiness Studies. 16 (5): 1185–1210. CiteSeerX 10.1.1.722.7369. doi:10.1007/s10902-014-9553-0. S2CID 58909959. 6. ^ Joshanloo, Mohsen (2018). "Fear and fragility of happiness as mediators of the relationship between insecure attachment and subjective well-being". Personality and Individual Differences. 123: 115–118. doi:10.1016/j.paid.2017.11.016. 7. ^ Joshanloo, Mohsen; Weijers, Dan, "It's time for Western psychology to recognise that many individuals, and even entire cultures, fear happiness", Journal of Happiness Studies, 15 (3): 717–735, doi:10.1007/s10902-013-9489-9, S2CID 144425713, retrieved October 4, 2014. 8. ^ a b Stephanie Pappas (20 March 2014), Why Happiness Scares Us, LiveScience, retrieved 4 October 2014. 9. ^ Susan Krauss Whitbourne (6 April 2013), 13 of Psychology's Newest and Coolest Ideas, Psychology Today, retrieved 4 October 2014. 10. ^ Tsai, Jeanne L.; Louie, Jennifer Y.; Chen, Eva E.; Uchida, Yukiko (2007). "Learning What Feelings to Desire: Socialization of Ideal Affect Through Children's Storybooks". Personality and Social Psychology Bulletin. 33 (1): 17–30. doi:10.1177/0146167206292749. PMID 17178927. S2CID 3163885. 11. ^ Tsai, Jeanne L (October 2017). "Ideal affect in daily life: implications for affective experience, health, and social behavior". Current Opinion in Psychology. 17: 118–128. doi:10.1016/j.copsyc.2017.07.004. PMC 5659332. PMID 28950957. * v * t * e Emotions (list) Emotions * Acceptance * Adoration * Aesthetic emotions * Affection * Agitation * Agony * Amusement * Anger * Angst * Anguish * Annoyance * Anticipation * Anxiety * Apathy * Arousal * Attraction * Awe * Boredom * Calmness * Compassion * Confidence * Contempt * Contentment * Courage * Cruelty * Curiosity * Defeat * Depression * Desire * Despair * Disappointment * Disgust * Distrust * Ecstasy * Embarrassment * Vicarious * Empathy * Enthrallment * Enthusiasm * Envy * Euphoria * Excitement * Fear * Flow (psychology) * Frustration * Gratification * Gratitude * Greed * Grief * Guilt * Happiness * Hatred * Hiraeth * Homesickness * Hope * Horror * Hostility * Humiliation * Hygge * Hysteria * Indulgence * Infatuation * Insecurity * Inspiration * Interest * Irritation * Isolation * Jealousy * Joy * Kindness * Loneliness * Longing * Love * Limerence * Lust * Mono no aware * Neglect * Nostalgia * Outrage * Panic * Passion * Pity * Self-pity * Pleasure * Pride * Grandiosity * Hubris * Insult * Vanity * Rage * Regret * Social connection * Rejection * Remorse * Resentment * Sadness * Melancholy * Saudade * Schadenfreude * Sehnsucht * Self-confidence * Sentimentality * Shame * Shock * Shyness * Sorrow * Spite * Stress * Suffering * Surprise * Sympathy * Tenseness * Trust * Wonder * Worry World views * Cynicism * Defeatism * Nihilism * Optimism * Pessimism * Reclusion * Weltschmerz Related * Affect * consciousness * in education * measures * in psychology * Affective * computing * forecasting * neuroscience * science * spectrum * Affectivity * positive * negative * Appeal to emotion * Emotion * and art * and memory * and music * and sex * classification * evolution * expressed * functional accounts * group * homeostatic * perception * recognition * in conversation * in animals * regulation * interpersonal * work * Emotional * aperture * bias * blackmail * competence * conflict * contagion * detachment * dysregulation * eating * exhaustion * expression * intelligence * and bullying * intimacy * isolation * lability * labor * lateralization * literacy * prosody * reasoning * responsivity * security * selection * symbiosis * well-being * Emotionality * bounded * Emotions * and culture * in decision-making * in the workplace * in virtual communication * history * moral * self-conscious * social * social sharing * sociology * Feeling * Gender and emotional expression * Group affective tone * Interactions between the emotional and executive brain systems * Meta-emotion * Pathognomy * Pathos * Social emotional development * Stoic passions * Theory * affect * appraisal * discrete emotion * somatic marker * constructed emotion [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Aversion to happiness	None	6,748	wikipedia	https://en.wikipedia.org/wiki/Aversion_to_happiness	2021-01-18T18:38:23	{"wikidata": ["Q18209757"]}
Chronic Epstein-Barr virus infection syndrome is a rare infectious disease characterized by familial, primary, chronic Epstein-Barr virus infection which typically manifests with persistent mononucleosis-like signs and symptoms, in the absence of secondary immunodeficiency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Chronic Epstein-Barr virus infection syndrome	c4016741	6,749	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2566	2021-01-23T19:00:59	{"gard": ["9534"], "omim": ["226990"], "icd-10": ["B27.0"], "synonyms": ["CAEBV syndrome", "Chronic EBV infection syndrome"]}
A rare ophthalmic disorder characterized by intraocular inflammation with the anterior chamber as the predominant site of inflammation, without any identifiable etiology. Presenting symptoms are pain, redness, photophobia, and sometimes blurred vision. Signs on examination include anterior chamber cell and flare, limbal vascular injection, and keratic precipitates, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Idiopathic anterior uveitis	c0339315	6,750	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280914	2021-01-23T18:25:37	{"umls": ["C0339315"], "icd-10": ["H20.0", "H20.1", "H20.2", "H20.8", "H20.9"]}
A number sign (#) is used with this entry because 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), also referred to as 3-methylglutaconic aciduria type VI (MGCA6), is caused by homozygous or compound heterozygous mutation in the SERAC1 gene (614725) on chromosome 6q25. Description MEGDEL is an autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome (256000). Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells (summary by Wortmann et al., 2012). About 50% of patients develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life, prompting some authors to suggest the name 'MEGDHEL' syndrome, with the 'H' referring to 'hepatopathy' (summary by Maas et al., 2017). Some patients may have a milder presentation with juvenile-onset spasticity and mild cognitive impairment, indicating a broader phenotypic spectrum (Roeben et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). Clinical Features Wortmann et al. (2006, 2009) reported 4 unrelated girls with an encephalomyopathy associated with mildly and intermittently increased urinary 3-methylglutaconic aciduria. Three children were born of 3 unrelated sets of consanguineous Turkish parents, and the fourth child was born of unrelated Dutch parents. All presented in the neonatal period with severe infections and had episodes of lactic acidosis and hypoglycemia. Other features included failure to thrive, loss of motor skills, mental retardation, sensorineural deafness, and hypotonia with progressive spasticity. One patient had delayed development, 1 did not develop at all, and the other 2 showed developmental regression during early childhood. Brain MRI showed cerebral and cerebellar atrophy as well as bilateral hyperintensities in the basal ganglia reminiscent of Leigh syndrome. Mitochondrial complex I deficiency was found in muscle and fibroblasts. Two patients died at age 3 and 16 years, respectively. Genetic analysis did not find mutations in several candidate genes. Wortmann et al. (2012) reported 11 additional patients with MEGDEL, including 2 relatives of 1 of the Turkish patients reported by Wortmann et al. (2006). The phenotype was relatively homogeneous, with psychomotor retardation, spasticity or dystonia, sensorineural deafness, Leigh syndrome-like lesions on brain imaging, and brain atrophy. Laboratory studies showed 3-methylglutaconic aciduria, increased serum lactate, and defects in oxidative phosphorylation. Patient fibroblasts showed an increased phosphatidylglycerol 34:1 to phosphatidylglycerol 36:1 ratio as well as abnormal cardiolipin subspecies. There was abnormal intracellular accumulation of unesterified cholesterol, and some patients had low serum cholesterol. Sarig et al. (2013) reported 4 males, 2 each from 2 unrelated, highly consanguineous families, with features consistent with MEGDEL syndrome, including 3-methylglutaconic aciduria, sensorineural deafness, encephalopathy, and brain magnetic resonance imaging with findings consistent with Leigh-like syndrome. All 4 patients presented at age 24 to 48 hours with hypotonia and evidence of liver dysfunction, including symptomatic hypoglycemia, lactic acidosis, elevated serum transaminase levels, coagulopathy, hyperammonemia, and markedly elevated serum alpha-fetoprotein. During periods of acute infection in the first year of life, the patients experienced a few episodes of liver dysfunction, but these episodes did not recur later in life. Electron microscopy of a liver biopsy from 1 patient showed hepatocyte steatosis with mitochondrial ultrastructural changes, consistent with a mitochondrial oxidative phosphorylation disorder and abnormal lipid metabolism. The patients subsequently developed features of MEGDEL syndrome. The families were found to have 2 homozygous mutations in the SERAC1 gene that led to decreased or absent gene expression. Sarig et al. (2013) suggested that neonatal liver disease is a component of the phenotypic spectrum of MEGDEL syndrome and proposed that the disease be renamed MEGDHEL syndrome. Tort et al. (2013) reported a girl, born of unrelated parents, with MEGDEL. She presented on the fourth day of life with respiratory distress, refusal to feed, and jaundice, and was found to have metabolic acidosis with ketonuria, hyperammonemia, and elevated liver enzymes. During the first few years of life, she developed oral dyskinesia, hypotonia, truncal ataxia, episodic ketotic hypoglycemia, and psychomotor deterioration. Brain imaging showed features typical of Leigh syndrome. Urinary analysis showed 3-methylglutaconic and 3-methylglutaric aciduria. Sensorineural deafness and optic atrophy became apparent in her teenage years. At age 19 years, she was severely affected, with microcephaly, poor communication skills, inability to hold up her head, and multiple joint problems. Maas et al. (2017) reviewed the clinical features of 67 patients with MEGDHEL, including 39 previously unreported individuals. Most (64%) of the families were consanguineous. Most of the individuals were of European ancestry, although several dozen patients were from Africa, Asia, the Middle East, or Australia, indicating that MEGDHEL is a panethnic disorder. With the exception of 2 families with a milder phenotype and onset later in childhood, all affected individuals showed a strikingly homogeneous phenotype and time course. Sixteen patients died at a median age of 9 years, mostly due to respiratory infections. In the neonatal period, 48% of patients showed liver dysfunction and hypoglycemia, with variable abnormal liver enzymes, increased bilirubin, and disturbed coagulation in the more severe cases. Signs of hepatic dysfunction during the first year of life were common in this group, but resolved afterwards. Other presenting symptoms of the disorder included neonatal sepsis, hypotonia, and delayed motor development. The majority of patients lost previously acquired skills in the first year of life. Patients had early-onset progressive spasticity, dystonia, and oropharyngeal dyskinesia, and most (78%) never learned to walk. All had intellectual disability that varied from mild (12%) to severe (73%), and nearly all (93%) were completely dependent for activities of daily living. Additional features included epilepsy (35%), sensorineural hearing impairment (79%), absent speech (58%), impaired vision (42%), retinal pigmentary changes (6%), optic atrophy (25%), recurrent respiratory infections (42%), scoliosis (39%), and poor feeding (79%), often necessitating tube feeding. Less common features included transient renal tubular dysfunction (12%) and cardiac abnormalities (7%). Laboratory studies showed increased urinary 3-MGA and increased serum lactate, and brain imaging showed lesions in the basal ganglia, consistent with Leigh syndrome. Maas et al. (2017) concluded that MEGDHEL is best classified as a disorder of the biosynthesis of complex lipids with secondary mitochondrial dysfunction, although MEGDHEL syndrome displays typical findings and the progressive course of a mitochondrial disorder. However, mitochondrial dysfunction in tissue varies greatly and may be unremarkable. ### Clinical Variability Roeben et al. (2018) reported a large consanguineous Iraqi kindred in which 6 individuals from 2 different family branches had a relatively mild form of MEGDEL, which was characterized by the authors as 'juvenile-onset complicated hereditary spastic paraplegia' (SPG). The patients ranged in age from 10 to 27 years. All patients were noted to have mild cognitive delay with learning disability and reduced verbal fluency between 2 and 7 years of age. In family branch I, 3 sibs had slowly progressive lower limb spasticity starting in adolescence, but retained the ability to walk. These 3 patients also had febrile seizures. The youngest sib, examined at age 10, did not show spasticity, seizures, or any neurologic signs besides mild cognitive impairment. In family branch II, both affected sibs presented with juvenile-onset progressive spasticity, which progressed more quickly to tetraspasticity. These individuals also had additional abnormalities, including dystonia, progressive speech reduction, and dysphagia. One 33-year-old sib had a sensorimotor mixed axonal and demyelinating peripheral neuropathy. Brain imaging of 5 individuals showed T2-hyperintensities in the basal ganglia, consistent with Leigh-like syndrome, and urine analysis of 2 patients showed a 10-fold increase of 3-MGA. None of the patients had optic atrophy, deafness, or a history of liver failure; history from the neonatal period was not available. Whole-exome sequencing identified a homozygous intronic variant in the SERAC1 gene (614725.0007). The mutation was confirmed by Sanger sequencing and segregated with the disorder in the family. Patient cells showed aberrant splicing and absence of the full-length SERAC1 protein, as well as impaired prostaglandin remodeling activity compared to wildtype. However, the prostaglandin imbalances were milder than those observed in patients with the classic infantile-onset disease, suggesting a basis for the milder phenotype in the Iraqi family. The findings expanded the phenotype resulting from SERAC1 mutations, showing a clinical spectrum of severity. Molecular Genetics In 15 individuals from 13 families with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, Wortmann et al. (2012) identified 14 different homozygous or compound heterozygous mutations in the SERAC1 gene (see, e.g., 614725.0001-614725.0005). The first 2 mutations were identified by exome sequencing and confirmed by Sanger sequencing. Four of the patients had previously been reported by Wortmann et al. (2006). In a patient with MEGDEL, Tort et al. (2013) identified a homozygous truncating mutation in the SERAC1 gene (R68X; 614725.0006). The mutation was found by exome sequencing and segregated with the disorder in the family. Among 67 patients with MEGDHEL, including 39 previously unreported individuals, Maas et al. (2017) identified 41 SERAC1 sequence variants, including 20 novel variants. The mutations were located throughout the gene, with no hotspots, although there were several recurrent mutations, suggesting founder effects in certain populations. Most of the mutations were predicted to result in a loss of function, suggesting that missense mutations may be better tolerated. Population Genetics Maas et al. (2017) estimated that approximately 27 children with MEGDHEL will be born each year worldwide. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Microcephaly (1 patient) Ears \- Hearing loss, sensorineural Eyes \- Optic atrophy Mouth \- Oropharyngeal dyskinesia ABDOMEN Liver \- Hepatic dysfunction, neonatal period (48%) \- Liver failure, neonatal period (in some patients), reversible Gastrointestinal \- Feeding problems MUSCLE, SOFT TISSUES \- Hypotonia \- Degrading mitochondria NEUROLOGIC Central Nervous System \- Psychomotor retardation \- Psychomotor regression \- Mental retardation \- Spasticity \- Dystonia \- Extrapyramidal symptoms \- Inability to walk \- Poor or absent speech \- Seizures (less common) \- Leigh syndrome \- Lesions in the basal ganglia \- Brain atrophy \- Cerebellar atrophy METABOLIC FEATURES \- Lactic acidosis \- Hypoglycemia IMMUNOLOGY \- Recurrent infections \- Neonatal sepsis LABORATORY ABNORMALITIES \- Increased serum lactate \- Defects in mitochondrial oxidative phosphorylation \- 3-methylglutaconic aciduria \- Abnormal phospholipid profile \- Abnormal phosphatidylglycerol profile (increased 34-to-1 and decreased 36-to-1 ratio) \- Abnormal cardiolipin subspecies composition \- Intracellular accumulation of unesterified cholesterol \- Decreased serum cholesterol (in some) \- Elevated serum transaminase levels \- Hyperammonemia \- Elevated serum alpha-fetoprotein \- Coagulopathy (INR = 2.2 - 3.5) MISCELLANEOUS \- Onset in infancy or early childhood \- There are estimated to be 27 affected children born worldwide each year \- Variable severity \- One family with a milder disorder without deafness has been reported (last curated February 2018) MOLECULAR BASIS \- Caused by mutation in the serine active site-containing protein 1 (SERAC1, 614725.0001 ) ▲ 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	3-METHYLGLUTACONIC ACIDURIA WITH DEAFNESS, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME	c3553597	6,751	omim	https://www.omim.org/entry/614739	2019-09-22T15:54:22	{"doid": ["0110001"], "omim": ["614739"], "orphanet": ["352328"], "synonyms": ["3-methylglutaconic aciduria with deafness-encephalopathy-Leigh-like syndrome", "Alternative titles", "3-METHYLGLUTACONIC ACIDURIA, TYPE VI", "3-METHYLGLUTACONIC ACIDURIA WITH DYSTONIA-DEAFNESS, HEPATOPATHY, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME"], "genereviews": ["NBK195853"]}
A type of arthritis in which there is long term inflammation of the joints of the spine Ankylosing spondylitis Other namesBekhterev's disease, Bechterew's disease, morbus Bechterew, Bekhterev–Strümpell–Marie disease, Marie's disease, Marie–Strümpell arthritis, Pierre–Marie's disease[1] A 6th-century skeleton showing fused vertebrae, a sign of severe ankylosing spondylitis SpecialtyRheumatology SymptomsBack pain, joint stiffness[2] Usual onsetYoung adulthood[2] DurationLong term[2] CausesUnknown[2] Diagnostic methodSymptom based, medical imaging, blood tests[2] TreatmentMedication, exercise, physical therapy MedicationNSAIDs, steroids, DMARDs,[2] TNF Inhibitor Frequency0.1 to 0.8%[3] Ankylosing spondylitis (AS) is a type of arthritis in which there is a long-term inflammation of the joints of the spine.[2] Typically the joints where the spine joins the pelvis are also affected.[2] Occasionally other joints such as the shoulders or hips are involved.[2] Eye and bowel problems may also occur.[2] Back pain is a characteristic symptom of AS, and it often comes and goes.[2] Stiffness of the affected joints generally worsens over time.[2][4] Although the cause of ankylosing spondylitis is unknown, it is believed to involve a combination of genetic and environmental factors.[2] More than 85% of those affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen.[5] The underlying mechanism is believed to be autoimmune or autoinflammatory.[6] Diagnosis is typically based on the symptoms with support from medical imaging and blood tests.[2] AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.[2] It is also within a broader category known as axial spondyloarthritis.[7] There is no cure for ankylosing spondylitis.[2] Treatments may improve symptoms and prevent worsening.[2] This may include medication, exercise, physical therapy, surgery in rare cases.[2] Medications used include NSAIDs, steroids, DMARDs such as sulfasalazine, and biologic agents such as TNF inhibitors.[2] Between 0.1% and 0.8% of people are affected.[3] Onset is typically in young adults.[2] Males and females are equally affected. It used to be thought that three times as many men as women had the disease. This was based on a diagnosis of the disease using x-ray. Men are more likely than women to experience changes to the bones and fusion, and thus they were being picked up using x-ray. Over time MRI’s were developed which could identify inflammation. Women are more likely than men to experience inflammation rather than fusion. source The condition was first fully described in the late 1600s by Bernard Connor, but skeletons with ankylosing spondylitis are found in Egyptian mummies.[8] The word is from Greek ankylos meaning crooked, curved or rounded, spondylos meaning vertebra, and -itis meaning inflammation.[2] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Imaging * 3.1.1 X-rays * 3.2 Blood parameters * 3.3 Genetic testing * 3.4 BASDAI * 3.5 Children * 3.6 Schober's test * 4 Treatment * 4.1 Medication * 4.2 Surgery * 4.3 Physical therapy * 5 Prognosis * 5.1 Mortality * 5.2 Gait * 6 Epidemiology * 7 Research * 8 History * 9 References * 10 External links ## Signs and symptoms[edit] Illustration depicting ankylosing spondylitis The signs and symptoms of ankylosing spondylitis often appear gradually, with peak onset being between 20 and 30 years of age.[9] Initial symptoms are usually a chronic dull pain in the lower back or gluteal region combined with stiffness of the lower back.[10] Individuals often experience pain and stiffness that awakens them in the early morning hours.[9] As the disease progresses, loss of spinal mobility and chest expansion, with a limitation of anterior flexion, lateral flexion, and extension of the lumbar spine, are seen. Systemic features are common, with weight loss, fever, or fatigue often present.[9] Pain is often severe at rest but may improve with physical activity, but inflammation and pain to varying degrees may recur regardless of rest and movement. AS can occur in any part of the spine or the entire spine, often with pain referred to one or the other buttock or the back of the thigh from the sacroiliac joint. Arthritis in the hips and shoulders may also occur. When the condition presents before the age of 18, it is more likely to cause pain and swelling of large lower limb joints, such as the knees.[11] In prepubescent cases, pain and swelling may also manifest in the ankles and feet where heel pain and enthesopathy commonly develop.[11] Less commonly ectasia of the sacral nerve root sheaths may occur.[citation needed] About 30% of people with AS will also experience anterior uveitis, causing eye pain, redness, and blurred vision. This is thought to be due to the association that both AS and uveitis have with the inheritance of the HLA-B27 antigen.[12] Cardiovascular involvement may include inflammation of the aorta, aortic valve insufficiency or disturbances of the heart's electrical conduction system. Lung involvement is characterized by progressive fibrosis of the upper portion of the lung.[citation needed] ## Pathophysiology[edit] The ankylosis process Ankylosing spondylitis (AS) is a systemic rheumatic disease, meaning it affects the entire body. 1–2% of individuals with the HLA-B27 genotype develop the disease.[13] Approximately 85% of people with AS express the HLA-B27 genotype, meaning there is a strong genetic association. Tumor necrosis factor-alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. Anti-neutrophil cytoplasmic antibodies (ANCAs) are associated with AS, but do not correlate with disease severity.[citation needed] Single nucleotide polymorphism (SNP) A/G variant rs10440635[14] close to the PTGER4 gene on human chromosome 5 has been associated with an increased number of cases of ankylosing spondylitis in a population recruited from the United Kingdom, Australia, and Canada. The PTGER4 gene codes for the prostaglandin EP4 receptor (EP4), one of four receptors for prostaglandin E2. Activation of EP4 promotes bone remodeling and deposition (see EP4, bone) and EP4 is highly expressed at vertebral column sites involved in ankylosing spondylitis. These findings suggest that excessive EP4 activation contributes to pathological bone remodeling and deposition in ankylosing spondylitis and that the A/G variant rs10440635a of PTGER4 predisposes to this disease, possibly by influencing EP4's production or expression pattern.[15][16] The association of AS with HLA-B27 suggests the condition involves CD8 T cells, which interact with HLA-B.[citation needed] This interaction is not proven to involve a self-antigen, and at least in the related reactive arthritis, which follows infections, the antigens involved are likely to be derived from intracellular microorganisms.[citation needed] There is, however, a possibility that CD4+ T lymphocytes are involved in an aberrant way, since HLA-B27 appears to have a number of unusual properties, including possibly an ability to interact with T cell receptors in association with CD4 (usually CD8+ cytotoxic T cell with HLAB antigen as it is a MHC class 1 antigen). "Bamboo spine" develops when the outer fibers of the fibrous ring (anulus fibrosus disci intervertebralis) of the intervertebral discs ossify, which results in the formation of marginal syndesmophytes between adjoining vertebrae. ## Diagnosis[edit] 34-year-old male with AS. Inflammatory lesions of the anterior chest wall are shown (curved arrows). Inflammatory changes are seen in the lower thoracic spine and L1 (arrows). Ankylosing spondylitis is a member of the more broadly defined disease axial spondyloarthritis.[17] Axial spondyloarthritis can be divided into (1) radiographic axial spondyloarthritis (which is a synonym for ankylosing spondylitis) and (2) non-radiographic axial spondyloarthritis (which include less severe forms and early stages of ankylosing spondylitis) [17] While ankylosing spondylitis can be diagnosed through the description of radiological changes in the sacroiliac joints and spine, there are currently no direct tests (blood or imaging) to unambiguously diagnose early forms of ankylosing spondylitis (non-radiographic axial spondyloarthritis). Diagnosis of non-radiologic axial spondyloarthritis is therefore more difficult and is based on the presence of several typical disease features.[17][18] These diagnostic criteria include: * Inflammatory back pain: Chronic, inflammatory back pain is defined when at least four out of five of the following parameters are present: (1) Age of onset below 40 years old, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon getting up) * Past history of inflammation in the joints, heels, or tendon-bone attachments * Family history for axial spondyloarthritis or other associated rheumatic/autoimmune conditions * Positive for the biomarker HLA-B27 * Good response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) * Signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate) * Manifestation of psoriasis, inflammatory bowel disease, or inflammation of the eye (uveitis) If these criteria still do not give a compelling diagnosis magnetic resonance imaging (MRI) may be useful.[17][18] MRI can show inflammation of the sacroiliac joint. ### Imaging[edit] #### X-rays[edit] The earliest changes demonstrable by plain x–ray shows erosions and sclerosis in sacroiliac joints. Progression of the erosions leads to widening of the joint space and bony sclerosis. X-ray spine can reveal squaring of vertebrae with bony spur formation called syndesmophyte. This causes the bamboo spine appearance. A drawback of X-ray diagnosis is the signs and symptoms of AS have usually been established as long as 7–10 years prior to X-ray-evident changes occurring on a plain film X-ray, which means a delay of as long as 10 years before adequate therapies can be introduced.[19] Options for earlier diagnosis are tomography and MRI of the sacroiliac joints, but the reliability of these tests is still unclear. * Lateral X-ray of the mid back in ankylosing spondylitis * Lateral X-ray of the neck in ankylosing spondylitisImaging * X-ray showing bamboo spine in a person with ankylosing spondylitis * CT scan showing bamboo spine in ankylosing spondylitis * T1-weighted MRI with fat suppression after administration of gadolinium contrast showing sacroiliitis in a person with ankylosing spondylitis ### Blood parameters[edit] During acute inflammatory periods, people with AS may show an increase in the blood concentration of CRP and an increase in the ESR, but there are many with AS whose CRP and ESR rates do not increase, so normal CRP and ESR results do not always correspond with the amount of inflammation that is actually present. In other words, some people with AS have normal levels of CRP and ESR, despite experiencing a significant amount of inflammation in their bodies.[citation needed] ### Genetic testing[edit] Variations of the HLA-B gene increase the risk of developing ankylosing spondylitis, although it is not a diagnostic test. Those with the HLA-B27 variant are at a higher risk than the general population of developing the disorder. HLA-B27, demonstrated in a blood test, can occasionally help with diagnosis, but in itself is not diagnostic of AS in a person with back pain. Over 85% of people that have been diagnosed with AS are HLA-B27 positive, although this ratio varies from population to population (about 50% of African Americans with AS possess HLA-B27 in contrast to the figure of 80% among those with AS who are of Mediterranean descent).[citation needed] ### BASDAI[edit] The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), developed in Bath (UK), is an index designed to detect the inflammatory burden of active disease. The BASDAI can help to establish a diagnosis of AS in the presence of other factors such as HLA-B27 positivity, persistent buttock pain which resolves with exercise, and X-ray or MRI-evident involvement of the sacroiliac joints.[20] It can be easily calculated and accurately assesses the need for additional therapy; a person with AS with a score of four out of a possible 10 points while on adequate NSAID therapy is usually considered a good candidate for biologic therapy. The Bath Ankylosing Spondylitis Functional Index (BASFI) is a functional index which can accurately assess functional impairment due to the disease, as well as improvements following therapy.[21] The BASFI is not usually used as a diagnostic tool, but rather as a tool to establish a current baseline and subsequent response to therapy. ### Children[edit] Juvenile ankylosing spondylitis (JAS) is a rare form of the disease which differs from the more common adult form.[11] Enthesophathy and arthritis of large joints of the lower extremities is more common than the characteristic early-morning back pain seen in adult AS.[11] Ankylosing tarsitis of the ankle is a common feature, as is the more classical findings of seronegative ANA and RF as well as presence of the HLA-B27 allele.[11] Primary engagement of the appendicular joints may explain delayed diagnosis, however other common symptoms of AS such as uveitis, diarrhea, pulmonary disease and heart valve disease may lead suspicion away from other juvenile spondyloarthropathies.[11] ### Schober's test[edit] The Schober's test is a useful clinical measure of flexion of the lumbar spine performed during the physical examination.[22] ## Treatment[edit] There is no cure for AS, although treatments and medications can reduce symptoms and pain. ### Medication[edit] The major types of medications used to treat ankylosing spondylitis are pain-relievers and drugs aimed at stopping or slowing the progression of the disease. All of these have potentially serious side effects. Pain-relieving drugs come in two major classes: * The mainstay of therapy in all seronegative spondyloarthropathies are anti-inflammatory drugs, which include NSAIDs such as ibuprofen, phenylbutazone, diclofenac, indomethacin, naproxen and COX-2 inhibitors, which reduce inflammation and pain. 2012 research showed that those with AS and elevated levels of acute phase reactants seem to benefit most from continuous treatment with NSAIDs.[23] Medications used to treat the progression of the disease include the following: * Disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine can be used in people with peripheral arthritis. For axial involvement, evidence does not support sulfasalazine.[24] Other DMARDS, such as methotrexate, did not have enough evidence to prove their effect. Generally, systemic corticosteroids were not used due to lack of evidence. Local injection with corticosteroid can be used for certain people with peripheral arthritis.[25][26] * Tumor necrosis factor-alpha (TNFα) blockers (antagonists), such as the biologics etanercept, infliximab, golimumab and adalimumab, have shown good short-term effectiveness in the form of profound and sustained reduction in all clinical and laboratory measures of disease activity.[27] Trials are ongoing to determine their long-term effectiveness and safety.[28] The major drawback is the cost. An alternative may be the newer, orally-administered non-biologic apremilast, which inhibits TNF-α secretion, but a recent study did not find the drug useful for ankylosing spondylitis.[29] * Anti-interleukin-6 inhibitors such as tocilizumab, currently approved for the treatment of rheumatoid arthritis,[30] and rituximab, a monoclonal antibody against CD20, are also undergoing trials.[31] * Interleukin-17A inhibitor secukinumab is an option for the treatment of active ankylosing spondylitis that has responded inadequately to (TNFα) blockers.[32] ### Surgery[edit] In severe cases of AS, surgery can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered very risky. However there has been one successful operation in China on a 46-year-old man. [33] In addition, AS can have some manifestations which make anesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anesthesia may be difficult owing to calcification of ligaments, and a small number of people have aortic insufficiency. The stiffness of the thoracic ribs results in ventilation being mainly diaphragm-driven, so there may also be a decrease in pulmonary function. ### Physical therapy[edit] Though physical therapy remedies have been scarcely documented, some therapeutic exercises are used to help manage lower back, neck, knee, and shoulder pain. Some therapeutic exercises include:[34][35] * Low intensity aerobic exercise * Transcutaneous electrical nerve stimulation (TENS) * Thermotherapy * Proprioceptive neuromuscular facilitation (PNF) * Exercise programs, either at home or supervised * Hydrotherapy * Group exercises eg Pilates Moderate-to-high impact exercises like jogging are generally not recommended or recommended with restrictions due to the jarring of affected vertebrae that can worsen pain and stiffness in some with AS. ## Prognosis[edit] Fracture of the T5 and C7 vertebra due to trauma in a person with ankylosing spondylitis as seen on a CT scan Prognosis is related to disease severity.[9] AS can range from mild to progressively debilitating and from medically controlled to refractory. Some cases may have times of active inflammation followed by times of remission resulting in minimal disability while others never have times of remission and have acute inflammation and pain, leading to significant disability.[9] As the disease progresses, it can cause the vertebrae and the lumbosacral joint to ossify, resulting in the fusion of the spine.[36] This places the spine in a vulnerable state because it becomes one bone, which causes it to lose its range of motion as well as putting it at risk for spinal fractures. This not only limits mobility but reduces the affected person's quality of life. Complete fusion of the spine can lead to a reduced range of motion and increased pain, as well as total joint destruction which could lead to a joint replacement.[37] Osteoporosis is common in ankylosing spondylitis, both from chronic systemic inflammation and decreased mobility resulting from AS. Over a long-term period, osteopenia or osteoporosis of the AP spine may occur, causing eventual compression fractures and a back "hump".[38] Hyperkyphosis from ankylosing spondylitis can also lead to impairment in mobility and balance, as well as impaired peripheral vision, which increases the risk of falls which can cause fracture of already-fragile vertebrae.[38] Typical signs of progressed AS are the visible formation of syndesmophytes on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. In compression fractures of the vertebrae, paresthesia is a complication due to the inflammation of the tissue surrounding nerves. Organs commonly affected by AS, other than the axial spine and other joints, are the heart, lungs, eyes, colon, and kidneys. Other complications are aortic regurgitation, Achilles tendinitis, AV node block, and amyloidosis.[39] Owing to lung fibrosis, chest X-rays may show apical fibrosis, while pulmonary function testing may reveal a restrictive lung defect. Very rare complications involve neurologic conditions such as the cauda equina syndrome.[39][40] ### Mortality[edit] Mortality is increased in people with AS and circulatory disease is the most frequent cause of death.[41] People with AS have an increased risk of 60% for cerebrovascular mortality, and an overall increased risk of 50% for vascular mortality.[42] About one third of those with ankylosing spondylitis have severe disease, which reduces life expectancy.[43] As increased mortality in ankylosing spondylitis is related to disease severity, factors negatively affecting outcomes include:[41][44] * Male sex [45] * Plus 3 of the following in the first 2 years of disease: * Erythrocyte sedimentation rate (ESR) >30 mm/h * Unresponsive to NSAIDs * Limitation of lumbar spine range of motion * Sausage-like fingers or toes * Oligoarthritis * Onset <16 years old ### Gait[edit] The hunched position that often results from complete spinal fusion can have an effect on a person's gait. Increased spinal kyphosis will lead to a forward and downward shift in center of mass (COM). This shift in COM has been shown to be compensated by increased knee flexion and ankle dorsiflexion. The gait of someone with ankylosing spondylitis often has a cautious pattern because they have decreased ability to absorb shock, and they cannot see the horizon.[46] ## Epidemiology[edit] Between 0.1% and 0.8% of people are affected.[3] The disease is most common in Northern European countries, and seen least in people of Afro-Caribbean descent.[9] Although the ratio of male to female disease is reportedly 3:1,[9] many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder cases of the disease. The majority of people with AS, including 95 percent of people of European descent with the disease, express the HLA-B27 antigen[47] and high levels of immunoglobulin A (IgA) in the blood.[48] ## Research[edit] In 2007, a collaborative effort by an international team of researchers in the United Kingdom, Australia and the United States led to the discovery of two genes that also contribute to the cause of AS: ARTS-1 and IL23R. The findings were published in the November 2007 edition of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases.[49] Together with HLA-B27, these two genes account for roughly 70 percent of the overall number of cases of the disease. ## History[edit] Drawing from 1857 of a severe case of AS See also: List of people with ankylosing spondylitis Ankylosing spondylitis has a long history, having been distinguished from rheumatoid arthritis by Galen as early as the 2nd century AD.[50] Skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was thought to be found in the skeletal remains of a 5000-year-old Egyptian mummy with evidence of bamboo spine.[51] However, a subsequent report found that this was not the case.[52] The anatomist and surgeon Realdo Colombo described what could have been the disease in 1559,[53] and the first account of pathologic changes to the skeleton possibly associated with AS was published in 1691 by Bernard Connor.[54] In 1818, Benjamin Brodie became the first physician to document a person believed to have active AS who also had accompanying iritis.[55] In 1858, David Tucker published a small booklet which clearly described the case of Leonard Trask, who suffered from severe spinal deformity subsequent to AS.[56] In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported: > It was not until he [Trask] had exercised for some time that he could perform any labor ... [H]is neck and back have continued to curve drawing his head downward on his breast. This account became the first documented case of AS in the United States, owing to its indisputable description of inflammatory disease characteristics of AS and the hallmark of deforming injury in AS. In the late nineteenth century, the neurophysiologist Vladimir Bekhterev of Russia in 1893,[57] Adolph Strümpell of Germany in 1897,[58] and Pierre Marie of France in 1898[59] were the first to give adequate descriptions which permitted an accurate diagnosis of AS prior to severe spinal deformity. For this reason, AS is also known as Bekhterev disease, Bechterew's disease or Marie–Strümpell disease. ## References[edit] 1. ^ Matteson EL, Woywodt A (November 2006). "Eponymophilia in rheumatology". Rheumatology. 45 (11): 1328–30. doi:10.1093/rheumatology/kel259. PMID 16920748. 2. ^ a b c d e f g h i j k l m n o p q r s t u "Questions and Answers about Ankylosing Spondylitis". NIAMS. June 2016. Archived from the original on 28 September 2016. Retrieved 28 September 2016. 3. ^ a b c Khan MA (2009). Ankylosing Spondylitis. Oxford University Press. p. 15. ISBN 9780195368079. Archived from the original on 8 September 2017. 4. ^ "Ankylosing spondylitis". GARD. 9 February 2015. Archived from the original on 2 October 2016. Retrieved 28 September 2016. 5. ^ Sheehan NJ (January 2004). "The ramifications of HLA-B27". Journal of the Royal Society of Medicine. 97 (1): 10–4. doi:10.1258/jrsm.97.1.10. PMC 1079257. PMID 14702356. 6. ^ Smith JA (January 2015). "Update on ankylosing spondylitis: current concepts in pathogenesis". Current Allergy and Asthma Reports. 15 (1): 489. doi:10.1007/s11882-014-0489-6. PMID 25447326. S2CID 24623808. 7. ^ Deodhar A, Reveille JD, van den Bosch F, Braun J, Burgos-Vargas R, Caplan L, et al. (October 2014). "The concept of axial spondyloarthritis: joint statement of the spondyloarthritis research and treatment network and the Assessment of SpondyloArthritis international Society in response to the US Food and Drug Administration's comments and concerns". Arthritis & Rheumatology. 66 (10): 2649–56. doi:10.1002/art.38776. PMID 25154344. S2CID 38228595. 8. ^ Boos N, Aebi M (2008). Spinal Disorders: Fundamentals of Diagnosis and Treatment. Springer Science & Business Media. p. 25. ISBN 9783540690917. Archived from the original on 8 September 2017. 9. ^ a b c d e f g "Ankylosing Spondylitis -Professional reference for Doctors - Patient UK". Patient UK. Archived from the original on 7 April 2014. Retrieved 26 May 2014. 10. ^ Longo DL, Fauci AS, Harrison TR, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (2012). Harrison's Principles of Internal Medicine. Vol. 1 (18th ed.). McGraw-Hill. ISBN 978-0-07-163244-7. 11. ^ a b c d e f Adrovic A, Barut K, Sahin S, Kasapcopur O (August 2016). "Juvenile Spondyloarthropathies". Current Rheumatology Reports. 18 (8): 55. doi:10.1007/s11926-016-0603-y. PMID 27402112. S2CID 26058238. 12. ^ Cantini F, Nannini C, Cassarà E, Kaloudi O, Niccoli L (November 2015). "Uveitis in Spondyloarthritis: An Overview". The Journal of Rheumatology. Supplement. 93: 27–9. doi:10.3899/jrheum.150630. PMID 26523051. S2CID 24715271. 13. ^ "Ankylosing Spondylitis – Professional reference for Doctors – Patient UK". Patient UK. Archived from the original on 24 December 2013. Retrieved 22 December 2013. 14. ^ "Reference SNP (refSNP) Cluster Report: Rs10440635". Archived from the original on 18 February 2017. Retrieved 14 February 2017. 15. ^ Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, et al. (July 2011). "Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility". Nature Genetics. 43 (8): 761–7. doi:10.1038/ng.873. PMC 3640413. PMID 21743469. 16. ^ Haroon N (June 2015). "Ankylosis in ankylosing spondylitis: current concepts". Clinical Rheumatology. 34 (6): 1003–7. doi:10.1007/s10067-015-2956-4. PMID 25935456. S2CID 25930196. 17. ^ a b c d Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. (June 2009). "The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection". Annals of the Rheumatic Diseases. 68 (6): 777–83. doi:10.1136/ard.2009.108233. PMID 19297344. 18. ^ a b Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D (August 2015). "Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis". Annals of the Rheumatic Diseases. 74 (8): 1483–7. doi:10.1136/annrheumdis-2014-207151. PMID 25990288. S2CID 42585224. 19. ^ Ostergaard M, Lambert RG (August 2012). "Imaging in ankylosing spondylitis". Therapeutic Advances in Musculoskeletal Disease. 4 (4): 301–11. doi:10.1177/1759720X11436240. PMC 3403247. PMID 22859929. 20. ^ Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (December 1994). "A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index". The Journal of Rheumatology. 21 (12): 2286–91. PMID 7699630. 21. ^ Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, Jenkinson T (December 1994). "A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index". The Journal of Rheumatology. 21 (12): 2281–5. PMID 7699629. 22. ^ Thomas E, Silman AJ, Papageorgiou AC, Macfarlane GJ, Croft PR (February 1998). "Association between measures of spinal mobility and low back pain. An analysis of new attenders in primary care". Spine. 23 (3): 343–7. doi:10.1097/00007632-199802010-00011. PMID 9507623. S2CID 41982757. 23. ^ Kroon F, Landewé R, Dougados M, van der Heijde D (October 2012). "Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis". Annals of the Rheumatic Diseases. 71 (10): 1623–9. doi:10.1136/annrheumdis-2012-201370. PMID 22532639. 24. ^ Chen J, Lin S, Liu C (November 2014). "Sulfasalazine for ankylosing spondylitis". The Cochrane Database of Systematic Reviews. 11 (11): CD004800. doi:10.1002/14651858.CD004800.pub3. PMID 25427435. 25. ^ Chen J, Veras MM, Liu C, Lin J (February 2013). "Methotrexate for ankylosing spondylitis". The Cochrane Database of Systematic Reviews. 2 (2): CD004524. doi:10.1002/14651858.CD004524.pub4. PMID 23450553. 26. ^ Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. (June 2011). "2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis". Annals of the Rheumatic Diseases. 70 (6): 896–904. doi:10.1136/ard.2011.151027. PMC 3086052. PMID 21540199. 27. ^ Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, et al. (April 2015). "TNF-alpha inhibitors for ankylosing spondylitis". The Cochrane Database of Systematic Reviews. 4 (4): CD005468. doi:10.1002/14651858.CD005468.pub2. PMID 25887212. 28. ^ Braun J, Sieper J (April 2007). "Ankylosing spondylitis". Lancet. 369 (9570): 1379–1390. doi:10.1016/S0140-6736(07)60635-7. PMID 17448825. 29. ^ Cush J. "POSTURE Study: Apremilast Fails in Ankylosing Spondylitis". Rheum Now. Archived from the original on 10 April 2017. Retrieved 10 April 2017. 30. ^ Henes JC, Horger M, Guenaydin I, Kanz L, Koetter I (December 2010). "Mixed response to tocilizumab for ankylosing spondylitis". Annals of the Rheumatic Diseases. 69 (12): 2217–8. doi:10.1136/ard.2009.126706. PMID 20525837. S2CID 31849478. 31. ^ Rodríguez-Escalera C, Fernández-Nebro A (November 2008). "The use of rituximab to treat a patient with ankylosing spondylitis and hepatitis B". Rheumatology. 47 (11): 1732–3. doi:10.1093/rheumatology/ken362. PMID 18786966. 32. ^ "Secukinumab for active Ankylosing Spondylitis". NICE. Archived from the original on 2 February 2017. Retrieved 26 January 2017. 33. ^ https://www.sznews.com/news/content/2019-12/15/content_22704729_0.htm 34. ^ "Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions: overview and methodology". Physical Therapy. 81 (10): 1629–40. October 2001. PMID 11589641. 35. ^ Dagfinrud H, Kvien TK, Hagen KB (January 2008). "Physiotherapy interventions for ankylosing spondylitis". The Cochrane Database of Systematic Reviews (1): CD002822. doi:10.1002/14651858.CD002822.pub3. PMID 18254008. 36. ^ Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A (December 2002). "Ankylosing spondylitis: an overview". Annals of the Rheumatic Diseases. 61 Suppl 3: iii8-18. doi:10.1136/ard.61.suppl_3.iii8. PMC 1766729. PMID 12381506. 37. ^ Bond D (December 2013). "Ankylosing spondylitis: diagnosis and management". Nursing Standard. 28 (16–18): 52–9, quiz 60. doi:10.7748/ns2013.12.28.16.52.e7807. PMID 24345154. 38. ^ a b Briot K, Roux C (2015). "Inflammation, bone loss and fracture risk in spondyloarthritis". RMD Open. 1 (1): e000052. doi:10.1136/rmdopen-2015-000052. PMC 4613172. PMID 26509065. 39. ^ a b Alpert JS (2006). The AHA Clinical Cardiac Consult. Lippincott Williams & Wilkins. ISBN 978-0-7817-6490-2. 40. ^ Ahn NU, Ahn UM, Nallamshetty L, Springer BD, Buchowski JM, Funches L, et al. (October 2001). "Cauda equina syndrome in ankylosing spondylitis (the CES-AS syndrome): meta-analysis of outcomes after medical and surgical treatments". Journal of Spinal Disorders. 14 (5): 427–33. doi:10.1097/00002517-200110000-00009. PMID 11586143. 41. ^ a b Bakland G, Gran JT, Nossent JC (November 2011). "Increased mortality in ankylosing spondylitis is related to disease activity". Annals of the Rheumatic Diseases. 70 (11): 1921–5. doi:10.1136/ard.2011.151191. PMID 21784726. S2CID 39397817. 42. ^ "Ankylosing Spondylitis Linked to Cardiovascular Mortality". Medscape. Archived from the original on 14 September 2015. Retrieved 7 October 2015. 43. ^ Braun J, Pincus T (2002). "Mortality, course of disease and prognosis of patients with ankylosing spondylitis". Clinical and Experimental Rheumatology. 20 (6 Suppl 28): S16-22. PMID 12463441. Archived from the original on 1 November 2016. 44. ^ Radford EP, Doll R, Smith PG (September 1977). "Mortality among patients with ankylosing spondylitis not given X-ray therapy". The New England Journal of Medicine. 297 (11): 572–6. doi:10.1056/NEJM197709152971103. PMID 887115. 45. ^ Lehtinen K (March 1993). "Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis". Annals of the Rheumatic Diseases. 52 (3): 174–6. doi:10.1136/ard.52.3.174. PMC 1005012. PMID 8484668. 46. ^ Del Din S, Carraro E, Sawacha Z, Guiotto A, Bonaldo L, Masiero S, Cobelli C (July 2011). "Impaired gait in ankylosing spondylitis". Medical & Biological Engineering & Computing. 49 (7): 801–9. doi:10.1007/s11517-010-0731-x. PMID 21229328. S2CID 17921823. 47. ^ Goldman L (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 607. ISBN 978-1-4377-2788-3. 48. ^ Veys EM, van Leare M (November 1973). "Serum IgG, IgM, and IgA levels in ankylosing spondylitis". Annals of the Rheumatic Diseases. 32 (6): 493–6. doi:10.1136/ard.32.6.493. PMC 1006157. PMID 4202498. 49. ^ Brionez TF, Reveille JD (July 2008). "The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis". Current Opinion in Rheumatology. 20 (4): 384–91. doi:10.1097/BOR.0b013e32830460fe. PMID 18525349. S2CID 205485848. 50. ^ Dieppe P (January 1988). "Did Galen describe rheumatoid arthritis?". Annals of the Rheumatic Diseases. 47 (1): 84–5. doi:10.1136/ard.47.1.84-b. PMC 1003452. PMID 3278697. 51. ^ Calin A (April 1985). "Ankylosing spondylitis". Clinics in Rheumatic Diseases. 11 (1): 41–60. PMID 3158467. 52. ^ Saleem SN, Hawass Z (December 2014). "Ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis in royal Egyptian mummies of 18th -20th Dynasties? CT and archaeology studies". Arthritis & Rheumatology. 66 (12): 3311–6. doi:10.1002/art.38864. PMID 25329920. S2CID 42296180. 53. ^ Benoist M (April 1995). "Pierre Marie. Pioneer investigator in ankylosing spondylitis". Spine. 20 (7): 849–52. doi:10.1097/00007632-199504000-00022. PMID 7701402. 54. ^ Blumberg BS (December 1958). "Bernard Connor's description of the pathology of ankylosing spondylitis". Arthritis and Rheumatism. 1 (6): 553–63. doi:10.1002/art.1780010609. PMID 13607268. 55. ^ Leden I (1994). "Did Bechterew describe the disease which is named after him? A question raised due to the centennial of his primary report". Scandinavian Journal of Rheumatology. 23 (1): 42–5. doi:10.3109/03009749409102134. PMID 8108667. 56. ^ "Life and sufferings of Leonard Trask" (PDF). Ankylosing Spondylitis Information Matrix. Archived (PDF) from the original on 8 July 2011. 57. ^ Bechterew W (1893). "Steifigkeit der Wirbelsaule und ihre Verkrummung als besondere Erkrankungsform". Neurol Centralbl. 12: 426–434. 58. ^ Strumpell A (1897). "Bemerkung uber die chronische ankylosirende Entzundung der Wirbelsaule und der Huftgelenke". Dtsch Z Nervenheilkd. 11 (3–4): 338–342. doi:10.1007/BF01674127. S2CID 34700673. 59. ^ Marie P (1898). "Sur la spondylose rhizomelique". Rev Med. 18: 285–315. ## External links[edit] Classification D * ICD-10: M08.1, M45 * ICD-9-CM: 720.0 * OMIM: 106300 * MeSH: D013167 * DiseasesDB: 728 External resources * MedlinePlus: 000420 * eMedicine: radio/41 * Patient UK: Ankylosing spondylitis * Ankylosing spondylitis at Curlie * Questions and Answers about Ankylosing Spondylitis \- US National Institute of Arthritis and Musculoskeletal and Skin Diseases * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte * v * t * e Spinal disease Deforming Spinal curvature * Kyphosis * Lordosis * Scoliosis Other * Scheuermann's disease * Torticollis Spondylopathy inflammatory * Spondylitis * Ankylosing spondylitis * Sacroiliitis * Discitis * Spondylodiscitis * Pott disease non inflammatory * Spondylosis * Spondylolysis * Spondylolisthesis * Retrolisthesis * Spinal stenosis * Facet syndrome Back pain * Neck pain * Upper back pain * Low back pain * Coccydynia * Sciatica * Radiculopathy Intervertebral disc disorder * Schmorl's nodes * Degenerative disc disease * Spinal disc herniation * Facet joint arthrosis * v * t * e 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 * 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template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Ankylosing spondylitis	c0038013	6,752	wikipedia	https://en.wikipedia.org/wiki/Ankylosing_spondylitis	2021-01-18T19:02:07	{"gard": ["9518"], "mesh": ["D013167"], "umls": ["C0038013"], "orphanet": ["825"], "wikidata": ["Q52849"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Intraretinal microvascular abnormalities" – news · newspapers · books · scholar · JSTOR (February 2018) (Learn how and when to remove this template message) Intraretinal microvascular abnormalities Human eye cross-sectional/ retina view SpecialtyOphthalmology Intraretinal microvascular abnormalities (IRMA) are abnormalities of the blood vessels that supply the retina of the eye, a sign of diabetic retinopathy. IRMA can be difficult to distinguish from and is likely a precursor to retinal neovascularization. One way to distinguish IRMA from retinal neovascularization is to perform fluorescein angiography. Since IRMA blood vessels are patent, unlike neovascular vessels, they do not leak, and therefore exhibit hyperfluorescence on fluorescein angiography. IRMA is deeper in the retina than neovascularization, has blurrier edges, is more of a burgundy than a red, does not appear on the optic disc, and is usually seen after a shorter period of poorly controlled diabetes than neovascularization. ## References[edit] ## External links[edit] Classification D * ICD-9-CM: 362.17 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Intraretinal microvascular abnormalities	c0154836	6,753	wikipedia	https://en.wikipedia.org/wiki/Intraretinal_microvascular_abnormalities	2021-01-18T18:36:13	{"umls": ["C0154836"], "icd-9": ["362.17"], "orphanet": ["71213"], "wikidata": ["Q6058536"]}
A number sign (#) is used with this entry because glycogen storage disease X (GSD10) is caused by homozygous or compound heterozygous mutation in the PGAM2 gene (612931), which encodes muscle phosphoglycerate mutase, on chromosome 7p13. Clinical Features DiMauro et al. (1981) studied a 52-year-old who had onset in adolescence of exercise-induced cramps, occasional myoglobinuria, and intolerance for strenuous exercise. However, he led a relatively normal life including service in the army. Physical examination showed gouty tophi and signs of severe coronary arteriosclerosis. Muscle phosphoglycerate mutase activity was 5 to 7% of the lowest control value. Bresolin et al. (1983) reported a 17-year-old girl with recurrent myoglobinuria after intense exercise. Muscle biopsy showed increased PAS stain with twice normal glycogen concentration. PGAM2 activity was 6% of normal controls. Intermediate PGAM activities, 39% and 50%, respectively, were found in muscle biopsies from the patient's asymptomatic parents, indicating autosomal recessive inheritance. Additional patients were reported by Kissel et al. (1985) and Vita et al. (1990). Tsujino et al. (1993) reported a 17-year-old girl with GSD10 who complained of exercise intolerance since age 8 years; intense exertion caused pain and cramps in the exercising muscles. During episodes of myalgia, increases of serum creatine kinase were documented but there was no pigmenturia. A brother complained of similar exercise intolerance with cramps and had persistently elevated serum creatine kinase. Tsujino et al. (1993) also reported a 30-year-old African American man with GSD10 who was admitted to the hospital because of pigmenturia that appeared a few hours after he ran a race. Serum creatine kinase was greatly elevated and myoglobin was demonstrated in the urine. He developed renal failure that required hemodialysis. He had had 2 similar episodes, at ages 21 and 22 years, both after strenuous exercise. Hadjigeorgiou et al. (1999) reported a Japanese family with GSD10 due to a G97D mutation (612931.0004) in the PGAM2 gene. Two family members heterozygous for the mutation presented with exercise intolerance and muscle cramps. Inheritance Autosomal recessive inheritance was supported by the finding of Bresolin et al. (1983) that muscle extracts from the unaffected parents of their patient exhibited approximately 50% of normal PGAM enzymatic activity. Molecular Genetics In 5 patients with muscle phosphoglycerate mutase deficiency, Tsujino et al. (1993) identified 3 homozygous or compound heterozygous mutations in the PGAM2 gene (612931.0001-612931.0003). Four of the 5 patients were African American; the fifth was Italian. INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Myoglobinuria \- Pigmenturia \- Renal failure may occur MUSCLE, SOFT TISSUES \- Muscle cramps (also seen in some heterozygotes) \- Exercise intolerance (also seen in some heterozygotes) \- Myalgia \- Muscle pain \- Rhabdomyolysis \- Muscle biopsy shows PAS-positive glycogen-containing vacuoles LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Decreased phosphoglycerate mutase 1 (PGAM2) activity (2 to 6% of normal values) MISCELLANEOUS \- Onset in childhood or teenage years \- Symptoms usually induced only by strenuous exercise MOLECULAR BASIS \- Caused by mutation in the phosphoglycerate mutase 2 gene (PGAM2, 612931.0001 ) ▲ 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	GLYCOGEN STORAGE DISEASE X	c0268149	6,754	omim	https://www.omim.org/entry/261670	2019-09-22T16:23:30	{"mesh": ["C536176"], "omim": ["261670"], "orphanet": ["97234"], "synonyms": ["Alternative titles", "GSD X", "PHOSPHOGLYCERATE MUTASE, MUSCLE, DEFICIENCY OF", "MYOPATHY DUE TO PHOSPHOGLYCERATE MUTASE DEFICIENCY", "PGAMM DEFICIENCY"]}
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (including an abnormal skull shape, hypertelorism, downslanting palpebral fissures, epicanthal folds, low-set ears, depressed nasal bridge, micrognathia), short stature, ectodermal anomalies (such as sparse eyebrows, eyelashes, and scalp hair, hypolastic toenails), developmental delay, and intellectual disability. Additional features may include cerebral/cerebellar malformations and mild renal involvement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome	c4310801	6,755	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=459061	2021-01-23T16:52:33	{"omim": ["616901"], "synonyms": ["Developmental delay-short stature-dysmorphic features-sparse hair syndrome", "Loucks-Innes syndrome"]}
A number sign (#) is used with this entry because of evidence that the variant form of Vohwinkel syndrome, mutilating keratoderma with ichthyosis, is caused by heterozygous mutation in the gene encoding loricrin (152445), a component of the epidermal differentiation complex (EDC), on chromosome 1q21. Classic Vohwinkel syndrome (VOWNKL; 124500) is caused by mutation in the gene for connexin-26 (GJB2; 121011). A form of mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted syndrome; 614594) is caused by mutation in the TRPV3 gene (607066). Clinical Features Maestrini et al. (1996) studied a large kindred with a variant form of Vohwinkel syndrome without hearing loss, associated with ichthyosiform dermatosis. The kindred, which originated in the central Ohio region of the US, had previously been reported as 3 presumably unrelated families by Camisa and Rossana (1984) and Camisa et al. (1988). By genealogic tracing it was possible for Maestrini et al. (1996) to connect the 3 families to a common ancestor who originated in the United Kingdom 8 generations previously in the mid-1700s, and an historical photograph showed pseudoainhum in a family member living in the 1800s. Examination of affected family members in 4 living generations revealed that the youngest was 18 months old and the oldest was 92 years old. Males and females were equally affected. The phenotype appeared fully penetrant even at 18 months, and there was some interfamilial variation in expressivity and clinical severity. However, each affected individual displayed the characteristic palmar and plantar honeycomb hyperkeratosis, with some having starfish keratoses. Nearly all affected family members showed evidence of pseudoainhum of the fifth digit of the hands; some individuals had pseudoainhum of all the digits of the hands, whereas others displayed bilateral autoamputation of the fifth toe. In addition to these characteristic findings of Vohwinkel syndrome, several individuals also had a diffuse generalized ichthyosiform dermatosis, and none of the affected individuals had hearing impairment. Skin histopathology in 2 affected individuals demonstrated the pathognomonic finding of hyperkeratosis with round retained nuclei, together with hypergranulosis. Ishida-Yamamoto et al. (1997) described a 3-generation Japanese family with what was initially believed to be a form of erythrokeratodermia (PSEK; see 133200). The proband was a 27-year-old woman who had diffuse facial erythema and erythrokeratotic plaques with white pityriasiform scales on the extensor and flexor surfaces of the extremities, abdomen, and buttocks. Her palms and soles showed waxy hyperkeratosis, with a honeycomb pattern on the palms. Pseudoainhum was present on the distal interphalangeal joints of both fifth fingers, with mild constrictions on the joints of other fingers. Her 57-year-old father had well-demarcated and widespread erythematous plaques on his extremities, hyperkeratosis of the palms and soles, and mild constrictions on the distal interphalangeal joints. There were no migratory or blistering lesions, and hair, teeth, nails, and hearing were all normal. Light microscopy of skin samples showed marked hyperkeratosis with parakeratosis and intranuclear granules in the upper granular cells. Immunoelectron microscopy demonstrated that the intranuclear granules were loricrin immunoreactive. Although the erythematous hyperkeratotic plaques of the proband and her father were similar to those seen in PSEK, Richard et al. (2000) suggested that the phenotype represented a form of Vohwinkel syndrome because of the presence of mutilating palmoplantar keratoderma (pseudoainhum), which is usually not seen in PSEK. Matsumoto et al. (2001) described what they designated as the sixth reported family with loricrin keratoderma. A 14-year-old Japanese boy and his 11-year-old sister were both born as collodion babies (see 242300) and were initially diagnosed as having nonbullous congenital ichthyosiform erythroderma (242100), but they later developed palmoplantar keratoderma with pseudoainhum. Their father was similarly affected. Hair, eyes, teeth, and nails were normal, and audiograms showed no hearing impairment. Light microscopy of palmar skin revealed marked compact hyperkeratosis, with round retained nuclei and hypergranulosis, with no epidermolysis. Direct immunofluorescence confirmed the presence of mutant loricrin in the nuclei of differentiated keratinocytes in palmar and plantar skin from all 3 affected individuals. Mapping Terminal keratinocyte differentiation involves coordinated expression of several functionally interdependent genes, many of which have been mapped to the epidermal differentiation complex (EDC) on chromosome 1q21. In an extended pedigree with a variant form of Vohwinkel syndrome involving ichthyosis but no deafness, Maestrini et al. (1996) identified linkage to markers flanking the EDC region, with a maximum multipoint lod score of 14.3. Korge et al. (1997) studied 2 families, one with typical Vohwinkel syndrome, including starfish keratoses and deafness, and the other with the variant form of Vohwinkel keratoderma. They demonstrated that the classic and variant forms of Vohwinkel syndrome are clinically and ultrastructurally distinct and that the classic form does not map to the loricrin locus. Molecular Genetics In an extended pedigree segregating an autosomal dominant variant form of Vohwinkel syndrome mapping to chromosome 1q21, Maestrini et al. (1996) sequenced the candidate gene loricrin and identified a heterozygous 1-bp insertion (730insG; 152445.0001). The authors stated that this was the first evidence for a defect in an EDC gene in human disease. In a family with a variant form of Vohwinkel keratoderma, involving ichthyosis but no deafness and mapping to 1q21, Korge et al. (1997) analyzed the loricrin gene and identified heterozygosity for the same 1-bp insertion (730insG) in affected individuals. In affected members of a 3-generation Japanese family with features of a progressive symmetric form of erythrokeratodermia (PSEK; see 133200), but who showed clinical and histologic similarities to the variant form of Vohwinkel keratoderma, Ishida-Yamamoto et al. (1997) identified heterozygosity for a 1-bp insertion in the loricrin gene (709insC; 152445.0002). INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Normal hearing Eyes \- Normal eyes Teeth \- Normal teeth SKIN, NAILS, & HAIR Skin \- Collodion membrane at birth (in some patients) \- Ichthyosiform dermatosis, diffuse generalized \- Palmoplantar keratoderma, with honeycomb pattern (in most patients) \- Transgradient extension of hyperkeratosis onto wrists (in some patients) \- Starfish keratoses (in some patients) \- Prominent knuckle pads (in some patients) \- Pseudoainhum of fingers, primarily of fifth digit (in most patients) \- Autoamputation of fifth toe, bilateral (in some patients) \- Ichthyosiform dermatosis, diffuse generalized \- Erythematous hyperkeratotic plaques on extremities (in some patients) Skin Histology \- Hyperkeratosis \- Round retained nuclei \- Hypergranulosis \- Parakeratosis \- Orthokeratosis \- Intranuclear granules in upper granular cells Electron Microscopy \- Loricrin-immunoreactive intranuclear granules Nails \- Normal nails Hair \- Normal hair MOLECULAR BASIS \- Caused by mutation in the loricrin gene (LOR, 152445.0001 ) ▲ 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	VOHWINKEL SYNDROME, VARIANT FORM	c1858805	6,756	omim	https://www.omim.org/entry/604117	2019-09-22T16:12:28	{"mesh": ["C565826"], "omim": ["604117"], "orphanet": ["79395"], "synonyms": ["Alternative titles", "VOHWINKEL SYNDROME WITH ICHTHYOSIS", "MUTILATING KERATODERMA WITH ICHTHYOSIS", "LORICRIN KERATODERMA"]}
A number sign (#) is used with this entry because of evidence that oculocutaneous albinism-3 is caused by homozygous or compound heterozygous mutation in tyrosinase-related protein-1 (TYRP1; 115501) on chromosome 9p23. For a discussion of genetic heterogeneity of OCA, see OCA1A (203100). Nomenclature This form of albinism was referred to as 'rufous oculocutaneous albinism (ROCA)' when it was found in southern African blacks. In blacks the disorder is characterized by bright copper-red coloration of the skin and hair and dilution of the color of the iris. Manga et al. (1997) suggested that albinism caused by mutation in the TYRP1 gene should be referred to as OCA3. Clinical Features Among 79 albinos in Nigeria, King et al. (1978) identified 23 with a seemingly 'new' variety of tyrosinase-positive oculocutaneous albinism. Sun sensitivity was less marked. In 86%, retinal pigment was present on funduscopy. Nystagmus was present in 22 and strabismus in 12. In New York City rather numerous cases are seen in Puerto Rican families from the Aguadilla-Arecibo area of northwestern Puerto Rico. Albinism in dark-skinned persons such as Puerto Ricans is not always obvious because freckled skin and reddish hair may be present. Red reflex on transillumination of the iris and nystagmus are important clues to the diagnosis. See King et al. (1986) for a full description. Boissy et al. (1996) described a set of African American fraternal twins, one of whom had light brown skin and hair and blue-gray irides with a red reflex consistent with brown oculocutaneous albinism. The unaffected twin had dark hair and skin pigment. The affected twin developed bilateral nystagmus by the age of 1 year. Family history indicated that a sib and the maternal grandmother were born with hypopigmentation associated with an increase in pigmentation with age. Boissy et al. (1996) used foreskins to develop melanocyte cultures. Melanocytes from the twins exhibited similar amounts of soluble melanin in the supernatants, but there was a 93% reduction in the amount of insoluble melanin in melanocytes from the affected twin. Ultrastructural studies of cultured melanocytes revealed that the melanocytes of the affected twin contained only early melanosomes, whereas melanocytes cultured from normal African American individuals contain numerous fully matured and pigmented stage IV melanosomes. Population Genetics Segregation analysis in 18 Nigerian OCA families led King and Rich (1986) to conclude that the trait is autosomal recessive with an estimated gene frequency of 0.025 +/- 0.007 in that population. Manga et al. (1997) stated that oculocutaneous albinism is the most common autosomal recessive disorder among southern African blacks. Three forms account for almost all OCA cases. Tyrosinase-positive OCA (OCA2; 203200), which is the most common, is caused by mutations in the P gene on chromosome 15 (e.g., 611409.0001). Brown OCA (BOCA; see 203200) and rufous OCA (ROCA) account for most of the remaining cases. The frequency of ROCA is approximately 1 in 8,500. Mapping By linkage analysis in 9 ROCA families, Manga et al. (1997) showed that the ROCA phenotype was linked to an intragenic marker at the TYRP1 locus and obtained a maximum lod score of 3.80 at theta = 0.00. Molecular Genetics Boissy et al. (1996) found that cultured melanocytes from an African American male with OCA, whose fraternal twin brother was unaffected, showed an absence of immune-reactive TYRP1 (115501). Analysis of mRNA revealed that transcription of TYRP1 was completely absent. Through amplification of exons by PCR for SSCP analysis, the affected twin was found to be homozygous for a 1-bp deletion in the TYRP1 gene (368delA; 115501.0001), resulting in premature termination at codon 384. Manga et al. (1997) analyzed the TYRP1 gene in 19 unrelated southern African blacks with rufous OCA (ROCA) and identified compound heterozygosity for 368delA and a nonsense mutation (S166X; 115501.0002) in 17 of the 19 patients; the remaining 2 patients carried the 1-bp deletion but no mutations were identified in the other allele. Manga et al. (1997) noted that 16 of the 19 unrelated individuals could be classified unambiguously as having ROCA, with red-bronze skin and ginger hair; however, visual anomalies were not always detectable: approximately 76% of these individuals had nystagmus, and only 14% had strabismus. In 1 family, 2 sibs displayed an atypical form of albinism involving hair that was similar to that found in OCA2 (203200) individuals but slightly red, whereas the skin was a much lighter, red-yellow color than is typical of the ROCA tinge; they were compound heterozygotes for 368delA and S166X in TYRP1, but were also found to be heterozygous for the common 2.7-kb deletion in the P gene (OCA2; 611409.0001). Manga et al. (1997) suggested that ROCA caused by mutations in the TYRP1 gene should be designated OCA3. Rooryck et al. (2006) studied a Caucasian German boy with yellow-gold hair with orange highlights, fair eyelashes, blue-green eyes with defects of the iris and nystagmus, several pigmented nevi, and pale yellow skin that did not tan but burned easily. No mutations were found in the TYR (606933) and OCA2 genes, but the patient was compound heterozygous for a missense mutation inherited from his mother (R356E; 115501.0004) and a de novo 1-bp deletion (106delT; 115501.0005) in the TYRP1 gene. Rooryck et al. (2006) noted that except for the unusual hair color, the phenotype in this patient was virtually identical to that seen in OCA1B (606952) or OCA2. In a boy of Asian Indian origin with reddish hair color, brown irides, nystagmus, and lightly pigmented skin, who was negative for mutations in the TYR, OCA2, and SLC45A2 (606202) genes, Chiang et al. (2009) identified homozygosity for a 4-bp deletion in the TYRP1 gene (115501.0006). The unaffected parents were both heterozygous for the deletion. History Barnicot (1957) suggested that this is a genetic trait distinct from albinism. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Red reflex on transillumination of the iris \- Retinal pigment present \- Dilution of color of iris \- Nystagmus \- Strabismus SKIN, NAILS, & HAIR Skin \- Bright copper-red coloration of skin (in darker-skinned individuals) \- Freckled skin (in some less dark-skinned individuals) \- Mild hypopigmentation (in light-skinned individuals) Hair \- Bright copper-red hair (in darker-skinned individuals) \- Reddish hair (in some less dark-skinned individuals) LABORATORY ABNORMALITIES \- Normal tyrosinase MOLECULAR BASIS \- Caused by mutation in the tyrosinase-related protein 1 gene (TYRP1, 115501.0001 ) ▲ 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	ALBINISM, OCULOCUTANEOUS, TYPE III	c0342683	6,757	omim	https://www.omim.org/entry/203290	2019-09-22T16:31:19	{"doid": ["0070097"], "mesh": ["C537189"], "omim": ["203290"], "orphanet": ["79433"], "synonyms": ["Alternative titles", "OCULOCUTANEOUS ALBINISM, TYPE III", "ALBINISM III", "RUFOUS OCULOCUTANEOUS ALBINISM", "XANTHISM"]}
A number sign (#) is used with this entry because of evidence that pituitary adenoma-4 (PITA4) is caused by somatic mutation in the USP8 gene (603158) on chromosome 15q21. Description Adrenocorticotropic hormone (ACTH) hypersecretion by corticotroph adenomas of the pituitary result in excess cortisol secretion, or Cushing disease. The clinical features of Cushing disease include central obesity, moon facies, 'buffalo hump,' diabetes, hypertension, fatigue, easy bruising, depression, and reproductive disorders. Cushing disease is associated with increased morbidity and mortality, mainly due to cardiovascular or cerebrovascular disease and infections (summary by Perez-Rivas et al., 2015). Mutations in the USP8 gene, leading to an upregulated epidermal growth factor receptor (EGFR; 131550) pathway, have been identified in about 36 to 62% of corticotroph adenomas (summary by Mete and Lopes, 2017). Clinical Features Salti and Mufarrij (1981) described Cushing disease in a 28-year-old woman and her niece, aged 25 years. The parents of the niece were first cousins; thus, the aunt and the niece were related to each other also as first cousins once removed. Endocrine studies established pituitary ACTH excess. The sella was normal-sized in the aunt and enlarged in the niece; both received external pituitary irradiation which in the aunt had produced clinical and hormonal remission for 9 years. Swinburn and Holdaway (1988) described 2 teenaged sisters with pituitary-based Cushing syndrome. In 1 patient, the disorder was cured by pituitary radiation; in the other, biopsy showed pituitary adenoma. Swinburn and Holdaway (1988) granted that 'despite the negative family history, these patients could still represent the first generation of a MEN I family.' Gardner et al. (1989) reported the cases of black sisters, aged 38 and 40 years, with Cushing disease due to ACTH-immunostaining pituitary adenoma demonstrated at transsphenoidal pituitary surgery. Gardner et al. (1989) considered it unlikely that these sisters had MEN I, because usually hyperparathyroidism is present at the time of diagnosis of MEN I. Serum calcium levels were normal on repeated occasions in these patients. Furthermore, there was no clinical evidence of pancreatic islet cell tumor in either patient. The clinical features of 79 Cushing syndrome patients with somatic mutations in the USP8 gene reported by Ma et al. (2015) included weight gain, moon facies, 'buffalo hump,' striae, peripheral edema, amenorrhea or menstrual abnormalities, thinning of hair or alopecia, acne, fatigue or weakness, emotional lability or depression, and easy bruising. A few patients had thin skin, recurrent or difficult to treat infections, and pigmentation. About half of the patients also had diabetes mellitus, hypertension, osteoporosis or osteopenia, or hypokalemia. Ma et al. (2015) identified USP8 mutations in significantly more females (67.7%) than males (38.1%). USP8-mutated tumors were small and diffusely distributed within the sella, whereas wildtype USP8 tumors were large and extended into the parasellar space. Recurrence rate and average recurrence period were unrelated to USP8 mutational status. Pathogenesis Cushing disease is a condition associated with increased blood cortisol resulting from ACTH-producing pituitary tumors that are resistant to glucocorticoid negative feedback. Bilodeau et al. (2006) found that 17 (47%) of 36 human corticotroph adenomas had altered expression and/or subcellular localization of either BRG1 (603254) or HDAC2 (605164) compared to adjacent normal pituitary tissue. The findings indicated that these proteins were essential for glucocorticoid-induced transrepression of the POMC gene (176830) via the glucocorticoid receptor (GCCR; 138040) in the negative feedback regulation mechanism. Molecular Genetics By exome sequencing of tumor/germline DNA sample pairs from 10 patients with Cushing disease, Reincke et al. (2015) identified heterozygous somatic missense mutations in the USP8 gene in 4 tumors. They then sequenced the entire coding sequence of USP8 in 43 additional adenomas, including 7 corticotroph adenomas, 2 Nelson tumors, 14 somatotroph adenomas, 10 prolactinomas, and 10 nonfunctional adenomas, and identified mutations in 6 of the pituitary adenomas but in none of the other tumors. All of the patients with USP8 mutations were female and appeared to have small tumors. A mutational hotspot was located between residues 713 and 720, within or adjacent to the 14-3-3 (see YWHAE, 605066) binding motif and close to the protein's catalytic domain. By whole-exome sequencing of 12 ACTH-secreting pituitary adenomas and matched blood samples, Ma et al. (2015) identified 3 recurrent heterozygous somatic mutations in the USP8 gene (603158.0002-603158.0004), all in exon 14, in 8 of the tumors. By screening an additional 258 pituitary adenomas, including 108 ACTH-secreting, 50 GH-secreting, 50 PRL-secreting, and 50 nonfunctional, they identified somatic USP8 mutations in 67 of the 108 ACTH-secreting tumors and in none of the other tumor types. The 3 recurrent mutations accounted for over 77% of the USP8 mutations. No germline USB8 mutations were identified. None of the 17 USP8 mutations identified were present in the dbSNP (build 138) or 1000 Genomes Project database. By Sanger sequencing in 134 functioning and 11 silent corticotroph adenomas from patients with Cushing disease, Perez-Rivas et al. (2015) identified heterozygous USP8 mutations in 48 functioning tumors (36%) but in none of the silent tumors. All of the mutations affected residues ser718 or pro720. Mutations reduced the interaction between USP and 14-3-3 and enhanced USP activity. USP8 mutants diminished EGFR ubiquitination and included POMC promoter activity in corticotropin cells. GU \- Kidney stones Neuro \- Mood alterations \- Psychotic mentation Inheritance \- Autosomal recessive vs. dominant MEN1 Skel \- Osteoporosis \- Codfish vertebrae \- Vertebral compression fractures \- Kyphosis Vascular \- Hypertension Muscle \- Muscle atrophy Metabolic \- Impaired glucose tolerance Endocrine \- Oligomnenorrhea Misc \- Central obesity \- Poor wound healing Lab \- Hypokalemia \- Hypochloremic alkalosis \- Elevated plasma cortisol \- Elevated urinary 17-hydroxycorticosteroids \- Dexamethasone suppression \- Elevated plasma ACTH Skin \- Thin \- Purpura \- Ecchymoses \- Purplish striae \- Hirsutism \- Edema \- Ruddy face and neck ▲ 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	PITUITARY ADENOMA 4, ACTH-SECRETING	c0010481	6,758	omim	https://www.omim.org/entry/219090	2019-09-22T16:29:13	{"doid": ["7004"], "mesh": ["D003480"], "omim": ["219090"], "icd-10": ["E24.0"], "orphanet": ["96253"], "synonyms": ["Alternative titles", "CUSHING DISEASE, PITUITARY"], "genereviews": ["NBK97965"]}
A rare disease characterized by malignant proliferation of lymphoid cells blocked at an early stage of differentiation and accounts for 75% of all cases of childhood leukaemia. ## Epidemiology About 3,000 children in the United States and 5,000 children in Europe are diagnosed with ALL per year. ## Clinical description The peak incidence occurs between 2 and 5 years of age. ALL may be either asymptomatic or acute with a life-threatening haemorrhage, infection, or episode of respiratory distress. Although ALL primarily affects the bone marrow and peripheral blood, any organ or tissue may be infiltrated by the abnormal cells. The most frequent signs are lymphadenopathies, hepatosplenomegaly, fever, signs of haemorrhage, and bone pain. ## Etiology Most cases show chromosomal and genetic abnormalities, occurring spontaneously in genes playing important regulatory roles in controlling the lymphoid cell population. The most common ALL translocation, the t(12;21), appears to have good prognostic implications. ## Diagnostic methods ALL is biologically heterogeneous and morphologic, immunologic, cytogenetic, biochemical, and molecular genetic characterisation of leukaemia lymphoblasts is needed to establish the diagnosis or to exclude other possible causes of bone marrow failure and, finally, to classify ALL subtypes. Biological findings include hyperleukocytosis due to circulating lymphoblasts, anaemia and thrombocytopaenia. Diagnosis is established by bone marrow biopsy revealing leukaemic cell infiltration. ## Management and treatment The chemotherapy protocols adopted by international cooperative groups have four main objectives: induction with the aim of complete remission, preventative therapy to avoid central nervous system involvement, consolidation/re-induction, and maintenance therapy. Although management of relapse remains largely controversial, high dose chemotherapy blocks and stem cell transplantation are approaches increasingly adopted in most cases. In 2006, clofarabine obtained EU marketing authorisation as an Orphan drug for second line treatment of paediatric ALL patients. A novel tyrosine-kinase inhibitor, dasatinib, has been shown to be a safe and effective treatment option for adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia and resistance or intolerance to imatinib. Clinical trials with this inhibitor are ongoing in the paediatric population. With the need to stratify patients into risk groups and to provide risk-adapted therapy, treatment requires high levels of organisation, expertise and knowledge. ## Prognosis The increase in the survival rate for children younger than 15 years of age has been dramatic, moving from less than 10% in the early 60's to about 75% in the late 90's. Unfortunately, however, results are still rather poor in countries with limited resources, which are home to around 80% of the child population. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Acute lymphoblastic leukemia	c0023449	6,759	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=513	2021-01-23T18:37:00	{"gard": ["522"], "omim": ["247640", "613065", "613067"], "umls": ["C0023449"], "icd-10": ["C91.0"], "synonyms": ["ALL", "Acute lymphoblastic leukemia/lymphoma", "Acute lymphocytic leukemia", "Precursor lymphoid neoplasm"]}
Patterson syndrome Other namesPseudoleprechaunism syndrome, Patterson type Patterson syndrome, also called pseudoleprechaunism, is an extremely rare syndrome, first mistaken as Donohue Syndrome (also known as Leprechaunism). It is named for Dr. Joseph Hanan Patterson.[1] It was described by Patterson and Watkins in 1962.[2]The pathogenesis and cause of the Patterson syndrome was unknown until 1981.[3] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 References * 5 External links ## Signs and symptoms[edit] Patterson syndrome is characterized by the patient's having an unusual facial look, similar to that caused by Leprechaunism. It primarily affects the connective tissue and the neuroendocrine system, giving rise to bronzed hyperpigmentation, cutis laxa of the hands and feet, bodily disproportion, intellectual disability, and major bony deformities. Radiographs reveal a characteristic generalised skeletal dysplasia.[citation needed] It comprises endocrine abnormality, hyperadrenocorticism, cushingoid features, and diabetes mellitus. One other case has shown premature adrenarche.[citation needed] ## Cause[edit] This section is empty. You can help by adding to it. (August 2017) ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2017) ## References[edit] 1. ^ Zach Samson (July 1, 2006). "Dr. Patterson, influential past president of AAP Georgia Chapter". AAP News. 27 (7): 39. Retrieved 2008-03-24. 2. ^ PATTERSON JH, WATKINS WL (1962). "Leprechaunism in a male infant". J. Pediatr. 60 (5): 730–9. doi:10.1016/S0022-3476(62)80100-0. PMID 14484402. 3. ^ David TJ, Webb BW, Gordon IR (1981). "The Patterson syndrome, leprechaunism, and pseudoleprechaunism". J. Med. Genet. 18 (4): 294–8. doi:10.1136/jmg.18.4.294. PMC 1048735. PMID 7277424. ## External links[edit] Classification D * ICD-10: E34.8 * OMIM: 169170 * MeSH: C536310 External resources * Orphanet: 2976 This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Patterson syndrome	c1868546	6,760	wikipedia	https://en.wikipedia.org/wiki/Patterson_syndrome	2021-01-18T18:36:18	{"gard": ["4259"], "mesh": ["C536310"], "umls": ["C1868546"], "orphanet": ["2976"], "wikidata": ["Q7148484"]}
Familial Alzheimer-like prion disease is an exceedingly rare form of prion disease (see this term) characterized by the neuropathological features of Alzheimer disease including memory impairment and depression, related to abnormal prion protein (PrP) caused by a gene mutation in PRNP. Patients present with a prolonged, atypical course (absence of myoclonus or ataxia) unlike other forms of prion disease with severe neurofibrillary tangle pathology and high levels of cerebral amyloidosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Familial Alzheimer-like prion disease	c4303482	6,761	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280397	2021-01-23T19:04:49	{"icd-10": ["A81.8"]}
A rare glial tumor characterized by a highly aggressive, diffusely infiltrative pontine lesion generally occurring in children, affecting local nerve fiber tracts and spreading contiguously to involve adjacent structures, but also metastasizing within the central nervous system. Patients mostly present with a short history of symptoms, typically including the classic triad of multiple cranial neuropathies, long tract signs, and ataxia. Signs and symptoms of increased intracranial pressure may present due to obstructive hydrocephalus. Prognosis is poor and not related to histological grade. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Diffuse intrinsic pontine glioma	c2986658	6,762	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=497188	2021-01-23T18:38:40	{"synonyms": ["DIPG"]}
A number sign (#) is used with this entry because of evidence that intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies (IMAGE) is caused by heterozygous mutation in the CDKN1C gene (600856) on chromosome 11p15. A recessive form of IMAGE with immunodeficiency (IMAGEI; 618336) is caused by mutation in the POLE gene (174762) on chromosome 12q24. Description IMAGE is a rare multisystem disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and steroid replacement therapy commenced. Other reported features in this condition include hypercalciuria and/or hypocalcemia, craniosynostosis, cleft palate, and scoliosis (summary by Balasubramanian et al., 2010). Clinical Features Vilain et al. (1999) reported 3 boys with adrenal hypoplasia congenita (AHC; see 300200) and additional findings representing a novel syndrome that they designated IMAGE: intrauterine growth retardation, metaphyseal dysplasia, AHC, and genital anomalies. The patients presented shortly after birth with growth retardation and severe adrenal insufficiency, and each had mild dysmorphic features, bilateral cryptorchidism, a small penis, and hypogonadotropic hypogonadism. Skeletal surveys revealed metaphyseal dysplasia in all 3 patients and epiphyseal dysplasia in 2. The patients had documented or suspected hypercalciuria and/or hypercalcemia, resulting in nephrocalcinosis in one and in prenatal liver and spleen calcifications in another. AHC presents most often either as an isolated abnormality, caused by mutations in the DAX1 gene (NR0B1; 300473), or as part of an Xp21 contiguous gene syndrome caused by a deletion of the Duchenne muscular dystrophy (DMD; 300377), glycerol kinase (GK; 300474), and DAX1 genes. All 3 patients with the IMAGE association had normal creatine kinase levels and no evidence of GK deficiency (307030). Sequence analysis revealed no mutation in the DAX1- or steroidogenic factor-1 (SF1; 184757)-coding sequences and no deletion of DAX1. Bergada et al. (2005) studied 4 children with IMAGE association (3 males, 1 female) from a large 5-generation pedigree. Ten additional members who died during the neonatal period who were born with intrauterine growth retardation (IUGR) and/or hyperpigmentation were presumed to have been affected as well. All patients in this series were diagnosed during the newborn period. Adrenal insufficiency was variable within patients. All had severe IUGR and marked postnatal growth failure. Sequence analysis from 2 patients revealed no mutation in DAX1. Analysis of the pedigree revealed a pattern consistent with inheritance via the maternal line. Hence, the pattern of inheritance in this family of this unusual disorder might be explained in terms of the genomic imprinting hypothesis, with expression through maternal transmission involving an autosomal gene. Balasubramanian et al. (2010) reported a 4-year-old boy who had typical features of IMAGE syndrome as well as bilateral sensorineural hearing loss, a feature not previously reported in this syndrome. The authors reviewed previously reported cases, noting that epiphyseal dysplasia had consistently been reported as a feature; they suggested that it should be considered as a diagnostic feature in the absence of clear evidence of metaphyseal dysplasia because the metaphyseal changes may be variable and confined to the short tubular bones or relatively mild. Mapping In a large 5-generation Argentinian family with IMAGE syndrome, originally reported by Bergada et al. (2005), Arboleda et al. (2012) detected a 17.2-Mb identical-by-descent region on chromosome 11 that was shared by 7 affected family members but not an unaffected sib, with a lod score of 5.4. No contiguous gene deletion or duplication was identified in the affected individuals. Molecular Genetics In 2 patients from the 5-generation Argentinian family with IMAGE syndrome originally reported by Bergada et al. (2005) and 3 additional unrelated patients, Arboleda et al. (2012) performed targeted high-throughput genomic sequencing of all exons within a conservative identical-by-descent region and identified 4 different heterozygous missense mutations in a single gene, CDKN1C (600856.0007-600856.0010). Analysis of CDKN1C in an additional patient with IMAGE syndrome identified another heterozygous mutation (600856.0011); all 5 mutations clustered in a highly conserved region within 6 amino acids of the PCNA (176740)-binding domain of CDKN1C and disrupted PCNA binding. Targeted expression of IMAGE-associated CDKN1C mutations in Drosophila caused restricted eye and wing growth, suggesting a gain-of-function mechanism. Familial analysis showed an imprinted mode of inheritance in the Argentinian family, in which only maternal transmission of the mutation resulted in IMAGE syndrome. INHERITANCE \- Autosomal dominant GROWTH \- Intrauterine growth retardation \- Postnatal growth failure HEAD & NECK Head \- Macrocephaly (in some patients) Face \- Prominent forehead Ears \- Low-set ears Nose \- Flat nasal bridge \- Short nose GENITOURINARY External Genitalia (Male) \- Micropenis \- Hypospadias External Genitalia (Female) \- Normal Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Normal Kidneys \- Renal calcification (in some patients) SKELETAL \- Epiphyseal dysplasia \- Metaphyseal dysplasia \- Delayed bone age NEUROLOGIC Central Nervous System \- Developmental delay (in some patients) ENDOCRINE FEATURES \- Adrenal hypoplasia, congenital \- Adrenal crisis in neonatal period \- Growth hormone deficiency LABORATORY ABNORMALITIES \- Hypercalcemia \- Hypercalciuria MOLECULAR BASIS \- Caused by mutation in the cyclin-dependent kinase inhibitor 1C gene (CDKN1C, 600856.0007 ) ▲ 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	INTRAUTERINE GROWTH RETARDATION, METAPHYSEAL DYSPLASIA, ADRENAL HYPOPLASIA CONGENITA, AND GENITAL ANOMALIES	c1846009	6,763	omim	https://www.omim.org/entry/614732	2019-09-22T15:54:22	{"doid": ["0050885"], "mesh": ["C564543"], "omim": ["614732"], "orphanet": ["85173"], "synonyms": ["Alternative titles", "IMAGE SYNDROME"], "genereviews": ["NBK190103"]}
## Description Hereditary benign intraepithelial dyskeratosis (HBID) is a rare inherited disease characterized by elevated plaques on the ocular and oral mucous membranes. The bulbar conjunctiva is involved, especially in the nasal and temporal perilimbal region. Dilated superficial vessels in association with the conjunctival plaques give the eye an overall red appearance, which accounts for the disease's nickname of 'red eye.' Morphologically, the lesions consist of a dyskeratotic hyperplastic epithelium. The oral lesions, which are typically asymptomatic and may go unrecognized, usually appear as thick, soft, white papules and plaques of various sizes, involving any part of the oral cavity. The ocular manifestations in this condition vary in severity from asymptomatic plaques on the bulbar conjunctiva to complete involvement of the cornea with severe vision loss. Patients commonly complain of symptoms of irritation, such as erythema, itching, excessive lacrimation, and photophobia. Periods of acute intensification of symptoms are common, especially in the spring. The lesions may become apparent in early infancy and may date from birth. The plaques persist throughout life and sometimes progress, but may wax and wane (summary by Witkop et al., 1960; Reed et al., 1979; and Baroni et al., 2009). Clinical Features Von Sallmann and Paton (1959, 1960) studied members of a large, triracial, consanguineous North Carolinian isolate population, so-called 'Halowar Indians,' who had dyskeratosis of the conjunctival epithelium. Of approximately 309 individuals who were examined, 74 were affected and 4 were equivocal. Patients displayed bilateral gelatinous plaques of the perilimbal bulbar conjunctiva of variable severity that were present at birth or shortly thereafter and persisted throughout life. A few patients had a corneal membrane or vascularized corneal opacity. Biopsies of the involved perilimbal conjunctiva from 5 patients all showed dyskeratosis and acanthosis of the conjunctival epithelium. The eye lesions were invariably associated with a comparable epithelial lesion of the oral mucosa. Witkop et al. (1960) also studied the triracial isolate in North Carolina, and identified 83 affected individuals. Characteristic histologic changes in the prickle cell layer of the mucosa include numerous round, waxy-looking, eosinophilic cells that appear to be engulfed by normal cells, giving a cell-within-cell appearance; these changes are seen in both oral and eye specimens. The oral lesion, which grossly resembles leukoplakia, is not precancerous. The eye lesions resemble pterygia (see 178000). The only symptoms are produced by involvement of the cornea, resulting in impairment of vision. Histologically, characteristic findings are obtained in oral and eye scraping. Penetrance is about 97% and there is little effect on reproductive fitness. Yanoff (1968) described the condition in mother and daughter. This was the only report of the condition in persons apparently unrelated to the North Carolinian triracial isolate, the 'Haliwa Indians,' studied by Witkop and Gorlin (1961). However, Gorlin (1971) stated that Yanoff's patients were in fact related to Witkop's. (Members of the triracial isolate are called Haliwa Indians because they live in Halifax and Warren Counties, North Carolina.) Shields et al. (1987) described an affected 37-year-old woman of Haliwa ancestry who was born in Philadelphia. Sadeghi and Witkop (1977) used transmission electron microscopy to examine biopsy specimens from the molar region of the buccal mucosa of a 16-year-old boy and a 22-year-old woman with hereditary benign intraepithelial dyskeratosis. Ultrastructural findings revealed a striking change in cellular differentiation toward keratinization in some but not all epithelial cells. HBID is differentiated from other dyskeratotic conditions of the mucous membranes by the presence of numerous vesicular bodies in immature dyskeratotic cells; a marked increase in the production of tonofilaments in dyskeratotic cells, densely filling the entire cytoplasm; disappearance of cellular interdigitation and desmosomes in mature dyskeratotic cells; and prominent nuclear degeneration. Reed et al. (1979) studied 13 patients with HBID, all of whom had the thickened opaque plaques on the bulbar conjunctiva adjacent to the limbus that are the hallmark of the disorder; in addition, 10 of the 13 had similar lesions on the cornea. The corneal abnormalities had 2 distinct features: deep, stromal vessels and thickened, opaque, gelatinous-appearing unilateral or bilateral epithelial plaques. The corneal epithelium was slightly abnormal in some cases and almost totally involved in other instances, covering the visual axis of 1 eye in 4 patients. Examination by light microscopy of surgically excised tissue from 5 of the patients showed similar features in all specimens, with markedly thickened mucosal epithelium that exhibited hyperkeratosis and acanthosis. Adjacent to the abnormal epithelium were portions of normal thickness and morphology. A mild to moderate infiltrate of lymphocytes and plasma cells was usually present beneath the hyperplastic and dyskeratotic epithelium. Reed et al. (1979) noted that although surgical procedures are commonly only of temporary benefit, excision is nonetheless recommended when chronic epithelial plaques significantly reduce vision; in addition, the tendency to regrowth may lead the clinician to conclude that the lesion is malignant and requires radical surgery, but the histopathologic attributes are diagnostic and unlike those of any premalignant or malignant neoplasm. Gombos et al. (1986) reported a 4-generation Italian family with HBID. The proband was a 65-year-old man, whose 3 sons and 1 daughter all exhibited similar symptoms in infancy; 2 of 8 grandchildren were also affected. The ocular lesions involved significant conjunctival hyperemia and gelatinous plaques, similar to pingueculae, located on the nasal and temporal bulbar conjunctiva. The oral manifestations consisted of soft and spongy white patches, round or linear, that were present on the corners and floor of the mouth, gingival mucosa, and ventral surface of the tongue. Gombos et al. (1986) noted that the daughter had primarily oral involvement, and the 2 grandchildren, a 12-year-old girl and a 7-year-old boy, had mild lesions of the oral mucosa as well as conjunctival hyperemia, with tearing and photophobia, particularly in the summer months. Histologic examination of a fragment of gingival mucosa showed a dyskeratotic, thickened epithelium, with loss of cell-cell adhesion towards the upper layers. Some cells in the upper-middle region of the Malpighian layer exhibited marked eosinophilia and early keratinization with a waxy appearance, and some of those cells also displayed a cell-within-cell appearance. Jham et al. (2007) described a 32-year-old Brazilian man who was referred for evaluation of multiple asymptomatic intraoral white, rough, diffuse, folded plaques bilaterally in the posterior buccal mucosa. He also had asymptomatic reddened gelatinous plaques and dilated vessels on the conjunctiva of both eyes. Intraoral incisional biopsy revealed increased epithelial thickness, hyperplasia, and acanthosis, with numerous large vacuolated cells throughout the epithelium. Dyskeratotic cells were observed in the suprabasal and superficial epithelium, with some cells appearing to be engulfed by the surrounding cells in a cell-within-cell pattern, findings that were compatible with HBID. The patient's brother had eye changes consistent with HBID, but had no oral lesions. Their mother and a sister were unaffected; their father was deceased. Baroni et al. (2009) reported a 12-year-old girl who presented with a 4-year history of asymptomatic soft, white spotty lesions, aggregated in roundish and linear spongy plaques on the buccal mucosa and lower lip. No ocular or associated skin or nail lesions were observed. A mucosal biopsy showed thickening of the epithelium, prominent dyskeratosis with decreased cell-cell adhesion in the superficial layers, and a cell-within-cell pattern of epithelial cells engulfed by other normal cells. Tzanck smear of the affected mucosa revealed epithelial cells with cytoplasm discolored in a yellow-orange-brown tobacco-like hue (so-called 'tobacco cells'). Examination of her mother revealed dilated vessels and a superficial gelatinous plaque on the bulbar conjunctiva; a maternal uncle and the maternal grandmother also had dilated vessels and superficial gelatinous plaque on the bulbar conjunctiva, as well as white papules on the buccal mucosa. All affected family members were asymptomatic. Baroni et al. (2009) noted that HBID oral lesions are remarkably similar to those of white sponge nevus (see 193900), but that in the latter disorder no eye lesions are observed, and the disorder also involves the external genitalia and rectum. Mapping By linkage analysis in 2 North Carolina families, one of which was originally described by Witkop et al. (1960) and later studied by Reed et al. (1979), Allingham et al. (2001) localized the benign intraepithelial dyskeratosis locus to chromosome 4q35 with a peak lod score of 8.97. Molecular analysis revealed that all affected individuals in the 2 large families studied had 3 alleles for 2 tightly linked markers, D4S1652 and D4S2390, which map to the telomeric region of 4q35. They suggested that a duplication is involved in the causation of the disorder. Molecular Genetics ### Exclusion Studies In 4 Native Americans with HBID, Soler et al. (2013) analyzed the NLRP1 gene (606636), mutation in which had been found to cause corneal intraepithelial dyskeratosis and ectodermal dysplasia (CIDED; 615225), but detected no pathogenic mutations. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Clear gelatinous pterygia-like plaques of the nasal and temporal perilimbal bulbar conjunctiva \- Lesions may involve cornea (in some patients) \- Extensive lesions may impair vision (in some patients) \- Dilated superficial vessels give 'red eye' appearance \- Asymptomatic (in some patients) \- Irritation of eye with itching (in some patients) \- Excessive lacrimation (in some patients) \- Photophobia (in some patients) Mouth \- Oral mucous membrane dyskeratosis resembling leukoplakia (may be in any part of oral cavity) \- Thick soft white papules and plaques of variable size (may be in any part of oral cavity) SKIN, NAILS, & HAIR Skin \- Clear gelatinous pterygia-like plaques of the nasal and temporal perilimbal bulbar conjunctiva MISCELLANEOUS \- Lesions are present at birth or become apparent in infancy \- Some patients report seasonal variation in symptoms \- Some patients have only ocular involvement or only oral involvement ▲ 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	DYSKERATOSIS, HEREDITARY BENIGN INTRAEPITHELIAL	c0265966	6,764	omim	https://www.omim.org/entry/127600	2019-09-22T16:42:04	{"mesh": ["C562551"], "omim": ["127600"], "orphanet": ["352657"], "synonyms": ["Alternative titles", "DKBI"]}
A clinically heterogeneous form of idiopathic inflammatory myopathy characterized by myositis, arthralgia, Raynaud phenomenon, mechanic hands, interstitial lung disease (ILD), and serum autoantibodies to aminoacyl transfer RNA synthetases (anti-ARS). ## Epidemiology Prevalence and annual incidence are not known. AS syndrome represents a subset of polymyositis and dermatomyositis (PM, DM, see these terms), disorders which have estimated prevalence of about 1/4,650. About a quarter of these patients may have AS syndrome, providing a prevalence estimate of 1/25,000 - 1/33,000 worldwide. The disorder affects females twice as often as males. ## Clinical description The age of onset is highly variable with a mean of 50 years (range 19 to 82). ILD is one of the clinical hallmarks. Respiratory symptoms (shortness of breath, coughing, dysphagia) are found in 40-60% of patients at disease onset. Respiratory insufficiency may be acute or develop gradually. Some patients develop clinically overt myositis while others have hypomyopathic or even amyopathic forms of the disorder. At onset, 20-70% of patients have muscle weakness of the proximal and axial muscles, and many have myalgia and muscle stiffness, similar to the milder presentations of PM/DM. The other main clinical features are fever, loss of appetite, weight loss, generally symmetrical arthritis, arthralgia, tenosynovitis, Raynaud phenomenon, heliotrophic rash, distal esophageal dysmotility, and mechanic's hands (fissuring and scaling of the lateral and distal aspects of the hands). Rarely reported manifestations include Shawl and V signs (erythema over the back and shoulders or over the anterior neck and chest in a V), and periungual erythema. Pulmonary arterial hypertension (PAH, see this term) has been reported as a severe complication in some patients. The incidence of malignancies appears to be fairly low. ## Etiology The exact mechanisms leading to the disorder are not known. Viral infections are thought to promote formation of antisynthetase antibodies. HLA-DRB10301, DQA10501 and DQB10201genes are risk factors for the development of anti-Jo-1+ AS syndrome. ## Diagnostic methods Patients are mostly positive for one of the seven antisynthetase autoantibodies that have been identified; anti-Jo-1 is the most common (70% of the cases). The diagnosis is based on the clinical features and is confirmed in the presence of positive serologic testing for anti-ARS antibodies (anti-Jo-1, anti-PL-12, anti-PL-7, anti-OJ; anti-KS). ILD is diagnosed by high resolution computed tomography (HRCT) of the lungs. Creatin kinase (CK) levels are often significantly elevated. Absence of myositis or ILD does not exclude the diagnosis of AS syndrome. Diagnosis is considered probable in patients with ILD and/or inflammatory myopathy in the presence of anti-ARS. ## Differential diagnosis Differential diagnoses include other inflammatory myopathies and idiopathic isolated ILD such as usual interstitial pneumonia. Joint involvement may also mimic or even overlap with rheumatoid arthritis (see this term). ## Management and treatment Oral corticosteroids (prednisone) and immunosuppressive agents are the mainstay of treatment. There is no consensus on treatment regimens in AS syndrome. Depending on the presentation and severity, drug therapy regimens may include azathioprine, methotrexate, cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, or rituximab. Dermatological symptoms have been treated effectively with hydroxychloroquine. In patients with associated ILD, the response to immunosuppressive treatment is generally good. ## Prognosis Prognosis is guarded in severe cases, sometimes with fatal outcomes. In other cases, stabilization or improvement may be achieved. Progression of ILD is the main prognostic factor. The disease course is chronic, requiring long-term treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States *[FDA]: Food and Drug Administration	Antisynthetase syndrome	c2609059	6,765	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=81	2021-01-23T17:29:37	{"gard": ["735"], "mesh": ["C537778"], "umls": ["C2609059"], "icd-10": ["M35.8"], "synonyms": ["AS syndrome", "Anti-Jo1 syndrome"]}
## Clinical Features Flex et al. (2003) reported a 3-generation Italian family in which 15 members were affected with autosomal dominant nonsyndromic sensorineural deafness. The hearing loss, which was bilateral and symmetrical, began in the second decade of life, progressing from moderate to profound loss and ultimately involving all frequencies. Mapping Flex et al. (2003) performed a genomewide scan in an Italian family with nonsyndromic sensorineural loss and demonstrated significant linkage with markers on chromosome 2p12 (maximum lod = 4.21 at theta = 0.0 for marker D2S139). Haplotype analysis defined a 9.6-cM disease gene interval without overlap with other identified loci. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural, bilateral symmetrical, progressive (severe later in life) \- Tinnitus (variable manifestation) MISCELLANEOUS \- Onset during the second/third decade of life with high frequency loss slowly progressing and extending to all frequencies by the fifth/sixth decade of life \- One 3-generation Italian family has been described (last curated August 2015) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	DEAFNESS, AUTOSOMAL DOMINANT 43	c1842108	6,766	omim	https://www.omim.org/entry/608394	2019-09-22T16:07:52	{"doid": ["0110568"], "mesh": ["C564246"], "omim": ["608394"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"]}
## Summary ### Clinical characteristics. HEXA disorders are best considered as a disease continuum based on the amount of residual beta-hexosaminidase A (HEX A) enzyme activity. This, in turn, depends on the molecular characteristics and biological impact of the HEXA pathogenic variants. HEX A is necessary for degradation of GM2 ganglioside; without well-functioning enzymes, GM2 ganglioside builds up in the lysosomes of brain and nerve cells. The classic clinical phenotype is known as Tay-Sachs disease (TSD), characterized by progressive weakness, loss of motor skills beginning between ages three and six months, decreased visual attentiveness, and increased or exaggerated startle response with a cherry-red spot observable on the retina followed by developmental plateau and loss of skills after eight to ten months. Seizures are common by 12 months with further deterioration in the second year of life and death occurring between ages two and three years with some survival to five to seven years. Subacute juvenile TSD is associated with normal developmental milestones until age two years, when the emergence of abnormal gait or dysarthria is noted followed by loss of previously acquired skills and cognitive decline. Spasticity, dysphagia, and seizures are present by the end of the first decade of life, with death within the second decade of life, usually by aspiration. Late-onset TSD presents in older teens or young adults with a slowly progressive spectrum of neurologic symptoms including lower-extremity weakness with muscle atrophy, dysarthria, incoordination, tremor, mild spasticity and/or dystonia, and psychiatric manifestations including acute psychosis. Clinical variability even among affected members of the same family is observed in both the subacute juvenile and the late-onset TSD phenotypes. ### Diagnosis/testing. The diagnosis of a HEXA disorder is established in a proband with abnormally low HEX A activity on enzyme testing and biallelic pathogenic variants in HEXA identified by molecular genetic testing. Targeted analysis for certain pathogenic variants can be performed first in individuals of specific ethnicity (e.g., French Canadian, Ashkenazi Jewish). Enzyme testing of affected individuals identifies absent to near-absent HEX A enzymatic activity in the serum, white blood cells, or other tissues in the presence of normal or elevated activity of the beta-hexosaminidase B enzyme. Pseudodeficiency refers to an in vitro phenomenon caused by specific HEXA variants that renders the enzyme unable to process the synthetic (but not the natural) GM2 substrates, and leads to false positive enzyme testing results. ### Management. Treatment of manifestations: Treatment is mostly supportive and directed to providing adequate nutrition and hydration, managing infectious disease, protecting the airway, and controlling seizures. The treatment for the subacute juvenile and late-onset Tay-Sachs phenotypes is directed to providing the services of a physiatrist and team of physical, occupational, and speech therapists for maximizing function and providing aids for activities of daily living. Agents/circumstances to avoid: Positioning that increases aspiration risk during feedings and seizure medication dosages that result in excessive sedation for those with acute infantile TSD; situations that increase the likelihood of contractures or pressure sores, such as extended periods of immobility; circumstances that exacerbate the risk of falls (i.e., walking on uneven or unstable surfaces) in those with subacute juvenile TSD; psychiatric medications that have been associated with disease worsening, including haloperidol, risperidone, and chlorpromazine. ### Genetic counseling. Acute infantile Tay-Sachs disease (TSD), subacute juvenile TSD, and late-onset TSD (comprising the clinical spectrum of HEXA disorders) are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are asymptomatic. Once both HEXA pathogenic variants have been identified in an affected family member, targeted analysis for the specific familial variants can be used for carrier testing in at-risk relatives. Molecular genetic testing and/or HEX A enzyme testing can be used for carrier detection in individuals who do not have a family history of TSD. If both members of a reproductive couple are known to be heterozygous for a HEXA pathogenic variant, molecular genetic prenatal testing and preimplantation genetic testing for the HEXA pathogenic variants identified in the parents are possible. ## Diagnosis HEXA disorders are best considered as a disease continuum based on the amount of residual beta-hexosaminidase A (HEX A) enzyme activity. This, in turn, depends on the molecular characteristics and biological impact of the HEXA pathogenic variants. HEX A is necessary for degradation of GM2 ganglioside; without well-functioning enzymes, GM2 ganglioside builds up in the lysosomes of brain and nerve cells. The classic clinical phenotype is known as Tay-Sachs disease (TSD), after ophthalmologist Warren Tay and neurologist Bernard Sachs, who originally described the disorder in the late 19th century. For convenience, the clinical phenotypes are often divided into acute infantile, subacute juvenile, and late-onset disorders, with unique phenotypes common to each subset. ### Suggestive Findings Acute infantile Tay-Sachs disease should be suspected in infants with the following clinical findings: * Progressive weakness and loss of motor skills beginning between ages three and six months * Decreased attentiveness * An increased or exaggerated startle response * A cherry-red spot of the fovea centralis of the macula of the retina * A normal-sized liver and spleen * Generalized muscular hypotonia with sustained ankle clonus and hyperreflexia * Onset of seizures beginning around age 12 months * Progressive macrocephaly with proportionate ventricular enlargement on neuroimaging beginning at age 18 months Subacute juvenile Tay-Sachs disease should be suspected in individuals with the following clinical findings: * A period of normal development until ages two to five years followed by a plateauing of skills and then loss of previously acquired developmental skills * Progressive spasticity resulting in loss of independent ambulation * Progressive dysarthria, drooling, and eventually absent speech * Normal-sized liver and spleen * Onset of seizures * Progressive global brain atrophy on neuroimaging [Nestrasil et al 2018] Late-onset Tay-Sachs disease should be suspected in individuals with the following clinical findings: * Onset of symptoms in teens or adulthood * Progressive neurogenic weakness of antigravity muscles in the lower extremities and frequent falls * Dysarthria, tremor, and incoordination * Acute psychiatric manifestations including psychosis (which can be the initial manifestation of disease) * Isolated cerebellar atrophy on neuroimaging ### Establishing the Diagnosis The diagnosis of a HEXA disorder is established in a proband with abnormally low HEX A activity on enzyme testing and biallelic pathogenic variants in HEXA identified by molecular genetic testing (see Table 1). Note: Identification of a heterozygous HEXA variant of uncertain significance does not establish or rule out the diagnosis of this disorder. HEX A enzymatic activity testing. Testing identifies absent to near-absent HEX A enzymatic activity in the serum, white blood cells, or other tissues in the presence of normal or elevated activity of the beta-hexosaminidase B (HEX B) enzyme [Hall et al 2014]. * Individuals with acute infantile TSD have no or extremely low HEX A enzymatic activity. * Individuals with subacute juvenile or late-onset TSD have some minimal residual HEX A enzymatic activity. Note: The enzyme HEX A is a heterodimer of one alpha subunit and one beta subunit (encoded by the genes HEXA and HEXB, respectively); the enzyme HEX B, on the other hand, is a homodimer composed of two beta subunits. Only HEX A is able to degrade GM2 ganglioside. Note: Pseudodeficiency refers to an in vitro phenomenon caused by specific HEXA variants that renders the enzyme unable to process the synthetic (but not the natural) GM2 substrates, and leads to false positive enzyme testing results. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing or a multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of HEXA disorders is broad, infants with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those (especially older individuals) with a phenotype indistinguishable from many other disorders presenting later in life with neurodegeneration or developmental regression are more likely to be diagnosed using comprehensive genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of a HEXA disorder, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of HEXA is performed first followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. Targeted analysis for pathogenic variants can be performed first in individuals of specific ethnicity: * French Canadian descent. A 7.6-kb genomic deletion of the HEXA promoter and exon 1 * Ashkenazi Jewish populations. p.Tyr427IlefsTer5, c.1421+1G>C, c.1073+G>A, p.Gly269Ser, and two pseudodeficiency alleles: p.Arg247Trp and p.Arg249Trp (See Table 13.) Note: (1) The presence of one pseudodeficiency allele reduces the in vitro HEX A enzymatic activity toward synthetic substrates but does not reduce enzymatic activity with the natural substrate, GM2 ganglioside. All enzymatic assays use the artificial substrate because the naturally occurring GM2 ganglioside is not a stable reagent and is not available. Thus, a problem emerges in interpreting enzymatic deficiency. Molecular genetic testing provides the basis to differentiate a pathogenic allele from a pseudodeficiency allele. (2) About 35% of non-Jewish individuals identified as heterozygotes by HEX A enzyme-based testing are carriers of a pseudodeficiency allele. (3) About 2% of Ashkenazi Jewish individuals identified as heterozygotes by HEX A enzyme-based testing in carrier screening programs are actually heterozygous for a pseudodeficiency allele (see Table 13). * A multigene panel that includes HEXA and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at a 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. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders characterized by a slowly progressive neurodegeneration, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by exome sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 2. Molecular Genetic Testing Used in HEXA Disorders View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method HEXASequence analysis 399% 4 Gene-targeted deletion/duplication analysis 5Rare 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. ## Clinical Characteristics ### Clinical Description The clinical phenotype of HEXA disorders comprises a continuum including acute infantile, subacute juvenile, and late-onset Tay-Sachs disease. Although classification into subtypes is somewhat arbitrary, it is helpful in understanding the variation observed in the timing of disease onset, presenting symptoms, rate of progression, and longevity. Although case reports of individuals from specific ethnic backgrounds abound, there is a paucity of prospective natural history studies for Tay-Sachs disease delineating the progression of disease subtypes over time. Subtypes of HEXA disorders include the following phenotypes: * Acute infantile Tay-Sachs disease with onset before six months, rapid progression, and death generally before age five years * Subacute juvenile Tay-Sachs disease with later onset and survival into late childhood or adolescence * Late-onset Tay-Sachs disease with long-term survival. Affected individuals may present with various phenotypes including lower motor neuronopathy with progressive lower-extremity weakness, atrophy and fasciculations, progressive dystonia, spinocerebellar deficits, dysarthria, and/or psychosis. #### Acute Infantile Tay-Sachs Disease Presentation. Affected infants generally appear to be completely normal at birth. * Progressive weakness begins between ages three and six months, along with myoclonic jerks and an exaggerated startle reaction to sudden stimuli. * Decreasing visual attentiveness and unusual eye movements at age three to six months may be the first sign prompting parents to seek medical attention, where subsequent ophthalmologic evaluation reveals the characteristic cherry-red macula seen in virtually all children with infantile disease. Progression. By age six to ten months, acquisition of developmental milestones plateaus and eventually ceases across multiple domains. Finally, children begin to lose previously demonstrated skills. * After age eight to ten months, progression of the disease is rapid. Spontaneous or purposeful voluntary movements diminish, and the infant becomes progressively less responsive. Vision deteriorates rapidly. Seizures are common by age 12 months. Subtle partial complex seizures or absence seizures typically become more frequent and severe. * Progressive enlargement of the head typically begins by age 18 months resulting from reactive cerebral gliosis but eventually followed by ventriculomegaly [Nestrasil et al 2018]. * Further deterioration in the second year of life results in decerebrate posturing, difficulties in swallowing, worsening seizures, and finally an unresponsive, vegetative state. Death from respiratory complications usually occurs between ages two and three years, although the use of a gastrostomy tube to minimize aspiration events and improved pulmonary hygiene with the use of vibrating vests has extended the life span of infantile patients to between five and seven years [Bley et al 2011, Regier et al 2016]. #### Subacute Juvenile Tay-Sachs Disease Presentation. Children attain normal developmental milestones up until around age two years. Between ages two and five years, gains in motor and speech parameters slow down and eventually plateau. Abnormal gait or dysarthria begins to emerge, followed by loss of previously acquired skills and cognitive decline. Progression. Spasticity, dysphagia, and seizures are present by the end of the first decade of life [Maegawa et al 2006]. * A decrease in visual acuity occurs much later in subacute juvenile Tay-Sachs disease than in the acute infantile form of the disease and the cherry-red spot is rarely observed. Optic atrophy and retinal pigmentation may be seen late in the course of the disease. * A vegetative state with decerebrate posturing begins to appear in many individuals by age ten to 15 years, followed within a few years by death, usually from aspiration. Newer measures in supportive care that protect airways and improve pulmonary toilet may extend life span. In some individuals, the disease pursues a particularly aggressive course, culminating in death within two to four years of symptom onset. Clinical variability is observed in the subacute juvenile form of TSD even among affected members of the same family. #### Late-Onset Tay-Sachs Disease (LOTS) Presentation. Affected individuals present with a slowly progressive spectrum of neurologic and psychiatric symptoms as older teenagers or young adults. In retrospect, many parents can describe nonspecific subtle clumsiness or developmental irregularities earlier in life. As most subjects achieve nearly normal milestones to adulthood and the disorder progresses slowly over decades, the presentation may resemble that of other "neurodegenerative" conditions of adults. The later development of symptoms compared to the acute infantile and subacute juvenile versions of Tay-Sachs disease is attributed to the presence of residual beta-hexosaminidase A (HEX A) enzyme activity, enough to forestall the onset of symptoms to adulthood. Early symptoms may range from neurogenic lower-extremity weakness with atrophy of the quadriceps muscles to dysarthria, incoordination, tremor, mild spasticity, and/or dystonia. Up to 40% of individuals with LOTS may experience psychiatric manifestations, including acute psychosis [Masingue et al 2020; Toro, personal observation]. Progression. Central nervous system involvement in LOTS is widespread, however, certain central nervous system structures appear to be more vulnerable to the disease than others, leading to particular clinical findings: * Most, if not all, individuals with LOTS develop progressive neurogenic muscle weakness and wasting. Early in the disease course, weakness involves the lower extremities, particularly the knee extensors and hip flexors. Atrophy, cramps, and fasciculations are common. Affected individuals relate progressive difficulty in climbing steps or bleachers, eventually requiring the aid of handrails. As knee extensor muscle weakness progresses, individuals hyperextend ("lock") their knees to support their weight, producing a characteristic gait. Failure to maintain knees locked results in collapse and injury. Upper-extremity strength may become affected years later with a predilection for elbow extension (triceps) weakness. Long tract findings including spasticity, upgoing toes, and brisk reflexes can be present but may be obscured by lower motor neuron weakness. * Dysarthria is common; the speech rate is fast and almost "pressured," which, together with poor articulation, affects speech intelligibility. The poor articulation emerges primarily from cerebellar dysfunction; however, patients may demonstrate associated features of focal laryngeal dystonia (spasmodic dysphonia), leading to a "strangled" voice and overflow activation of neck and facial muscles. Despite prominent dysarthria, dysphagia and aspiration events are not common early in LOTS. * Decreased balance requiring a wide base of support, decreased dexterity, and tremor are frequent findings in LOTS. These – along with the presence of saccadic dysmetria and abnormal saccadic gain during formal extraocular movement examination – are attributed at least in part to cerebellar dysfunction [Stephen et al 2020]. Cerebellar atrophy is evident even early in the disease, at times out of proportion to the extent of cerebellar deficits, and is almost universal in LOTS. * Psychiatric manifestations including comorbid anxiety and depression are common. Acute psychosis and mania can occur, representing the initial manifestation of disease in some individuals. * Deficits in executive function and memory are reported in some individuals and can be associated with progressive brain volume loss. Contrary to the acute infantile and subacute juvenile phenotypes, however, declines in higher cortical functioning develop slowly, often over decades after the onset of disease symptoms. Clinical variability is significant for LOTS, even within a single family with more than one affected individual. Psychosis may be severe by age 20 years in one individual, whereas another older affected sib may function well into adulthood with mainly neuromuscular complaints [Author, personal observation]. ### Neuropathology Children with the acute infantile form of TSD have excessive and ubiquitous neuronal glycolipid storage (≤12% of the brain dry weight), of which the enormous predominance is the specific glycolipid GM2 ganglioside. Individuals with the adult-onset forms have less accumulation of glycolipid; it may even be restricted to specific brain regions. For example, in LOTS the neocortex may be spared, while the hippocampus, brain stem nuclei, and the spinal cord are markedly affected [Gravel et al 2001]. ### Genotype-Phenotype Correlations In general, individuals with two null (nonexpressing) alleles have the infantile form, individuals with one null allele and one missense allele have the subacute juvenile-onset phenotype, and individuals with two missense alleles have the milder late-onset phenotype. This reflects the inverse correlation of the level of the residual activity of the HEX A enzyme with the severity of the disease: the lower the level of the enzymatic activity, the more severe the phenotype is likely to be. ### Nomenclature Tay-Sachs disease was originally described as "infantile amaurotic idiocy" and "amaurotic familial infantile idiocy" by Tay and Sachs, respectively. When GM2 ganglioside was identified as the major accumulating substrate, the nomenclature included the terms "infantile ganglioside lipidosis," "type 1 GM2 gangliosidosis," and "acute infantile GM2 gangliosidosis." When deficient HEX A enzymatic activity was identified, the disease was then referred to as "hexosaminidase A deficiency," "HEX A deficiency," or "type 1 hexosaminidase A deficiency." When the subacute juvenile and late-onset phenotypes were identified, they were referred to as the "B1 variant of GM2 gangliosidoses" or "juvenile (subacute) hexosaminidase deficiency" and "chronic or adult-onset hexosaminidase A deficiency," respectively. ### Prevalence Before the advent of population-based carrier screening, education, and counseling programs for the prevention of TSD in Jewish communities, the incidence of TSD was estimated at 1:3,600 Ashkenazi Jewish births. At that birth rate, the carrier rate for TSD is approximately 1:30 among Jewish Americans of Ashkenazi extraction (i.e., from Central and Eastern Europe). Carrier screening studies have indicated that the frequency of the Ashkenazi Jewish founder variants in individuals whose parents and respective grandparents were of Ashkenazi Jewish descent is 1:27.4 [Scott et al 2010]. As the result of extensive genetic counseling of carriers identified through carrier screening programs and monitoring of at-risk pregnancies, the incidence of TSD in the Ashkenazi Jewish population of North America has been reduced by greater than 90% [Kaback et al 1993, Kaback 2000]. Among Sephardic Jews and all non-Jews, the disease incidence has been observed to be about 100 times lower, corresponding to a tenfold lower carrier frequency (between 1:250 and 1:300). TSD has been reported in children of virtually all ethnic, racial, and religious groups. Other genetically isolated populations have been found to carry founder HEXA pathogenic variants at frequencies comparable to or even greater than those observed in Ashkenazi Jews. These include: * French Canadians of the eastern St Lawrence River Valley area of Quebec; * Cajuns from Louisiana. ## Differential Diagnosis The neurologic symptoms that develop in the course of HEXA disorders are not unique and can be caused by a wide array of hereditary and acquired conditions, including toxic and infectious/post-infectious disorders. ### Hereditary Disorders #### Infantile Onset ### Table 3. Genetic Disorders of Interest in the Differential Diagnosis of Acute Infantile Tay-Sachs Disease View in own window GeneDisorderCherry-Red Spot (≤12 mos)Onset of Neurologic RegressionOther Features / CommentFeatures Distinguishing the Disorder from Acute Infantile TSD ASPACanavan disease–≤6 mosMacrocephaly, head lag, hypotonia, seizuresLeukoencephalopathy, ↑ N-acetyl aspartate in CSF CLN5 CLN6 CLN8 CTSD MFSD8 PPT1 TPP1Neuronal ceroid lipofuscinoses, infantile & late-infantile (OMIM PS256730)–≤6 mosVisual deficits, seizuresAbnormal ERG CTSAGalactosialidosis (OMIM 256540)+<6 mosSeizuresHepatosplenomegaly w/coarse features & skeletal disease GALCKrabbe disease–≤6 mosSeizuresLeukodystrophy, peripheral neuropathy, irritability GBAGaucher disease type 2–≤6 mosSeizures in some personsOculomotor abnormalities, hypertonia, opisthotonos GFAPAlexander disease, infantile form–≤6 mosMacrocephaly, seizuresLeukodystrophy GLB1GM1 gangliosidosis type 1 (See GLB1 Disorders.)+≤12 mosSeizuresHepatosplenomegaly w/coarse facies, skeletal disease GM2AActivator-deficient TSD 1 (GM2 gangliosidosis, AB variant) (OMIM 272750)+≤6 mosPhenotype identical to classic TSD; 2 extremely rare disorderNo distinguishing features GNPTABMucolipidosis II (I-cell disease) (See GNPTAB Disorders.)–≤12 mosHepatosplenomegaly w/coarse facies, hyperplastic gums, skeletal disease; absence of seizures HEXBSandhoff disease 3 (OMIM 268800)+≤6 mosSeizuresHepatosplenomegaly, skeletal abnormalities, deficiency of both HEX A & HEX B enzyme activity NEU1Sialidosis type II (OMIM 256550)+≤12 mosSeizuresHepatosplenomegaly w/coarse facies, skeletal abnormalities SMPD1Niemann-Pick disease type A (See Acid Sphingomyelinase Deficiency.)+≤12 mosHepatosplenomegaly, feeding difficulties, severe failure to thrive, xanthomas; absence of seizures The disorders included in Table 3 are inherited in an autosomal recessive manner, with the exception of Alexander disease, which is an autosomal dominant disorder. CSF = cerebrospinal fluid; ERG = electroretinogram; HEX A = beta-hexosaminidase A; HEX B = hexosaminidase B; TSD = Tay-Sachs disease 1\. In activator-deficient TSD, enzymatic activity of both HEX A and HEX B is normal, but GM2 ganglioside accumulation occurs because of a deficit of the intralysosomal glycoprotein ("GM2 activator") that is required for the degradation of GM2 ganglioside. 2\. Progressive weakness and loss of motor skills between ages six and 12 months, associated with an increased startle response, a cherry-red spot of the macula of the retina, and normal-size liver and spleen 3\. In Sandhoff disease, the activity of HEX A is deficient, as is the activity of HEX B, since both enzymes lack the common beta subunit. #### Subacute Juvenile Onset ### Table 4. Genetic Disorders of Interest in the Differential Diagnosis of Subacute Juvenile Tay-Sachs disease View in own window GeneDisorderCherry-Red Spot (≤12 mos)Onset of Neurologic RegressionOther Features / CommentFeatures Distinguishing the Disorder from Subacute Juvenile TSD ASPACanavan disease–≤6 mosMacrocephaly, head lag, hypotonia, seizuresLeukoencephalopathy & ↑ N-acetyl aspartate in CSF CLN3CLN3 disease (OMIM 204200) (Batten disease)–9-18 yrsSeizuresProgressive visual loss (onset age 4-5 yrs), retinitis pigmentosa, cataracts, myoclonus, parkinsonism, abnormal ERG, ultrastructural abnormalities in lymphocytes, skin & other tissues CTSAGalactosialidosis (OMIM 256540)+>12 mosSeizuresHepatosplenomegaly w/coarse features, skeletal disease GBAGaucher disease type 3–≥12 mosSeizuresCharacteristic looping of saccadic eye movements GLB1GM1 gangliosidosis type II (See GLB1 Disorders.)–1-5 yrsSeizuresSkeletal disease HEXBSandhoff disease (OMIM 268800)+3-5 yrsClinical course nearly the same as subacute juvenile TSDDeficiency of both HEX A & HEX B enzyme activity The disorders included in Table 4 are inherited in an autosomal recessive manner. CSF = cerebrospinal fluid; ERG = electroretinogram; HEX A = beta-hexosaminidase A; HEX B = hexosaminidase B; TSD = Tay-Sachs disease Spinocerebellar ataxia (SCA). Some spinocerebellar ataxia syndromes (e.g., ataxia caused by mutation of FGF14, MTCL1, or TXN2 or SCA7 with extreme anticipation) may be associated with early onset and can be considered in the differential diagnosis of subacute juvenile TSD (see Hereditary Ataxia Overview). #### Late Onset ### Table 5. Genetic Disorders in the Differential Diagnosis of Late-Onset Tay-Sachs Disease View in own window GeneDisorderMOIOverlapping FeaturesDistinguishing Features ARSpinal & bulbar muscular atrophy (SBMA)XLNeurogenic weakness/atrophy (proximal > distal), tremor, cramps & fasciculations, slow progressionIn SBMA: tongue atrophy, facial weakness, androgen insensitivity, gynecomastia, & glucose intolerance C9orf72 FUS SOD1 TARDBP (>30 genes) 1Amyotrophic lateral sclerosis (ALS)AD AR XLProgressive neurogenic atrophy, cramps fasciculations, spasticityIn ALS: neurogenic atrophy is often asymmetrical, bulbar onset (in some persons); absence of cerebellar deficits CLN6 CTSF DNAJC5Adult-onset neuronal ceroid-lipofuscinosis (CLN) (OMIM 204300, 615362, 162350)AR ADAtaxiaIn adult-onset CLN: seizures, myoclonus, early intellectual deterioration FXNFriedreich ataxia (FRDA)ARAtaxia, abnormal eye movements, dysarthria, neurogenic weakness & long tract findings, slow progressionIn FRDA: cardiomyopathy, EKG conduction defects, diabetes, pes cavus, scoliosis, slow sensory nerve conduction velocity, optic atrophy, hearing loss, neurogenic bladder HEXBSandhoff disease (OMIM 268800)ARProgressive motor weakness beginning in lower extremitiesIn Sandhoff disease: sensory neuropathy, less dysarthria than in LOTS SMN1Later-onset spinal muscular atrophy (SMA types III & IV)ARTremor, fasciculations, atrophy, cramps, proximal muscle involvementIn SMA: early scoliosis, tongue fasciculations, progressive ↓ in pulmonary function, absence of ataxia CHCHD10 TFG VAPBLate onset SMA (See CHCHD10-Related Disorders.) & SMA-like disorder (OMIM 604484, 182980)ADNeurogenic atrophyLarge kindreds, no cerebellar deficits, ↑ CPK in some affected persons AD = autosomal dominant; AR = autosomal recessive; CPK = creatine phosphokinase; EKG = electrocardiogram; LOTS = late-onset Tay-Sachs disease; MOI = mode of inheritance; XL = X-linked 1\. C9orf72, FUS, SOD1, and TARDBP are the most commonly involved genes; for other genes associated with amyotrophic lateral sclerosis see OMIM Phenotypic series: Amyotrophic lateral sclerosis. Spinocerebellar ataxia (SCA). Similar to late-onset TSD, SCA is associated with tremor, cerebellar atrophy, and dysarthria and can be considered in the differential diagnosis (see Hereditary Ataxia Overview). ### Acquired Disorders Lead and other heavy metal poisoning, infectious and postinfectious meningoencephalitis, subacute sclerosing panencephalitis, hydrocephalus, and neurologic manifestations of other systemic diseases may mimic the neurologic findings associated with HEXA disorders. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a HEXA disorder, the evaluations summarized in Tables 6, 7, and 8 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 6. Recommended Evaluations Following Initial Diagnosis in Individuals with Acute Infantile Tay-Sachs Disease View in own window System/ConcernEvaluationComment NeurologicNeurology eval * To incl brain MRI * Consider EEG if seizures are a concern. Musculoskeletal systemPhysical medicine & rehab / PT/OT evalTo incl assessment of: * Gross motor & fine motor skills * Need for adaptive devices * Need for PT (to prevent deformities) Gastrointestinal/ FeedingGastroenterology / nutrition / feeding team eval * To incl swallow study for eval of aspiration risk & nutritional status * Consider eval for gastric tube placement in those w/dysphagia &/or aspiration risk. * Assess for constipation. EyesOphthalmologic examEval for macular degeneration, cherry-red spot, visual loss RespiratoryEvaluate aspiration risk.Assess need for airway toileting. Genetic counselingBy genetics professionals 1To inform paffected persons & families re nature, MOI, & implications of this disorder to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support; * Need for home nursing referral. EEG = electroencephalogram; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy 1\. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse ### Table 7. Recommended Evaluations Following Initial Diagnosis in Individuals with Subacute Juvenile Tay-Sachs Disease View in own window System/ConcernEvaluationComment NeurologicNeurology eval * To incl brain MRI * Consider EEG if seizures are a concern. * Evaluate for spasticity. DevelopmentDevelopmental assessment * To incl motor, adaptive, cognitive, & speech/language eval * Eval for IEP Musculoskeletal systemPhysical medicine & rehab / PT/OT evalTo incl assessment of: * Gross motor & fine motor skills * Mobility, independence in ADL, & need for adaptive devices * Need for PT (to prevent fixed deformities) Gastrointestinal/ FeedingGastroenterology / nutrition / feeding team eval * To incl swallow study for eval of aspiration risk & nutritional status * Consider eval for gastric tube placement in those w/dysphagia &/or aspiration risk. * Assess for constipation. EyesOphthalmologic examAssess visual acuity. RespiratoryEvaluate aspiration risk.Assess need for airway toileting & percussion vest. Genetic counselingBy genetics professionals 1To inform affected persons & families re nature, MOI, & implications of this disorder to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support. ADL = activities of daily living; EEG = electroencephalogram; IEP = individualized education program; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy 1\. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse ### Table 8. Recommended Evaluations Following Initial Diagnosis in Individuals with Late-Onset Tay-Sachs Disease View in own window System/ConcernEvaluationComment NeurologicNeurology evalAssess for weakness & tremor. DysarthriaSpeech eval PsychiatricNeuropsychiatric evalAssess for psychosis, anxiety, & depression. Musculoskeletal systemPhysical medicine & rehab / PT/OT evalTo incl assessment of: * Gross motor & fine motor skills * Mobility, ADL, & need for adaptive devices * Need for PT (to prevent falls & pressure wounds) &/or OT to maximize independence in ADL Genetic counselingBy genetics professionals 1To inform affected persons & families re nature, MOI, & implications of this disorder to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources; * Need for social work involvement for support. ADL = activities of daily living; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy 1\. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse ### Treatment of Manifestations For the most part, treatment for acute infantile Tay-Sachs disease (TSD) is supportive and directed to providing adequate nutrition and hydration, managing infectious disease, protecting the airway, and controlling seizures. The treatment for the subacute juvenile and late-onset TSD phenotypes is directed to providing the services of a physiatrist and team of physical, occupational, and speech therapists for maximizing function and providing aids for activities of daily living. ### Table 9. Treatment of Manifestations in Individuals with Acute Infantile Tay-Sachs Disease View in own window Manifestation/ConcernTreatmentConsiderations/Other SeizuresStandardized treatment w/AEDs by experienced neurologist * Seizures are often progressive & refractory. * Many AEDs may be effective; none has been demonstrated effective specifically for this disorder. * Complete seizure control is seldom achieved & requires balancing w/sedative side effects of AEDs. * Education of parents/caregivers 1 Abnormal tone / Impaired mobilityPT/OTFor prevention of deformities Feeding difficultiesGastrostomy tubeWill ↑ longevity but not preserve developmental function Bowel dysfunctionMonitor for constipation.Stool softeners, prokinetics, osmotic agents, or laxatives as needed Aspiration risks / Excess secretionGastrostomy tube, vibrator vest, improved pulmonary toilet, suppression of saliva productionWill ↓ aspiration & improve longevity but not developmental function Family supportIn-home nursing & respite careSupport for health & quality of life of caregivers & sibs AED = antiepileptic drug; OT = occupational therapy; PT = physical therapy 1\. Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. ### Table 10. Treatment of Manifestations in Individuals with Subacute Juvenile Tay-Sachs Disease View in own window Manifestation/ConcernTreatmentConsiderations/Other SeizuresStandardized treatment w/AEDs by experienced neurologist * Seizures are often progressive & refractory. * Many AEDs may be effective; none has been demonstrated effective specifically for this disorder. * Complete seizure control is seldom achieved & requires balancing w/sedative side effects of AEDs. * Education of parents/caregivers 1 SpasticityStretching, splints, pharmacologic treatment Developmental plateau / Cognitive declineIEP Feeding difficultiesGastrostomy tubeWill ↑ longevity but not preserve developmental function Bowel dysfunctionMonitor for constipation.Stool softeners, prokinetics, osmotic agents, or laxatives as needed Saliva pooling / DroolingBotulinum toxin to salivary glands, topical (drops) anticholinergic agentsBotox may spread to adjacent bulbar muscles, worsening dysphagia. Family supportIn-home nursing & respite care as needed w/progression of diseaseSupport for health & quality of life of caregivers & sibs IEP = individualized education program 1\. Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. ### Table 11. Treatment of Manifestations in Individuals with Late-Onset Tay-Sachs Disease View in own window Manifestation/ConcernTreatmentConsiderations/Other Weakness / Impaired mobilityPT/OTAdaptive equipment & mobility assists Spasticity/TremorSymptom-targeted pharmacotherapy by experienced neurologist Communication needsVoice therapyFocus on strategies to slow speech rate. Occupational counselingVocational rehab Psychiatric issues * Antidepressant or antipsychotic medications may be used, but clinical response is variable & can be poor. * Cognitive behavioral therapy ↑ coping skills. * Electroconvulsive therapy reported beneficial in some cases Treatment needs to be individualized. Family supportIn-home nursing & respite careCould be indicated for patients w/advanced disease OT = occupational therapy; PT = physical therapy ### Surveillance There are no formal guidelines for surveillance for those affected with HEXA disorders. Neurology evaluations should commence at the time of diagnosis for all subtypes of TSD if not previously established, and follow up should be dictated by emergent clinical concerns. ### Agents/Circumstances to Avoid For individuals with acute infantile TSD, avoid: * Positioning that increases aspiration risk during feedings; * Seizure medication dosages that result in excessive sedation. For individuals with subacute juvenile TSD, avoid: * Situations that increase the likelihood of contractures or pressure sores, such as extended periods of immobility; * Circumstances that exacerbate the risk of falls. For individuals with late-onset TSD, avoid: * Situations that exacerbate fall risk (i.e., walking on uneven or unstable surfaces); * Psychiatric medications that have been associated with disease worsening (e.g., haloperidol, risperidone, and chlorpromazine) [Shapiro et al 2006]. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Current studies include: * A Phase II study to assess the safety and efficacy of N-acetyl-L-leucine for the treatment of GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease); * A multicenter study to assess the efficacy and pharmacodynamics of daily oral dosing of venglustat when administered over a 104-week period in late-onset and subacute juvenile GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease); * A combination therapy using miglustat and the ketogenic diet for infantile and juvenile patients with gangliosidoses; * A survey of miglustat therapeutic effects on neurologic and systemic symptoms of infantile type of Tay-Sachs and Sandhoff Disease. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on other clinical studies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	HEXA Disorders	None	6,767	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1218/	2021-01-18T21:22:23	{"synonyms": ["Beta-Hexosaminidase A Deficiency; GM2 Gangliosidosis", "Type I; Tay-Sachs Disease"]}
Hutchinson's mask is a patient's sensation that the face is covered with a mask or a gauzy network like cobwebs. This medical sign is associated with tabes dorsalis[1] affecting the trigeminal nerve (fifth cranial nerve CN V). It is named in honour of the English physician Sir Jonathan Hutchinson (1828–1913). > Subjective sensations of various kinds, as numbness, pins and needles, formication, a cold trickling feeling in the skin, a feeling in the soles of the feet of walking on putty, wool, or velvet may be complained of. In rare cases Hutchinson's mask, due to affection of the fifth, occurs. The patient says his face feels stiff, and he feels as if it were covered by a cobweb.[2] ## References[edit] 1. ^ Bartolucci, S L.; Stedman, T L.; Forbis, P. (2005), Stedman's Medical Eponyms, Lippincott Williams & Wilkins, p. 348, ISBN 0-7817-5443-7 2. ^ Mott, Frederick Walker, ed. (1908). Archives of Neurology and Psychiatry from the Pathological Laboratory of the London County Asylums, Clabury, Essex. Vol. 2. p. 45. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Hutchinson's mask	c0686769	6,768	wikipedia	https://en.wikipedia.org/wiki/Hutchinson%27s_mask	2021-01-18T18:52:02	{"wikidata": ["Q28403848"]}
A number sign (#) is used with this entry because glycogen storage disease VI (GSD6) is caused by homozygous or compound heterozygous mutation in the PYGL gene (613741), which encodes liver glycogen phosphorylase, on chromosome 14. Clinical Features The clinical picture in glycogen storage disease VI is one of mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. The prognosis seems to be excellent (Hers, 1959; Hers and van Hoof, 1968). Wallis et al. (1966) determined erythrocyte glycogen concentration and leukocyte phosphorylase activity in 17 members of 4 generations of the family of a boy with biopsy-proved glycogen storage disease type VI. Chang et al. (1998) studied a Mennonite family in which the diagnosis of glycogen storage disease type VI had first been made in a 22-month-old girl in 1962. The patient had hepatomegaly, fatigue, and decelerating linear growth. Liver and muscle biopsies showed enlarged hepatocytes with a granular substance consistent with glycogen. Muscle glycogen was normal but liver glycogen was 20%, approximately 4 times the control values. Seventeen individuals with glycogen storage disease were studied. Pedigree analysis showed that all families could be traced back to a couple who lived in eastern Pennsylvania in the 1830s. One instance of pseudodominance was observed; an affected mother married to a distant cousin had an affected son. Roscher et al. (2014) reported on 21 patients (17 males and 4 females) from 17 unrelated families with glycogen storage disease (GSD) IXa (306000), GSD IXb (261750), GSD IXc (613027), or GSD VI, which are caused by phosphorylation deficiencies. The average age was 11.66 years, with a range of 3 to 18 years. Eleven patients (53%) had GSD IXa1; 3 (14%) had GSD IXb; 3 (14%) had GSD IXc; and 4 (19%) had GSD VI. The average age of initial presentation was 20 months (range 4-160 months). The GSD IXb patients presented earliest at the age of 5 months (range 4-6 months). Hepatomegaly was present in 95% of patients on physical examination and 100% on liver ultrasound. Four patients presented with failure to thrive, and 2 with short stature. None of the patients had intellectual disability or global developmental delay at most recent evaluation, although some had early developmental delay. Alanine transaminase (ALT) was elevated in 18 patients (86%), and aspartate transaminase (AST) was elevated in 19 (90%). Hypercholesterolemia was present in 14 of the 21 patients, and hypertriglyceridemia was present in 16. While previous reports noted hypoglycemia in 17 to 44% of patients with GSD VI or subtypes of GSD IX, hypoglycemia occurred in less than 5% of the patients in the cohort of Roscher et al. (2014). Two patients had developed likely liver adenomas at long-term follow-up, which had not been theretofore reported. Mapping In a Mennonite family segregating glycogen storage disease VI, Chang et al. (1998) found linkage of the disorder to the PYGL locus on chromosome 14, with a multipoint lod score of 4.7. Inheritance Glycogen storage disease VI is an autosomal recessive disorder (Burwinkel et al., 1998; Chang et al., 1998). Molecular Genetics In 3 patients with Hers disease, Burwinkel et al. (1998) identified mutations in the PYGL gene in homozygous or compound heterozygous state (613741.0001-613741.0004). By sequencing genomic DNA in a Mennonite family segregating glycogen storage disease VI, Chang et al. (1998) identified a homozygous abnormality of the intron 13 splice donor (613741.0005). This mutation was estimated to be present on 3% of Mennonite chromosomes and the frequency of the disease was estimated to be 1 in 1,000 in that population. Determination of the mutation provided a basis for the development of a simple and noninvasive diagnostic test for the disease and the carrier state in this population. History Hers and Van Hoof (1968) suggested that glycogen storage disease type VI was a 'waiting room' from which new entities will be separated in the future; type VI was later reserved for cases with liver phosphorylase deficiency as the primary defect. There is confusion in the numbering system of the glycogen storage diseases: hepatic phosphorylase deficiency, here designated GSD VI, was labeled GSD VIII in Stanbury et al. (1983). INHERITANCE \- Autosomal recessive GROWTH Height \- Growth retardation as children \- Final adult height normal ABDOMEN Liver \- Hepatomegaly \- Increased liver glycogen content METABOLIC FEATURES \- Hypoglycemia LABORATORY ABNORMALITIES \- Hepatic phosphorylase deficiency \- Variable hyperlipidemia \- Variable hypoglycemia \- No lactic acidosis \- No hyperuricemia MISCELLANEOUS \- Presentation in early childhood \- Hepatomegaly improves with age and disappears around puberty MOLECULAR BASIS \- Caused by mutation in the liver glycogen phosphorylase gene (PYGL, 613741.0001 ) ▲ 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	GLYCOGEN STORAGE DISEASE VI	c0017925	6,769	omim	https://www.omim.org/entry/232700	2019-09-22T16:27:25	{"doid": ["2754"], "mesh": ["D006013"], "omim": ["232700"], "icd-10": ["E74.09"], "orphanet": ["369"], "synonyms": ["Alternative titles", "GSD VI", "HERS DISEASE", "PHOSPHORYLASE DEFICIENCY GLYCOGEN-STORAGE DISEASE OF LIVER"], "genereviews": ["NBK5941"]}
A number sign (#) is used with this entry because of evidence that long QT syndrome-15 (LQT15) is caused by heterozygous mutation in the CALM2 gene (114182) on chromosome 2p21. For a general phenotypic description and discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500). Clinical Features Crotti et al. (2013) reported a Hispanic girl in whom fetal bradycardia was first noted at 21 weeks' gestation; fetal echocardiogram showed normal cardiac anatomy and function except for bradycardia. Two hours after birth she exhibited sinus bradycardia, T-wave alternans, markedly prolonged QTc (690 ms), and 2:1 AV block. At 3 weeks of age, she underwent cardiac arrest with multiple episodes of ventricular fibrillation (VF), during which time she also suffered a cerebral infarction of the right parietal lobe. She continued to have multiple episodes of VF, and developed seizures at age 2 years that were attributed to the prior brain injury; at age 3, she exhibited developmental delays. Her parents and an older sister were asymptomatic with normal electrocardiograms (ECGs), and there was no history of arrhythmia, miscarriage, sudden death, seizures, or drowning in the family. Makita et al. (2014) studied 5 unrelated patients of varying ancestry who had prolonged QTc intervals and demonstrated congenital arrhythmia susceptibility. The first patient was a 16-year-old Japanese girl with a history of fetal bradycardia who had her first episode of syncope at age 19 months. ECG at that time showed marked QTc prolongation (579 ms) with atypical notched, late-peaking T waves. Subsequently, she experienced multiple episodes of cardiac arrest during exertion when she failed to take her antiarrhythmic medication, prompting placement of an internal cardioverter-defibrillator (ICD) at age 14 years. Family history was negative for LQT syndrome or sudden death, and both parents and 2 brothers had normal QTc intervals. The second patient was a 12-year-old Japanese boy who at age 5 years had 2 episodes of syncope with seizure while running. ECG showed QTc prolongation (478 ms), whereas echocardiogram, electroencephalogram, and brain MRI were normal. There was no family history of arrhythmia or sudden death, and his unaffected parents and brother had normal QTc intervals. The third patient was a 29-year-old German woman who experienced perinatal bradycardia and neonatal LQT syndrome, which was treated with medication. At 9 years of age, following interruption of therapy, she had a syncopal episode while swimming, at which time there was evidence of exercise-induced polymorphic ventricular ectopy. Her resting ECG showed QTc prolongation (465-578 ms) with T-wave abnormalities. Echocardiogram at age 22 was normal, but cardiac MRI revealed features consistent with noncompaction of the left ventricular myocardium (see 604169). Both parents had normal QTc intervals. The fourth patient was a Moroccan girl who had syncope with prolonged unconsciousness at 8 years of age, at which time prolonged QTc (500 ms) with ventricular bigeminy was noted. She had no neurologic dysfunction, and echocardiogram and head CT were normal. She died at age 11 while dancing at a wedding. Her parents and 4 sisters were asymptomatic. The fifth patient was a 2.5-year-old English boy who had cardiac arrest due to ventricular fibrillation at 17 months of age. ECG showed bradycardia and prolonged QTc interval (555 ms). There was no family history of cardiac arrhythmia, and both parents had normal QTc intervals. The boy underwent placement of an ICD; there were no discharges over the following year. Molecular Genetics In a Hispanic girl with markedly prolonged QTc intervals and multiple episodes of ventricular fibrillation, who was negative for mutation in the 5 genes most frequently associated with LQT syndrome (LQTS), Crotti et al. (2013) performed exome sequencing and identified a heterozygous de novo missense mutation the CALM2 gene (D96V; 114182.0001). The mutation was not found in 92 Hispanic American controls or in public databases. Functional analysis demonstrated a several-fold reduction in calcium-binding affinity with the D96V mutant compared to wildtype calmodulin. Among 12 unrelated Japanese patients with LQTS who were negative for mutation in genes known to be associated with life-threatening arrhythmias, Makita et al. (2014) used next-generation sequencing and identified heterozygosity for a de novo mutation in the CALM2 gene (D134H; 114182.0002) in a 16-year-old girl. Analysis of exome-sequencing data from 190 unrelated mutation-negative Japanese patients with LQTS revealed another missense mutation in CALM2 (N98S; 114182.0003) in a 12-year-old boy. Exome sequencing in an affected English boy identified heterozygosity for a different mutation at codon 98 in CALM2 (N98I; 114182.0004). Candidate gene screening of the 3 calmodulin genes revealed 2 more heterozygous missense mutations in CALM2: D132E (114182.0005) in a 29-year-old German woman with LQTS, and Q136P (114182.0006) in a Moroccan girl who died suddenly during exertion at age 11 years. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Recurrent episodes of ventricular fibrillation \- Bradycardia (in some patients) \- Cardiac arrest (in some patients) \- Sudden death (in some patients) Prolonged QTc interval on electrocardiogram (ECG) \- Notched T waves on ECG (in some patients) \- Exercise-induced polymorphic ventricular ectopy on ECG (rare) PRENATAL MANIFESTATIONS \- Fetal bradycardia (in some patients) MISCELLANEOUS \- Onset at birth or in early childhood MOLECULAR BASIS \- Caused by mutation in the calmodulin-2 gene (CALM2, 114182.0001 ) ▲ 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	LONG QT SYNDROME 15	c1141890	6,770	omim	https://www.omim.org/entry/616249	2019-09-22T15:49:28	{"doid": ["0110656"], "omim": ["616249"], "orphanet": ["768", "101016"], "genereviews": ["NBK1129"]}
Synovial chondromatosis is a type of non-cancerous tumor that arises in the lining of a joint. The knee is most commonly affected, however it can affect any joint. The tumors begin as small nodules of cartilage. These nodules can separate and become loose within the joint. Some tumors may be no larger than a grain of rice. Synovial chondromatosis most commonly occurs in adults ages 20 to 50. Signs and symptoms may include pain, swelling, a decreased range of motion, and locking of the joint. The exact underlying cause of the condition is unknown. Treatment may involve surgery to remove the tumor. Recurrence of the condition is common. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Synovial Chondromatosis	c0008476	6,771	gard	https://rarediseases.info.nih.gov/diseases/6054/synovial-chondromatosis	2021-01-18T17:57:27	{"mesh": ["D015838"], "umls": ["C0008476"], "synonyms": ["Synovial osteochondromatosis"]}
2,4-Dienoyl-CoA reductase deficiency is associated with hypotonia and respiratory acidosis in infancy. This condition may be associated with the DECR1 gene and likely has an autosomal recessive pattern of inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	2,4-Dienoyl-CoA reductase deficiency	c1857252	6,772	gard	https://rarediseases.info.nih.gov/diseases/10327/24-dienoyl-coa-reductase-deficiency	2021-01-18T18:02:26	{"mesh": ["C565624"], "omim": ["222745"], "umls": ["C1857252"], "orphanet": ["42641"], "synonyms": ["Dienoyl-CoA reductase deficiency", "2,4-alpha dienoyl-CoA reductase deficiency"]}
This article is about the thalidomide scandal and birth defect crisis. For the drug, see thalidomide. Phocomelia Cases of severe thalidomide-induced phocomelia. Baby born to a mother who had taken thalidomide while pregnant In the late 1950s and early 1960s, the use of thalidomide in pregnant women in 46 countries resulted in the "biggest man‐made medical disaster ever", resulting in more than 10,000 children born with a range of severe deformities, such as phocomelia, as well as thousands of miscarriages.[1][2] Thalidomide was introduced in 1956 and was aggressively marketed by the German pharmaceutical company Chemie Grünenthal under the trade name Contergan as a medication for anxiety, trouble sleeping, "tension", and morning sickness.[3][4] It was introduced as a sedative and medication for morning sickness without having been tested on pregnant women.[5] While initially deemed to be safe in pregnancy, concerns regarding birth defects were noted in 1961, and the medication was removed from the market in Europe that year.[3][6] ## Contents * 1 Birth defect crisis * 1.1 United Kingdom * 1.2 Spain * 1.3 Australia and New Zealand * 1.4 Germany * 1.5 Canada * 1.6 United States * 1.7 Austria * 2 Aftermath of scandal * 2.1 Grünenthal criminal trial * 3 Notable cases * 4 Change in drug regulations * 5 References * 6 Further reading * 7 External links ## Birth defect crisis[edit] Thalidomide was developed and first released by the German pharmaceutical company Chemie Grünenthal in 1957. The company had been established as a soap maker after World War II to address the urgent market need for antibiotics. Chemist Heinrich Mückter, who was a known Nazi war criminal,[7] was appointed to head the discovery programme based on his experience researching and producing an anti-typhus vaccine for Nazi Germany. The total number of people affected by the use of thalidomide during the mother's pregnancy is estimated at more than 10,000, of whom approximately 40 percent died at or shortly after the time of birth.[3][8] Those who survived had limb, eye, urinary tract, and heart defects.[6] Its initial entry into the US market was prevented by Frances Kelsey at the FDA.[4] The birth defects of thalidomide led to the development of greater drug regulation and monitoring in many countries.[4][6] The severity and location of the deformities depended on how many days into the pregnancy the mother was before beginning treatment; thalidomide taken on the 20th day of pregnancy caused central brain damage, day 21 would damage the eyes, day 22 the ears and face, day 24 the arms, and leg damage would occur if taken up to day 28. Thalidomide did not damage the fetus if taken after 42 days' gestation.[9] It is not known exactly how many worldwide victims of thalidomide embryopathy there have been, although estimates range from 10,000 to 20,000.[10] ### United Kingdom[edit] These artificial limbs were made for an affected child in the 1960s by the Department of Health and Social Security's Limb Fitting Centre in Roehampton, London In the UK, the drug was licensed in 1958 and withdrawn in 1961. Of the approximately 2,000 babies born with defects, around half died within a few months and 466 survived to at least 2010.[11] In 1968, after a long campaign by The Sunday Times, a compensation settlement for the UK victims was reached with Distillers Company (now part of Diageo), which had distributed the drug in the UK.[12][13] Distillers Biochemicals paid out approximately £28m in compensation following a legal battle.[14] The British Thalidomide Children’s Trust was set up in 1973 as part of a £20 million legal settlement between Distillers Company and 429 children with thalidomide-related disabilities. In 1997, Diageo (formed by a merger between Grand Metropolitan and Guinness, who had taken over Distillers in 1990) made a long-term financial commitment to support the Thalidomide Trust and its beneficiaries.[15] The UK government gave survivors a grant of £20 million, to be distributed through the Thalidomide Trust, in December 2009.[16] ### Spain[edit] In Spain, thalidomide was widely available throughout the 1970s, and perhaps even into the 1980s. There were two reasons for this. First, state controls and safeguarding were poor; indeed, it was not until 2008 that the government even admitted the country had ever imported thalidomide. Second, Grünenthal failed to insist that its sister company in Madrid warn Spanish doctors, and permitted it to not warn them. The Spanish advocacy group for victims of thalidomide estimates that in 2015, there were 250–300 living victims of thalidomide in Spain.[17] ### Australia and New Zealand[edit] Although the Australian obstetrician William McBride took credit for raising the alarm about thalidomide, it was a midwife called Sister Pat Sparrow who first suspected the drug was causing birth defects in the babies of patients under McBride's care at Crown Street Women's Hospital in Sydney.[18] German paediatrician Widukind Lenz, who also suspected the link, is credited with conducting the scientific research that proved thalidomide was causing birth defects in 1961.[19][20] McBride was later awarded a number of honors, including a medal and prize money by L'Institut de la Vie in Paris,[21] but he was eventually struck off the Australian medical register in 1993 for scientific fraud related to work on Debendox.[18][22] Further animal tests were conducted by Dr George Somers, Chief Pharmacologist of Distillers Company in Britain, which showed foetal abnormalities in rabbits.[23] Similar results were also published showing these effects in rats[24][25] and other species.[26] Melbourne woman Lynette Rowe, who was born without limbs, led an Australian class action lawsuit against the drug's manufacturer, Grünenthal, which fought to have the case heard in Germany. The Supreme Court of Victoria dismissed Grünenthal's application in 2012, and the case was heard in Australia.[27] On 17 July 2012, Rowe was awarded an out-of-court settlement, believed to be in the millions of dollars and paving the way for class action victims to receive further compensation.[28] In February 2014, the Supreme Court of Victoria endorsed the settlement of $89 million AUD to 107 victims of the drug in Australia and New Zealand.[29][30] ### Germany[edit] In East Germany, thalidomide was rejected by the Central Committee of Experts for the Drug Traffic in the GDR, and was never approved for use. There are no known thalidomide babies born in East Germany.[31] Meanwhile, in West Germany, it took some time before the increase in dysmelia at the end of the 1950s was connected with thalidomide. In 1958, Karl Beck, a former pediatric doctor in Bayreuth, wrote an article in a local newspaper claiming a relationship between nuclear weapons testing and cases of dysmelia in children.[32] Based on this, FDP whip Erich Mende requested an official statement from the federal government.[32] For statistical reasons, the main data series used to research dysmelia cases started by chance at the same time as the approval date for thalidomide.[32] After the Nazi regime with its Law for the Prevention of Hereditarily Diseased Offspring used mandatory statistical monitoring to commit various crimes, western Germany had been very reluctant to monitor congenital disorders in a similarly strict way.[33] The parliamentary report rejected any relation with radioactivity and the abnormal increase of dysmelia.[32] Also the DFG research project installed after the Mende request was not helpful. The project was led by pathologist Franz Büchner, who ran the project to propagate his teratological theory. Büchner saw lack of healthy nutrition and behavior of the mothers as being more important than genetic reasons.[33] Furthermore, it took a while to install a Surgeon General in Germany; the Federal Ministry of Health was not founded until 1962, some months after thalidomide was banned from the market.[32] In West Germany approximately 2,500 thalidomide babies were born.[20] ### Canada[edit] Despite its severe side effects, thalidomide was sold in pharmacies in Canada until 1962.[34][35] The effects of thalidomide increased fears regarding the safety of pharmaceutical drugs. The Society of Toxicology of Canada was formed after the effects of thalidomide were made public, focusing on toxicology as a discipline separate from pharmacology.[36] The need for the testing and approval of the toxins in certain pharmaceutical drugs became more important after the disaster. The Society of Toxicology of Canada is responsible for the Conservation Environment Protection Act, focusing on researching the impact to human health of chemical substances.[36] Thalidomide brought on changes in the way drugs are tested, what type of drugs are used during pregnancy, and increased the awareness of potential side effects of drugs. According to Canadian news magazine programme W5, most, but not all, victims of thalidomide receive annual benefits as compensation from the Government of Canada. Excluded are those who cannot provide the documentation the government requires.[37] A group of 120 Canadian survivors formed The Thalidomide Victims Association of Canada, the goal of which is to prevent the approval of drugs that could be harmful to pregnant women and babies.[38][39] The members from the thalidomide victims association were involved in the STEPS programme, which aimed to prevent teratogenicity.[40] ### United States[edit] In the U.S., the FDA refused approval to market thalidomide, saying further studies were needed. This reduced the impact of thalidomide in U.S. patients. The refusal was largely due to pharmacologist Frances Oldham Kelsey who withstood pressure from the Richardson-Merrell Pharmaceuticals Co. She subsequently was given a distinguished service award by President John F. Kennedy.[2] Although thalidomide was not approved for sale in the United States at the time, over 2.5 million tablets had been distributed to over 1,000 physicians during a clinical testing programme. It is estimated that nearly 20,000 patients, several hundred of whom were pregnant women, were given the drug to help alleviate morning sickness or as a sedative, and at least 17 children were consequently born in the United States with thalidomide-associated deformities.[41][42] While pregnant, children's television host Sherri Finkbine took an over-the-counter sedative her husband had purchased in Europe.[43] When she learned that thalidomide was causing fetal deformities she wanted to abort her pregnancy, but the laws of Arizona allowed abortion only if the mother's life was in danger. Finkbine traveled to Sweden to have the abortion. Thalidomide was found to have deformed the fetus.[41] 1962: FDA pharmacologist Frances Oldham Kelsey receives the President's Award for Distinguished Federal Civilian Service from President John F. Kennedy for blocking sale of thalidomide in the United States. For denying the application despite the pressure from Richardson-Merrell Pharmaceuticals Co., Kelsey eventually received the President's Award for Distinguished Federal Civilian Service at a 1962 ceremony with President John F. Kennedy. In September 2010, the FDA honored Kelsey with the first Kelsey award, given annually to an FDA staff member. This came 50 years after Kelsey, then a new medical officer at the agency, first reviewed the application from the William S. Merrell Pharmaceuticals Company of Cincinnati.[44] Cardiologist Helen B. Taussig learned of the damaging effects of the drug thalidomide on newborns and in 1967, testified before Congress on this matter after a trip to Germany where she worked with infants with phocomelia (severe limb deformities). As a result of her efforts, thalidomide was banned in the United States and Europe.[45] ### Austria[edit] Ingeborg Eichler, a member of the Austrian pharmaceutical admission conference, enforced restrictions on the sale of thalidomide (tradename Softenon) under the rules of prescription medication and as a result relatively few affected children were born in Austria and Switzerland.[46] ## Aftermath of scandal[edit] The numerous reports of malformations in babies brought about the awareness of the side effects of the drug on pregnant women. The birth defects caused by the drug thalidomide can range from moderate malformation to more severe forms. Possible birth defects include phocomelia, dysmelia, amelia, bone hypoplasticity, and other congenital defects affecting the ear, heart, or internal organs.[40] Franks et al. looked at how the drug affected newborn babies, the severity of their deformities, and reviewed the drug in its early years. Webb in 1963 also reviewed the history of the drug and the different forms of birth defects it had caused. "The most common form of birth defects from thalidomide is shortened limbs, with the arms being more frequently affected. This syndrome is the presence of deformities of the long bones of the limbs resulting in shortening and other abnormalities."[34] ### Grünenthal criminal trial[edit] In 1968, a large criminal trial began in Germany, charging several Grünenthal officials with negligent homicide and injury. After Grünenthal settled with the victims in April 1970, the trial ended in December 1970 with no finding of guilt. As part of the settlement, Grünenthal paid 100 million DM into a special foundation; the German government added 320 million DM. The foundation paid victims a one-time sum of 2,500–25,000 DM (depending on severity of disability) and a monthly stipend of 100–450 DM. The monthly stipends have since been raised substantially and are now paid entirely by the government (as the foundation had run out of money). Grünenthal paid another €50 million into the foundation in 2008. On 31 August 2012, Grünenthal chief executive Harald F. Stock who served as the Chief Executive Officer of Grünenthal GmbH from January 2009 to May 28, 2013 and was also a Member of Executive Board until 28 May 2013, apologised for the first time for producing the drug and remaining silent about the birth defects.[47] At a ceremony, Stock unveiled a statue of a disabled child to symbolise those harmed by thalidomide and apologised for not trying to reach out to victims for over 50 years. At the time of the apology, there were 5,000 to 6,000 sufferers still alive. Victim advocates called the apology "insulting" and "too little, too late", and criticised the company for not compensating victims. They also criticised the company for their claim that no one could have known the harm the drug caused, arguing that there were plenty of red flags at the time.[48] ## Notable cases[edit] Niko von Glasow, German filmmaker * Lorraine Mercer MBE of the United Kingdom, born with phocomelia of both arms and legs, is the only thalidomide survivor to carry the Olympic Torch.[49] * Thomas Quasthoff, an internationally acclaimed bass-baritone, who describes himself: "1.34 meters tall, short arms, seven fingers — four right, three left — large, relatively well-formed head, brown eyes, distinctive lips; profession: singer".[50] * Niko von Glasow produced a documentary called NoBody's Perfect, based on the lives of 12 people affected by the drug, which was released in 2008.[51][52] * Mercédes Benegbi, born with phocomelia of both arms, drove the successful campaign for compensation from her government for Canadians who were affected by thalidomide.[53] * Mat Fraser, born with phocomelia of both arms, is an English rock musician, actor, writer and performance artist. He produced a 2002 television documentary, Born Freak, which looked at this historical tradition and its relevance to modern disabled performers. This work has become the subject of academic analysis in the field of disability studies.[54] ## Change in drug regulations[edit] The disaster prompted many countries to introduce tougher rules for the testing and licensing of drugs, such as the Kefauver Harris Amendment[55] (U.S.), Directive 65/65/EEC1 (E.U.),[56] and the Medicines Act 1968 (UK).[57][58] In the United States, the new regulations strengthened the FDA, among other ways, by requiring applicants to prove efficacy and to disclose all side effects encountered in testing.[2] The FDA subsequently initiated the Drug Efficacy Study Implementation to reclassify drugs already on the market. ## References[edit] 1. ^ Vargesson, Neil. “Thalidomide-induced teratogenesis: history and mechanisms.” Birth defects research. Part C, Embryo today : reviews vol. 105,2 (2015): 140–56. doi:10.1002/bdrc.21096 2. ^ a b c Bren L (28 February 2001). "Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History". FDA Consumer. U.S. Food and Drug Administration. Retrieved 23 December 2009. 3. ^ a b c Miller MT (1991). "Thalidomide Embryopathy: A Model for the Study of Congenital Incomitant Horizontal Strabismus". Transactions of the American Ophthalmological Society. 81: 623–674. PMC 1298636. PMID 1808819. 4. ^ a b c Loue S, Sajatovic M (2004). Encyclopedia of Women's Health. Springer Science & Business Media. p. 644. ISBN 9780306480737. 5. ^ Sneader W (2005). Drug discovery: a history (Rev. and updated ed.). Chichester: Wiley. p. 367. ISBN 978-0-471-89979-2. 6. ^ a b c Cuthbert A (2003). The Oxford Companion to the Body. Oxford University Press. p. 682. doi:10.1093/acref/9780198524038.001.0001. ISBN 9780198524038. 7. ^ Thomas, Katie (2020-03-23). "The Unseen Survivors of Thalidomide Want to Be Heard". The New York Times. ISSN 0362-4331. Retrieved 2020-03-23. 8. ^ "Thalidomide Monograph for Professionals". Drugs.com. Retrieved 14 November 2019. 9. ^ "Thalidomide: The Fifty Year Fight (no longer available)". BBC. 15 May 2014. Retrieved 13 September 2015. 10. ^ Zimmer C (15 March 2010). "Answers Begin to Emerge on How Thalidomide Caused Defects". New York Times. Retrieved 2010-03-21. "As they report in the current issue of Science, a protein known as cereblon latched on tightly to the thalidomide" 11. ^ "Apology for thalidomide survivors". BBC News. 14 January 2010. Retrieved 14 January 2010. 12. ^ Ryan C (1 April 2004). "They just didn't know what it would do". BBC News:Health. BBC news. Archived from the original on 2004-07-07. Retrieved 1 May 2009. 13. ^ Flintoff J (23 March 2008). "Thalidomide: the battle for compensation goes on". The Sunday Times. London: Times Newspapers Ltd. Archived from the original on 2008-05-13. Retrieved 2009-05-01. 14. ^ "Thalidomide survivors to get £20m". BBC News. 23 December 2009. Archived from the original on 14 January 2013. Retrieved 26 July 2011. 15. ^ "About Us". The Thalidomide Trust. Retrieved 21 April 2020. 16. ^ "Thalidomide survivors to get £20m". BBC News. 23 December 2009. Archived from the original on 14 January 2013. Retrieved 26 July 2011. 17. ^ Scott C, Haupt O (3 May 2015). "The forgotten victims". The Sunday Times Magazine. pp. 12–19. Retrieved 8 May 2015. 18. ^ a b Swan, Norman (28 June 2018). "Dr William McBride: The Flawed Character Credited with Linking Thalidomide to Birth Defects." ABC.net.au. Retrieved 29 May 2019. 19. ^ Anon. "Widukind Lenz". who name it?. Ole Daniel Enersen. Retrieved 1 May 2009. 20. ^ a b Anon (7 June 2002). "Thalidomide:40 years on". BBC news. BBC. Retrieved 1 May 2009. 21. ^ "Report of Thalidomide at University of New South Wales". Embryology.med.unsw.edu.au. Archived from the original on 28 October 2012. Retrieved 30 December 2012. 22. ^ Millikin, Robert (20 February 1993). "'Thalidomide Doctor' Guilty of Medical Fraud: William McBride, Who Exposed the Danger of One Anti-Nausea Drug, Has Been Disgraced by Experiments with Another." The Independent. Retrieved 28 May 2019. 23. ^ Somers GF (1963). "The foetal toxicity of thalidomide". Proc. European Soc. Study Drug Toxicity. 1: 49. 24. ^ King C, Kendrick F (1962). "Teratogenic effects of thalidomide in the Sprague Dawley rat". The Lancet. 280 (7265): 409–17. doi:10.1016/S0140-6736(62)90822-X. PMID 14288814. 25. ^ McColl JD, Globus M, Robinson S (1965). "Effect of some therapeutic agents on the developing rat fetus". Toxicology and Applied Pharmacology. 7 (7265): 409–17. doi:10.1016/S0140-6736(62)90822-X. PMID 14288814. 26. ^ Botting J (April 2015). "Chapter 18". Animals and Medicine: The Contribution of Animal Experiments to the Control of Disease. OpenBook Publishers. ISBN 9781783741175. Retrieved 12 August 2015. 27. ^ "Australian thalidomide victims win right for hearing". ABC News. 19 December 2011. 28. ^ Petrie A (19 July 2012). "Landmark thalidomide payout offers hope for thousands". The Sydney Morning Herald. Retrieved 14 February 2017. 29. ^ Farnsworth S (7 February 2014). "Supreme Court formally approves $89m compensation payout for Thalidomide victims". Australian Broadcasting Corporation. Retrieved 14 February 2017. 30. ^ Australian Associated Press (7 February 2014). "Thalidomide survivors' compensation approved". The Sunday Star-Times. Retrieved 14 February 2017. 31. ^ "DDR-Bürger schliefen ohne Contergan" [East German citizens slept without thalidomide]. Neues Deutschland (in German). 4 November 2007. Retrieved June 6, 2013. 32. ^ a b c d e Thomann K (2007). "Die Contergan-Katastrophe: Die trügerische Sicherheit der "harten" Daten" [The thalidomide disaster: The false security of 'hard' data]. Deutsches Ärzteblatt (in German). 104 (41): A–2778 / B–2454 / C–2382. Archived from the original on July 28, 2012. Retrieved June 6, 2013. Alt URL 33. ^ a b Zichner L, Rauschmann MA, Thomann KD (2005). Die Contergankatastrophe eine Bilanz nach 40 Jahren [The thalidomide catastrophe takes stock after 40 years] (in German). Darmstadt: Steinkopff. ISBN 978-3-7985-1479-9. 34. ^ a b Webb JF (November 1963). "Canadian Thalidomide Experience". Canadian Medical Association Journal. 89: 987–92. PMC 1921912. PMID 14076167. 35. ^ "Turning Points of History–Prescription for Disaster". History Television. Archived from the original on September 29, 2011. Retrieved 24 February 2010. 36. ^ a b Racz WJ, Ecobichon DJ, Baril M (August 2003). "On-line sources of toxicological information in Canada". Toxicology. 190 (1–2): 3–14. doi:10.1016/S0300-483X(03)00192-6. PMID 12909394. 37. ^ "The plight of the thalidomide 'sample babies' who don't qualify for gov't compensation". W5. Retrieved 28 November 2016. 38. ^ Warren R (2001). "Living in a world with thalidomide: a dose of reality". FDA Consumer. 35 (2): 40. PMID 11444250. 39. ^ "TVAC and its mission – Thalidomide". June 24, 2009. Archived from the original on 2009-06-24. 40. ^ a b Franks ME, Macpherson GR, Figg WD (May 2004). "Thalidomide". Lancet. 363 (9423): 1802–11. doi:10.1016/S0140-6736(04)16308-3. PMID 15172781. S2CID 208789946. 41. ^ a b Braun W (29 December 2015). "Thalidomide: The Connection Between a Statue in Trafalgar Square, a 1960s Children's Show Host and the Abortion Debate". Huffington Post. Retrieved 2 December 2017. 42. ^ Mekdeci B. "Bendectin Part 1: How a Commonly Used Drug Caused Birth Defects". Archived from the original on 18 December 2013. 43. ^ "Click – Debating Reproductive Rights – Reproductive Rights and Feminism, History of Abortion Battle, History of Abortion Debate, Roe v. Wade and Feminists". www.cliohistory.org. Retrieved 2 December 2017. 44. ^ Harris G (13 September 2010). "The Public's Quiet Savior From Harmful Medicines". The New York Times. 45. ^ "Dr. Helen Brooke Taussig", Bethesda, MD: U.S. National Library of Medicine (3 June 2015): https://cfmedicine.nlm.nih.gov/physicians/biography_316.html 46. ^ "10.000 Fälle von Missbildungen" [10,000 cases of malformations] (in German). ORF. Archived from the original on 2009-08-14. Retrieved June 6, 2013. 47. ^ "Speech on the occasion of the inauguration of Thalidomide-Memorial". Grünenthal GmbH Website. Archived from the original on 1 September 2012. 48. ^ "Thalidomide apology insulting, campaigners say". BBC News. September 1, 2012. Archived from the original on 16 March 2016. 49. ^ Tamplin H (12 June 2015). "Mid Sussex residents honoured by Queen". Mid Sussex Times. Retrieved 27 December 2015. 50. ^ "Orpheus lives: A small good thing in Quastoff". The Portland Phoenix. April 19, 2002. Archived from the original on 6 March 2012. Retrieved 6 June 2013. 51. ^ "NoBody's Perfect (2008): Release Info". IMDB. Retrieved 6 June 2013. 52. ^ Brussat F, Brussat MA. "Film Review: NoBody's Perfect". Spirituality & Practice. Retrieved 6 June 2013. 53. ^ "Outstanding eight to receive honorary doctorates at Convocation". Daily News. Windsor, Ontario, Canada: University of Windsor. 9 June 2016. Retrieved 6 March 2017. 54. ^ Mitchell D, Snyder S (June 2005). "Exploitations of embodiment: Born Freak and the academic bally plank". Disability Studies Quarterly. 25 (3). doi:10.18061/dsq.v25i3.575. 55. ^ "50 Years: The Kefauver-Harris Amendments". Food and Drug Administration (United States). Retrieved 6 June 2013. 56. ^ "Thalidomide". National Health Service (England). Archived from the original on 3 December 2013. Retrieved 6 June 2013. 57. ^ Conroy S, McIntyre J, Choonara I (March 1999). "Unlicensed and off label drug use in neonates". Archives of Disease in Childhood: Fetal and Neonatal Edition. 80 (2): F142–4, discussion F144–5. doi:10.1136/fn.80.2.F142. PMC 1720896. PMID 10325794. 58. ^ "The evolution of pharmacy, Theme E, Level 3 Thalidomide and its aftermath" (PDF). Royal Pharmaceutical Society. 2011. Archived from the original (PDF) on 14 October 2011. ## Further reading[edit] * Stephens T, Brynner R (2001-12-24). Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine. Perseus Books. ISBN 978-0-7382-0590-8. * Knightley P, Evans H (1979). Suffer The Children: The Story of Thalidomide. New York: The Viking Press. ISBN 978-0-670-68114-3. ## External links[edit] * WHO Pharmaceuticals Newsletter No. 2, 2003 – See page 11, Feature Article * CBC Digital Archives – Thalidomide: Bitter Pills, Broken Promises * Remind me again, what is thalidomide and how did it cause so much harm?. The Conversation, 7 December 2015 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Thalidomide scandal	c0432365	6,773	wikipedia	https://en.wikipedia.org/wiki/Thalidomide_scandal	2021-01-18T18:41:09	{"gard": ["2313"], "umls": ["C0432365"], "orphanet": ["3312"], "wikidata": ["Q875992"]}
Bilateral choanal atresia is a congenital anomaly that is usually sporadic (but some familial cases have been reported), is more commonly seen in females than in males (2:1), and where the nose is blocked on both sides by bony or soft tissue formed during embryological development. It is characterized by respiratory distress relieved by crying and rhinorrhea that presents at birth. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Choanal atresia, bilateral	None	6,774	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137920	2021-01-23T18:01:02	{"icd-10": ["Q30.0"]}
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-46 (RP46) is caused by homozygous mutation in the isocitrate dehydrogenase 3B gene (IDH3B; 604526) on chromosome 20p13. For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Clinical Features Hartong et al. (2008) provided results of an ophthalmologic examination of 2 individuals with autosomal recessive IDH3B-related retinitis pigmentosa. The index case and the other individual, identified in a screen of patients with recessive or simplex retinitis pigmentosa, were evaluated at ages 47 and 38 years, respectively. Both had subnormal visual acuities, concentrically constricted visual fields, fundi typical of retinitis pigmentosa (pale optic discs, attenuated arterioles, and intraretinal pigment deposits), impaired dark adaptation, and reduced electroretinogram amplitudes indicating substantial loss of rod and cone photoreceptor function. They reported no other relevant health problems and, in particular, no problems typically associated with mitochondrial dysfunction such as reduced muscle strength, cardiac dysrhythmias, or reduced athletic stamina. Molecular Genetics In an individual with retinitis pigmentosa and in her affected brother, Hartong et al. (2008) found homozygosity for a 1-basepair deletion in codon 197 of the IDH3B gene (604526.0001). The parents of the affected individual were first cousins; 4 of the unaffected sibs were heterozygous, and 1 was wildtype. Hartong et al. (2008) subsequently sequenced all 12 exons of the IDH3B gene in 261 individuals with recessive retinitis pigmentosa and 285 individuals with simplex retinitis pigmentosa (most of whom were presumed to have autosomal recessive retinitis pigmentosa). One individual was homozygous for a missense mutation (L98P; 604526.0002). This individual's parents were first cousins, and the individual's 3 sibs, all unaffected, were heterozygous. Neither mutation was identified after screening leukocyte DNA from 95 control individuals without retinitis pigmentosa. The IDH3B gene encodes the beta subunit of nicotinamide adenine dinucleotide-specific isocitrate dehydrogenase (NAD-IDH), which catalyzes the oxidation of isocitrate to alpha-ketoglutarate in the citric acid cycle. Cells from affected individuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase of the Michaelis constant (Km) for NAD. NADP-IDH (IDH2; 147650), an enzyme that catalyzes the same reaction as NAD-IDH, was normal in the affected individuals. These findings supported the hypothesis that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst for this reaction in the citric acid cycle outside the retina, and that the retina has a particular requirement for NAD-IDH. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	RETINITIS PIGMENTOSA 46	c0035334	6,775	omim	https://www.omim.org/entry/612572	2019-09-22T16:01:09	{"doid": ["0110409"], "mesh": ["D012174"], "omim": ["612572"], "orphanet": ["791"], "synonyms": ["Alternative titles", "RETINITIS PIGMENTOSA, AUTOSOMAL RECESSIVE, IDH3B-RELATED"], "genereviews": ["NBK1417"]}
Paroxysmal hand hematoma Other namesAchenbach syndrome Paroxysmal hand hematoma Achenbach syndrome; it appears often on the internal surface of the finger and rather under the middle finger or forefinger at the joints of the first or second phalanx. SpecialtyDermatology SymptomsAchenbach's is of unknown etiology, however, it is also not a cause for concern. While it can look sort of awful - the finger turns shades of purple and red and can swell, the condition resolves by itself. Paroxysmal hand hematoma is a skin condition characterized by spontaneous focal hemorrhage into the palm or the volar surface of a finger, which results in transitory localized pain, followed by rapid swelling and localized blueish discoloration.[1]:828 ## See also[edit] * List of cutaneous conditions * Hematoma * Phalanx bone ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2\. New England Journal of Medicine, 376;26 nejm.org June 29, 2017. This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Paroxysmal hand hematoma	c0473563	6,776	wikipedia	https://en.wikipedia.org/wiki/Paroxysmal_hand_hematoma	2021-01-18T18:51:18	{"umls": ["C0473563"], "wikidata": ["Q1728132"]}
A rare biliary tract disease characterized by external compression and subsequent obstruction of an extrahepatic biliary duct by one or more gallstones in the cystic duct or the gallbladder. Patients may present with acute or chronic cholecystitis with right upper abdominal pain, nausea, and vomiting, jaundice, or cholangitis. Cholecystobiliary or -enteric fistulae can arise due to chronic inflammation and ulceration. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Mirizzi syndrome	c0267878	6,777	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=521219	2021-01-23T18:28:11	{"mesh": ["D057792"], "synonyms": ["Extrinsic biliary compression syndrome"]}
Glassy cell carcinoma of the cervix Other namesGlassy cell carcinoma Micrograph of a glassy cell carcinoma of the cervix. H&E stain. SpecialtyOncology Glassy cell carcinoma of the cervix, also glassy cell carcinoma, is a rare aggressive malignant tumour of the uterine cervix.[1] The tumour gets its name from its microscopic appearance; its cytoplasm has a glass-like appearance. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 See also * 6 Additional images * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] The signs and symptoms are similar to other cervical cancers and may include post-coital bleeding and/or pain during intercourse (dyspareunia). Early lesions may be completely asymptomatic.[citation needed] ## Cause[edit] This section is empty. You can help by adding to it. (July 2017) ## Diagnosis[edit] The diagnosis is based on tissue examination, e.g. biopsy. Under the microscope, glassy cell carcinoma tumours are composed of cells with a glass-like cytoplasm, typically associated with an inflammatory infiltrate abundant in eosinophils and very mitotically active. PAS staining highlights the plasma membrane.[2] ## Treatment[edit] The treatment is dependent on the stage. Advanced tumours are treated with surgery (radical hysterectomy and bilateral salpingo-opherectomy), radiation therapy and chemotherapy.[2] ## See also[edit] * Cervix * Cervical cancer * Villoglandular adenocarcinoma ## Additional images[edit] * Low mag. * High mag. ## References[edit] 1. ^ Nasu, K.; Takai, N.; Narahara, H. (Jun 2009). "Multimodal treatment for glassy cell carcinoma of the uterine cervix". J Obstet Gynaecol Res. 35 (3): 584–7. doi:10.1111/j.1447-0756.2008.00968.x. PMID 19527406. 2. ^ a b Deshpande, AH.; Kotwal, MN.; Bobhate, SK. (2004). "Glassy cell carcinoma of the uterine cervix a rare histology. Report of three cases with a review of the literature". Indian J Cancer. 41 (2): 92–5. PMID 15318016. ## Further reading[edit] * Greer, Benjamin E.; Koh, Wui-Jin; Abu-Rustum, Nadeem; Bookman, Michael A.; Bristow, Robert E.; Campos, Susana M.; Cho, Kathleen R.; Copeland, Larry; Crispens, Marta Ann; Eifel, Patricia J.; Huh, Warner K.; Jaggernauth, Wainwright; Kapp, Daniel S.; Kavanagh, John J.; Lurain, John R.; Morgan, Mark; Morgan, Robert J.; Powell, C. Bethan; Remmenga, Steven W.; Reynolds, R. Kevin; Secord, Angeles Alvarez; Small, William; Teng, Nelson (1 May 2009). "Uterine Neoplasms". Journal of the National Comprehensive Cancer Network. 7 (5): 498–531. doi:10.6004/jnccn.2009.0035. ISSN 1540-1405. PMID 19460278. Retrieved 19 July 2017. ## External links[edit] Classification D * ICD-10: C53.0 C53.1 C53.8 External resources * Orphanet: 213833 * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Glassy cell carcinoma of the cervix	c2012072	6,778	wikipedia	https://en.wikipedia.org/wiki/Glassy_cell_carcinoma_of_the_cervix	2021-01-18T19:02:08	{"gard": ["8437"], "mesh": ["C536823"], "icd-10": ["C53"], "orphanet": ["213833"], "synonyms": [], "wikidata": ["Q5567200"]}
Paraneoplastic syndrome POEMS syndrome Other namesCrow–Fukase syndrome SpecialtyOncology POEMS syndrome (also termed osteosclerotic myeloma, Crow–Fukase syndrome, Takatsuki disease, or PEP syndrome) is a rare paraneoplastic syndrome caused by a clone of aberrant plasma cells. The name POEMS is an acronym for some of the disease's major signs and symptoms (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), as is PEP (polyneuropathy, endocrinopathy, plasma cell dyscrasia). The signs and symptoms of most neoplasms are due to their mass effects caused by the invasion and destruction of tissues by the neoplasms' cells. Signs and symptoms of a cancer causing a paraneoplastic syndrome result from the release of humoral factors such as hormones, cytokines, or immunoglobulins by the syndrome's neoplastic cells and/or the response of the immune system to the neoplasm. Many of the signs and symptoms in POEMS syndrome are due at least in part to the release of an aberrant immunoglobulin, i.e. a myeloma protein, as well as certain cytokines by the malignant plasma cells.[1][2][3] POEMS syndrome typically begins in middle age – the average age at onset is 50 – and affects up to twice as many men as women. ## Contents * 1 Signs and symptoms * 1.1 Common features * 1.2 Possible features * 2 Pathogenesis * 3 Diagnosis * 3.1 Laboratory findings * 3.2 Differential diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] The signs and symptoms of POEMS syndrome are highly variable. This often leads to long delays (e.g. 13–18 months) between the onset of initial symptoms and diagnosis.[1][2] In addition to the signs and symptoms indicated by the POEMS acronym, the PEST acronym is used to describe some of the other signs and symptoms of the disease. PEST stands for Papilledema, evidence of Extravascular volume overload (ascites, pleural effusion, pericardial effusion, and lower extremity edema), Sclerotic bone lesions, and Thrombocytosis/erythrocytosis (i.e. increased in blood platelets and red blood cells). Other features of the disease include a tendency toward leukocytosis, blood clot formation, abnormal lung function (restrictive lung disease, pulmonary hypertension, and impaired lung diffusion capacity), very high blood levels of the cytokine vascular endothelial growth factor (VEGF), and an overlap with the signs and symptoms of multicentric Castleman disease.[2] ### Common features[edit] The more common features of the disease are summarized in the acronym POEMS: Papilledema (swelling of the optic disc) often but not always due to increased intracranial pressure) is the most common ocular sign of POEMS syndrome, occurring in ≥29% of cases. Less frequent ocular findings include cystoid macular edema, serous macular detachment, infiltrative orbitopathy, and venous sinus thrombosis.[4] Pulmonary disease/ Polyneuropathy: The lungs are often affected at more severe stages of the illness, although since by then physical exertion is usually limited by neuropathy, shortness of breath is unusual. Pulmonary hypertension is the most serious effect on the lungs, and there may also be restriction of chest expansion or impaired gas exchange.[2][3] Organomegaly: The liver may be enlarged, and less often the spleen or lymph nodes, though these organs usually function normally.[2][3] Edema: Leakage of fluid into the tissues is a common and often severe problem. This may take several forms, including dependent peripheral edema, pulmonary edema, effusions such as pleural effusion or ascites, or generalized capillary leakage (anasarca).[2][3] Endocrinopathy: In women, amenorrhea, and in men, gynecomastia, erectile dysfunction and testicular atrophy, are common early symptoms due to dysfunction of the gonadal axis. Other hormonal problems occurring in at least a quarter of patients include type 2 diabetes, hypothyroidism, and adrenal insufficiency.[2][3] Monoclonal paraprotein: In most cases a serum myeloma protein can be detected, although this is not universal. This may represent IgG or IgA, but the light chain type is almost always lambda. This is in contrast to most paraproteinemic neuropathies, in which the paraprotein is usually an IgM antibody.[1] Skin changes: A very wide variety of skin problems have been reported in association with POEMS syndrome. The most common is non-specific hyperpigmentation. The fingernails may be clubbed or white. There may be thickening of the skin, excess hair or hair in unusual places (hypertrichosis), skin angiomas or hemangiomas, or changes reminiscent of scleroderma.[5] ### Possible features[edit] Some features have been observed in patients with POEMS syndrome but are not yet certain to form part of the syndrome itself. These include a predisposition to forming blood clots, joint pain, cardiomyopathy (systolic dysfunction), fever, low vitamin B12 levels, and diarrhea.[6] ## Pathogenesis[edit] While the main features of this paraneoplastic disease have been described, the exact mechanism behind its development, progression, and manifestations remain elusive. Overproduction of the myeloma protein and VEGF may underlie some, but are insufficient to explain all, of the multi-organ features of the disease. It is suggested that various other cytokines produced by the clonal plasma cells, perhaps working in concert with each other as well as with VEGF and the myeloma proteins, mediate many of the features of POEMS syndrome. The other cytokines detected in, and suspected of contributing to, POEMS syndrome include interleukin 1β, interleukin 6, and TNFα. Nonetheless, it seems likely that some of these paraneoplastic factors, operating individually, make a major contribution to certain features of the disease. For example, VEGF, given its ability to stimulate blood vessel formation, would seem likely to be the major contributor to the pathologic hyper-vascularization changes seem in many tissues, such as lymph nodes, afflicted by POEMS syndrome.[6] ## Diagnosis[edit] The diagnosis of POEMS syndrome is based on meeting its two mandatory criteria, meeting at least one of its 3 other major criteria, and meeting at least one of its 6 minor criteria. These criteria are:[7] * Mandatory major criteria * Plasma cell dyscrasia: This is evidenced by 1) the presence of a serum myeloma protein, typically an IgG or IgA isotype (occurs in nearly 100% of cases; in >95% of instances the myeloma proteins contain a λ chain that is restricted to either of two V lambda 1 subfamily members viz., IGLV1-4001 and IGLV1-4401 (see V lambda family); 2) any, but often a small, increase above the normal value of <1.5% in the percentage of nucleated bone marrow cells that are clonal plasma cells (occurs ~67% of cases); and/or 3) presence of a plasma cell tumor (i.e. plasmacytoma) usually in bone (occurs in ~33% of cases).[2] * Polyneuropathy: The nerve damage is usually symmetrical, located in distal extremities, and due to the nerve losing its fatty myelin coating and axonal damage. Neurons of the Sensory, motor and autonomic nervous systems are all affected. The typical symptoms are therefore numbness, tingling, and weakness in the feet, later affecting the legs and hands. Pain is unusual, but the weakness may eventually become severe and disabling. The autonomic neuropathy may cause excessive sweating and erectile dysfunction; hormonal changes may also contribute to the latter. It is usually the symptoms of neuropathy which prompt a person with POEMS syndrome to seek medical attention.[8] * Other major criteria * Castleman disease: The lymphoproliferative disorder Castleman disease associated with POEMS syndrome is multicentric and occurs in ~15 of cases. It is characterized by a morphology in lymph nodes termed angiofollicular lymph node hyperplasia; an overly activate immune system; excessive production of cytokines including particularly IL-6 and to lesser extents, proliferation of immune B cells and T cells, enlarged lymph nodes, enlarged liver and spleen, capillary leak syndrome, anasarca, evidence of extravascular fluid overload, and organ failure. Patients with Castleman disease without a plasma cell dyscrasia and peripheral neuropathy but having other signs and symptoms of POEMS syndrome can be classified as a Castleman disease variant of POEMS syndrome.[2] * Sclerotic bone lesions: These lesions consist of plasma cell tumors encased within or associated with abnormally dense bone structures; in different studies, they have been observed to occur in 27% to 97% of cases.[2][7] * Elevated VEGF: VEGF is a cytokine that stimulates angiogenesis (i.e. capillary formation), increases capillary permeability, and contributes to polyneuropathy. It is elevated in almost all cases of POEMS syndrome and has become a clinically useful marker for the syndrome's presence, severity, and response to treatment. However, its role in mediating the symptoms of this disease are unclear. A second cytokine, IL-12, is similar to VEGF in being highly correlated with the disease activity level in POEMS syndrome.[2] * Minor criteria * Organomegaly: Enlargement spleen, liver, and/or lymph nodes occurs in 45% to 85% of cases.[7] * Extravascular volume overload: Ascites, pleural effusions, pericardial effusions, and/or lower extremity edema occur in 27% to 89% of cases.[7] * Endocrinopathy: Gynecomastia occurs in 12% to 18% of cases; endocrine abnormalities involving the regulation of gonadotrophins, adrenal gland corticosteroids, and prolactin occur in 55% to 89%, 16% to 33%, and 55 to 20% of cases, respectively. Diabetes and hypothyroidism also occur in 3% to 36% and 9% to 67%, respectively, of cases but are not considered to be criteria for the presence of POEMS syndrome because of their frequent occurrence in the general population.[7] * Skin changes: Skin changes occur in 68% to 89% of POEMS syndrome patients. These changes most commonly are hyperpigmentation and/or hypertrichosis (abnormal amount of hair growth over the body) but less commonly include glomeruloid hemangioma, signs or symptoms of Hypervolemia (e.g. edema and ascites), acrocyanosis (blue discoloration of the extremities due to blood flow abnormalities), flushing, and/or white nails.[3] * Papilledema: Papilledema (swelling of retinal optical discs) occurs in 29% to 64% of cases. Papilledema in POEMS syndrome patients may occur with or without visual disturbances, increased intracranial pressure, or changes in cerebral spinal fluid protein levels.[3][9] * Thrombocytosis/polycythemia: Thrombocytosis (increase in blood platelet count) and polycythemia (increase in red blood cells) occurs 54% to 88% and 12% to 19%, respectively, of POEMS syndrome patients and may be may underlying causes of these patients to experience thrombosis events.[3] ### Laboratory findings[edit] In addition to tests corresponding to the above findings (such as EMG for neuropathy, CT scan, bone marrow biopsy to detect clonal plasma cells, plasma or serum protein electrophoresis to myeloma proteins, other tests can give abnormal results supporting the diagnosis of POEMS syndrome. These included raised blood levels of VEGF, thrombocytes, and/or erythrocyte parameters.[2] ### Differential diagnosis[edit] Patients diagnosed as having Castleman disease but also exhibiting many of the symptoms and signs of POEMS syndrome but lacking evidence of a peripheral neuropathy and/or clonal plasma cells should not be diagnosed as having POEMS syndrome. They are better classified as having Castleman disease variant of POEMS syndrome. These patients may exhibit high blood levels of the interleukin-6 cytokine and have an inferior overall survival compared to POEMS syndrome patients. Treatment of patients with this POEMS syndrome variant who have evidence of bone lesions and/or myeloma proteins are the same as those for POEMS syndrome patients. In the absence of these features, treatment with rituximab, a monoclonal antibody preparation directed against B cells bearing the CD20 antigen, or siltuximab, a monoclonal antibody preparation directed against interleukin-6, may be justified.[2][3] ## Treatment[edit] As reported by Dispenzieri et al.[3] Mayo Clinic treatment regimens are tailored to treat the clinical manifestations and prognosis for the rate of progression of the POEMS syndrome in each patient. In rare cases, patients may have minimal or no symptoms at presentation or after successful treatment of their disorder. These patients may be monitored every 2–3 months for symptoms and disease progression. Otherwise, treatment is divided based on the local versus systemic spread of its clonal plasma cells. Patients with one or two plasmacytoma bone lesions and no clonal plasma cells in their bone marrow biopsy specimens are treated by surgical removal or radiotherapy of their tumors. These treatments can relieve many of the syndromes clinical manifestations including neuropathies, have a 10-year overall survival of 70% and a 6-year progression-free survival of 62%. Patients with >2 plasmacytoma bone lesions and/or increases in bone marrow clonal plasma cells are treated with a low-dose or high-dose chemotherapy regimen, i.e. a corticosteroid such as dexamethasone plus an alkylating agents such as melphalan. Dosage regimens are selected on the basis of patient tolerance. Hematological response rates to the dexamethasone/melphalan regimens have been reported to be in the 80% range with neurological response rates approaching 100%. Patients successfully treated with the high-dose dexamethasone/melphalan regimen have been further treated with autologous stem cell transplantation. In 59 patients treated with the chemotherapy/transplantation regimen, the Mayo Clinic reported progression-free survival rates of 98%, 94%, and 75% at 1, 2, and 5 years, respectively.[3] Other treatment regiments are being studied. Immunomodulatory imide drugs such as thalidomide and lenalidomide have been used in combination with dexamethasone to treat POEMS syndrome patients. While the mechanism of action of these immunomodulators are not clear, they do inhibit the production of cytokines suspected of contributing to POEMS syndrome such as VEGF, TNFα, and IL-6 and stimulate T cells and NK cells to increase their production of interferon gamma and interleukin 2 (see immunomodulatory imide drug's mechanism of action). A double blind study of 25 POEMS syndrome patients found significantly better results (VEGF reduction, neuromuscular function improvement, quality of life improvement) in patients treated with thalidomide plus dexamethasone compared to patients treated with a thalidomide placebo plus dexamethasone.[2] Since VEGF plays a central role in the symptoms of POEMS syndrome, some have tried bevacizumab, a monoclonal antibody directed against VEGF. While some reports were positive, others have reported capillary leak syndrome suspected to be the result of overly rapid lowering of VEGF levels. It therefore remains doubtful as to whether this will become part of standard treatment for POEMS syndrome.[10] ## History[edit] R. S. Crow, working in Bristol, first described the combination of osteosclerotic myeloma, polyneuropathy and various unusual features (such as pigmentation and clubbing) in two patients aged 54 and 67.[11] ## References[edit] 1. ^ a b c Castillo JJ (2016). "Plasma Cell Disorders". Primary Care. 43 (4): 677–691. doi:10.1016/j.pop.2016.07.002. PMID 27866585. 2. ^ a b c d e f g h i j k l m n Warsame R, Yanamandra U, Kapoor P (2017). "POEMS Syndrome: an Enigma". Current Hematologic Malignancy Reports. 12 (2): 85–95. doi:10.1007/s11899-017-0367-0. PMID 28299525. S2CID 31324035. 3. ^ a b c d e f g h i j k Dispenzieri A (2017). "POEMS syndrome: 2017 Update on diagnosis, risk stratification, and management". American Journal of Hematology. 92 (8): 814–829. doi:10.1002/ajh.24802. PMID 28699668. 4. ^ Kaushik M, Pulido JS, Abreu R, Amselem L, Dispenzieri A (2011). "Ocular findings in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome". Ophthalmology. 118 (4): 778–82. doi:10.1016/j.ophtha.2010.08.013. PMID 21035860. 5. ^ Dispenzieri A, Buadi FK (December 2013). "A review of POEMS syndrome". Oncology (Williston Park, N.Y.). 27 (12): 1242–50. PMID 24624542. 6. ^ a b Dispenzieri A, Kyle RA, Lacy MQ, et al. (2003). "POEMS syndrome: definitions and long-term outcome". Blood. 101 (7): 2496–506. doi:10.1182/blood-2002-07-2299. PMID 12456500. Archived from the original on 2009-01-25. Retrieved 2008-04-13. 7. ^ a b c d e Dispenzieri A (2014). "POEMS syndrome: 2014 update on diagnosis, risk-stratification, and management". American Journal of Hematology. 89 (2): 214–23. doi:10.1002/ajh.23644. PMID 24532337. S2CID 33370434. 8. ^ Rosenbaum E, Marks D, Raza S (2017). "Diagnosis and management of neuropathies associated with plasma cell dyscrasias". Hematological Oncology. 36 (1): 3–14. doi:10.1002/hon.2417. PMID 28397326. S2CID 3440992. 9. ^ Lam C, Margolin E (2016). "A case of POEMS and chronic papilledema with preserved optic nerve function". Canadian Journal of Ophthalmology. 51 (1): e8–10. doi:10.1016/j.jcjo.2015.08.015. PMID 26874176. 10. ^ Samaras P, Bauer S, Stenner-Liewen F, et al. (2007). "Treatment of POEMS syndrome with bevacizumab". Haematologica. 92 (10): 1438–9. doi:10.3324/haematol.11315. PMID 18024383. 11. ^ Crow RS (1956). "Peripheral neuritis in myelomatosis". Br Med J. 2 (4996): 802–4. doi:10.1136/bmj.2.4996.802. PMC 2035359. PMID 13364332. ## External links[edit] Classification D * ICD-10: D47.7 * ICD-9-CM: 273.8 * MeSH: D016878 * DiseasesDB: 29226 External resources * eMedicine: derm/771 * Orphanet: 2905 * v * t * e Immunoproliferative immunoglobulin disorders PCDs/PP * Plasmacytoma * Multiple myeloma (Plasma cell leukemia) * MGUS * IgM (Macroglobulinemia/Waldenström's macroglobulinemia) * heavy chain (Heavy chain disease) * light chain (Primary amyloidosis) Other hypergammaglobulinemia * Cryoglobulinemia * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	POEMS syndrome	c3898068	6,779	wikipedia	https://en.wikipedia.org/wiki/POEMS_syndrome	2021-01-18T19:01:35	{"gard": ["7411"], "mesh": ["D016878"], "umls": ["C3898068"], "icd-9": ["273.8"], "icd-10": ["D47.7"], "orphanet": ["2627", "2905"], "wikidata": ["Q2553422"]}
Nausea caused by exposure to a VR environment Virtual reality sickness occurs when exposure to a virtual environment causes symptoms that are similar to motion sickness symptoms.[1] The most common symptoms are general discomfort, headache, stomach awareness, nausea, vomiting, pallor, sweating, fatigue, drowsiness, disorientation, and apathy.[2] Other symptoms include postural instability and retching.[2] Virtual reality sickness is different from motion sickness in that it can be caused by the visually-induced perception of self-motion; real self-motion is not needed.[1] It is also different from simulator sickness; non-virtual reality simulator sickness tends to be characterized by oculomotor disturbances, whereas virtual reality sickness tends to be characterized by disorientation.[3] ## Contents * 1 Consequences * 2 Theories * 3 Technical aspects * 4 Techniques for reducing VR sickness * 5 Newest technology * 6 Individual differences in susceptibility * 7 References ## Consequences[edit] Virtual reality sickness may have undesirable consequences beyond the sickness itself. For example, Crowley (1987) argued that flight simulator sickness could discourage pilots from using flight simulators, reduce the efficiency of training through distraction and the encouragement of adaptive behaviors that are unfavorable for performance, compromise ground safety or flight safety when sick and disoriented pilots leave the simulator.[4] Similar consequences could be expected for virtual reality systems. Although the evidence for performance decrements due to virtual reality sickness is limited,[5] research does suggest that virtual reality sickness is a major barrier to using virtual reality,[6] indicating that virtual reality sickness may be a barrier to the effective use of training tools and rehabilitation tools in virtual reality. Estimates of the multi-study incidence and main symptoms of virtual reality sickness (also called cybersickness) have been made.[7] ## Theories[edit] Currently, there are very few theories as to why virtual reality sickness in particular occurs; however, it is closely related to simulator and motion sickness. Sensory conflict theory provides a framework for understanding motion sickness; however, it can be applied to virtual reality sickness to better understand how it can occur,[8] and is commonly used for that purpose.[2] Sensory conflict theory posits that sickness will occur when a user's perception of self-motion is based on incongruent sensory inputs from the visual system, vestibular system, and non-vestibular proprioceptors, and particularly so when these inputs are at odds with the user's expectation based on prior experience.[9] Applying this theory to virtual reality, sickness can be minimized when the sensory inputs inducing self-motion are in agreement with one another. The physiology behind VR sickness is not currently clearly understood. Fortunately, research has uncovered some clear indications of certain conditions that cause VR sickness. It seems that the images projected from virtual reality have a major impact on sickness. The refresh rate of on-screen images is often not high enough when VR sickness occurs. Because the refresh rate is slower than what the brain processes, it causes a discord between the processing rate and the refresh rate, which causes the user to perceive glitches on the screen. When these two components do not match up, it can cause the user to experience the same feelings as simulator and motion sickness which is mentioned below. The resolution on animation can also cause users to experience this phenomenon. When animations are poor, it causes another type of discord between what is expected and what is actually happening on the screen. When onscreen graphics do not keep the pace with the users' head movements, it can trigger a form of motion sickness. Another trigger of virtual reality sickness is when there is disparity in apparent motion between the visual and vestibular stimuli. This disparity occurs if there is a disagreement between what the stimuli from the eyes and inner ear are sending to the brain. This is a fundamental cause of both simulator and motion sickness as well. In virtual reality, the eyes transmit that the person is running and jumping through a dimension, however, the ears transmit that no movement is occurring and that the body is sitting still. Since there is this discord between the eyes and the ears, a form of motion sickness can occur. Not all scientists agree with sensory conflict theory.[2] A second theory of motion sickness, which has also been used to explain virtual reality sickness, is the theory of postural instability.[10] This theory holds that motion sickness and related sicknesses occur because of poor postural adaptations in response to unusual coupling between visual stimuli and motor coordination. Characteristic markers of postural instability occur prior to appearance of symptoms and predict the later development of symptoms.[11] This theory can explain some otherwise surprising situations in which motion sickness did not occur in the presence of sensory conflict.[12] ## Technical aspects[edit] There are various technical aspects of virtual reality that can induce sickness, such as mismatched motion,[13] field of view,[14] motion parallax,[15] and viewing angle.[16] Additionally, the amount of time spent in virtual reality can increase the presence of symptoms.[16] Mismatched motion can be defined as a discrepancy between the motion of the simulation and the motion that the user expects.[13] It is possible to induce motion sickness in virtual reality when the frequencies of mismatched motion are similar to those for motion sickness in reality, such as seasickness.[13] These frequencies can be experimentally manipulated, but also have the propensity to arise from system errors. Generally, increasing the field of view increases incidence of simulator sickness symptoms. This relationship has been shown to be curvilinear, with symptoms approaching an asymptote for fields of view above 140°.[14] Altering motion parallax distances to those less than the distance between the human eyes in large multiple-screen simulation setups can induce oculomotor distress, such as headaches, eyestrain, and blurred vision.[15] There are fewer reports of oculomotor distress on smaller screens; however, most simulation setups with motion parallax effects can still induce eyestrain, fatigue, and general discomfort over time.[citation needed] Viewing angle has been shown to increase a user's sickness symptoms, especially at extreme angles.[16] One example of such an extreme angle would be when a user must look downwards a short distance in front of their virtual feet. As opposed to a forward viewing angle, an extreme downward angle such as this has been shown to markedly increase sickness in virtual environments.[16] Time spent immersed in a virtual environment contributes to sickness symptom presence due to the increasing effects of fatigue on the user.[16] Oculomotor symptoms are the most common to occur due to immersion time, but the nature of the user's movements (e.g., whole-body vs. head-only) is suggested to be the primary cause of nausea or physical sickness.[16] ## Techniques for reducing VR sickness[edit] According to several studies, introducing a static frame of reference (independent visual background) may reduce simulation sickness.[17][18][19] A technique called Nasum Virtualis shows a virtual nose as a fixed frame of reference for VR headsets.[20][21] Other techniques for reducing nausea involve simulating ways of displacement that don't create or reduce discrepancies between the visual aspects and body movement, such as reducing rotational motions during navigation,[22] dynamically reducing the field of view,[23] teleportation,[24] and movement in zero gravity.[25] In January 2020, the French start-up Boarding Ring, known for their glasses against motion sickness,[26] released an add-on device against virtual reality sickness.[27] Using two small screens in the user's peripheral field of view, the device displays visual information consistent with vestibular inputs, avoiding the sensory conflict. Galvanic vestibular stimulation, which creates the illusion of motion by electric stimulation of the vestibular system, is another technique being explored for its potential to mitigate or eliminate the visual-vestibular mismatch.[28] ## Newest technology[edit] With the integration of virtual reality into the more commercial mainstream, issues have begun to arise in relation to VR sickness in head-mounted gaming devices.[29] While research on head-mounted VR for gaming dates back to the early 1990s,[30] the potential for mass usability has only become recently realized. While certain features are known to moderate VR sickness in head-mounted displays, such as playing from a seated position rather than standing,[30] it has also been found that this merely puts off the onset of sickness, rather than completely preventing it. This inherently presents an issue, in that this type of interactive VR often involves standing or walking for a fully immersive experience.[29] Gaming VR specialists argue that this unique brand of VR sickness is only a minor issue, claiming that it disappears with time spent (multiple days) using the head-mounted displays, relating it to "getting your sea legs".[31] However, getting users interested in sickness for multiple days with the promise of "probably getting over it" is a struggle for developers of head-mounted gaming tech. Surveys have shown that a large percentage of people won't develop their "VR legs," in particular women.[32] These same developers also argue that it has more to do with the individual game being played, and that certain gaming aspects are more likely to create issues, such as change in speed, walking up stairs, and jumping,[31] which are all, unfortunately, fairly normal game functions in predominant genres. ## Individual differences in susceptibility[edit] Individuals vary widely in their susceptibility to simulator and virtual reality sickness.[2] Some of the factors in virtual reality sickness are listed below:[2] * Age: Susceptibility to motion sickness is highest between the ages of 2 and 12. It then decreases rapidly until about age 21, and continues to decrease more slowly after that.[9] It has been suggested that virtual reality sickness might follow a similar pattern,[2] but more recent research has suggested that adults over the age of 50 are more susceptible than younger adults to virtual reality sickness.[6] * Postural stability: Postural instability has been found to increase susceptibility to visually-induced motion sickness.[33] It is also associated with increased susceptibility to nausea and disorientation symptoms of virtual reality sickness.[2][34] * Flicker fusion frequency threshold: Because flicker in the display has been associated with increased risk of virtual reality sickness, people with a low threshold for detecting flicker may be more susceptible to virtual reality sickness.[2] * Ethnicity: Asian people may be more susceptible to virtual reality sickness.[5] Chinese women appear to be more susceptible to virtual reality sickness than European-American and African-American women; research suggests that they are more susceptible to vision-based motion sickness.[35] Tibetans and Northeast Indians also appear to be more susceptible to motion sickness than Caucasian people,[36] suggesting that they would also be more susceptible to virtual reality sickness, since susceptibility to motion sickness predicts susceptibility to a wide range of motion-sickness related disturbances.[5] * Experience with the system: Users seem to become less likely to develop virtual reality sickness as they develop familiarity with a virtual reality system. Adaptation may occur as quickly as the second exposure to the virtual reality system.[37] * Gender: Women are more susceptible than men to virtual reality sickness.[38][39][40][41] This may be due to hormonal differences,[38][40] it may be because women have a wider field of view than men,[38] or gender differences in depth cue recognition.[41] Women are most susceptible to virtual reality sickness during ovulation[42] and a wider field of view is also associated with an increase in virtual reality sickness.[43] In more recent research, there is some disagreement as to whether gender or sex is a clear factor in susceptibility to virtual reality sickness. [44] [45] * Health: Susceptibility to virtual reality sickness appears to increase in people who are not at their usual level of health, suggesting that virtual reality may not be appropriate for people who are in ill health.[43] This includes people who are fatigued; have not had enough sleep; are nauseated; or have an upper respiratory illness, ear trouble, or influenza.[2][46] * Mental rotation ability: Better mental rotation ability appears to reduce susceptibility to virtual reality sickness, suggesting that training users in mental rotation may reduce the incidence of virtual reality sickness.[46] * Field dependence/independence: Field dependence/independence is a measure of perceptual style. Those with strong field dependence exhibit a strong influence of surrounding environment on their perception of an object, whereas people with strong field independence show a smaller influence of surrounding environment on their perception of the object. While the relationship between field dependence/independence and virtual reality sickness is complex, it appears that, in general, people without a strong tendency towards one extreme or the other are most susceptible to virtual reality sickness.[5] * Motion sickness sensitivity: Those who are more sensitive to motion sickness in reality are also more sensitive to virtual reality sickness.[13] ## References[edit] 1. ^ a b LaViola, J. J. Jr (2000). "A discussion of cybersickness in virtual environments". ACM SIGCHI Bulletin. 32: 47–56. CiteSeerX 10.1.1.544.8306. doi:10.1145/333329.333344. 2. ^ a b c d e f g h i j Kolasinski, E. M. "Simulator sickness in virtual environments (ARI 1027)". www.dtic.mil. U.S. Army Research Institute for the Behavioral and Social Sciences. Retrieved 22 July 2014. 3. ^ Stanney, K. M.; Kennedy, R. S.; Drexler, J. M. (1997). "Cybersickness is not simulator sickness". Proceedings of the Human Factors and Ergonomics Society Annual Meeting. 41 (2): 1138–1142. doi:10.1177/107118139704100292. 4. ^ Crowley, J. S. (1987). "Simulator sickness: A problem for Army Aviation". Aviation, Space, and Environmental Medicine. 58 (4): 355–357. PMID 3579825. 5. ^ a b c d Barrett, J. (2004). "Side effects of virtual environments: A review of the literature (DSTO-TR-1419)" (PDF). Edinburgh, Australia: Defense Sciences and Technology Organisation Information Sciences Laboratory. Cite journal requires `\|journal=` (help) 6. ^ a b Brooks, J. O.; Goodenough, R. R.; Crisler, M. C.; Klein, N. D.; Alley, R. L.; Koon, B. L.; ...; Wills, R. F. (2010). "Simulator sickness during driving simulation studies". Accident Analysis & Prevention. 42 (3): 788–796. doi:10.1016/j.aap.2009.04.013. PMID 20380904.CS1 maint: numeric names: authors list (link) 7. ^ Lawson, B. D. (2014). "Motion sickness symptomatology and origins". Handbook of Virtual Environments: Design, Implementation, and Applications. pp. 531–599. 8. ^ Johnson, D. (April 2005). "Introduction to and Review of Simulator Sickness Research (Research Report 1832)". U.S. Army Research Institute for the Behavioral and Social Sciences. Cite journal requires `\|journal=` (help) 9. ^ a b Reason, J. T.; Brand, J. J. (1975). Motion sickness. London: Academic Press. 10. ^ Stoffregen, T. A.; Riccio, G. E. (1988). "An ecological theory of orientation and the vestibular system". Psychological Review. 95 (1): 3–14. doi:10.1037/0033-295x.95.1.3. PMID 3281178. 11. ^ Smart, L. J.; Stoffregen, T. A. & Bardy, B. G. (2002). "Visually induced motion sickness predicted by postural instability". Human Factors. 44 (3): 451–465. doi:10.1518/0018720024497745. PMID 12502162. 12. ^ Riccio, G. E.; Martin, E. J.; Stoffregen, T. A. (1992). "The role of balance dynamics in the active perception of orientation". Journal of Experimental Psychology: Human Perception and Performance. 18 (3): 624–644. doi:10.1037/0096-1523.18.3.624. 13. ^ a b c d Groen, E.; Bos, J. (2008). "Simulator sickness depends on frequency of the simulator motion mismatch: An observation". Presence. 17 (6): 584–593. doi:10.1162/pres.17.6.584. 14. ^ a b Lin, J. J.; Duh, H. B. L.; Parker, D. E.; Abi-Rached, H.; Furness, T. A. (2002). "Effects of field of view on presence, enjoyment, memory, and simulator sickness in a virtual environment". Proceedings IEEE Virtual Reality 2002. 9. pp. 164–171. doi:10.1109/VR.2002.996519. ISBN 978-0-7695-1492-5. 15. ^ a b Jinjakam, C.; Kazuhiko, H. (2011). "Study on parallax affect on simulator sickness in one-screen and three-screen immersive virtual environment". 東海大学紀要情報通信学部. 4 (1): 34–39. 16. ^ a b c d e f Ruddle, R. A. (2004). "The effect of environment characteristics and user interaction on levels of virtual environment sickness". IEEE Virtual Reality 2004. 11. pp. 141–148. CiteSeerX 10.1.1.294.5953. doi:10.1109/VR.2004.1310067. ISBN 978-0-7803-8415-6. 17. ^ Lin, James Jeng-Weei; Abi-Rached, Habib; Kim, Do-Hoe; Parker, Donald E.; Furness, Thomas A. (2002-09-01). "A "Natural" Independent Visual Background Reduced Simulator Sickness". Proceedings of the Human Factors and Ergonomics Society Annual Meeting. 46 (26): 2124–2128. CiteSeerX 10.1.1.897.4716. doi:10.1177/154193120204602605. ISSN 1541-9312. 18. ^ Prothero, J. D.; Draper, M. H.; Furness, T. A.; Parker, D. E.; Wells, M. J. (March 1999). "The use of an independent visual background to reduce simulator side-effects". Aviation, Space, and Environmental Medicine. 70 (3 Pt 1): 277–283. ISSN 0095-6562. PMID 10102741. 19. ^ Duh, Henry Been-Lirn; Parker, Donald E.; Furness, Thomas A.; A, Henry B. L. Duh; B, Donald E. Parker; A, Thomas A. Furness (2001). Does a Peripheral Independent Visual Background Reduce Scene-Motion-Induced Balance Disturbance in an Immersive Environment?. CiteSeerX 10.1.1.29.3699. 20. ^ Whittinghill, D. M., Ziegler, B., Moore, J., & Case, T. (2015). Nasum Virtualis: A Simple Technique for Reducing Simulator Sickness in Head Mounted VR. In Game Developers Conference. San Francisco. [1] 21. ^ "How to Reduce VR Sickness? Just Add a Virtual Nose". WIRED. Retrieved 2017-10-11. 22. ^ Kemeny, Andras; George, Paul; Mérienne, Frédéric; Colombet, Florent (2017-01-29). "New VR Navigation Techniques to Reduce Cybersickness". Electronic Imaging. 2017 (3): 48–53. doi:10.2352/ISSN.2470-1173.2017.3.ERVR-097. 23. ^ Fernandes, A. S.; Feiner, S. K. (March 2016). "Combating VR sickness through subtle dynamic field-of-view modification". 2016 IEEE Symposium on 3D User Interfaces (3DUI). pp. 201–210. doi:10.1109/3DUI.2016.7460053. ISBN 978-1-5090-0842-1. 24. ^ "Combating VR Sickness: Debunking Myths And Learning What Really Works". ARVI Games. 25. ^ "How game designers find ways around VR motion sickness". The Verge. Retrieved 2017-10-11. 26. ^ "Could These Glasses Cure Your Motion Sickness? - smithsonianmag.com". smithsonianmag.com. 27. ^ "The Seenetic VR Sickness Solution - intotomorrow.com". 28. ^ "Mayo Clinic May Have Just Solved One Of Virtual Reality's Biggest Problems". Forbes. Retrieved 2019-03-08. 29. ^ a b Lang, B. (January 16, 2014). "First impressions of Valve's VR head mounted display prototype". Road to Virtual Reality. Retrieved 14 July 2014. 30. ^ a b Merhi, O.; Faugloire, E.; Flanagan, M.; Stoffregen, T. A. (2007). "Motion sickness, video games, and head-mounted displays". Human Factors. 49 (5): 920–934. doi:10.1518/001872007x230262. PMID 17915607. 31. ^ a b "The Promise and Challenges of Head-Mounted Virtual Reality Displays - Tested.com". Tested.com. Retrieved 14 July 2014. 32. ^ "VR Motion Sickness Statistics - Age, Gender, Experience and More. VRHeaven.io". VRHeaven.io. Retrieved 17 July 2020. 33. ^ Smart, L. J., Jr.; Stoffregen, T. A.; Bardy, B. G. (2002). "Visually induced motion sickness predicted by postural instability". Human Factors. 44 (3): 451–465. doi:10.1518/0018720024497745. PMID 12502162. 34. ^ Kolasinski, E. M.; Jones, S. A.; Kennedy, R. S.; Gilson, R. D. (January 1994). "Postural stability and its relation to simulator sickness". Poster Presented at the 38th Annual Meeting of the Human Factors and Ergonomics Society. 38 (15): 980. doi:10.1177/154193129403801571. 35. ^ Stern, R. M.; Hu, S.; LeBlanc, R.; Koch, K. L. (1993). "Chinese hyper-susceptibility to vection-induced motion sickness". Aviation, Space, and Environmental Medicine. 64 (9 Pt 1): 827–830. PMID 8216144. 36. ^ Sharma, K; Aparna (1997). "Prevalence and correlates of susceptibility to motion sickness". Acta Geneticae Medicae et Gemellologiae. 46 (2): 105–121. doi:10.1017/S0001566000000660. PMID 9492893. 37. ^ Uliano, K. C.; Lambert, E. Y.; Kennedy, R. S.; Sheppard, D. J. "The effects of asynchronous visual delays on simulator flight performance and the development of simulator sickness symptomatology (NAVTRASYSCEN 85-D-0026-1)". Orlando, FL: Naval Training Systems Center. Cite journal requires `\|journal=` (help) 38. ^ a b c Kennedy, R. S.; Frank, L. H. (September 1983). "A review of motion sickness with special reference to simulator sickness". Paper Presented at the National Academy of Sciences/National Research Council Committee on Human Factors. Monterey, CA. 39. ^ Park, G. D.; Allen, R. W.; Fiorentino, D.; Rosenthal, T. J.; Cook, M. L. (2006). "Simulator sickness scores according to symptom susceptibility, age, and gender for an older driver assessment study". Proceedings of the Human Factors and Ergonomics Society Annual Meeting. 50 (26): 2702–2706. doi:10.1177/154193120605002607. 40. ^ a b Kennedy, R. S.; Lilienthal, M. G.; Berbaum, K. S.; Baltzley, D. R.; McCauley, M. E. (1989). "Simulator sickness in U.S. Navy flight simulators". Aviation, Space, and Environmental Medicine. 60 (1): 10–16. PMID 2923588. 41. ^ a b Boyd, Danah (2001). Depth Cues in Virtual Reality and the Real World: Understanding Differences in Depth Perception by Studying Shape-from-shading and Motion Parallax (PDF) (Undergraduate honors thesis). Brown University. Retrieved 8 January 2016. 42. ^ Clemes, S. A.; Howarth, P. A. (2005). "The menstrual cycle and susceptibility to virtual simulator sickness". Journal of Biological Rhythms. 20 (1): 71–82. doi:10.1177/0748730404272567. PMID 15654072. 43. ^ a b Kennedy, R. S.; Berbaum, K. S.; Lilienthal, M. G.; Dunlap, W. P.; Mulligan, B. F.; Funaro, J. F. (1987). "Guidelines for alleviation of simulator sickness symptomatology (NAVTRASYSCEN TR-87007)". Orlando, FL: Naval Training Systems Center. Cite journal requires `\|journal=` (help) 44. ^ Lawson, Ben (2014-08-13), "Motion Sickness Symptomatology and Origins", Handbook of Virtual Environments, CRC Press, pp. 531–600, ISBN 978-1-4665-1184-2, retrieved 2020-10-11 45. ^ Saredakis, Dimitrios; Szpak, Ancret; Birckhead, Brandon; Keage, Hannah AD; Rizzo, Albert; Loetscher, Tobias (2019-12-13). "Factors associated with virtual reality sickness in head-mounted displays: a systematic review and meta-analysis". dx.doi.org. Retrieved 2020-10-11. 46. ^ a b Parker, D. E.; Harm, D. L. (1992). "Mental rotation: A key to mitigation of motion sickness in the virtual environment?". Presence. 1 (3): 329–333. doi:10.1162/pres.1992.1.3.329. PMID 11538019. * v * t * e Mixed and virtual reality Concepts * Applications of virtual reality * Artificial reality * Augmented reality * Degrees of freedom * Immersion * Projection augmented model * Real life * Reality–virtuality continuum * Room-scale * Telepresence * Virtual reality sickness * Virtual world * persistent Technology * Omnidirectional treadmill * Wearable computer * Haptic suit Display * Head-mounted display * optical * Head-up display * Virtual retinal display * Virtual reality headset (comparison) 3D interaction * Positional tracking * Eye tracking * Finger tracking * Simultaneous localization and mapping Software * Asynchronous reprojection * Foveated rendering * Image-based modeling and rendering Photography * Free viewpoint television * 360-degree video * VR photography * Omnidirectional camera Peripherals * Cyberith Virtualizer * Oculus Touch * Leap Motion * PlayStation Move * Razer Hydra * Virtuix Omni * Wired glove * Wizdish ROVR Immersive devices Current * Google Cardboard * HTC Vive * Nintendo Labo VR Kit * Oculus Go * Oculus Quest * 2 * Oculus Rift * CV1 * Rift S * OSVR * Magic Leap * Samsung Gear VR * PlayStation VR * Pimax * Valve Index * Vuzix Blade * Windows Mixed Reality * Microsoft HoloLens * 2 * Google Glass Legacy * Famicom 3D System * Google Daydream * Liquid Image * Sensorama * Sega VR * Sword of Damocles * Vuzix VFX1 Headgear * Virtual Boy * Virtuality Applications * ARToolKit * ARCore * Interactive art * Virtual graffiti * OpenVR * OpenXR * Pervasive game * WebVR Games * List of HTC Vive games * List of Oculus Quest games * List of Oculus Rift games * List of PlayStation VR games * v * t * e Motion sickness Types * Airsickness * Seasickness * Simulator sickness * Ski sickness * Space adaptation syndrome * Virtual reality sickness Medicine treatment * Bonine * Cinnarizine * Dramamine * Marezine * Promethazine * Transdermscop Related * Bárány chair * Sickness bag [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Virtual reality sickness	None	6,780	wikipedia	https://en.wikipedia.org/wiki/Virtual_reality_sickness	2021-01-18T18:29:00	{"wikidata": ["Q4219957"]}
A number sign (#) is used with this entry because of evidence that spermatogenic failure-29 (SPGF29) is caused by homozygous mutation in the SPINK2 gene (605753) on chromosome 4q12. One such family has been reported. Description Spermatogenic failure-29 is characterized by nonobstructive azoospermia or oligozoospermia. Sperm that are present are immotile and exhibit abnormal morphology, primarily defects of the acrosome and head-neck junction (Kherraf et al., 2017). For a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). Clinical Features Kherraf et al. (2017) reported 2 infertile 46,XY French brothers (Br1 and Br2), born of second-cousin parents. Analysis of ejaculates showed absence of sperm in Br1; Br2 had a very low sperm concentration, and all spermatozoa were immotile and exhibited abnormal morphology, with a pin-shaped head lacking the acrosome and detached flagella. In addition, ejaculates from both brothers had a significant concentration of germ cells, likely corresponding to spermatids, consistent with a severe defect in sperm production. Testicular sperm extraction from Br1 was unsuccessful, suggesting a diagnosis of postmeiotic nonobstructive azoospermia. Histologic examination of seminiferous tubule tissue from Br1 showed disorganization of tubular structure; lumens filled with immature germ cells, indicating intense desquamation of the germinal epithelium; and a reduced number of round spermatids, with overrepresentation of early round spermatids. The brothers had 4 sisters, 3 of whom had multiple children; sperm samples from their father were unavailable. The authors also studied an unrelated man (P105) who experienced a 5-year period of infertility after marriage, before spontaneous conception resulting in a healthy boy. Examination of ejaculate revealed oligospermia, with a reduced percentage of progressively motile spermatozoa. More than 60% of sperm showed abnormal morphology, primarily defects of the acrosome and head-neck junction. Molecular Genetics In 2 infertile French brothers, who were negative for Y-chromosome deletions at the AZF loci, Kherraf et al. (2017) performed whole-exome sequencing and identified a splice site mutation in the SPINK2 gene (605753.0001). Their second-cousin parents were both heterozygous for the mutation, which was not found in the ExAC database; sperm samples from the father were not available for analysis. Analysis of SPINK2 whole coding sequences in 611 additional men with oligo- or azoospermia identified 1 man (P105) with oligospermia who was heterozygous for a mutation in the start codon; he had spontaneously fathered 1 child after a 5-year period of infertility. The authors suggested that heterozygous mutations in SPINK2 may induce a milder phenotype with incomplete penetrance. Animal Model Kherraf et al. (2017) knocked out the Spink2 gene in mice and found that male homozygous knockout mice were completely infertile, whereas no reproductive defects were observed in female knockouts. Spink2 -/- mice had smaller testes and a smaller testis/body weight ratio compared with wildtype mice. Histologic studies on the seminiferous tubules of Spink2 -/- males showed that the absence of Spink2 did not impact spermatogonial survival, but led to a spermiogenesis blockade at the round-spermatid stage. Analysis of the ultrastructure of round spermatids by electronic microscopy revealed that the fusion of proacrosomal vesicles was hampered and the Golgi apparatus was fragmented in Spink2 -/- mice. The round spermatids from these mice also displayed the presence of multivesicular bodies, a known biomarker of microautophagy; however, there were no detectable signs of morphologic hallmarks of apoptosis, demonstrating that the absence of Spink2 at the round-spermatid stage did not activate the apoptotic pathway. INHERITANCE \- Autosomal recessive GENITOURINARY Internal Genitalia (Male) \- Oligozoospermia \- Azoospermia \- Immotile sperm \- Pin-shaped sperm heads \- Absent acrosome \- Detached flagella \- Disorganization of seminiferous tubular structure \- Immature germ cells in lumen of seminiferous tubules \- Overrepresentation of early round spermatids in seminiferous tubules MISCELLANEOUS \- Based on report of 2 affected brothers (last curated August 2018) \- Heterozygotes may exhibit oligoteratozoospermia with reduced fertility MOLECULAR BASIS \- Caused by mutation in the Kazal-type serine protease inhibitor-2 gene (SPINK2, 605753.0001 ) ▲ 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	SPERMATOGENIC FAILURE 29	None	6,781	omim	https://www.omim.org/entry/618091	2019-09-22T15:43:39	{"omim": ["618091"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Ectopia" medicine – news · newspapers · books · scholar · JSTOR (May 2019) (Learn how and when to remove this template message) An ectopia (/ɛkˈtoʊpiə/) is a displacement or malposition of an organ or other body part, which is then referred to as ectopic (/ɛkˈtɒpɪk/). Most ectopias are congenital, but some may happen later in life. ## Examples[edit] * Ectopic ACTH syndrome, also known as small-cell carcinoma. * Ectopic calcification, a pathologic deposition of calcium salts in tissues or bone growth in soft tissues * Cerebellar tonsillar ectopia, aka Chiari malformation, a herniation of the brain through the foramen magnum, which may be congenital or caused by trauma. * Ectopic cilia, a hair growing where it isn't supposed to be, commonly an eyelash on an abnormal spot on the eyelid, distichia * Ectopia cordis, the displacement of the heart outside the body during fetal development * Ectopic enamel, a tooth abnormality, where enamel is found in an unusual location, such as at the root of a tooth * Ectopic expression, the expression of a gene in an abnormal place in an organism * Ectopic hormone, a hormone produced by a tumor, such as small-cell carcinoma, can cause Cushing's syndrome * Ectopia lentis, the displacement of the crystalline lens of the eye * Neuronal ectopia * Ectopic pancreas, displacement of pancreatic tissue in the body with no connection, anatomical or vascular, to the pancreas * Ectopic recombination, the recombination between sequences (like leu2 sequences) present at different genomic locations * Renal ectopia occurs when both kidneys are on the same side of the body * Ectopic testis, a testis that has moved to an unusual location * Ectopic thymus, where thymus tissue is found in an abnormal location * Ectopic thyroid, where an entire or parts of the thyroid are located elsewhere in the body * Ectopic tooth * Ectopic ureter, where the ureter terminates somewhere other than the urinary bladder * Ectopia vesicae, a congenital anomality in which part of the urinary bladder is present outside the body ## See also[edit] * Ectopic beat of the heart * Cervical ectropion * Ectopic pregnancy, where the fertilized egg implants anywhere other than the uterine wall * Heterotopia (medicine) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Ectopia (medicine)	None	6,782	wikipedia	https://en.wikipedia.org/wiki/Ectopia_(medicine)	2021-01-18T18:32:58	{"wikidata": ["Q10480798"]}
Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect. Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age). Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge. Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair. Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems. ## Frequency Meier-Gorlin syndrome is a rare condition; however, its prevalence is unknown. ## Causes Meier-Gorlin syndrome can be caused by mutations in one of several genes. Each of these genes, ORC1, ORC4, ORC6, CDT1, and CDC6, provides instructions for making one of a group of proteins known as the pre-replication complex. This complex regulates initiation of the copying (replication) of DNA before cells divide. Specifically, the pre-replication complex attaches (binds) to certain regions of DNA known as origins of replication, allowing copying of the DNA to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide. Mutations in any one of these genes impair formation of the pre-replication complex and disrupt replication licensing; however, it is not clear how a reduction in replication licensing leads to Meier-Gorlin syndrome. Researchers speculate that such a reduction delays the cell division process, which impairs growth of the bones and other tissues during development. Some research suggests that some of the pre-replication complex proteins have additional functions, impairment of which may contribute to features of Meier-Gorlin syndrome, such as delayed development of the kneecaps and ears. ### Learn more about the genes associated with Meier-Gorlin syndrome * CDC6 * CDT1 * ORC1 * ORC4 * ORC6 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Meier-Gorlin syndrome	c4552001	6,783	medlineplus	https://medlineplus.gov/genetics/condition/meier-gorlin-syndrome/	2021-01-27T08:25:54	{"gard": ["2033"], "omim": ["224690", "613800", "613803", "613804", "613805"], "synonyms": []}
Deficit of micronutrients, vine. Physiological plant disorders are caused by non-pathological conditions such as poor light, adverse weather, water-logging, phytotoxic compounds or a lack of nutrients, and affect the functioning of the plant system. Physiological disorders are distinguished from plant diseases caused by pathogens, such as a virus or fungus.[1] While the symptoms of physiological disorders may appear disease-like, they can usually be prevented by altering environmental conditions. However, once a plant shows symptoms of a physiological disorder it is likely that, that season’s growth or yield will be reduced. ## Contents * 1 Diagnosis of disorders * 2 Weather damage * 3 Nutrient deficiencies * 4 References ## Diagnosis of disorders[edit] Diagnosis of the cause of a physiological disorder (or disease) can be difficult, but there are many web-based guides that may assist with this. Examples are: Abiotic plant disorders: Symptoms, signs and solutions;[1] Georgia Corn Diagnostic Guide;[2] Diagnosing Plant Problems (Kentucky);[3] and Diagnosing Plant Problems (Virginia).[4] Sunburn at apple. Some general tips to diagnosing plant disorders: * Examine where symptoms first appear on a plant—on new leaves, old leaves or all over? * Note the pattern of any discolouration or yellowing—is it all over, between the veins or around the edges? If only the veins are yellow, deficiency is probably not involved. * Note general patterns rather than looking at individual plants—are the symptoms distributed throughout a group of plants of the same type growing together? In the case of a deficiency all of the plants should be similarly effected, although distribution will depend on past treatments applied to the soil. * Soil analysis, such as determining pH, can help to confirm the presence of physiological disorders. * Considering recent conditions, such as heavy rains, dry spells, frosts, etc., may also help to determine the cause of plant disorders. ## Weather damage[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (July 2017) (Learn how and when to remove this template message) Drought. Frost and cold are major causes of crop damage to tender plants, although hardy plants can also suffer if new growth is exposed to a hard frost following a period of warm weather. Symptoms will often appear overnight, affecting many types of plants. Leaves and stems may turn black, and buds and flowers may be discoloured, and frosted blooms may not produce fruit. Many annual plants, or plants grown in frost free areas, can suffer from damage when the air temperature drops below 40 degrees Fahrenheit (4 degrees Celsius). Tropical plants may begin to experience cold damage when the temperature is 42 to 48 °F (5 to 9 °C), symptoms include wilting of the top of the stems and/or leaves, and blackening or softening of the plant tissue. Frost or cold damage can be avoided by ensuring that tender plants are properly hardened before planting, and that they are not planted too early in the season, before the risk of frost has passed. Avoid planting susceptible plants in frost pockets, or where they will receive early morning sun. Protect young buds and bloom with horticultural fleece if frost is forecast. Cold, drying easterly winds can also severely inhibit spring growth even without an actual frost, thus adequate shelter or the use of windbreaks is important. Drought can cause plants to suffer from water stress and wilt. Adequate irrigation is required during prolonged hot, dry periods. Rather than shallow daily watering, during a drought water should be directed towards the roots, ensuring that the soil is thoroughly soaked two or three times a week. Mulches also help preserve soil moisture and keep roots cool. Heavy rains, particularly after prolonged dry periods, can also cause roots to split, onion saddleback (splitting at the base), tomatoes split and potatoes to become deformed or hollow. Using mulches or adding organic matter such as leaf mold, compost or well rotted manure to the soil will help to act as a 'buffer' between sudden changes in conditions. Water-logging can occur on poorly drained soils, particularly following heavy rains. Plants can become yellow and stunted, and will tend to be more prone to drought and diseases. Improving drainage will help to alleviate this problem. Hail can cause damage to soft skinned fruits, and may also allow brown rot or other fungi to penetrate the plant. Brown spot markings or lines on one side of a mature apple are indicative of a spring hailstorm. Plants affected by salt stress are able to take water from soil, due to an osmotic imbalance between soil and plant. ## Nutrient deficiencies[edit] Iron deficiency. Poor growth and a variety of disorders such as leaf discolouration (chlorosis) can be caused by a shortage of one or more plant nutrients. Poor plant uptake of a nutrient from the soil (or other growing medium) may be due to an absolute shortage of that element in the growing medium, or because that element is present in a form that is not available to the plant.[5] The latter can be caused by incorrect pH, shortage of water, poor root growth or an excess of another nutrient.[5] Plant nutrient deficiencies can be avoided or corrected using a variety of approaches including the consultation of experts on-site, the use of soil and plant-tissue testing services, the application of prescription-blend fertilizers, the application of fresh or well-decomposed organic matter, and the use of biological systems such as cover crops, intercropping, improved fallows,[6] ley cropping, permaculture, or crop rotation. Nutrient (or mineral) deficiencies include: * Boron deficiency * Calcium deficiency * Iron deficiency * Magnesium deficiency * Manganese deficiency * Molybdenum deficiency * Nitrogen deficiency * Phosphorus deficiency * Potassium deficiency * Zinc deficiency ## References[edit] 1. ^ a b Schutzki, R.E.; Cregg, B. (2007). "Abiotic plant disorders: Symptoms, signs and solutions. A diagnostic guide to problem solving" (PDF). Michigan State University Department of Horticulture. Michigan State University. Archived from the original (PDF) on 24 September 2015. Retrieved 10 April 2015. 2. ^ Lee, R.D. (2012). "Georgia Corn Diagnostic Guide". extension.uga.edu. University of Georgia Cooperative Extension. Retrieved 10 April 2015. 3. ^ Green, J.L.; Maloy, O.; Capizzi, J.; Hartman, J.; Townsend, L. (2011). "Diagnosing Plant Problems: Kentucky Master Gardener Manual Chapter 7" (PDF). www2.ca.uky.edu. Kentucky Cooperative Extension. Retrieved 10 April 2015. 4. ^ Niemiera, A.X. (2009). "Diagnosing Plant Problems". pubs.ext.vt.edu. Virginia Cooperative Extension. Retrieved 10 April 2015. 5. ^ a b Mengel, K.; Kirkby, E.A. (2001). Principles of plant nutrition (5th ed.). Dordrecht: Kluwer Academic Publishers. ISBN 079237150X. 6. ^ "Improved fallows". teca.fao.org. FAO. Archived from the original on 13 November 2017. Retrieved 10 April 2015. "Improved fallow is also land resting from cultivation but the vegetation comprises planted and managed species of leguminous trees, shrubs and herbaceous cover crops. These cover crops rapidly replenish soil fertility in one or at most two growing seasons. They shorten the time required to restore soil fertility; they help to improve farmland productivity because the plant vegetation that follows them is superior in quality; and they increase the range of outputs, because the woody fallow species can also produce fuel wood and stakes." * v * t * e Plant disorders / control * Physiological plant disorders * Plant pathology * Plant stress measurement * Transplant shock * v * t * e Plant nutrition / Fertilizer Imbalances * Boron deficiency * Calcium deficiency * Iron deficiency * Magnesium deficiency#Plants * Manganese deficiency * Molybdenum deficiency * Nitrogen deficiency * Phosphorus deficiency * Potassium deficiency * Zinc deficiency * Micronutrient deficiency * Chlorosis * Fertilizer burn Assimilation * Nitrogen assimilation * Phosphorus assimilation * Sulfur assimilation * Microbial assistance * Photorespiration Methods * Fertigation * Fertilizer tree * Green manure * Hoagland solution * Hydroponic dosers * Living mulch * Nutrient budgeting * Nutrient management * Organic fertilizer * Plant tissue test Miscellaneous * Soil fertility * Nutrient pollution * Soil pH * Agrobiology Related concepts * Algal nutrient solutions * v * t * e Physiology types Animals * Fish physiology * Human physiology * Insect physiology * Physiology of dinosaurs Plants * Plant physiology * Plant perception (physiology) * Physiological plant disorders Cells * Cell physiology Related topics * Comparative physiology * Ecophysiology * Electrophysiology * Evolutionary physiology * Molecular physiology * Neurophysiology [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Physiological plant disorder	None	6,784	wikipedia	https://en.wikipedia.org/wiki/Physiological_plant_disorder	2021-01-18T18:52:53	{"wikidata": ["Q8294850"]}
Konigsmark et al. (1970) described congenital moderate neural hearing loss in 3 sibships with apparent recessive inheritance. They concluded that this type had not been described previously. Inheritance \- Autosomal recessive Ears \- Neural hearing loss \- Congenital hearing loss ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	DEAFNESS, NEURAL, CONGENITAL MODERATE	c1857337	6,785	omim	https://www.omim.org/entry/221500	2019-09-22T16:28:54	{"mesh": ["C565640"], "omim": ["221500"]}
Scrotodynia SpecialtyDermatology Scrotodynia is a condition characterized by dysesthesia of the scrotum.[1] ## See also[edit] * Vulvodynia * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 100, 1069, 1070. ISBN 978-1-4160-2999-1. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Scrotodynia	None	6,786	wikipedia	https://en.wikipedia.org/wiki/Scrotodynia	2021-01-18T18:40:41	{"wikidata": ["Q7439312"]}
A rare polymorphic disorder, subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1), characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia. ## Epidemiology Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome (ADCA-DN) has been reported in more than 80 patients to date from Sweden, the United States, Italy, Brazil, Belgium, China, New Zealand, UK, Taiwan, Germany, and Canada. ## Clinical description Disease onset usually occurs in adulthood (from the ages of 30-40). Cases have been reported in adolescents. The clinical features include cerebellar ataxia, narcolepsy with cataplexy, sensorineural deafness and dementia including executive dysfunction and global cognitive impairement. Optic atrophy, cataracts, psychosis, depression, sensory neuropathy, pseudobulbar signs, incontinence and limb lymphedema have also been reported but present later in the disease course. Mild brain atrophy with cerebellum involvement is visible with magnetic resonance imaging (MRI). ## Etiology ADCA-DN is caused by a mutation in the DNA methyltransferase (DNMT1) gene located on chromosome 19p13.2. It encodes an enzyme essential for the repression of transcriptional activity in numerous postmitotic cells. ## Diagnostic methods Diagnosis is based on the characteristic clinical findings and molecular genetic testing, the finding of a mutation in the DNMT1 gene. ## Differential diagnosis Differential diagnosis includes other types of autosomal dominant cerebellar ataxia (ADCA), and hereditary. ## Antenatal diagnosis Antenatal diagnosis is possible in families with a known mutation. ## Genetic counseling ADCA-DN is inherited autosomal dominantly and genetic counseling is possible. Sporadic cases have also been reported. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. ## Management and treatment There is no cure for ADCA-DN and treatment is supportive. Physical therapy, as well as the use of canes and walkers, should be offered in order to maximize strength and maintain activity as well as to avoid falls. Wheelchairs are eventually necessary. Speech therapy and communication devices may be useful to those with dysarthria. Annual neurological examinations are recommended to monitor disease progression. ## Prognosis Disease duration from disease onset to death is estimated to be between 10 to 30 years. Almost all affected individuals survive at least until late 40's. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome	c3807295	6,787	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314404	2021-01-23T18:26:39	{"gard": ["12372"], "omim": ["604121"], "icd-10": ["G11.0"], "synonyms": ["ADCA-DN syndrome", "Autosomal dominant cerebellar ataxia-hearing loss-narcolepsy syndrome"]}
Melanosis SpecialtyDermatology Melanosis is a form of hyperpigmentation associated with increased melanin.[1] It can also refer to: * Melanism * Ocular melanosis * Smoker's melanosis * Oral melanosis * Riehl melanosis ## See also[edit] Look up melanosis in Wiktionary, the free dictionary. * List of cutaneous conditions ## References[edit] 1. ^ Melanosis at the US National Library of Medicine Medical Subject Headings (MeSH) ## External links[edit] Classification D * MeSH: D008548 * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Melanosis	c0016689	6,788	wikipedia	https://en.wikipedia.org/wiki/Melanosis	2021-01-18T18:49:33	{"mesh": ["D008548"], "wikidata": ["Q6811539"]}
## Summary ### Clinical characteristics. Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported. ### Diagnosis/testing. The diagnosis of THES is established in a proband with biallelic pathogenic variants in either TTC37 or SKIV2L. ### Management. Treatment of manifestations: To promote maximal weight gain and linear growth, most children initially require parenteral nutrition (PN). As tolerated, oral feeding (typically a semi-elemental diet) can be combined with PN. On the rare occasion that PN is unnecessary, anecdotal reports describe use of mainly an amino acid-based formula. To reduce the burden of infections, immunoglobulins can be supplemented in those with low immunoglobulin levels or immunoglobulin functional abnormalities. Patient-specific management of ID is based on age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills. Surveillance: For children not receiving PN: close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention as needed. Yearly assessment of: diarrhea for changes that could suggest inflammatory bowel disease; liver function and size; immunoglobulin serum concentration and functionality; TSH level for evidence of hypothyroidism. Periodic assessment of: cognitive development, speech and language, and psychosocial skills for evidence of ID. ### Genetic counseling. THES is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SKIV2L or TTC37 pathogenic variants have been identified in an affected family member, carrier testing of at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible. ## Diagnosis To date, no diagnostic algorithm for trichohepatoenteric syndrome (THES) has been published. ### Suggestive Findings THES should be suspected in individuals with the following clinical findings [Fabre & Badens 2014, Fabre et al 2014]: * Growth failure. * Intrauterine growth restriction (IUGR) / small for gestational age (SGA), short stature * Intractable/chronic diarrhea * beginning in infancy that persists despite bowel rest or, on rare occasion, shows very early-onset inflammatory bowel disease (VEOIBD) of infancy. Endoscopic evaluation is often normal, but can resemble IBD. Intestinal biopsy findings range from mild villous atrophy to severe villous atrophy [Goulet et al 2008, Fabre et al 2014]. * Woolly, brittle, easily breakable hair. Hair analysis using light microscopy showed trichorrhexis nodosa in 42/52 individuals [Fabre & Badens 2014, Fabre et al 2014]. * Immunodeficiency that is poorly characterized, but typically low immunoglobulin levels and/or poor antibody production after immunization. Monoclonal hyper-IgA has been described [Fabre & Badens 2014, Fabre et al 2014, Rider et al 2015]. * Liver disease, mostly hepatomegaly and/or elevated liver enzymes; fibrosis or cirrhosis can occur. Hemochromatosis has been described, particularly when liver findings are significant [Verloes et al 1997, Hartley et al 2010]. * Café au lait spots or dyschromic spots have been described in nearly half of individuals reported [Fabre et al 2014]. Of note, a subset of affected individuals from the Arabian peninsula have pelvic, girdle, and lower-limb skin hyperpigmentation [Monies et al 2015]. * The association of neonatal intractable diarrhea and IUGR suggests the diagnosis of THES. ### Establishing the Diagnosis The diagnosis of THES is established in a proband with biallelic pathogenic variants in TTC37 or SKIV2L (Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (serial single-gene testing or a multigene panel) and comprehensive genomic testing depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of THES is broad, children with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with diarrhea, liver disease, and immunodeficiency will be more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of THES, molecular genetic testing approaches can include serial single-gene testing or use of a multigene panel. * Serial single-gene testing. Sequence analysis of TTC37 is performed first and – if no pathogenic variants are identified – followed by sequence analysis of SKIV2L. If only one pathogenic variant is found, gene-targeted deletion/duplication analysis could be considered; however, to date no exon or whole-gene deletions or duplications have been reported in either gene. * A multigene very early-onset IBD (VEOIBD) panel that includes SKIV2L and TTC37 and other genes of interest (see Differential Diagnosis) typically provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting identification of 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; conversely, given the rarity of THES, some panels for diarrhea, hepatic disease, and immunodeficiency may not include these genes. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders with diarrhea, hepatic disease, and immunodeficiency, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible, although not yet easily analyzed in a clinical setting. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Trichohepatoenteric Syndrome View in own window Gene 1Proportion of THES Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method Sequence analysis 3Gene-targeted deletion/ duplication analysis 4 SKIV2L16/52 5 (31%)All variants reported to dateUnknown, none reported to date TTC3736/52 6 (69%)All variants reported to dateUnknown, none reported to date 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 5\. n=6: Fabre et al [2012]; n=4: Monies et al [2015] (patients #1, 2, 3, 5); n=2: Lee et al [2016b] (patients LL, LF); n=1: Morgan et al [2013], Kammermeier et al [2014], Zheng et al [2016], Kammermeier et al [2017] 6\. n=12: Hartley et al [2010]; n=9: Fabre et al [2011]; n=2: Kotecha et al [2012], Chong et al [2015], Lee et al [2016a], Kinnear et al [2017]; n=1: Bozzetti et al [2013], Kammermeier et al [2014], Monies et al [2015] (patient #4), Oz-Levi et al [2015], Rider et al [2015], Lee et al [2016b] (patient CHT), Kammermeier et al [2017] ## Clinical Characteristics ### Clinical Description Trichohepatoenteric syndrome (THES) is considered a syndrome of neonatal enteropathy [Canani et al 2015]. THES is characterized by the association of intractable diarrhea (seen in almost all affected children), woolly hair (seen in all, but may not be obvious at a young age or due to cultural grooming practices), intrauterine growth restriction (IUGR), facial dysmorphism, and short stature, as well as poorly characterized immunodeficiency (sometimes with macrophage activation syndrome), recurrent infections, skin abnormalities, and liver disease. Intellectual disability (ID) is seen in about 50% of children. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported (see Table 1). Intractable diarrhea usually begins in the first days of life but sometimes can be delayed until later in the first year of life. The diarrhea persists despite bowel rest (i.e., use of parenteral nutrition). Stools are watery; in rare cases blood can be found. The diarrhea leads to malabsorption and failure to thrive, which typically requires parenteral nutrition (see Management). To date, the diarrhea has appeared to be lifelong [Fabre & Badens 2014]. Very rarely, the clinical presentation can resemble so-called very early-onset inflammatory bowel disease (VEOIBD). In the only instance in which immunodeficiency was reported to be the major clinical finding, the child never manifested the characteristic diarrhea [Rider et al 2015]. Woolly, brittle hair. Detailed clinical descriptions of the hair provided for 41 individuals included the following: woolly (n=22), poorly pigmented / light (n=18), easily removable / brittle (n=19), and unmanageable / unable to be combed (n=15) (e.g., Bozzetti et al [2013], Busoni et al [2017]). Growth failure * Intrauterine growth restriction (IUGR) / small for gestational age (SGA). Most children are below the 10th centile at birth either for height or for weight [Fabre & Badens 2014, Fabre et al 2014]. * Short stature. Despite adequate nutrition, the last recorded height in more than 50% of affected individuals was below the 3rd centile [Fabre & Badens 2014]. Although to date no adult with THES has been described in detail, the heights in the three older individuals for whom that information was available were the following: * 148 cm (-2.36 SD) in a woman age 27 years [Martinez-Vinson 2004] * 171 cm (-0.74 SD) in a man age 18 years [Martinez-Vinson 2004] * -5 SD in a woman age 17 years [Barabino et al 2004] Immunodeficiency. Children are prone to recurrent infection [Girault et al 1994, Martinez-Vinson 2004, Zheng et al 2016, Bick et al 2017]. Both viral infections (respiratory syncytial virus [Lee et al 2016a], Epstein Barr virus [Martinez-Vinson 2004, Fabre & Badens 2014]) and bacterial infections [Martinez-Vinson 2004, Rider et al 2015] have been reported. Nine of 15 individuals with THES had a transient hemophagocytic syndrome / macrophage activation syndrome [Fabre & Badens 2014]; however, no specific data were provided about diagnosis or management. Infection was implicated in the death of seven of 21 patients. Liver disease, found in about half of patients, is mostly cirrhosis and fibrosis [Fabre et al 2014]. In seven of 17 individuals for whom the cause of death was described, liver disease (mostly liver failure or cirrhosis) was implicated [Girault et al 1994, Verloes et al 1997, Kinnear et al 2017]. One patient developed a hepatoblastoma [Bozzetti et al 2013]. Pathology showed iron overload and sometimes hemochromatosis [Hartley et al 2010, Fabre et al 2014]. In some instances, hemochromatosis improved with time [Fabre et al 2007]. Mild intellectual disability, described in about half of patients [Goulet et al 2008, Fabre & Badens, Fabre et al 2014], is poorly characterized. Brain MRI – when performed – appears normal [Fabre & Badens 2014]. Skin abnormalities. The most common are café au lait spots that preferentially appear on the lower limbs [Monies et al 2015]. Later in life, xerosis and/or rubbery skin can be observed. Congenital cardiac defects, which are seldom seen, vary. The following were observed among 12 patients with cardiac or aortic defects: ventricular septal defect (n=2) [Hartley et al 2010, Bick et al 2017]; atrial septal defect (n=2) [Chong et al 2015, Lee et al 2016a]; tetralogy of Fallot (n=1) [Hartley et al 2010]. Others had a bicuspid aortic valve with or without other anomalies, an aortic defect, or a mildly dilated aortic sinus. Platelets can be enlarged with no known functional defect [Hartley et al 2010]. Facial dysmorphism that is mild and nonspecific is observed in nearly all affected individuals. The main findings (coarse features, a wide forehead, broad nasal root, and hypertelorism) can become more apparent with time [Fabre & Badens 2014, Fabre et al 2014]. Findings observed in a few affected individuals that could be part of the phenotypic spectrum of THES or unrelated findings include the following: * Hypothyroidism. n=3/15 affected individuals [Fabre & Badens 2014] * Dental abnormalities: * Peg teeth. n=2 [Monies et al 2015] * Narrow pointed teeth and dental dysplasia. n=2 [Fabre & Badens 2014] * Inguinal hernia. n=2 [Hartley et al 2010, Fabre & Badens 2014] One individual each: * Small kidneys [Hartley et al 2010] * Perthe syndrome [Hartley et al 2010] * Glaucoma [Fabre & Badens 2014] * Polycystic kidney [Fabre et al 2014] * Thymus atrophy (in an individual without a molecular diagnosis) [Stankler et al 1982] ### Phenotype Correlations by Gene Current data suggest that individuals with biallelic pathogenic variants in either SKIV2L or TTC37 are indistinguishable clinically. ### Genotype-Phenotype Correlations Because most pathogenic variants are private, genotype/phenotype correlations are difficult. Of note, the phenotypes were indistinguishable in the five individuals with the recurrent TTC37 variant (Trp936Ter) and those with other TTC37 pathogenic variants [Fabre et al 2014]. ### Prevalence THES is rare. To date about 50 affected individuals have been reported. The best estimate of prevalence is 1:1,000,000 births, based on the French cohort of Fabre & Badens [2014]. Affected individuals have been reported worldwide. As with all autosomal recessive disorders, the prevalence may be increased in highly consanguineous populations. ## Differential Diagnosis ### Table 3. Monogenic Disorders with Intractable Diarrhea to Consider in the Differential Diagnosis of Trichohepatoenteric Syndrome View in own window DisorderGeneMOIDistinguishing Clinical Features of Differential Diagnosis Disorder Congenital tufting enteropathy (OMIM 613217)EPCAMARSpecific intestinal pathology (tuft) IPEX syndromeFOXP3XLLow regulatory T cells Gastrointestinal defects and immunodeficiency syndrome (OMIM 243150)TTC7AARDuodenal atresia Syndromic congenital tufting enteropathy (OMIM 270420)SPINT2ARSpecific intestinal pathology (tuft) Choanal atresia AR = autosomal recessive; IPEX = immune dysregulation, polyendocrinopathy, enteropathy, X-linked; MOI = mode of inheritance; XL = X-linked See Diarrhea, congenital: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with trichohepatoenteric syndrome (THES), the following evaluations are recommended: * Nutritional evaluation by a specialist pediatric nutritionist * Immunologic assessment with serum IgG, IgM, IgA; immunophenotyping; if immunization has been performed before, evaluation of the level of specific antibodies to detect a rapid loss of protective antibodies, which would require immunoglobulin supplementation * Liver assessment: ultrasound evaluation; assessment of liver enzymes (ALT/AST, GGT); in case of abnormalities, consult a pediatric hepatologist for recommendations on additional investigations * Cardiac evaluation for congenital malformations * Age-appropriate assessment of cognitive development, speech and language development, and psychosocial skills * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations No specific treatment is available. The goals of the treatment are to promote maximal weight gain and linear growth, to reduce the burden of infections, and to provide patient-specific management of intellectual disability. Weight gain. Most children, when first diagnosed, require parenteral nutrition (PN) to achieve appropriate weight gain and catch-up growth. Although PN is usually required, it can be combined (as tolerated) with oral feeding – typically a semi-elemental diet [Goulet et al 2008]. About 30%-50% of patients can become independent of parenteral nutrition after prolonged PN. Of note, promotion of oral feeding as tolerated (rather than enteral tube feeding) should help prevent future eating disorders. To date nine individuals have been reported in whom PN was unnecessary [Kotecha et al 2012, Chong et al 2015, Rider et al 2015, Lee et al 2016a, Mahjoub et al 2016, Zheng et al 2016]. In three of the nine, the diet was an amino acid formula [Lee et al 2016a, Lee et al 2016b, Zheng et al 2016]; it is not clear if weight gain was adequate, or if catch-up growth was achieved. When early-onset manifestations are those of inflammatory bowel disease (IBD), infections should be ruled out and routine management of IBD with steroids, azathioprine, and anti-TNF (tumor necrosis factor) antibody can be considered; however, this routine IBD management may result in only transient improvement, or no improvement [Busoni et al 2017, Kammermeier et al 2017]. Growth. Anecdotal experience shows no efficacy of growth hormone treatment [Fabre & Badens 2014]. Infection. Immunoglobulin supplementation for those with low immunoglobulin levels appears to lower the rate of infection [Fabre et al 2014, Rider et al 2015]. Of note, hematopoietic stem cell transplantation (HSCT) – reported twice to date – has been unsuccessful: one patient succumbed to infection [Girault et al 1994] and the other showed only mild improvement [Kammermeier et al 2014]. Intellectual disability is managed specifically according to the results of age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills. Tooth shape abnormalities. Evaluation of abnormal dentition in children is especially important because teeth are required for development of speech, nutrition, self-esteem, and well-being. The National Foundation for Ectodermal Dysplasias (NFED) website provides further resources and information. Hair changes. Fragile hair and hair loss can have a deeper-than-expected emotional impact on a patient and family. Counseling may be helpful. Also, hair prosthetics (wigs) are available through Locks of Love and other organizations; some insurance provides two wigs per year in growing children with alopecia. A prescription for a cranial prosthesis may or may not aid insurance reimbursement. ### Surveillance Although there are no consensus guidelines, the following surveillance is recommended: * For children not receiving parenteral nutrition, close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention should nutritional deficiency become a concern * Yearly assessment of the following main features: * Diarrhea. If the nature of the diarrhea changes (e.g., appearance of bloody diarrhea), investigation of possible inflammatory bowel disease (IBD) is warranted [Busoni et al 2017]. * Liver function. Ultrasound examination and measurement of liver enzymes (AST, ALT, GGT), International Normalized Ratio (INR), and bilirubin * Serum concentration of IgG, IgM, IgA, and immunoglobulin functionality (i.e., immunophenotyping) even if results at the time of initial evaluation were normal. Consultation with an immunologist is warranted if immunoglobulin levels are low or if normal immunoglobulin levels are associated with a loss of specific protective antibody. * TSH level for evidence of hypothyroidism * Assessment of cognitive development, speech and language, and psychosocial skills for evidence of intellectual disability at ages 2, 4, 8, 12, and 15 years unless concerns appear earlier * As evolution of the dermatologic features (mostly hypo- or hyperpigmented patches and hair abnormalities) is unknown, regular evaluation by a dermatologist seems reasonable. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Trichohepatoenteric Syndrome	c1857276	6,789	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK475802/	2021-01-18T20:52:12	{"mesh": ["C565627"], "synonyms": ["Phenotypic Diarrhea of Infancy", "Syndromic Diarrhea/Tricho-Hepato-Enteric Syndrome (SD/THE)", "THES"]}
Play media Alcohol and health (two minute video) Alcohol (also known as ethanol) has a number of effects on health. Short-term effects of alcohol consumption include intoxication and dehydration. Long-term effects of alcohol consumption include changes in the metabolism of the liver and brain and alcoholism. Alcohol intoxication affects the brain, causing slurred speech, clumsiness, and delayed reflexes. Alcohol stimulates insulin production, which speeds up glucose metabolism and can result in low blood sugar, causing irritability and possibly death for diabetics.[1][medical citation needed] There is an increased risk of developing an alcohol use disorder for teenagers while their brain is still developing.[2] Adolescents who drink have a higher probability of injury including death.[2] Even light and moderate alcohol consumption increases cancer risk in individuals.[3][4] A 2014 World Health Organization report found that harmful alcohol consumption caused about 3.3 million deaths annually worldwide.[5] Negative efforts are related to the amount consumed with no safe lower limit seen.[6] Some nations have introduced alcohol packaging warning messages that inform consumers about alcohol and cancer, as well as fetal alcohol syndrome.[7] The median lethal dose of alcohol in test animals is a blood alcohol content of 0.45%. This is about six times the level of ordinary intoxication (0.08%), but vomiting or unconsciousness may occur much sooner in people who have a low tolerance for alcohol.[8] The high tolerance of chronic heavy drinkers may allow some of them to remain conscious at levels above 0.40%, although serious health hazards are incurred at this level. Alcohol also limits the production of vasopressin (ADH) from the hypothalamus and the secretion of this hormone from the posterior pituitary gland. This is what causes severe dehydration when alcohol is consumed in large amounts. It also causes a high concentration of water in the urine and vomit and the intense thirst that goes along with a hangover. Stress, hangovers, and the oral contraceptive pill may increase the desire for alcohol because these things will lower the level of testosterone and alcohol will acutely elevate it.[9] Tobacco has the same effect of increasing the craving for alcohol.[10] ## Contents * 1 Short-term effects * 2 Long-term effects * 3 Pregnancy * 4 Cardiovascular disease * 5 Breastfeeding * 6 Alcohol education * 7 Alcohol expectations * 7.1 Drug treatment programs * 8 Alcohol abuse * 8.1 Alcohol abuse prevention programs * 8.2 Recommended maximum intake * 8.3 Sobriety * 9 Injury and deaths * 10 Genetic differences * 10.1 Alcohol flush and respiratory reactions * 10.2 American Indian alcoholism * 10.3 Genetics and amount of consumption * 11 Gender differences * 11.1 Alcoholism * 11.2 Sensitivity * 11.3 Metabolism * 11.4 Depression * 12 See also * 13 References * 14 External links ## Short-term effects[edit] Main article: Short-term effects of alcohol consumption The short-term effects of alcohol consumption range from a decrease in anxiety and motor skills at lower doses to unconsciousness, anterograde amnesia, and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every cell in the body. The concentration of alcohol in blood is measured via blood alcohol content (BAC). The amount and circumstances of consumption play a large part in determining the extent of intoxication; for example, eating a heavy meal before alcohol consumption causes alcohol to absorb more slowly.[11] Hydration also plays a role, especially in determining the extent of hangovers. After excessive drinking, unconsciousness can occur and extreme levels of consumption can lead to alcohol poisoning and death (a concentration in the blood stream of 0.40% will kill half of those affected[12][medical citation needed]). Alcohol may also cause death indirectly, by asphyxiation from vomit. Alcohol can greatly exacerbate sleep problems. During abstinence, residual disruptions in sleep regularity and sleep patterns[clarification needed] are the greatest predictors of relapse.[13] ## Long-term effects[edit] Main article: Long-term effects of alcohol According to the World Health Organization's 2018 Global Status Report on Alcohol and Health, there are more than 3 million people who die from the harmful effects of alcohol each year, which amounts to more than 5% of the burden of disease world-wide.[14] The US National Institutes of Health similarly estimates that 3.3 million deaths (5.9% of all deaths) were believed to be due to alcohol each year.[15] Guidelines in the US and the UK advise that if people choose to drink, they should drink moderately.[16][17] Even light and moderate alcohol consumption increases cancer risk in individuals, especially with respect to squamous cell carcinoma of the esophagus, oropharyngeal cancer, and breast cancer.[3][4] A systematic analysis of data from the Global Burden of Disease Study, which was an observational study, found that long-term consumption of any amount of alcohol is associated with an increased risk of death in all people, and that even moderate consumption appears to be risky. Similar to prior analyses, it found an apparent benefit for older women in reducing the risks of death from ischemic heart disease and from diabetes, but unlike prior studies it found those risks cancelled by an apparent increased risk of death from breast cancer and other causes.[18] A 2016 systematic review and meta-analysis found that moderate ethanol consumption brought no mortality benefit compared with lifetime abstention from ethanol consumption.[19] Risk is greater in younger people due to heavy episodic drinking which may result in violence or accidents.[20] Long-term heavy use of alcohol damages nearly every organ and system in the body.[21] Risks include alcoholism, malnutrition, chronic pancreatitis, alcoholic liver disease and cancer. In addition, damage to the central nervous system and peripheral nervous system can occur from chronic alcohol abuse.[22][23] The developing adolescent brain is particularly vulnerable to the toxic effects of alcohol.[24] ## Pregnancy[edit] See also: Fetal alcohol spectrum disorders Medical organizations strongly discourage drinking alcohol during pregnancy.[25][26][27] Alcohol passes easily from the mother's bloodstream through the placenta and into the bloodstream of the fetus,[28] which interferes with brain and organ development.[29] Alcohol can affect the fetus at any stage during pregnancy, but the level of risk depends on the amount and frequency of alcohol consumed.[29] Regular heavy drinking and heavy episodic drinking (also called drinking binges), entailing four or more measures (a pint of beer or 50 ml drink of a spirit such as whisky corresponds to about two units of alcohol) of alcohol beverages on any one occasion, pose the greatest risk for harm, but lesser amounts can cause problems as well.[29] There is no known safe amount or safe time to drink during pregnancy, and the U.S. CDC recommends complete abstinence for women who are pregnant, trying to become pregnant, or are sexually active and not using birth control.[30][31] Prenatal alcohol exposure can lead to fetal alcohol spectrum disorders (FASDs). The most severe form of FASD is fetal alcohol syndrome (FAS).[30] Problems associated with FASD include facial anomalies, low birth weight, stunted growth, small head size, delayed or uncoordinated motor skills, hearing or vision problems, learning disabilities, behavior problems, and inappropriate social skills compared to same-age peers.[32][33] Those affected are more likely to have trouble in school, legal problems, participate in high-risk behaviors, and develop substance use disorders like excessive drinking themselves.[32] ## Cardiovascular disease[edit] Main article: Alcohol and cardiovascular disease In 2010, a systematic review reported that moderate consumption of alcohol does not cause harm to people with cardiovascular disease. However, the authors did not encourage people to start drinking alcohol in the hope of any benefit.[34] In a 2018 study on 599,912 drinkers, a roughly linear association was found with alcohol consumption and a higher risk of stroke, coronary disease excluding myocardial infarction, heart failure, fatal hypertensive disease and fatal aortic aneurysm, even for moderate drinkers.[35] The position of the American Heart Association is that people who are currently nondrinkers should not start drinking alcohol.[36] ## Breastfeeding[edit] The UK National Health Service states that "an occasional drink is unlikely to harm" a breastfed baby, and recommends consumption of "no more than one or two units of alcohol once or twice a week" for breastfeeding mothers (where a pint of beer or 50 ml drink of a spirit such as whisky corresponds to about two units of alcohol).[37] The NHS also recommends to wait for a couple of hours before breastfeeding or express the milk into a bottle before drinking.[37] Researchers have shown that intoxicated breastfeeding reduces the average milk expression but poses no immediate threat to the child as the amount of transferred alcohol is insignificant.[38] ## Alcohol education[edit] Main article: Alcohol education Alcohol education is the practice of disseminating information about the effects of alcohol on health, as well as society and the family unit.[39] It was introduced into the public schools by temperance organizations such as the Woman's Christian Temperance Union in the late 19th century.[39] Initially, alcohol education focused on how the consumption of alcoholic beverages affected society, as well as the family unit.[39] In the 1930s, this came to also incorporate education pertaining to alcohol's effects on health.[39] Organizations such as the National Institute on Alcohol Abuse and Alcoholism in the United States were founded to promulgate alcohol education alongside those of the temperance movement, such as the American Council on Alcohol Problems.[39][40] ## Alcohol expectations[edit] Alcohol expectations are beliefs and attitudes that people have about the effects they will experience when drinking alcoholic beverages. They are just largely beliefs about alcohol's effects on a person's behaviors, abilities, and emotions. Some people believe that if alcohol expectations can be changed, then alcohol abuse might be reduced. Men tend to become more aggressive in laboratory studies in which they are drinking only tonic water but believe that it contains alcohol. They also become less aggressive when they believe they are drinking only tonic water, but are actually drinking tonic water that contains alcohol.[41] The phenomenon of alcohol expectations recognizes that intoxication has real physiological consequences that alter a drinker's perception of space and time, reduce psychomotor skills, and disrupt equilibrium.[42] The manner and degree to which alcohol expectations interact with the physiological short-term effects of alcohol, resulting in specific behaviors, is unclear. A single study found that if a society believes that intoxication leads to sexual behavior, rowdy behavior, or aggression, then people tend to act that way when intoxicated. But if a society believes that intoxication leads to relaxation and tranquil behavior, then it usually leads to those outcomes. Alcohol expectations vary within a society, so these outcomes are not certain.[43] People tend to conform to social expectations, and some societies expect that drinking alcohol will cause disinhibition. However, in societies in which the people do not expect that alcohol will disinhibit, intoxication seldom leads to disinhibition and bad behavior.[42] Alcohol expectations can operate in the absence of actual consumption of alcohol. Research in the United States over a period of decades has shown that men tend to become more sexually aroused when they think they have been drinking alcohol—even when they have not been drinking it. Women report feeling more sexually aroused when they falsely believe the beverages they have been drinking contained alcohol (although one measure of their physiological arousal shows that they became less aroused).[citation needed] ### Drug treatment programs[edit] Most addiction treatment programs encourage people with drinking problems to see themselves as having a chronic, relapsing disease that requires a lifetime of attendance at 12-step meetings to keep in check. However, some people do not develop lifelong problems.[citation needed] ## Alcohol abuse[edit] See also: Alcohol abuse and Substance abuse prevention Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Alcohol was ranked 6th in dependence, 11th in physical harm, and 2nd in social harm.[44] ### Alcohol abuse prevention programs[edit] More than 200 injuries and disease conditions are caused due to alcohol abuse.[45] It is a causative agent influencing maternal health and development, noncommunicable diseases (including cancer and cardiovascular diseases), injuries, violence, mental health, and infectious diseases such as TB and HIV/AIDS.[46] Harmful use of alcohol has been identified as a global health issue, and its management is a priority in the 2030 Agenda for Sustainable Development.[47] In 2018, WHO launched the initiative SAFER, to decrease the number of deaths, diseases and injuries caused by alcohol misuse. It has been developed to address the regional, country and global health and developmental goals using high-impact, cost-effective, evidence-based interventions. Using a set of WHO tools and resources SAFER will concentrate on the more cost-effective interventions to reduce and preventive alcohol related abuse.[48] The five WHO “best buys” for decreasing alcohol misuse are priority in this action plan:[45] * Strengthen restrictions on alcohol availability. * Advance and enforce drink driving countermeasures. * Facilitate access to screening, brief interventions, and treatment. * Enforce bans or comprehensive restrictions on alcohol advertising, sponsorship, and promotion. * Raise prices on alcohol through excise taxes and pricing policies. The promotion and success of the SAFER initiative is based on three key principles to implement, to monitor, and to protect.[45] ### Recommended maximum intake[edit] Main article: Recommended maximum intake of alcoholic beverages Binge drinking is becoming a major problem in the UK. Advice on weekly consumption is avoided in United Kingdom.[49] Since 1995 the UK government has advised that regular consumption of three to four units (one unit equates to 10 mL of pure ethanol) a day for men and or two to three units for women, would not pose significant health risks. However, consistently drinking more than four units a day (for men) and three units (women), is not advisable.[50] Previously (from 1992 until 1995), the advice was that men should drink no more than 21 units per week, and women no more than 14.[51] (The difference between the sexes was due to the typically lower weight and water-to-body-mass ratio of women.) This was changed because a government study showed that many people were in effect "saving up" their units and using them at the end of the week, a phenomenon referred to as binge drinking.[citation needed] The Times reported in October 2007 that these limits had been "plucked out of the air" and had no scientific basis.[52] ### Sobriety[edit] See also: Sobriety A midshipman is subjected to a random breathalyzer test to determine sobriety. Sobriety is the condition of not having any measurable levels, or effects from mood-altering drugs. According to WHO "Lexicon of alcohol and drug terms..." sobriety is continued abstinence from psychoactive drug use.[53] Sobriety is also considered to be the natural state of a human being given at a birth. In a treatment setting, sobriety is the achieved goal of independence from consuming or craving mind-altering substances. As such, sustained abstinence is a prerequisite for sobriety. Early in abstinence, residual effects of mind-altering substances can preclude sobriety. These effects are labeled "PAWS", or "post acute withdrawal syndrome". Someone who abstains, but has a latent desire to resume use, is not considered truly sober. An abstainer may be subconsciously motivated to resume drug use, but for a variety of reasons, abstains (e.g. such as a medical or legal concern precluding use).[54] Sobriety has more specific meanings within specific contexts, such as the culture of Alcoholics Anonymous, other 12 step programs, law enforcement, and some schools of psychology. In some cases, sobriety implies achieving "life balance".[55] ## Injury and deaths[edit] Injury is defined as physical damage or harm that is done or sustained. The potential of injuring oneself or others can be increased after consuming alcohol due to the certain short term effects related to the substance such as lack of coordination, blurred vision, and slower reflexes to name a few.[56] Due to these effects the most common injuries include head, fall, and vehicle-related injuries. A study was conducted of patients admitted to the Ulster Hospital in Northern Ireland with fall related injuries. They found that 113 of those patients admitted to that hospital during that had consumed alcohol recently and that the injury severity was higher for those that had consumed alcohol compared to those that had not.[57] Another study showed that 21% of patients admitted to the Emergency Department of the Bristol Royal Infirmary had either direct or indirect alcohol related injuries. If these figures are extrapolated it shows that the estimated number of patients with alcohol related injuries are over 7,000 during the year at this emergency department alone.[58] In the United States alcohol resulted in about 88,000 deaths in 2010.[59] The World Health Organization calculated that more than 3 million people, mostly men, died as a result of harmful use of alcohol in 2016. This was about 13.5% of the total deaths of people between 20 and 39. More than 5% of the global disease burden was caused by the harmful use of alcohol.[60] There are even higher estimates for Europe.[61] ## Genetic differences[edit] ### Alcohol flush and respiratory reactions[edit] See also: Alcohol flush reaction, Alcohol-induced respiratory reactions, and Short-term effects of alcohol consumption Alcohol flush reaction is a condition in which an individual's face or body experiences flushes or blotches as a result of an accumulation of acetaldehyde, a metabolic byproduct of the catabolic metabolism of alcohol. It is best known as a condition that is experienced by people of Asian descent. According to the analysis by HapMap Project, the rs671 allele of the ALDH2 gene responsible for the flush reaction is rare among Europeans and Africans, and it is very rare among Mexican-Americans. 30% to 50% of people of Chinese and Japanese ancestry have at least one ALDH2 allele.[62] The rs671 form of ALDH2, which accounts for most incidents of alcohol flush reaction worldwide, is native to East Asia and most common in southeastern China. It most likely originated among Han Chinese in central China,[63] and it appears to have been positively selected in the past. Another analysis correlates the rise and spread of rice cultivation in Southern China with the spread of the allele.[64] The reasons for this positive selection aren't known, but it's been hypothesized that elevated concentrations of acetaldehyde may have conferred protection against certain parasitic infections, such as Entamoeba histolytica.[65] The same SNP allele of ALDH2, also termed glu487lys, and the abnormal accumulation of acetaldehyde following the drinking of alcohol, is associated with the alcohol-induced respiratory reactions of rhinitis and asthma that occur in Eastern Asian populations.[66] H − C \| H H \| − C \| H H \| − O − H → ADH H − C \| H H \| − C ‖ O H \| → ALDH H − C \| H H \| − C ‖ O H \| − O − H {\displaystyle {\ce {H}}{-}{\overset {\displaystyle {\ce {H}} \atop \|}{\underset {\| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{-}{\overset {\displaystyle {\ce {H}} \atop \|}{\underset {\| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{\ce {-O-H->[{\ce {ADH}}]H}}{-}{\overset {\displaystyle {\ce {H}} \atop \|}{\underset {\| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{-}{\overset {\displaystyle {\ce {H}} \atop \|}{\underset {\\| \atop \displaystyle {\ce {O}}}{\ce {C}}}}{\ce {->[{\ce {ALDH}}]H}}{-}{\overset {\displaystyle {\ce {H}} \atop \|}{\underset {\| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{-}{\overset {\color {white}{\displaystyle {\ce {H}} \atop \|}}{\underset {\\| \atop \displaystyle {\ce {O}}}{\ce {C}}}}{\ce {-O-H}}} Metabolism of alcohol (ethanol) to acetaldehyde (ethanal) and then acetic acid (ethanoic acid) ### American Indian alcoholism[edit] Main article: Alcohol and Native Americans Compared with the United States population in general, the Native American population is much more susceptible to alcoholism and related diseases and deaths.[67] From 2006 to 2010, alcohol-attributed deaths accounted for 11.7 percent of all Native American deaths, more than twice the rates of the general U.S. population. The median alcohol-attributed death rate for Native Americans (60.6 per 100,000) was twice as high as the rate for any other racial or ethnic group.[68] Males are affected disproportionately more by alcohol-related conditions than females.[69] The highest risk of alcohol-related deaths is between 45 and 64 years of age. Chronic liver disease and cirrhosis are 3.9 times as prevalent in the Native American population than the general US population. Of all alcohol-attributable deaths, motor vehicle accidents account for 27.5% and alcoholic liver disease accounts for 25.2%. Alcohol-related fatal car accidents are three times more prevalent among Native Americans than in other ethnicities. Native American populations exhibit genetic differences in the alcohol-metabolizing enzymes alcohol dehydrogenase and ALDH,[70][71] although evidence that these genetic factors are more prevalent in Native Americans than other ethnic groups has been a subject of debate.[72][73][74] According to one 2013 review of academic literature on the issue, there is a "substantial genetic component in Native Americans" and that "most Native Americans lack protective variants seen in other populations."[72] Many scientists have provided evidence of the genetic component of alcoholism by the biopsychosocial model of alcoholism, but the molecular genetics research currently has not found one specific gene that is responsible for the rates of alcoholism among Native Americans, implying the phenomenon may be due to an interplay of multiple genes and environmental factors.[75][76] Research on alcoholism in family systems suggests that learned behavior augments genetic factors in increasing the probability that children of alcoholics will themselves have problems with alcohol.[77] ### Genetics and amount of consumption[edit] Having a particular genetic variant (A-allele of ADH1B rs1229984) is associated with non-drinking and lower alcohol consumption. This variant is also associated with favorable cardiovascular profile and a reduced risk of coronary heart disease compared to those without the genetic variant, but it is unknown whether this may be caused by differences in alcohol consumption or by additional confounding effects of the genetic variant itself.[78] ## Gender differences[edit] Historically, according to the British Medical Journal, "men have been far more likely than women to drink alcohol and to drink it in quantities that damage their health, with some figures suggesting up to a 12-fold difference between the sexes".[79] However, analysis of data collected over a century from multiple countries suggests that the gender gap in alcohol consumption is narrowing, and that young women (born after 1981) are consuming alcohol more than their male counterparts. Such findings have implications for the way in which alcohol-use prevention and intervention programs are designed and implemented.[80] ### Alcoholism[edit] Based on combined data from SAMHSA's 2004-2005 National Surveys on Drug Use & Health, the rate of past year alcohol dependence or abuse among people aged 12 or older varied by level of alcohol use: 44.7% of past month heavy drinkers, 18.5% binge drinkers, 3.8% past month non-binge drinkers, and 1.3% of those who did not drink alcohol in the past month met the criteria for alcohol dependence or abuse in the past year. Males had higher rates than females for all measures of drinking in the past month: any alcohol use (57.5% vs. 45%), binge drinking (30.8% vs. 15.1%), and heavy alcohol use (10.5% vs. 3.3%), and males were twice as likely as females to have met the criteria for alcohol dependence or abuse in the past year (10.5% vs. 5.1%).[81] Over time the difference between males and females has narrowed. According to a 2016 systematic review, for those born at the end of the 20th century men were 1.2 times as likely to drink to problematic levels, and 1.3 times as likely to develop health problems from drinking.[80] ### Sensitivity[edit] Several biological factors make women more vulnerable to the effects of alcohol than men.[82] Body fat. Women tend to weigh less than men, and—pound for pound—a woman's body contains less water and more fatty tissue than a man's. Because fat retains alcohol while water dilutes it, alcohol remains at higher concentrations for longer periods of time in a woman's body, exposing her brain and other organs to more alcohol. * Enzymes. Women have lower levels of two enzymes—alcohol dehydrogenase and aldehyde dehydrogenase—that metabolize (break down) alcohol in the stomach and liver. As a result, women absorb more alcohol into their bloodstreams than men. * Hormones. Changes in hormone levels during the menstrual cycle may also affect how a woman metabolizes alcohol. ### Metabolism[edit] Females demonstrated a higher average rate of elimination (mean, 0.017; range, 0.014–0.021 g/210 L) than males (mean, 0.015; range, 0.013–0.017 g/210 L). Female subjects on average had a higher percentage of body fat (mean, 26.0; range, 16.7–36.8%) than males (mean, 18.0; range, 10.2–25.3%).[83] ### Depression[edit] The link between alcohol consumption, depression, and gender was examined by the Centre for Addiction and Mental Health (Canada). The study found that women taking antidepressants consumed more alcohol than women who did not experience depression as well as men taking antidepressants. The researchers, Dr. Kathryn Graham and a PhD Student Agnes Massak analyzed the responses to a survey by 14,063 Canadian residents aged 18–76 years. The survey included measures of quantity, frequency of drinking, depression and antidepressants use, over the period of a year. The researchers used data from the GENACIS Canada survey, part of an international collaboration to investigate the influence of cultural variation on gender differences in alcohol use and related problems. The purpose of the study was to examine whether, like in other studies already conducted on male depression and alcohol consumption, depressed women also consumed less alcohol when taking anti-depressants. According to the study, both men and women experiencing depression (but not on anti-depressants) drank more than non-depressed counterparts. Men taking antidepressants consumed significantly less alcohol than depressed men who did not use antidepressants. Non-depressed men consumed 436 drinks per year, compared to 579 drinks for depressed men not using antidepressants, and 414 drinks for depressed men who used antidepressants. Alcohol consumption remained higher whether the depressed women were taking anti-depressants or not. 179 drinks per year for non-depressed women, 235 drinks for depressed women not using antidepressants, and 264 drinks for depressed women who used antidepressants. The lead researcher argued that the study "suggests that the use of antidepressants is associated with lower alcohol consumption among men suffering from depression. But this does not appear to be true for women."[84] ## See also[edit] * Alcoholic beverage * Short-term effects of alcohol consumption * Long-term effects of alcohol consumption ## References[edit] 1. ^ "Alcohol and diabetes: Drinking safely – Mayo Clinic". 2. ^ a b "Risks of Adolescent Alcohol Use". HHS.gov. 19 January 2018. Retrieved 3 June 2020. 3. ^ a b Cheryl Platzman Weinstock (8 November 2017). "Alcohol Consumption Increases Risk of Breast and Other Cancers, Doctors Say". Scientific American. Retrieved 13 November 2018. "The ASCO statement, published in the Journal of Clinical Oncology, cautions that while the greatest risks are seen with heavy long-term use, even low alcohol consumption (defined as less than one drink per day) or moderate consumption (up to two drinks per day for men, and one drink per day for women because they absorb and metabolize it differently) can increase cancer risk. Among women, light drinkers have a four percent increased risk of breast cancer, while moderate drinkers have a 23 percent increased risk of the disease." 4. ^ a b Noelle K. LoConte, Abenaa M. Brewster, Judith S. Kaur, Janette K. Merrill, and Anthony J. Alberg (7 November 2017). "Alcohol and Cancer: A Statement of the American Society of Clinical Oncology". Journal of Clinical Oncology. 36 (1). "Clearly, the greatest cancer risks are concentrated in the heavy and moderate drinker categories. Nevertheless, some cancer risk persists even at low levels of consumption. A meta-analysis that focused solely on cancer risks associated with drinking one drink or fewer per day observed that this level of alcohol consumption was still associated with some elevated risk for squamous cell carcinoma of the esophagus (sRR, 1.30; 95% CI, 1.09 to 1.56), oropharyngeal cancer (sRR, 1.17; 95% CI, 1.06 to 1.29), and breast cancer (sRR, 1.05; 95% CI, 1.02 to 1.08), but no discernable associations were seen for cancers of the colorectum, larynx, and liver."CS1 maint: multiple names: authors list (link) 5. ^ "Global status report on alcohol and health" (PDF). World Health Organization. 2014. pp. vii. Retrieved 23 November 2015. 6. ^ Griswold, MG; Fullman, N; Hawley, C; Arian, N; Zimsen, SM; et al. (August 2018). "Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016". The Lancet. 392 (10152): 1015–1035. doi:10.1016/S0140-6736(18)31310-2. PMC 6148333. PMID 30146330. 7. ^ "Cancer warning labels to be included on alcohol in Ireland, minister confirms". Belfasttelegraph.co.uk. Belfast Telegraph. 26 September 2018. 8. ^ Meyer, Jerold S. and Linda F. Quenzer. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates, Inc.: Sunderland, Massachusetts. 2005. Page 228. 9. ^ helsinki.fi – Effect of alcohol on hormones in women Archived 11 August 2017 at the Wayback Machine, Helsinki 2001 10. ^ helsinki.fi – Clinical studies on dependence and drug effects Archived 21 February 2013 at the Wayback Machine, ESBRA 2009 11. ^ Horowitz M, Maddox A, Bochner M, et al. (1989). "Relationships between gastric emptying of solid and caloric liquid meals and alcohol absorption". Am. J. Physiol. 257 (2 Pt 1): G291–6298. doi:10.1152/ajpgi.1989.257.2.G291. PMID 2764113. 12. ^ "Carleton College: Wellness Center: Blood Alcohol Concentration (BAC)". Archived from the original on 14 September 2009. Retrieved 29 August 2015. 13. ^ Feige B, Scaal S, Hornyak M, Gann H, Riemann D (2007). "Sleep electroencephalographic spectral power after withdrawal from alcohol in alcohol-dependent patients". Alcohol. Clin. Exp. Res. 31 (1): 19–27. doi:10.1111/j.1530-0277.2006.00260.x. PMID 17207097. 14. ^ "WHO \| Global status report on alcohol and health 2018". 15. ^ "Alcohol Facts and Statistics". Retrieved 9 May 2015. 16. ^ "Appendix 9. Alcohol - 2015-2020 Dietary Guidelines - health.gov". U.S. Department of Health and Human Services. 17. ^ "New alcohol advice issued". NHS. 8 January 2016. 18. ^ GBD 2016 Alcohol Collaborators (August 2018). "Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016". Lancet. 392 (10152): 1015–1035. doi:10.1016/S0140-6736(18)31310-2. PMC 6148333. PMID 30146330. 19. ^ Stockwell T, Zhao J, Panwar S, Roemer A, Naimi T, Chikritzhs T (2016). "Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality". J Stud Alcohol Drugs. 77 (2): 185–198. doi:10.15288/jsad.2016.77.185. PMC 4803651. PMID 26997174. 20. ^ O'Keefe, JH; Bhatti, SK; Bajwa, A; DiNicolantonio, JJ; Lavie, CJ (2014). "Alcohol and cardiovascular health: the dose makes the poison...or the remedy". Mayo Clinic Proceedings. 89 (3): 382–393. doi:10.1016/j.mayocp.2013.11.005. PMID 24582196. 21. ^ Caan, Woody; Belleroche, Jackie de, eds. (11 April 2002). Drink, Drugs and Dependence: From Science to Clinical Practice (1st ed.). Routledge. pp. 19–20. ISBN 978-0-415-27891-1. 22. ^ Müller D, Koch RD, von Specht H, Völker W, Münch EM (March 1985). "Neurophysiologic findings in chronic alcohol abuse". Psychiatr Neurol Med Psychol (Leipz) (in German). 37 (3): 129–32. PMID 2988001. 23. ^ Testino G (2008). "Alcoholic diseases in hepato-gastroenterology: a point of view". Hepatogastroenterology. 55 (82–83): 371–377. PMID 18613369. 24. ^ Guerri, C.; Pascual, M.A. (2010). "Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence". Alcohol. 44 (1): 15–26. doi:10.1016/j.alcohol.2009.10.003. PMID 20113871. 25. ^ Vice Admiral Richard H. Carmona (2005). "A 2005 Message to Women from the U.S. Surgeon General" (PDF). Retrieved 12 June 2015. 26. ^ Committee to Study Fetal Alcohol Syndrome, Division of Biobehavioral Sciences and Mental Disorders, Institute of Medicine (1995). Fetal alcohol syndrome : diagnosis, epidemiology, prevention, and treatment. Washington, D.C.: National Academy Press. doi:10.17226/4991. ISBN 978-0-309-05292-4.CS1 maint: uses authors parameter (link) 27. ^ "Australian Government National Health and Medical Research Council". Archived from the original on 5 November 2012. Retrieved 4 November 2012. 28. ^ Nathanson, Vivienne; Nicky Jayesinghe; George Roycroft (27 October 2007). "Is it all right for women to drink small amounts of alcohol in pregnancy? No". BMJ. 335 (7625): 857. doi:10.1136/bmj.39356.489340.AD. PMC 2043444. PMID 17962287. 29. ^ a b c "Fetal Alcohol Exposure". April 2015. Retrieved 10 June 2015. 30. ^ a b "Facts about FASDs". 16 April 2015. Retrieved 10 June 2015. 31. ^ "More than 3 million US women at risk for alcohol-exposed pregnancy". Centers for Disease Control and Prevention. 2 February 2016. Retrieved 3 March 2016. "'drinking any alcohol at any stage of pregnancy can cause a range of disabilities for their child,' said Coleen Boyle, Ph.D., director of CDC's National Center on Birth Defects and Developmental Disabilities." 32. ^ a b Coriale; et al. (2013). "Fetal Alcohol Spectrum Disorder (FASD): neurobehavioral profile, indications for diagnosis and treatment". Rivista di Psichiatria. 48 (5): 359–69. doi:10.1708/1356.15062. PMID 24326748. 33. ^ Chudley; et al. (2005), "Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis", CMAJ, 172 (5 Suppl): S1–S21, doi:10.1503/cmaj.1040302, PMC 557121, PMID 15738468 34. ^ Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G (2010). "Alcohol consumption and mortality in patients with cardiovascular disease: a meta-analysis". J. Am. Coll. Cardiol. 55 (13): 1339–1347. doi:10.1016/j.jacc.2010.01.006. PMID 20338495. 35. ^ Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, Bolton T, et al. (2018). "Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies". The Lancet. 391 (10129): 1513–1523. doi:10.1016/S0140-6736(18)30134-X. PMC 5899998. PMID 29676281. 36. ^ "Alcohol and Heart Health". American Heart Association. 15 August 2014. 37. ^ a b Choices, N. H. S. (1 May 2017). "Breastfeeding and drinking alcohol – Pregnancy and baby guide – NHS Choices". 38. ^ Haastrup, MB; Pottegård, A; Damkier, P (2014). "Alcohol and Breastfeeding". Basic & Clinical Pharmacology & Toxicology. 114 (2): 168–173. doi:10.1111/bcpt.12149. PMID 24118767. S2CID 31580580. "even in a theoretical case of binge drinking, the children would not be subjected to clinically relevant amounts of alcohol" 39. ^ a b c d e Moore, Mark Harrison; Gerstein, Dean R. (1981). Alcohol and Public Policy. National Academies. p. 90–93. 40. ^ Martin, Scott C. (2014). The SAGE Encyclopedia of Alcohol: Social, Cultural, and Historical Perspectives. SAGE Publications. ISBN 9781483374383. 41. ^ Grattan, Karen E.; Vogel-Sprott, M. (2001). "Maintaining Intentional Control of Behavior Under Alcohol". Alcoholism: Clinical and Experimental Research. 25 (2): 192–7. doi:10.1111/j.1530-0277.2001.tb02198.x. PMID 11236832. 42. ^ a b MacAndrew, C. and Edgerton. Drunken Comportment: A Social Explanation. Chicago: Aldine, 1969. 43. ^ Marlatt GA, Rosenow (1981). "The think-drink effect". Psychology Today. 15: 60–93. 44. ^ Nutt, D; King, LA; Saulsbury, W; Blakemore, C (24 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. 45. ^ a b c "WHO \| THE SAFER INITIATIVE". WHO. Retrieved 21 November 2019. 46. ^ World Health Organization. (14 February 2019). Global status report on alcohol and health 2018. World Health Organization,, World Health Organization. Management of Substance Abuse Team. Geneva. ISBN 978-92-4-156563-9. OCLC 1089229677. 47. ^ Nations, United (31 December 2015). "Transforming governance for the 2030 agenda for sustainable development": 73–87. doi:10.18356/e5a72957-en. Cite journal requires `\|journal=` (help) 48. ^ Global action plan for the prevention and control of noncommunicable diseases : 2013-2020. World Health Organization. Geneva, Switzerland. ISBN 978-92-4-150623-6. OCLC 960910741.CS1 maint: others (link) 49. ^ "Sensible Drinking". Aim-digest.com. Archived from the original on 19 November 2010. Retrieved 5 February 2013. 50. ^ "Alcohol misuse : Department of Health". Dh.gov.uk. Retrieved 5 February 2013. 51. ^ "Alcohol and health: how alcohol can affect your long and short term health". Drinkaware.co.uk. Retrieved 5 February 2013. 52. ^ Drink limits 'useless’, The Times, 20 October 2007 53. ^ "Lexicon and drug terms". Who.int. 9 December 2010. Retrieved 5 February 2013. 54. ^ MD Basharin K.G. (2010). "Scientific grounding for sobriety: Western experience" (PDF). Retrieved 5 February 2013. 55. ^ Twelve Steps and Twelve Traditions (PDF). Alcoholics Anonymous World Services. April 1953. ISBN 978-0-916856-01-4. Retrieved 31 December 2018. (Electronic .PDF version, September 2005). 56. ^ "Drinkwise Australia". DrinkWise Australia. 57. ^ Johnson J, McGovern S (2003). "Alcohol related falls: an interesting pattern of injuries". Emergency Medicine Journal. 21 (2): 185–188. doi:10.1136/emj.2003.006130. PMC 1726307. PMID 14988344. 58. ^ Hoskins R, Benger J (2013). "What is the burden of alcohol-related injuries in an inner city emergency department?". Alcoholism: Clinical and Experimental Research. 33 (9): 1532–1538. doi:10.1111/j.1530-0277.2009.00981.x. PMC 2757258. PMID 19485974. 59. ^ "Alcohol-attributable deaths and years of potential life lost — 11 states, 2006–2010". www.cdc.gov. 60. ^ "Alcohol". World health Organization. 21 September 2018. Retrieved 5 November 2018. 61. ^ Korotayev, A., Khaltourina, D., Meshcherina, K., & Zamiatnina, E. Distilled Spirits Overconsumption as the Most Important Factor of Excessive Adult Male Mortality in Europe. Alcohol and Alcoholism, 2018, 53(6), 742-752. 62. ^ "Rs671". SNPmedia. 63. ^ Hui Li; et al. (2009). "Refined Geographic Distribution of the Oriental ALDH2504Lys (nee 487Lys) Variant". Ann Hum Genet. 73 (Pt 3): 335–345. doi:10.1111/j.1469-1809.2009.00517.x. PMC 2846302. PMID 19456322. 64. ^ Yi Peng; Hong Shi; Xue-bin Qi; Chun-jie Xiao; Hua Zhong; Run-lin Z Ma; Bing Su (2010). "The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history". BMC Evolutionary Biology. 10 (1): 15. doi:10.1186/1471-2148-10-15. PMC 2823730. PMID 20089146. 65. ^ Oota H, Pakstis AJ, Bonne-Tamir B, Goldman D, Grigorenko E, Kajuna SL, et al. (2004). "The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination". Ann. Hum. Genet. 68 (Pt 2): 93–109. doi:10.1046/j.1529-8817.2003.00060.x. PMID 15008789. S2CID 31026948. 66. ^ Adams, KE; Rans, TS (2013). "Adverse reactions to alcohol and alcoholic beverages". Annals of Allergy, Asthma & Immunology. 111 (6): 439–445. doi:10.1016/j.anai.2013.09.016. PMID 24267355. 67. ^ Philip A. May, "Overview of Alcohol Abuse Epidemiology for American Indian Populations," in Changing Numbers, Changing Needs: American Indian Demography and Public Health, Gary D. Sandefur, Ronald R. Rindfuss, Barney Cohen, Editors. Committee on Population, Commission on Behavioral and Social Sciences and Education National Research Council. National Academy Press: Washington, D.C. 1996 68. ^ Gonzales, K; Roeber, J; Kanny, D; Tran, A; Saiki, C; Johnson, H; Yeoman, K; Safranek, T; Creppage, K; Lepp, A; Miller, T; Tarkhashvili, N; Lynch, KE; Watson, JR; Henderson, D; Christenson, M; Geiger, SD (2014). "Alcohol-attributable deaths and years of potential life lost--11 States, 2006-2010". MMWR Morb Mortal Wkly Rep. 63 (10): 213–6. PMC 5779340. PMID 24622285. 69. ^ Whitesell, NR; Beals, J; Crow, CB; Mitchell, CM; Novins, DK (2012). "Epidemiology and etiology of substance use among American Indians and Alaska Natives: risk, protection, and implications for prevention". Am J Drug Alcohol Abuse. 38 (5): 376–82. doi:10.3109/00952990.2012.694527. PMC 4436971. PMID 22931069. 70. ^ Ehlers, CL (2007). "Variations in ADH and ALDH in Southwest California Indians". Alcohol Res Health. 30 (1): 14–7. PMC 3860438. PMID 17718395. 71. ^ Ehlers, CL; Liang, T; Gizer, IR (2012). "ADH and ALDH polymorphisms and alcohol dependence in Mexican and Native Americans". Am J Drug Alcohol Abuse. 38 (5): 389–94. doi:10.3109/00952990.2012.694526. PMC 3498484. PMID 22931071. 72. ^ a b Ehlers CL, Gizer IR. "Evidence for a genetic component for substance dependence in Native Americans." Am J Psychiatry. 1 Feb 2013;170(2):154–164. 73. ^ Caetano, Raul; Clark, Catherine L.; Tam, Tammy (1998). "Alcohol consumption among racial/ethnic minorities". Alcohol Health and Research World. 22 (4): 233–241. CiteSeerX 10.1.1.556.6875. 74. ^ Karen Chartier and Raul Caetano, "Ethnicity and health disparities in alcohol research," Alcohol Res Health 2010, vol. 33: 1-2 pp. 152-160 75. ^ Wall, Tamara L.; Carr, Lucinda G.; Ehlers, Cindy L. (2003). "Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians". American Journal of Psychiatry. 160 (1): 41–46. doi:10.1176/appi.ajp.160.1.41. PMID 12505800. 76. ^ Wilhelmsen, KC; Ehlers, C (2005). "Heritability of substance dependence in a native American population". Psychiatr Genet. 15 (2): 101–7. doi:10.1097/00041444-200506000-00006. PMID 15900224. S2CID 5859834. 77. ^ Brockie, TN; Heinzelmann, M; Gill, J (2013). "A Framework to Examine the Role of Epigenetics in Health Disparities among Native Americans". Nurs Res Pract. 2013: 410395. doi:10.1155/2013/410395. PMC 3872279. PMID 24386563. 78. ^ Holmes, Michael V.; et al. (2014). "Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data". BMJ. 349: g4164. doi:10.1136/bmj.g4164. PMC 4091648. PMID 25011450. 79. ^ "Women catching up with men in alcohol consumption and its associated harms" (PDF). BMJ Open (Press release). 25 October 2016. 80. ^ a b Slade T, Chapman C, Swift W, Keyes K, Tonks Z, Teesson M (2016). "Birth cohort trends in the global epidemiology of alcohol use and alcohol-related harms in men and women: systematic review and metaregression". BMJ Open. 6 (10): e011827. doi:10.1136/bmjopen-2016-011827. PMC 5093369. PMID 27797998. 81. ^ "Gender differences in alcohol use and alcohol dependence or abuse: 2004 or 2005." The NSDUH Report. Accessed 22 June 2012. 82. ^ "Women & Alcohol: The Hidden Risks of Drinking". Helpguide.org. Archived from the original on 3 January 2013. Retrieved 5 February 2013. 83. ^ Cowan, JM Jr; Weathermon, A; McCutcheon, JR; Oliver, RD (September 1996). "Determination of volume of distribution for ethanol in male and female subjects". J Anal Toxicol. 20 (5): 287–90. doi:10.1093/jat/20.5.287. PMID 8872236. 84. ^ Graham, K.; Massak, A. (2007). "Alcohol consumption and the use of antidepressants". Canadian Medical Association Journal. 176 (5): 633–637. doi:10.1503/cmaj.060446. PMC 1800314. 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(AFR) Gastrointestinal diseases * Alcoholic liver disease (ALD): * Alcoholic hepatitis * Auto-brewery syndrome (ABS) Endocrine diseases * Alcoholic ketoacidosis (AKA) Nervous system diseases * Alcohol-related dementia (ARD) * Alcohol intoxication * Hangover Neurological disorders * Alcoholic hallucinosis * Alcoholic polyneuropathy * Alcohol-related brain damage * Alcohol withdrawal syndrome (AWS): * Alcoholic hallucinosis * Delirium tremens (DTs) * Fetal alcohol spectrum disorder (FASD) * Fetal alcohol syndrome (FAS) * Korsakoff syndrome * Positional alcohol nystagmus (PAN) * Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis) * Wernicke encephalopathy (WE) Respiratory tract diseases * Alcohol-induced respiratory reactions * Alcoholic lung disease SUD * Alcoholism (alcohol use disorder (AUD)) * Binge drinking Caffeine * SID * Caffeine-induced anxiety disorder * Caffeine-induced sleep disorder * Caffeinism * SUD * Caffeine dependence Cannabis * SID * Cannabis arteritis * Cannabinoid hyperemesis syndrome (CHS) * SUD * Amotivational syndrome * Cannabis use disorder (CUD) * Synthetic cannabinoid use disorder Cocaine * SID * Cocaine intoxication * Prenatal cocaine exposure (PCE) * SUD * Cocaine dependence Hallucinogen * SID * Acute intoxication from hallucinogens (bad trip) * Hallucinogen persisting perception disorder (HPPD) Nicotine * SID * Nicotine poisoning * Nicotine withdrawal * SUD * Nicotine dependence Opioids * SID * Opioid overdose * SUD * Opioid use disorder (OUD) Sedative / hypnotic * SID * Kindling (sedative–hypnotic withdrawal) * benzodiazepine: SID * Benzodiazepine overdose * Benzodiazepine withdrawal * SUD * Benzodiazepine use disorder (BUD) * Benzodiazepine dependence * barbiturate: SID * Barbiturate overdose * SUD * Barbiturate dependence Stimulants * SID * Stimulant psychosis * amphetamine: SUD * Amphetamine dependence Volatile solvent * SID * Sudden sniffing death syndrome (SSDS) * Toluene toxicity * SUD * Inhalant abuse [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Alcohol and health	c0236970	6,790	wikipedia	https://en.wikipedia.org/wiki/Alcohol_and_health	2021-01-18T18:44:58	{"mesh": ["D020751"], "icd-10": ["F10"], "wikidata": ["Q11290178"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (July 2016) This scientific article needs additional citations to secondary or tertiary sources such as review articles, monographs, or textbooks. Please add such references to provide context and establish the relevance of any primary research articles cited. Unsourced or poorly sourced material may be challenged and removed. (August 2018) (Learn how and when to remove this template message) Compulsive decluttering is a pattern of behavior that is characterized by an excessive desire to discard objects in one's home and living areas.[1] Other terms for such behavior includes obsessive compulsive spartanism.[2] The homes of compulsive declutterers are often empty.[3] It is the opposite of compulsive hoarding. Compulsive decluttering is a type of disorder that is classified within a broad name, obsessive compulsive disorder, or OCD. Compulsive decluttering is the act of throwing items, or clutter, away, or getting rid of them in an attempt to "clean up" what one with the disorder may think is cluttered. Even though it is the polar opposite of compulsive hoarding, the two are related because they both fall under the umbrella of OCD in different ways. Compulsive decluttering is also known as compulsive decluttering disorder, and is also known as "compulsive spartanism."[4] Because a clean environment typically looks better and more organized than a "cluttered" one, people can start to get into the habit of decluttering, which can lead to the extreme of compulsive decluttering. People can often misunderstand compulsive decluttering with a typical "spring cleaning," oftentimes due to the fact that somebody with the disorder tends to declutter year round.[1] People that have compulsive decluttering disorder think that any items around them are cluttering or disrupting their every day lives.[3] Throwing these items away gives them satisfaction, and gives them the idea that they are in control of their lives. ## Contents * 1 Signs and symptoms * 2 Effects * 3 Treatments * 4 References ## Signs and symptoms[edit] Symptoms of compulsive decluttering include repetitive discarding of materials and consistent reorganizing of one's immediate surroundings. Some people with the disorder may question whether or not they have enough of particular items, and may never feel relaxed even if everything is in their desired "order." In some circumstances, a symptom is for the person to constantly feel as though they need to delete texts, emails, browser history, even photos from their electronic devices.[5] ## Effects[edit] The effects of compulsive decluttering on one who has it can be significant. Because this disorder involves throwing away anything that may discomfort a person due to the clutter that it may add to their lives, there is a significant financial burden.[6] This disorder causes people to think they are better off getting rid of what they currently have, because it is in the way, and buying a replacement if and when they need one.[4] For example, if a pen is sitting on a desk, and it makes the desk look disorganized, somebody with compulsive decluttering disorder would most likely throw it away in an effort to declutter the desk, and when they need a pen to write with, then they would go out and buy a new one.[4] When this process begins to repeat, it is a sign that they have compulsive decluttering disorder. The financial burden comes from the repetitive repurchasing of the things that people would otherwise own for a long time, and normally would not need to repurchase. Depending on the severity of the disorder, the items that are being replaced can get to be much more expensive. These things that people may begin to get rid of and repurchase can include phones, furniture and even jewelry. The effects that this disorder has are very similar to those defined by OCD, even though these effects may be portrayed in significantly different ways. ## Treatments[edit] While there are no specific treatments for compulsive decluttering at this time, attempts at treatment are included in the different ways OCD is treated. ## References[edit] 1. ^ a b Garrett, Leslie. "The Mental Illness That Makes People Throw Away Their Possessions". The Atlantic. 2. ^ "Hoarding vs Clutter Phobia, which one is really OCD". A Life Lived Ridiculously (blog). 3. ^ a b Yaqub, Reshma Mernon. “Confessions of a Compulsive Declutterer.” CNN, Cable News Network, 1 Mar. 2012, www.cnn.com/2012/03/01/living/confessions-compulsive-declutterer/index.html. 4. ^ a b c KHONNewsHawaii. “Too Much Decluttering? Disorder Can Affect Many, Including Seniors.” YouTube, KHONNews, 3 Sept. 2016, www.youtube.com/watch?v=LssC7c6BPaE. 5. ^ Sonorryan, Jemima. “Obsessive-Compulsive Spartanism: When Mental Illness Hijacks Your Decluttering Efforts.” Medium, Augmenting Humanity, 8 Sept. 2017, medium.com/@jemima.s/obsessive-compulsive-spartanism-when-mental-illness-hijacks-your-decluttering-efforts-1e0abadef1f8. 6. ^ Carlo, and Molly Wickham. “Obsessive Compulsive Decluttering.” Anxiety Boss, 22 Apr. 2018, anxietyboss.com/obsessive-compulsive-decluttering/. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Compulsive decluttering	None	6,791	wikipedia	https://en.wikipedia.org/wiki/Compulsive_decluttering	2021-01-18T18:43:00	{"wikidata": ["Q25338549"]}
Infective dermatitis associated with HTLV-1 is a rare and severe chronic disease characterized by recurrent chronic eczema (with erythematous, scaly and crusted lesions) mainly affecting seborrheic areas (e.g. scalp, forehead, eyelids, paranasal and periauricular skin, neck, axillae, and groin), a generalized fine papular rash, chronic nasal discharge with crusting of the anterior nares, and non-virulent Staphylococcus aureus or beta-hemolytic Streptococcus infections, thought to be a result of HTLV-1-induced immunosuppression. Lymphadenopathy, anemia, mild to moderate pruritus and increased incidence of other infections (e.g. crusted scabies) have also been reported in some patients. Patients may subsequently develop other HTLV-1 associated conditions such as adult T-cell leukemia/lymphoma and tropical spastic paraparesis (see these terms). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Infective dermatitis associated with HTLV-1	None	6,792	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=289347	2021-01-23T18:25:24	{"icd-10": ["L30.3"], "synonyms": ["IDH", "Infective dermatitis associated with human T-lymphotropic virus type 1", "Infective dermatitis associated with human T-lymphotropic virus type I"]}
Trichorhinophalangeal syndrome type 1 (TRPS1) is an extremely rare inherited multisystem disorder. TRPS1 is characterized by a distinctive facial appearance that includes sparse scalp hair; a rounded nose; a long, flat area between the nose and the upper lip (philtrum); and a thin upper lip. Individuals with this condition also have skeletal abnormalities such as cone-shaped epiphyses in their fingers and toes and short stature. The range and severity of symptoms may vary from case to case. Transmission of TRPS1 is autosomal dominant, linked to mutations in the TRPS1 gene localized to 8q24.12. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Trichorhinophalangeal syndrome type 1	c0432233	6,793	gard	https://rarediseases.info.nih.gov/diseases/7800/trichorhinophalangeal-syndrome-type-1	2021-01-18T17:57:18	{"mesh": ["C536820"], "omim": ["190350"], "umls": ["C0432233"], "orphanet": ["77258"], "synonyms": ["TRPS1", "Giedion syndrome"]}
Malignant edema (or malignant oedema[1]) is an acute, generally rapidly fatal wound infection (toxemia) most common in grazing animals. It affects cattle, horses, sheep, goats, pigs, and deer. It is caused by one or more species of bacteria in the genus Clostridium.[2][3] "A similar infection in humans is not uncommon."[4] ## References[edit] 1. ^ 'Oedema' is the standard form defined in the Concise Oxford English Dictionary (2011), with the precision that the spelling in the United States is 'edema'. 2. ^ The Merck Veterinary Manual, "Malignant Edema" 3. ^ A World of Petcare, "Malignant Oedema" Archived 2011-07-06 at the Wayback Machine 4. ^ The Merck Veterinary Manual, "Malignant Edema" This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Malignant edema	c0017105	6,794	wikipedia	https://en.wikipedia.org/wiki/Malignant_edema	2021-01-18T19:08:44	{"mesh": ["D005738"], "wikidata": ["Q6743505"]}
A number sign (#) is used with this entry because mitochondrial DNA depletion syndrome-3 (MTDPS3) is caused by homozygous or compound heterozygous mutation in the DGUOK gene (601465) on chromosome 2p13. Biallelic mutation in the DGUOK gene can also cause adult-onset PEOB4 (617070). Description Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion (Mandel et al., 2001). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Clinical Features Boustany et al. (1983) reported a patient who died at age 9 months of hepatic failure with generalized aminoaciduria, but without lactic acidosis or muscle involvement. Liver biopsy showed enlarged mitochondria and decreased cytochrome c oxidase activity (less than 10% of normal). Kidney mitochondria showed normal cytochromes. A second cousin, related through the maternal grandfather, had a fatal mitochondrial myopathy characterized by progressive generalized hypotonia, progressive external ophthalmoplegia, and severe lactic acidosis. In an addendum, the authors noted that another family member presented at 2 months of age with hypotonia, ophthalmoplegia, and lactic acidosis. In tissue samples from the patient reported by Boustany et al. (1983), Moraes et al. (1991) found a quantitative defect of mtDNA involving liver (12% of control values). There was no evidence of an mtDNA mutation in the areas surrounding the origin of replication of the heavy strand (H-strand) or light strand (L-strand) of mtDNA. Moraes et al. (1991) concluded that affected individuals exhibit variable levels of mtDNA depletion (up to 98%) in affected tissues, while unaffected tissues have relatively normal levels of mtDNA. In addition, different tissues may be involved in related patients. Mazziotta et al. (1992) reported a 3-month-old girl who presented with frequent vomiting and hypotonia. She had severe metabolic acidosis, hepatomegaly, and rapidly progressive fatal liver failure with death at age 4 months. Mitochondrial DNA was 90% depleted in liver and activity of mitochondrial-encoded respiratory chain enzymes were markedly decreased. Bodnar et al. (1993) studied fibroblasts from a patient described by Leonard et al. (1991). The fourth child of healthy, unrelated parents and the product of an uncomplicated full-term pregnancy, the infant soon after birth developed progressive liver failure, widespread edema, hyponatremia, hypoalbuminemia, marked prolongation of clotting times, and lactic acidosis. He became progressively more hypotonic and unresponsive and died at 4 months of age. An older sister had a clinically similar illness and died at 4 months of age. One older brother was noted to be hypertonic and jittery on the second day of life and died suddenly and unexpectedly at 4 weeks of age. Clinical presentation and family history were similar to those reported for cases of mtDNA depletion. Studies on cultured skin fibroblasts from patient 1 revealed a decrease in activities of the respiratory-chain enzymes and a quantitative decrease in mtDNA. It was also observed that the fibroblasts were dependent on uridine and pyruvate for growth, which is a well-characterized requirement for rho(0) cells, which have been depleted of mtDNA by long-term exposure to low concentrations of ethidium bromide. This property of the patient's fibroblasts provided a selectable marker for experiments performed by Bodnar et al. (1993) because complementation of these metabolic requirements indicated the reconstitution of mitochondrial function. The nuclear genome of this patient was represented by enucleated fibroblasts and human-derived rho(0) cell lines. The resulting cybrids grew in medium lacking pyruvate and uridine, indicating restoration of respiratory chain function. Taanman et al. (1997) studied myoblast cell cultures from a patient with the mtDNA depletion syndrome and demonstrated complementation by normal nuclei. The patient presented at 8 weeks of age with hypotonia, poor visual fixation, and variable lactic acidemia. He died of progressive liver failure at the age of 7.5 months. Taanman et al. (1997) stated that the mitochondrial DNA depletion syndrome had been documented in 29 children. Blake et al. (1999) reported 2 sibs with the disorder. In the proband, they used immunocytochemical techniques to demonstrate that the disorder was expressed in amniotic fluid cells. The proband, the second child in the family, was well at birth but developed hypoglycemia during the first 24 hours of life. Later, she developed lactic acidemia with progressive liver failure. Liver biopsy showed micronodular cirrhosis with proliferation of bile ducts and abundant neutral fat and bile pigment in hepatocytes. The activity of cytochrome c oxidase was severely depleted in liver. Assay of phosphoenolpyruvate carboxykinase (PEPCK; 614168) in liver mitochondria revealed evidence of reduced mitochondrial PEPCK activity, but PEPCK activity measured in amniotic fluid cells and fibroblasts was within normal limits. The patient died of progressive liver failure at the age of 6 months. Skeletal muscle obtained at postmortem showed relatively uniform fibers with no evidence of ragged-red fibers. There was an excess of coarse lipid droplets in many muscle fibers. Cytochrome c oxidase activity was normal and present in all fibers. The patient's elder brother was well at birth but very soon developed symptoms compatible with liver failure. Blood lactate was variably increased. The child died at the age of 7 weeks of progressive liver failure. Mandel et al. (2001) reported 19 affected members from 3 unrelated Israeli-Druze families with the hepatocerebral form of mtDNA depletion syndrome. Affected individuals presented between birth and 6 months of age with hepatic failure, severe failure to thrive, oscillating eye movements, and neurologic abnormalities, accompanied by lactic acidosis, hypoglycemia, and markedly elevated amounts of alpha-fetoprotein in plasma. Death usually occurred before 1 year of age. Enzymatic activities of the mitochondrial respiratory chain complexes containing mtDNA-encoded subunits (complexes I, III, and IV) were reduced to various extents, whereas complex II enzymatic activity, which is encoded solely by nuclear genes, was normal. Muscle tissue from 7 affected patients showed normal histology and respiratory chain complex activities. Mancuso et al. (2005) reported 2 sibs and 1 unrelated patient with hepatocerebral DNA depletion syndrome caused by mutations in the DGUOK gene. Common features included poor feeding, vomiting, failure to thrive, hypothermia, metabolic acidosis, and hypoglycemia in the neonatal period. Signs of overt liver failure developed in the first months of life with ascites, jaundice, hepatomegaly, abnormal liver function tests, hyperbilirubinemia, and coagulopathy. Liver biopsy of 2 patients showed severe micronodular cirrhosis, marked cholestasis, steatosis, hepatocellular loss, and fibrosis. Ultrastructural examination in 1 patient showed excessive and abnormal mitochondria. Liver specimens showed 84 to 90% mtDNA depletion. All patients showed variable encephalopathic signs including nystagmus, cerebral atrophy, microcephaly, hypotonia, and in 1 patient, optic dysplasia. Although 1 patient underwent liver transplantation, all 3 died by 5 months of age. ### Clinical Variability Ducluzeau et al. (1999) described the case of a 28-month-old French boy who presented with a transient liver cholestasis, beginning at the age of 2 months, complicated by progressive fibrosis due to liver mtDNA depletion but without extrahepatic involvement. Lactate levels and lactate/pyruvate ratio were elevated. On the third liver biopsy, micronodular cirrhosis was fully established. Mitochondrial enzyme analyses and Southern blots were abnormal in liver, but normal in skin and skeletal muscle. Ducluzeau et al. (2002) reported clinical follow-up of the patient reported by Ducluzeau et al. (1999), who was 6 years old at the time of the second report. At about 32 months of age, the patient's liver tests began to improve spontaneously, and this was associated with an increase in clotting factors, a dramatic decrease of liver fibrosis and normal appearance of hepatocytes on biopsy, an increase in liver mtDNA content, and almost complete restoration of respiratory chain complex activities containing mtDNA-encoded subunits. He showed normal psychomotor development at age 46 months. Ducluzeau et al. (2002) suggested that the most probable hypotheses for such a highly unusual recovery of mtDNA level include somatic mosaicism for a mutation in the nuclear genome or spontaneous reversion to normal of one of the putative mutations. In the patient reported by Ducluzeau et al. (1999), Mousson de Camaret et al. (2007) identified compound heterozygous missense mutations in the DGUOK gene (N46S, 601465.0008 and L266R, 601465.0009). In vitro studies showed that these mutations retained 10 to 14% residual enzymatic activity, which likely contributed to the unusual phenotypic reversal in this patient. Inheritance Moraes et al. (1991) found no evidence of maternal inheritance, and suggested that mtDNA depletion may be inherited as an autosomal recessive disorder. Alternatively, they also suggested that this phenotype may be the result of a dominant nuclear mutation expressed only when combined with a certain mitochondrial genotype. Mazziotta et al. (1992) suggested that it is an autosomal dominant trait with incomplete penetrance. All 29 patients reviewed by Taanman et al. (1997) were born to clinically normal parents, and family histories were compatible with autosomal recessive inheritance in all but 1 pedigree, where the pattern of inheritance could be explained by autosomal dominant transmission with incomplete penetrance (Mazziotta et al., 1992). Whether recessive or dominant, the autosomal inheritance supported the involvement of a nuclear-encoded factor. Complementation with nuclear DNA from a normal cell line (Bodnar et al., 1993) indicated involvement of the nuclear genome. Douglas et al. (2011) reported a patient, born of unrelated Mexican parents, with classic hepatocerebral mtDNA depletion syndrome due to an apparently homozygous mutation in the DGUOK gene. However, analysis of parental DNA showed that only the father carried the mutation in the heterozygous state. Analysis of patient tissue ruled out gene deletion, and SNP array analysis showed only paternal inheritance of informative markers and no inheritance of maternal alleles. There was copy-neutral absence of heterozygosity across the entire chromosome 2, consistent with uniparental isodisomy for the DGUOK gene. The findings had implications for genetic counseling. Mapping Mandel et al. (2001) used homozygosity mapping in 3 kindreds of Druze origin segregating for the hepatocerebral mtDNA depletion syndrome and mapped the disorder to a region of 6.1 cM on chromosome 2p13. Molecular Genetics In 3 Israeli-Druze kindreds with hepatocerebral mtDNA depletion syndrome-3, Mandel et al. (2001) identified a 1-bp deletion in the DGUOK gene (204delA; 601465.0001) that segregated with the disease. Western blot analysis failed to detect deoxyguanosine kinase protein in the liver of affected individuals. The main supply of deoxyribonucleotides (dNTPs) for mtDNA synthesis comes from the salvage pathway initiated by deoxyguanosine kinase and thymidine kinase-2. The association of mtDNA depletion with mutated DGUOK suggested that the salvage pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools. In 3 (14%) of 21 patients with hepatocerebral mtDNA depletion syndrome-3, Salviati et al. (2002) identified mutations in the DGUOK gene (601465.0003-601465.0006). The findings suggested that other genes may also be responsible for mitochondrial depletion in the liver. Tadiboyina et al. (2005) reported 3 patients with the hepatocerebral form of mtDNA depletion syndrome together with cystathioninuria. All 3 children were homozygous for a D255Y mutation (601465.0007) in the DGUOK gene but had no mutations in the cystathionine gamma-lyase gene (CTH; 607657), indicating that the hepatocerebral form of mtDNA depletion syndrome might be associated with secondary cystathioninuria. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth \- Failure to thrive HEAD & NECK Head \- Microcephaly (less common) Eyes \- Nystagmus \- Disconjugate eye movements \- Optic dysplasia ABDOMEN External Features \- Ascites \- Portal hypertension Liver \- Hepatomegaly \- Abnormal liver function tests \- Liver tissue shows 80 to 99% depletion of mitochondrial DNA (mtDNA) with decreased activities of mitochondrial-encoded respiratory chain complexes \- Biopsy shows micronodular cirrhosis \- Cholestasis \- Steatosis \- Jaundice \- Hepatocellular loss \- Hepatocellular necrosis \- Periportal fibrosis \- Pseudoacinar formation \- Electron microscopy shows increased and abnormal mitochondria \- Hepatic failure Spleen \- Splenomegaly Gastrointestinal \- Poor feeding \- Vomiting SKIN, NAILS, & HAIR Skin \- Jaundice NEUROLOGIC Central Nervous System \- Encephalopathy \- Nystagmus \- Hypotonia \- Hyperreflexia \- Seizures \- Cerebral atrophy Peripheral Nervous System \- Peripheral neuropathy METABOLIC FEATURES \- Hypoglycemia \- Hypothermia \- Lactic acidosis HEMATOLOGY \- Coagulopathy due to hepatic failure \- Thrombocytopenia LABORATORY ABNORMALITIES \- Hyperbilirubinemia \- Abnormal liver function tests \- Hypoalbuminemia \- Generalized aminoaciduria MISCELLANEOUS \- Onset as neonate \- Hepatic failure develops in first months of life \- Most patients die of hepatic failure by 9 months of age MOLECULAR BASIS \- Caused by mutation in the nuclear-encoded mitochondrial deoxyguanosine kinase gene (DGUOK, 601465.0001 ). ▲ 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	MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)	c3151513	6,795	omim	https://www.omim.org/entry/251880	2019-09-22T16:25:05	{"doid": ["0080121"], "omim": ["251880"], "orphanet": ["279934"], "synonyms": [], "genereviews": ["NBK7040", "NBK487393"]}
A rare disorder characterized by focal inflammation within the spinal cord due to a known cause, usually an inflammatory disease. ## Epidemiology Exact incidence is unknown as there are many potential causes. ## Clinical description The age of onset, signs and symptoms, severity and clinical course (monophasic or relapsing) vary depending on the associated disease. The signs and symptoms of secondary acute transverse myelitis (ATM) may be similar to those of idiopathic ATM and also depend on the size and site of the inflammation. Common signs and symptoms include motor involvement (limb weakness, stiffness and muscle spasms with impaired respiratory function in some cases), sensory manifestations (back pain, paraesthesia, numbness and neuropathic pain) and autonomic findings (sexual dysfunction, urinary urge/retention, bowel urgency/retention and autonomic dysreflexia). However, other parts of the nervous system may be involved in secondary ATM, depending on the associated disease: the optic nerves in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), and the peripheral nerves in patients with systemic lupus erythematosus (SLE; see these terms). ## Etiology Secondary ATM may also occur as a result of direct bacterial, parasitic or viral invasion of the spinal cord, and in patients with Sjögren's syndrome (see this term). ## Diagnostic methods Diagnosis requires MRI of the spinal cord to confirm the presence of myelitis: for example, long lesions in patients with NMO, short and multifocal lesions in patients with MS. Laboratory tests are also essential for identifying the cause of secondary ATM: analysis of the cerebrospinal fluid may reveal the presence of oligoclonal bands (commonly seen in MS) or bacterial/viral/parasitic infections; serology may reveal the presence of autoantibodies to aquaporin-4 (NMO), anti-double-stranded DNA antibodies (SLE) or anti-Ro/SS-A antibodies (Sjögren's syndrome). Visual evoked responses may be abnormal. ## Differential diagnosis The differential diagnosis should include idiopathic ATM which is thought to be due to a late immune response to a recent infection, as well as acute transverse myelopathy associated with arteriovenous fistulae, tumors, trauma, spinal cord infarcts and compression. ## Management and treatment Treatment approaches depend on the underlying cause with acute treatment options including administration of steroids and plasma exchange in steroid-resistant patients. Long-term care should include symptomatic management, rehabilitative therapy and long-term maintenance treatments to prevent future relapses or slow disease progression. ## Prognosis The prognosis is variable and depends on the response to treatment, the associated disease and the prevention of further episodes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Secondary acute transverse myelitis	None	6,796	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139420	2021-01-23T18:31:19	{"icd-10": ["G37.3"], "synonyms": ["Disease-associated transverse myelitis"]}
Flat-chested kitten syndrome (FCKS) is a disorder in cats wherein kittens develop a compression of the thorax (chest/ribcage) caused by lung collapse. This is a soft-tissue problem and is not caused by vertebral or bony malformation. However lung collapse can be a secondary symptom caused by bony deformity affecting the thorax such as pectus excavatum. In mild cases, the underside of the chest becomes flattened (hence the name of the condition); in extreme cases the entire thorax is flattened, looking as if the kitten has been stepped on. The kitten will appear to go from normal to flat in the space of about 2–3 hours, and will usually then stabilise. FCKS is frequently misdiagnosed as pectus excavatum due to inadequate veterinary literature or lack of experience with the condition on the part of the clinician. FCKS is most frequently caused by collapsed lungs (and not as formerly believed, by a muscle spasm in the intercostal muscles). There are numerous causes for lung collapse, and therefore numerous causes for FCKS. One possible cause for flat chestedness that develops soon after birth is atelectasis. Causes of atelectasis include insufficient attempts at respiration by the newborn, bronchial obstruction, or absence of surfactant (a substance secreted by alveoli that coats the lungs and prevents the surfaces from sticking together). Lack of surfactant reduces the surface area available for effective gas exchange causing lung collapse if severe. There can be many reasons for atelectasis in kittens, but probably the most common cause is prematurity. Newborn atelectasis would not be unusual in a very large litter of kittens (such as 10), where the size of the litter may lead all the kittens to be small and mildly underdeveloped. Unlike human babies, kittens are born very immature: blind, deaf, the intestinal tract not fully developed etc., so even slight prematurity may tip them over the edge from being viable to non viable. Many FCKS kittens may have fallen just the wrong side of this boundary in their development at the time of birth. Further, if a kitten does not scream or open its lungs well enough at birth, even if it is fully mature and has sufficient surfactant, it may end up with atelectasis. Patches of atelectasis in the lungs mean that part of a lung is not operating properly. If the kitten goes to sleep and its respiratory rate drops, the patches of atelectasis can slowly expand until large areas of the lung collapse and cannot be reinflated. Good advice to any breeder therefore would be to ensure that kittens cry loudly when they are born, to make sure that the airways are clear, but also that the lungs expand as fully as possible. (This was the reason newborn babies were always held upside down immediately after birth (so that any residual fluid drains downwards) and smacked to make them cry strongly.) Some kittens suffer from congenital 'secondary' atelectasis, which presents shortly after birth. There have been no reports of kittens born flat (primary atelectasis). Hyaline membrane disease is a type of respiratory distress syndrome of the newborn in which there is formation of a hyaline-like membrane lining the terminal respiratory passages, and this may also be a (rarer) cause of FCKS. Pressure from outside the lung from fluid or air can cause atelectasis as well as obstruction of lung air passages by mucus resulting from various infections and lung diseases – which may explain the development of FCKS in older kittens (e.g. 10 days old) who are not strong enough to breathe through even a light mucus, or who may have inhaled milk during suckling. Tumors and inhaled objects (possible if bedding contains loose fluff) can also cause obstruction or irritation of the airway, leading to lung collapse and secondary atelectasis. In an older cat the intercostal muscles are so well developed, and the ribs rigid enough that the ribcage will not flatten if the lung collapses: in kittens the bones are much more flexible, and the tendons and muscles more flaccid, allowing movement of the thorax into abnormal positions. Other causes of lung collapse can include diaphragmatic hernia, or diaphragmatic spasm (breeders report the position of the gut and thorax as appearing to be like a 'stalled hiccup'). Diaphragmatic spasm is easily checked by pinching the phrenic nerve in the neck between the fingertips. Kittens with this type of FCKS will improve almost immediately, but may require repeated pinching to prevent the spasm from recurring. ## Contents * 1 Evidential basis and statistical analysis * 2 Onset and diagnosis * 3 Causes * 3.1 Genetic/Heredity * 3.2 Developmental * 3.3 Infection * 3.4 Diaphragmatic spasm * 3.5 Colic * 4 Treatment * 4.1 Drugs * 4.2 Splinting and physical therapy * 5 Survival and long-term prognosis * 6 Breeding with FCKS * 7 Other conditions * 8 Flat chestedness in other animals * 9 References * 10 External links * 11 Bibliography * 11.1 Literature on Pectus Excavatum ## Evidential basis and statistical analysis[edit] Reports of kittens with FCKS by breed 1999-2018 GCCF statistics for numbers of kittens registered 1999-2018 Almost all reporting of FCKS is treated as anecdotal, since it comes from breeders and not from veterinary practitioners. However, in the absence of robust clinical studies breeder-reporting is the only source of information currently available. Reporting about type of FCKS is hampered by the lack of differentiation between one type and another by both breeders and vets. The data informing this article came from three sources: * Analysis of emails reporting cases of FCKS sent to the owner of a website giving information about the condition and methods of treatment, 1999-2019 [87 of these kittens were examined in person by the author] * Data gathered by the THINK project 2005-2015 who published an online questionnaire (the project is now defunct) * Directly solicited reports requested from 27 individual breeders of Abyssinian (4 responded) and 35 breeders of British Shorthair (2 responded) in the UK The 20-year analysis was compared with the Governing Council of the Cat Fancy in the UK (GCCF) analysis of numbers of kittens registered during the same period. The full report is to be published during 2020.[1] Only direct reports from owners (362) about their own cats or vets examining kittens (2) were considered. Kittens exhibiting any other condition (including pectus excavatum) were excluded. The overwhelming majority of reports (76%) were of single FCKS cases in a litter, with the remainder whole or part litters. The data comprised 311 reports of litters of kittens in which one or more developed FCKS, for a total of 464 affected kittens (see table). Reports in which the sex was specified showed breakdown by sex of male 56%/female 44%. 16 breeders reported that whereas they might have expected the smallest kitten in a litter (if any) to develop FCKS, it was the largest and strongest kittens that developed flat chests, and these were often males. The condition does not appear to be sex-linked, but the preponderance of male kittens in this reporting group may be due to the fact that males tend to be larger than females and these are the kittens getting most milk or suckling hardest because they are stronger, in which case the type of FCKS in these litters may have been due to colic caused by overfeeding (see Causes, below). Reports originated from 21 countries (Australia (15), Austria (11), Belgium (2), Canada (8), Denmark (3), Finland (2), France (24), Germany (13), Hungary (1), Japan (2), Netherlands (14), New Zealand (6), Norway (5), Portugal (1), Singapore (1), Slovakia (1), South Africa (5), Sweden (11), Switzerland (1), UK (100), USA (85)) and covered 39 breeds (including non-pedigree domestic shorthair, non-pedigree domestic longhair, and some ‘unrecognised’ crosses between two pedigree breeds or pedigree breeds x DSH). 10 reports did not specify breed. High numbers of reports in certain breeds has in the past been taken to imply that some breeds are more prone to the condition than others, but the data is skewed by various factors: a) the numbers of kittens bred; b) cluster-reporting in response to articles in breed club circulars or c) the work of a particular group of breeders (cf Burmese) in attempting to address a problem that they had seen in their own lines d) the culture within an individual breed of information-sharing or reporting problems. Breeders are generally not inclined to discuss health issues because of a culture of blame and gossip, having a dramatic effect on information-sharing. No ‘cluster’ triggers have been identified for the relatively high number of reports in the Maine Coon or Bengal breeds, while the Burmese cat club commissioned a study into the condition in 1997 by Sturgess et al, and the THINK project solicited reports from Burmese breeders specifically. However statistics on the registration of kittens provided by the GCCF show that Bengal, Burmese and Maine Coon are consistently in the top nine breeds by number of kittens registered (see table). The breeds showing highest numbers of kittens registered therefore broadly correlate demographically to reports of FCKS. More significant is perhaps the low number of reported cases in the British Shorthair (especially when compared with the Manx), but this seems to be attributable to the culture of breeders and level of diagnostic awareness in that group. Mortality: of 195 cases where the outcome was notified, 88 died, or were euthanised due to distress; 107 recovered and survived beyond 3 months of age. Those that recovered fully did not appear to suffer any long-term respiratory effects (Interference of the development of the upper spine while the body was held in an incorrect position by the FCKS led to long-term kyphosis in some, but not all, cases), although reporting is patchy. Mentions of FCKS in the veterinary literature (usually no more than a single sentence) include no descriptive information and have no evidential basis, in particular the claim in Saperstein, Harris & Leipold (1976) that the condition may be hereditary, which has been repeated in subsequent literature. ## Onset and diagnosis[edit] FCKS develops usually in kittens around three days of age, and sometimes affects whole litters, sometimes only individuals or part of a litter. Kittens can go flat any time during early maturation, some flattening as late as 10 days of age or (in very rare cases) later. It is possible that the later-developing cases are due to Respiratory tract infection or pneumonia. Until 2010 FCKS was believed to be caused by a spasm in the intercostal muscles, but re-examination of old post-mortem data (i.e. that kittens remain flat even when they are dead and therefore cannot maintain a muscular spasm) and new data has led to the conclusion that flattening is caused by failure of the lungs to inflate normally or, when it occurs in older kittens, by lung collapse. This cause is now cited by the veterinary community (Sturgess 2016) but without any source acknowledgement. Gross physical symptoms include flattening of the underside of the thorax in moderate cases (a ridge can usually be felt along the sides of the ribcage, running parallel to the spine); complete flattening of the upper body in extreme cases (the kitten looks as if it has been stepped on); moderate to extreme effort and/or gasping during breathing; the gut is drawn upwards during the in-breath. Breathing is not usually rapid (as in pneumonia or pyrexia) but at a normal rate when compared with unaffected kittens. The position of the thorax and activity of the abdomen is not unlike that seen during normal hiccups, but the sudden spasm in hiccups is slowed down or halted in FCKS: where a hiccup releases, returning the body to a normal position, FCKS breathing does not release. There may be involvement with digestive difficulty in FCKS kittens (see Colic, below). Banana used to demonstrate FCKS shape Determining whether a kitten has FCKS or not can be difficult with only text descriptions: a mild case of FCKS causes the thorax to feel similar to the shape of a banana when held curve downward. The ribcage is not fixed in position, and the most noticeable effect in mild cases is the ridge along the side of the ribcage. The condition causes weight-gain to halt, respiratory distress, inability to feed normally and, in a significant proportion of cases, death. However, since a significant percentage of kittens survive the condition immediate euthanasia is not indicated, and supportive treatments can be employed to increase the likelihood of survival (see Treatment, below). The condition is often misdiagnosed as Pectus excavatum,[2] with which it has no direct connection, although FCKS kittens may also have PE. Although the condition is believed to be more prevalent in the Burmese breed it is found in every breed of cat, including non-pedigree domestic cats, and the apparent prevalence in the Burmese is most likely due to better communication between breeders and reporting of the condition, as well as the naturally more barrel-shaped chest of this particular genotype.[3] Since early reporting of the condition identified the Burmese as susceptible the Bengal breed, with a similar physiology, has emerged, and shows a similarly large number of FCKS kittens, however this may be due to specific interest in the condition among those working with the breeds. It is reported in all breeds and in domestic non-pedigree cats, both those kept as pets and those living as 'barn cats'. An article in a Swedish cat club newsletter about FCKS led to a spike in reporting of the condition in Ragdolls in Sweden. Egyptian Mau kitten with FCKS Rex kitten with FCKS and Kyphosis - note narrowing of thorax around the shoulders Oriental kitten with moderate to extreme FCKS. Pectus Excavatum is not present. The kitten was wrapped in a 'corset' for about 2 weeks. It is now a healthy adult. The syndrome is life-threatening in a significant number of cases (possibly around 40%) mainly due to a lack of understanding of the underlying cause of the condition, failure to treat colic (leading to slow starvation) and insufficient sources of information in veterinary literature. ## Causes[edit] ### Genetic/Heredity[edit] There is no statistical evidence to suggest that FCKS may be due to genetic factors: certain bloodlines seem to produce a preponderance of kittens with the condition, but this may be due to enhanced reporting within the breed. The literature citing heredity as a cause (Saperstein, Harris & Leipold (1976)) does not provide any evidential support and the information is repeated in later literature citing that source as authority. The majority of cases are of single kittens, with low but significant numbers of whole or part litters reported. Numerous breeders experience periods in which FCKS seems to occur over a number of matings, but then stops, suggesting an environmental cause. Incidences of the condition have been reported in many litters that were repeat matings of previously healthy litters; matings repeated after the incidence of FCKS do not produce flat kittens any more frequently than non-repeat matings; recovered FCKS that have been bred from have likewise not produced offspring that suffered from the condition any more frequently than normal cats, but numbers in this category are obviously low. It is possible that some lines in which the queens provide excessive milk may lead to colic-related FCKS in the kittens, leading to the supposition of heredity. Although after experiencing cases of FCKS most breeders do not repeat matings. In 59 cases of repeat matings 52 litters did not result in FCKS again while 7 did. ### Developmental[edit] It is possible that the lung collapse in neo-nates (i.e. around 3 days of age) could be due to a lack of surfactant \- the coating of the inside of the lung that prevents the inner surfaces of the alveoli from sticking together. (Causes of surfactant deficiency are not discussed here, but the role of surfactant is discussed in a number of articles in the British Journal of Anaesthesia vol. 65, 1990.[4]). Kittens are born immature in many ways, and full inflation of the lungs does not happen immediately, but takes place gradually over a period of several days after birth. Although a kitten may seem active and thriving, its lungs will not be fully inflated until approx. day 3 after birth. Thus if inflation fails to happen correctly the negative pressure in the chest cavity will cause the ribcage – which is extremely flexible – to collapse inward, dragged in by the lungs, and not collapsing due to muscular cramping, and compressing the lungs. ### Infection[edit] Neo-natal and Later lung collapse may be due to lung infection, or possibly to a malfunction in the epiglottis, causing the in-breath to draw air into the digestive tract rather than the lungs. A short term malfunction of this sort may be perpetuated by the resulting colic creating a feedback loop that interrupts the correct breathing process. Autopsy and analysis of lung aspirate in a group of flat-chested kittens bred by a US Vet showed the presence of Herpes virus. ### Diaphragmatic spasm[edit] Position of the Phrenic Nerve (diagram) Spasm in the diaphragm leads to the muscle 'locking up' so that all breathing effort falls to the intercostal muscles. The resulting loss of movement causes the lungs to deflate gradually. This is easily diagnosed and treated (see Treatment below) by short-term interruption of the Phrenic nerve. ### Colic[edit] A kitten that has difficulty in breathing is very likely also to suffer from colic (which can cause weight loss in the early development of a normal kitten), and a very small daily (or twice daily) dose of liquid paraffin (one or two drops placed on the tongue of the kitten, or 0.1 ml) should help to alleviate this problem. FCKS kittens who do not maintain weight are usually among the group which die, but many of them may simply be unable to feed properly due to colic, becoming increasingly weak and lethargic, and fading due to malnutrition as much as to the thoracic problems. Colic has many causes, but in a kitten with respiratory difficulty it is possible that a malfunction during the breathing process leads the kitten to swallow air instead of taking it into its lungs. The GI tract fills with air while the lungs do not receive a proper air supply, preventing them from inflating fully. Pressure from the stomach exacerbates the condition. Treating for colic with liquid paraffin seems to shorten recovery time from 4–10 weeks to a matter of days. ## Treatment[edit] Position of Phrenic nerve in a sleeping kitten. The nerve bifurcates and runs down both sides of the neck. Treatment is difficult to define given the number of different causes and the wealth of anecdotal information collected by and from cat breeders. Treatments have hitherto been based on the assumption that FCKS is caused by a muscular spasm, and their effectiveness is impossible to assess because some kittens will recover spontaneously without intervention. FCKS cannot be corrected surgically. Diaphragmatic spasm is easily tested for and treated by short term interruption of the Phrenic nerve. The nerve runs down the outside of the neck where the neck joins to the shoulder, within a bundle of muscles and tendons at this junction. The cluster can be pinched gently and held for a few seconds each time. Kittens with spasmodic FCKS will show almost immediate improvement, but the treatment may need to be repeated several times over a few days as the spasm may have a tendency to recur, particularly after suckling. It is sometimes evident that the spasm only affects one side of the diaphragm, as interruption of the nerve is only necessary or effective on one side. Continuous positive air pressure (CPAP) is used in human babies with lung collapse, but this is impossible with kittens. It is possible that the success of some breeders in curing kittens by splinting the body, thus putting pressure on the ribcage, was successful as it has created the effect of positive air pressure, thus gradually re-inflating the lungs by pulling them open rather than pushing them open as is the case with CPAP (see below). ### Drugs[edit] The use of steroids (Dexamethasone) coupled with an antibiotic (Amoxicillin) will support the kitten in a number of ways, the steroid enhancing maturation and the antibiotic addressing the possibility of underlying infection and compensating for the immuno-depressant properties of the steroid. The steroid will also encourage the kitten to feed more energetically, keeping its weight up. However the primary supportive mechanism must be nutritional. Kittens who are only supported with feeding and do not receive drugs seem to have a similar prognosis to those receiving drugs. Drug treatment cannot be used to replace nutritional support (i.e. supplementary feeding). Two breeders having read the report by Sturgess et al (which was inconclusive) believe that Taurine plays a part in the condition. These breeders give the queen large doses of Taurine (1000 mg) daily until the kittens recover – apparently within a few days. Long-term use of high doses of Taurine should be monitored by a veterinarian. Kittens have a much higher metabolism than adults, so drugs cannot simply be calibrated based on adult protocols but adjusted for weight. Antibiotics administered 2x daily in adults need to be given 3x daily in kittens, and doses given at 24-hour intervals in adults need to be given at 18- to 20-hour intervals in kittens. In addition, because the liver does not metabolise drugs as efficiently as in adults, a higher dose relative to body weight may need to be given. Little information is available in veterinary literature about drug dosing in neonates; almost all treatment protocols are based on adult animals. The neonatal human literature is here used as a guide. See Lawrence C. Ku and P. Brian Smith, 'Dosing in neonates: Special considerations in physiology and trial design' and multiple other sources of information. Observation of drug responses in neonatal kittens indicates increased frequency is essential. ### Splinting and physical therapy[edit] Splinting the kitten in a specially-constructed corset made from a rigid material such as a toilet roll, section of plastic bottle or high-density foam encourages the ribcage to a more normal position, and reported mortality seemed to decline when this practice was introduced.[5] This may be because encouraging the chest to a more correct position helps the lungs to re-inflate. However a large proportion of kittens cannot tolerate a splint, and the distress it causes is extremely counterproductive. It can also be dangerous in cases where pressure on the sides causes the sternum to move inwards rather than outwards, and should only be undertaken with veterinary support and advice. Some kittens recover without intervention, so it is not known whether the various treatments based on encouraging the thorax to return to a normal shape contributed to recovery.[6] Some breeders have found that applying manual pressure to the sides of the ribcage can help, as the chest rounds out with encouragement (gentle pressure timed to coincide with the natural movement of the thorax in breathing), but usually the chest goes flat again as soon as massage is discontinued. It may however help in encouraging the lungs to inflate a little more with each breath, but should not be used if it causes distress to the kitten. Many breeders report that affected kittens seem to enjoy massage. Encouraging a kitten to lie on its side can be helpful, and draping another kitten (or the mother's arm) over it while it is sleeping on its side places a gentle continuous pressure on the ribcage which may also be helpful. If the kitten is uncomfortable it will move away. (It is important to ensure that pressure is not placed on the kitten if it is lying flat on its chest.) Over-handling FCKS kittens can lead to unnecessary weight loss and lethargy, so the use of massage, waking the kitten for extra feeds from the mother etc. should be checked against gains and losses in weight. Some vets believe that encouraging the kitten to cry and also to have to move more to reach its mother may be helpful. There is no data from breeders supporting this theory. ## Survival and long-term prognosis[edit] It is difficult to determine whether a kitten that goes flat will survive or not. A good indicator is the weight of the kitten: those that continue to gain weight generally have a better chance of survival. Supplement feeding is therefore recommended in all cases, together with vitamin supplements,[7] although many of these kittens will not accept hand feeding. Liquid Paraffin to alleviate colic seems to be significant in assisting normal feeding and weight-gain. Another indicator to the severity of the case is the use of the stomach when breathing: normal kittens use only the ribcage, a flat-chested kitten may manage to breathe only using the ribcage, or may suck the gut upwards with every breath – if the latter is the case then the likelihood of survival seems to be lower, though still not sufficient to warrant immediate euthanasia. If the condition is stable (i.e. the flatness does not increase over time) or improving, the kitten is more likely to survive. If the condition worsens over several days, survival is less likely. Kittens with FCKS may die (or have to be euthanised) very soon after onset. There are two points at which breeders report kittens that were otherwise doing well deteriorating and dying: at 10 days of age and at 3 weeks. Generally if the kitten is still flat, but survives the 3-week developmental stage, its prognosis is good. Many will have returned to a normal shape by this time. Those retaining some degree of flatness often grow out of the condition at any point in the ensuing 6 months, and the vast majority of survivors appear to lead normal lives with no side-effects, either physical or immunological. FCKS kittens that survive but who have not been given any drug treatment or support other than supplementary feeding, generally recover over a period of 4–10 weeks, and are usually normal by 12 weeks of age, though some take as long as 6 months to normalise. In the very small number of kittens reported so far treated with steroids, antibiotics and liquid paraffin (to address colic) recovery is usually seen within a matter of days. Given the number of different types of FCKS these kittens (all with the minor form of the condition) may not be representative of all cases. More data is required for statistical analysis. A small proportion of severe FCKS kittens are left with long-term respiratory problems, kyphosis, and in some cases cardiac issues caused by the compression of the thorax during the early developmental stages (particularly where the condition has been coupled with Pectus Excavatum). Cardiac issues are generally audible on physical examination; further indications include the kitten becoming breathless after play, less active than siblings, and failure to grow and develop normally. ## Breeding with FCKS[edit] Crucial in the decision to breed would be the primary cause of FCKS in the litter, which may or may not be genetic (see Heredity above). Some recovered FCKS adults have produced FCKS offspring in their turn, and some queens consistently produce flat kittens, so breeding from those lines is therefore inadvisable. However, repeat matings in which FCKS has appeared does not result in further FCKS kittens any more often than non-repeat matings. Queens and studs who consistently throw complete litters of kittens with the condition are generally neutered, but isolated instances of single flat kittens in an otherwise healthy litter seem to be unlikely to have a genetic component and neutering of parents of such kittens is not usually necessary in pedigree breeding, particularly where doing so may have detrimental effects on the gene pool. If the cause of flattening is colic related to over-production of milk then this would not be cause for neutering. The only way to determine if the cause is digestive would be if the condition was alleviated by pinching the phrenic nerve and/or use of liquid paraffin to relieve colic, resulting in improvement in the condition. Line-breeding or inbreeding is highly inadvisable in any situation, and particularly so in lines where FCKS has appeared, given the possibility of inheritance of any underlying condition or breeding factor that may cause kittens to develop FCKS. ## Other conditions[edit] Kittens with FCKS sometimes also show bony deformities such as pectus excavatum or kyphosis (characterised in kittens by a dip in the spine just behind the shoulder blades). Although a kitten may be born with these deformities, extreme forms of FCKS may cause kyphosis to develop in an otherwise normal kitten, as the kitten grows with the spine held in an abnormal position due to the flattened ribcage. When there are bony deformities in the upper body, or other problems present, these may contribute to malfunctioning in soft-tissue organs such as the respiratory and digestive systems. ## Flat chestedness in other animals[edit] Flat chest occurs in piglets and puppies, may be known in cattle (anecdotal information only), and is also recorded in humans, though possibly in humans this is not the same type of condition and may be a bone deformity. ## References[edit] 1. ^ Reference will be provided when publication information is available. 2. ^ Kit Sturgess et al: An investigation of Taurine levels as a possible cause of FCKS. Burmese Cat Club Newsletter 1980, downloadable pdf files accessible from this page 3. ^ Edinburgh FAB resident, Royal Dick Veterinary Hospital: Report in FAB Journal (1993), vol. 31 (1) 71-72 4. ^ particularly B A Hills: The role of lung surfactant, British Journal of Anaesthesia 1990, 65, 13-29 5. ^ Information regarding splinting of FCKS kittens 6. ^ Although corsets can be improvised easily from e.g. plastic drinks bottles etc., one breeder has marketed a 'corset' design that she found successful with her kittens www.fck-flat-korsett.de 7. ^ Information about kitten milk and other supplements further down the page ## External links[edit] * Vetstream article on FCKS in journal Felis ISSN 2398-2950 * Flat-Chested Kitten Syndrome * Marine Minnaert: Étude rétrospective de la cage thoracique plate chez le chat : caractéristiques épidémiologiques et cliniques, pronostic et aspects génétiques, PhD thesis (2014) pdf * International Cat Care website; based on Sturgess 1997, which is out of date and incorrect in many particulars * Sturgess C P, Waters L, Gruffydd-Jones T J et al (1997) Investigation of the association between whole blood and tissue taurine levels and the development of thoracic deformities in neonatal Burmese kittens. Vet Rec 141, 566-570 * Feline Medicine and Therapeutics By E. A. Chandler, R. M. Gaskell, C. J. Gaskell describes the condition very briefly and refers to it as 'almost certainly hereditary' without any evidence for doing so. No other information is given as to cause. * In Arthur's Veterinary Reproduction and Obstetrics E-Book By David E. Noakes FCKS is listed in a table of hereditary defects in cats, again without any supporting citation or information * Google Books link to article in Feline Medicine and Therapeutics By E. A. Chandler, R. M. Gaskell, C. J. Gaskell * Sturgess, C. P. (2016) Thoracic wall deformities in kittens: what do you do? Australian and New Zealand College of Veterinary Scientists Science Week, Small Animal Medicine and Feline Chapters ## Bibliography[edit] * Blunden, A. S., Hill, C. M., Brown, B. D. and Morley C. J. (1987) Lung surfactant composition in puppies dying of fading puppy complex. Research in Veterinary Science 42: 113–118 * Blunden, T. S. (1998) The neonate: congenital defects and fading puppies. In: Manual of Small Animal Reproduction and Neonatology. Simpson, G., England, G. C. W. & Harvey, M. (eds). British Small Animal Veterinary Association, Cheltenham, UK. * Chandler, E. A., Gaskell, R. M., Gaskell, C. J. eds. (2004) Feline Medicine and Therapeutics. 3rd edn. Blackwell, Oxford (for BSAVA), 369. [Warning: this source mentions FCKS very briefly and refers to it as 'almost certainly hereditary'. No evidence, sources or further information are given.] * Charlesworth, T. M., Schwarz, T., Sturgess, C. P. (2015) Pectus excavatum: computed tomography and medium-term surgical outcome in a prospective cohort of 10 kittens. Journal of Feline Medicine and Surgery Jun 18, 11 * Fossum, T. W., Boudrieau, R. J., Hobson, H. P., Rudy, R. L. (1989). Surgical correction of pectus excavatum using external splintage in two dogs and a cat. Journal of the American Veterinary Medical Association 195: 91–97 * Hosgood, G., Hoskins J. D. (1998) Small Animal Paediatric Medicine and Surgery. Pergamon Veterinary Handbooks. Butterworth-Heinemann * Malik, R. (2001) Genetic diseases of cats, Proceedings of ESFM Symposium at BSAVA Congress, Journal of Feline Medicine and Surgery 3, 109–113 * Noakes, D. E., Parkinson, T. J., England, G. C. W. (2009) Arthur's Veterinary Reproduction and Obstetrics E-Book. 9th edn. Saunders/Elsevier, Edinburgh, 128. FCKS is listed in a table of hereditary defects in cats. * Robinson (1991) Genetics for Cat Breeders 3rd Revised edition, Butterworth-Heinemann * Saperstein G., Harris S., Leipold H.W. (1976). Congenital defects in domestic cats. Feline Practice, 6, 18. * Schultheiss, P. C., Gardner, S. A., Owens, J. M., Wenger, D. A., Thrall, M. A. (2000). Mucopolysaccharidosis VII in a cat. Veterinary Pathology 37, 502–505. * Soderstrom, M. J., Gilson, S. D., Gulbas, N. (1995) Fatal reexpansion Pulmonary Edema in a Kitten Following Surgical Correction of Pectus Excavatum. Journal of the American Animal Hospital Association 31, 133–136 * Sturgess C. P., Waters L., Gruffydd-Jones T. J., Nott H. M. R., Earle, K. E. (1997) Investigation of the association between whole blood and tissue taurine levels and the development of thoracic deformities in neonatal Burmese kittens. Veterinary Record 141, 566–570. [Warning: much information now superseded] * Vella, C. M., Shelton L. M., McGonagle, J. J., Stanglein, T. W. (1999) Robinson's Genetics for Cat Breeders and Veterinarians, 4th edn, Butterworth-Heinemann ### Literature on Pectus Excavatum[edit] * Boudrieau, R. J., Fossum, T. W., Hartsfield, S. M., Hobson, H. P., Rudy, R. L. (1990). Pectus Excavatum in Dogs and Cats. Compendium of Continuing Education 12, 341–355 * Fossum, T. W, Boudrieau, R. J., Hobson, H. P. (1989). Pectus Excavatum in Eight Dogs and Six Cats. Journal of the American Animal Hospital Association 25, 595–605 * McAnulty, J. F., Harvey, C. E. (1989) Repair of pectus excavatum by percutaneous suturing and temporary external coaptation in a kitten. Journal of the American Veterinary Medical Association 194, 1065–1067 * Shires, PK, Waldron, DR and Payne, J. (1988) Pectus Excavatum in Three Kittens. Journal of the American Animal Hospital Association 24, 203–208 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Flat-chested kitten syndrome	None	6,797	wikipedia	https://en.wikipedia.org/wiki/Flat-chested_kitten_syndrome	2021-01-18T18:57:45	{"wikidata": ["Q5457689"]}
A number sign (#) is used with this entry because some patients with benign hereditary chorea (BHC or BCH) have mutations in the NKX2-1 gene (600635) encoding thyroid transcription factor-1 (TITF1). See also choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress (610978), an allelic disorder with a more severe phenotype. Clinical Features Pincus and Chutorian (1967) and Haerer et al. (1967) described an early-onset, nonprogressive form of chorea not associated with intellectual deterioration. Bird et al. (1976) pointed out that hereditary benign chorea is a socially embarrassing condition and, perhaps for that reason, may be associated with behavioral problems and learning difficulties. For purposes of genetic counseling and prognostication, it is important to distinguish BCH from Huntington disease (HD; 143100). Robinson and Thornett (1985) reported a 10-year-old boy with this disorder whose father was the only other affected person known in the family. Corticosteroids given in multiple courses for asthma invariably were associated with an abrupt improvement in frequency and amplitude of his chorea. The authors suggested that the improvement resulted from modulation of neurotransmitter function by the agent. Schady and Meara (1988) described a family in which chorea began in childhood and affected predominantly the head, face, and arms. Dysarthria appeared later, followed in 2 family members by elements of an axial dystonia. There was no intellectual impairment. Unlike previously described families, symptoms progressed steadily up to the eighth decade, causing considerable physical disability. Kleiner-Fisman et al. (2003) reported a family in which 5 members over 4 generations had typical features of BHC. Delayed motor development and chorea began in early childhood and followed a slowly progressive course. Neuropathologic examination of 1 patient showed mild frontal-parietal-temporal atrophy, but no other abnormalities, including normal striatum and pigmented substantia nigra. Other regions of the brain showed nonspecific astrocytosis without noticeable neuronal loss. Inheritance Possible dominant inheritance of BHC was demonstrated in 2 families by Chun et al. (1973). Harper (1978) favored autosomal dominant inheritance with reduced penetrance in females. He pointed out that male-to-male transmission occurred in the families of Pincus and Chutorian (1967) and possibly in the family of Sadjadpour and Amato (1973), excluding X-linked inheritance. Furthermore, X-linked inheritance appears to be excluded by the apparent transmission through an unaffected male in the family of Pincus and Chutorian (1967). Both a dominant and a recessive form (215450) may exist. Mapping ### Exclusion Linkage In a study of 5 families with BCH, Quarrell et al. (1988) found that the disorder was not closely linked to the D4S10 marker, thus excluding the possibility that benign hereditary chorea is allelic with Huntington disease. Furthermore, when the expanded repeat sequence was discovered as the basis of Huntington disease, these families were restudied by MacMillan et al. (1993). In 4 of the families, the (CAG)n repeat was not found; in 1 family, expanded repeats were found. Because of the small size of the family and the uninformativeness of typing, this linkage to 4p16 could not be excluded in the original study of this family. Yapijakis et al. (1995) likewise excluded linkage to the HD locus in an affected Greek family. ### Linkage to 14q In a large Dutch kindred with BHC, de Vries et al. (2000) found strong evidence for linkage between the disorder and markers on 14q (maximum lod score of 6.32 at recombination fraction 0.0). The BHC locus in this family was located between markers D14S49 and D14S1064, a region spanning approximately 20.6 cM and containing several candidate genes involved in the development and/or maintenance of the central nervous system, including glia maturation factor-beta (GMFB; 601713), GTP cyclohydrolase I (GCH1; 600225), and SMN-interacting protein-1 (SIP1; 602595). Fernandez et al. (2001) reported a 4-generation family with BCH showing linkage to 14q. Haplotype analysis defined a 6.93-cM critical region between D14S1068 and D14S1064, excluding SIP1 as a candidate gene. Direct sequencing of the GCH1 gene in this family revealed no mutations. ### Genetic Heterogeneity Breedveld et al. (2002) reported clinical and genetic heterogeneity in 6 families with BHC and the large Dutch family reported by de Vries et al. (2000). Three of the 7 families showed linkage to chromosome 14 between markers D14S49 and D14S278, and haplotype analysis narrowed the critical interval for the BHC locus to 8.4 cM. In the remaining 4 families, linkage to 14q was excluded. The 3 families with linkage to 14q had a similar clinical phenotype including onset in infancy and childhood, chorea, and absence of mental deterioration. Other variable features in these families included gait difficulties, pyramidal signs, slow saccades, and abnormal reflexes. The 4 unlinked families had a slightly later age at onset and other signs besides chorea, including myoclonic jerks, dystonia, tremor, and tics. Molecular Genetics Breedveld et al. (2002) reported a small BHC family with a de novo deletion of 1.2 Mb, including the TITF1 gene (600635.0001). They also described 3 other multigenerational families with BHC who had heterozygous point mutations in the TITF1 gene (600635.0002-600635.0004). In a family with BHC, Kleiner-Fisman et al. (2003) identified a heterozygous mutation in the TITF1 gene (600635.0007). Nomenclature Schady and Meara (1988) discussed the use of the label 'benign' and concurred with Behan and Bone (1977) that the most accurate term was 'hereditary chorea without dementia.' INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Chorea \- Delayed motor development \- Dysarthria may occur \- Gait abnormalities may occur \- Movements are exacerbated by anxiety \- Severity of symptoms peak in the second decade and do not progress \- No dementia \- Mildly decreased intelligence has been reported MISCELLANEOUS \- Variable phenotype \- Onset in childhood (usually before age 5 years) \- Allelic disorder to choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress ( 610978 ), which is a more severe disorder MOLECULAR BASIS \- Caused by mutation in the thyroid transcription factor-1 gene (TITF1, 600635.0001 ) ▲ 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	CHOREA, BENIGN HEREDITARY	c0393584	6,798	omim	https://www.omim.org/entry/118700	2019-09-22T16:43:21	{"doid": ["12859"], "mesh": ["D002819"], "omim": ["118700"], "orphanet": ["1429"], "synonyms": ["Alternative titles", "BCH", "HEREDITARY PROGRESSIVE CHOREA WITHOUT DEMENTIA"], "genereviews": ["NBK185066"]}
Disseminated peritoneal leiomyomatosis (DPL) is characterized by the proliferation of multiple benign smooth muscle cell-containing nodules in the peritoneal cavity. ## Epidemiology Fewer than 150 cases have been reported in the literature to date. ## Clinical description DPL manifests during adulthood and is predominantly found in women. Most patients are asymptomatic but clinical features such as abdominal and pelvic pain, rectal or vaginal bleeding and, more rarely, gastrointestinal disorders have been reported. Malignant transformation is rare and in a few cases, metastases have been found in the liver and lungs. ## Etiology Etiology is unknown but DPL seems to be a multifactorial disease with a genetic or hormonal component (high levels of estrogen and progesterone) leading to metaplasia of peritoneal mesenchymal cells. In some women, DPL seems to originate from proliferation of fragments of uterine leiomyoma in the abdominal cavity after laparoscopic surgery. ## Diagnostic methods Imaging techniques such as ultrasound examination are required for detection of DPL. Diagnosis is confirmed by biopsy of the nodules which reveals the presence of smooth-muscle cells with no atypia or necrosis, fibroblasts and myofibroblasts. ## Differential diagnosis Differential diagnosis includes parasitic leiomyoma, intravenous leiomyomatosis and other primitive or secondary peritoneal carcinomatoses. ## Management and treatment Depending on the extent of the disease, first-line treatment for DPL is surgical excision or cytoreductive surgery. Hormone intake (e.g. oral contraceptives) must be discontinued. Systemic chemotherapy (off-label use) has been suggested as a treatment option for the rare cases of unresectable or metastatic tumors. ## Prognosis Prognosis is usually good. Death has however been observed in some cases presenting unresectable or metastatic tumors. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Disseminated peritoneal leiomyomatosis	c0267785	6,799	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=71274	2021-01-23T18:35:50	{"gard": ["12843"], "icd-10": ["D20.1"], "synonyms": ["DPL", "Diffuse peritoneal leiomyomatosis", "LPD", "Leiomyomatosis peritonealis disseminate"]}

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