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## Clinical Features Among the children of a Pakistani couple related as first cousins, Woods et al. (1992) observed a distinctive nonprogressive disorder characterized by variable phalangeal anomalies, microcephaly, pre- and postnatal growth retardation, poor vision, dystonic movements, characteristic face, and severe mental retardation. Three children, 2 girls and a boy, were affected. The 2 girls had bilateral complete cutaneous syndactyly of the third and fourth fingers; the boy had bilateral single palmar creases. All 3 children showed dystonic tongue movements with tongue protrusion. One of the children had an asymptomatic ventricular septal defect and the same child developed a venous varix behind the right eye, causing proptosis and occasional subluxation of the eye, during the second year. She had bilateral optic atrophy. The second sister also showed optic atrophy; ophthalmoscopy was not performed in the brother. The facies were described as showing broad and hairy forehead, broad nasal bridge, prominent columella, relatively hypoplastic alae nasi, short philtrum, and a straight mouth with thin lips. Woods et al. (1992) concluded that the condition in their family was different from Filippi syndrome (272440) because the facial appearances were different and children with Filippi syndrome do not have localizing neurologic signs. For a similar craniofacial syndrome, see 251255. Inheritance Consanguinity in the family reported by Woods et al. (1992) suggested autosomal recessive inheritance of the disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	WOODS SYNDROME	c0796203	8,400	omim	https://www.omim.org/entry/615236	2019-09-22T15:52:45	{"omim": ["615236"], "orphanet": ["137658"], "synonyms": ["Woods-Crouchman-Huson syndrome"]}
Nishimura et al. (1998) reported the cases of 4 Japanese sibs (3 brothers and a sister) with an apparently previously unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate, and mental retardation. Most clinical manifestations were evident neonatally, but skeletal changes and cataracts became substantial in early childhood. Radiologic anomalies comprised coronal synostosis, mild epiphyseal dysplasia, particularly in the distal tibias, strikingly delayed patellar ossification, mild metaphyseal splaying, hypoplastic ilia with iliac flare, and platyspondyly with ovoid-shaped or posteriorly humped vertebral bodies. The nonconsanguineous parents were mildly mentally retarded, and sibs of both gender were equally affected; thus, autosomal recessive inheritance was considered likely by the authors. The cleft palate was associated with micrognathia. The skeletal changes gave rise to mild micromelia in infancy and short trunk with thoracolumbar kyphoscoliosis in late childhood. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	SPONDYLOEPIPHYSEAL DYSPLASIA WITH CORONAL CRANIOSYNOSTOSIS, CATARACTS, CLEFT PALATE, AND MENTAL RETARDATION	c1865134	8,401	omim	https://www.omim.org/entry/602611	2019-09-22T16:13:37	{"mesh": ["C566515"], "omim": ["602611"], "orphanet": ["163649"]}
A number sign (#) is used with this entry because of evidence that dyschromatosis universalis hereditaria-3 (DUH3) is caused by heterozygous mutation in the ABCB6 gene (605452) on chromosome 2q35. Description Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant genodermatosis characterized by irregularly shaped asymptomatic hyper- and hypopigmented macules that appear in infancy or early childhood and occur in a generalized distribution over the trunk, limbs, and sometimes the face. Involvement of the palms or soles is unusual. Abnormalities of hair and nails have been reported, and DUH may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications (summary by Zhang et al., 2013). For a discussion of genetic heterogeneity of DUH, see DUH1 (127500). Clinical Features Zhang et al. (2013) studied a large Chinese family with dyschromatosis universalis hereditaria in which 13 members over 5 generations were affected. The proband was a 9-year-old boy who had normal skin at birth. Hyperpigmented and hypopigmented macules appeared initially on his trunk at age 2 years, then gradually extended to involve his face, neck, and limbs. He had no pruritus or pain. Examination of the skin showed motley hyper- and hypopigmented macules over nearly the entire body. The lesions occurred in a symmetric pattern and were most prominent on the face, neck, trunk, and dorsa of hands and feet. His palms and soles, oral mucosa, hair, nails, and teeth were normal. Histopathologic examination of a skin lesion biopsy showed a pigmented basal layer of the epidermis, pigmentary incontinence in the papillary dermis, and some melanophages and lymphocytes in the upper dermis. None of the affected family members had skin cancer or ocular defects. Cui et al. (2013) studied a large Han Chinese family in which 24 individuals over 5 generations exhibited typical features of DUH without other systemic disease; in particular, none had skin cancer or ocular coloboma. The proband was a 33-year-old woman who had hypo- and hyperpigmented 3- to 7-mm macules scattered over her entire body, sparing the palms, soles, and mucous membranes. Hair, teeth, and nails were normal. The proband stated that the macules appeared within 2 months after birth, and became darker when exposed to sun. Skin biopsy of hypo- and hyperpigmented lesions revealed a normal number of melanocytes in the basal layer in both samples; however, whereas the content and distribution of mature melanosomes in hyperpigmented patient skin were similar to control skin, the content in hypopigmented skin was less than control, and many immature melanosomes were observed. Cui et al. (2013) suggested that DUH may represent a disorder of melanosome maturation rather than of melanocyte number. Mapping By linkage and haplotype analysis in a 5-generation Chinese family segregating autosomal dominant dyschromatosis universalis hereditaria in which mapping to the 2 known DUH loci had been excluded, Zhang et al. (2013) found linkage to the 2q33.1-q36.1 region, between D2S325 and D2S126. Multipoint analysis yielded a maximum lod score of 3.49 at D2S2382. By parametric multipoint linkage analysis in a large 5-generation Han Chinese family segregating autosomal dominant DUH, Cui et al. (2013) detected 2 regions of linkage: an approximately 17-Mbp interval at chromosome 2q35-q37.2 with a lod score of 4.68, and an approximately 0.3-Mbp interval at 6p22 with a lod score of 4.59. No annotated gene was identified in the 6p22 region. Molecular Genetics By whole-exome and Sanger sequencing in a 5-generation Chinese family segregating autosomal dominant dyschromatosis universalis hereditaria mapping to chromosome 2q33.1-q36.1, Zhang et al. (2013) identified a heterozygous missense mutation in the ABCB6 gene (L356P; 605452.0008) that segregated with disease in the family and was not found in 500 geographically matched controls. Screening of the ABCB6 gene in 6 sporadic DUH patients revealed heterozygosity for missense mutations (S170G, 605452.0009; G579E, 605452.0010) in 2 patients. Neither of the mutations in the sporadic patients was found in 400 controls or in the 1000 Genomes Project or UCSC Genome Browser databases. By exome sequencing in 3 affected members and 1 unaffected member of a 5-generation Han Chinese family with DUH mapping to chromosome 2q35-q37.2, Cui et al. (2013) identified heterozygous mutations in 4 candidate genes. Sanger sequencing excluded 3 of the genes; the remaining missense mutation in the ABCB6 gene (Q555K; 605452.0011) was present in 21 affected family members but absent in 14 unaffected relatives. Analysis of ABCB6 in 3 sporadic Chinese DUH patients also revealed a 1-bp deletion (c.459delC, g.776delC) in 1 of them. Neither mutation was found in 455 ethnically matched controls or in the dbSNP database. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Hyperpigmented macules of variable size and shape located in a symmetrical pattern primarily on face, neck, trunk, and dorsa of hands and feet Skin Histology \- Pigmented basal layer of epidermis \- Pigmentary incontinence in the papillary dermis \- Some melanophages and lymphocytes in the upper dermis MISCELLANEOUS \- Lesions appear in infancy or early childhood \- Hair, nails, and teeth are normal MOLECULAR BASIS \- Caused by mutation in the ATP-binding cassette, subfamily B, member 6 gene (ABCB6, 605452.0008 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 3	c1306229	8,402	omim	https://www.omim.org/entry/615402	2019-09-22T15:52:14	{"doid": ["0060304"], "omim": ["615402"], "orphanet": ["241"]}
HIV/AIDS in El Salvador has a less than 1 percent prevalence of the adult population reported to be HIV-positive, El Salvador and therefore there is a low-HIV-prevalence country, but the virus remains a significant threat in high-risk communities, such as commercial sex workers (CSWs) and men who have sex with men (MSM). ## Contents * 1 Prevalence * 2 National response * 3 See also * 4 References ## Prevalence[edit] Overall prevalence has increased since the first case was detected in 1984. Since that time, 18,282 HIV/AIDS cases have been reported in the country. Incidence appears to have declined since 2004, but there is a fear that because of the lack of an effective monitoring system, many HIV/AIDS cases are not reported (according to a UNAIDS May 2006 report, 40 to 50 percent of cases are under-reported). Heterosexual sex is the main route of HIV transmission in El Salvador, accounting for 79 percent of HIV cases in the country. The epidemic is predominantly in urban areas and is becoming increasingly feminized as the percent of women with HIV rises. Although prevalence is 3 percent among sex workers, it is as high as 16 percent in specific areas, such as Puerto de Acajutla. Prevalence is also high among MSM (17.8 percent, the highest in Central America). One study from 2002 reported by UNAIDS in 2007 demonstrated that infection levels among MSM in El Salvador were 22 times higher than among the general population. Moreover, stigma and discrimination (S&D) against MSM lead to hidden behaviors, and, as a result, there is probably considerable under-reporting of the epidemic among this group. The National AIDS Program (NAP) estimates that 51 percent of reported AIDS cases occur in the 25- to 34-year-old age group. Although estimates vary, about 85 percent of infections are sexually transmitted, of which 4 percent are cases of homosexual transmission and 3 percent bisexual transmission. According to the national sexually transmitted disease (STD) and HIV/AIDS program, the range for new HIV/AIDS infections per day is between 4.5 and 5.5 cases. Mortality due to AIDS represented the seventh-leading cause of death in hospitals for the population as a whole and the leading cause in the 20 to 59 age group. El Salvador contributes 18.4 percent of all cases in the Central America subregion and has the third-largest number of cases behind Honduras and Guatemala.[1] Factors that put El Salvador at risk of a larger epidemic include early initiation of sex, limited knowledge or practice of preventive practices among people engaging in high-risk behaviors, and the country’s large mobile population. The National Health Survey conducted in 2002 and 2003 indicated that 32 percent of females aged 15 to 19 were already sexually active. Knowledge about HIV/AIDS remains somewhat limited, as evidenced by one multicenter study in which 40 percent of MSM had false beliefs about the modes of transmission of HIV. Among sex workers, an estimated 90 percent do not use condoms with regular partners. Compounding these issues are S&D toward HIV-infected individuals and at-risk groups, which can deter people from getting tested and receiving adequate support if they have the disease.[1] ## National response[edit] Although the Government of El Salvador began initial HIV/AIDS prevention activities as early as 1988, stigma surrounding HIV persists. In 2001, El Salvador passed legislation protecting patients’ rights and guaranteeing access to treatment. El Salvador’s NAP was established in 1987, and it continues to work closely with various state ministries, civil society, the private sector, and nongovernmental organizations (NGOs). The country is now implementing its fourth HIV/AIDS strategic plan for 2005 to 2010. The new plan aims to improve the population’s knowledge about HIV/AIDS, strengthen preventive and protective measures, and extend coverage of HIV/AIDS services for vulnerable groups.[1] Following the worldwide Three Ones principles, El Salvador formed the National AIDS Commission (CONASIDA) to act as the country’s AIDS coordinating mechanism. One of the achievements of CONASIDA was the development of the 2005 National Policy for Comprehensive HIV Care. Important government activities include signing the Declaration of San Salvador for fighting AIDS in Central America and the Caribbean and the creation of an HIV/AIDS/sexually transmitted infection (STI) prevention program for mobile populations. The latter is particularly important because El Salvador is a corridor for migrants. El Salvador is also implementing the Regional HIV/STI Plan for the Health Sector 2006-2015 of the Pan American Health Organization.[1] Free HIV testing began in El Salvador in 1997, and in January 2002, the Ministry of Health (MOH) began to offer antiretroviral treatment (ART). By December 2006, 174 health facilities and two mobile clinics offered HIV testing for free, and 3,447 people were receiving ART without charge. In cooperation with other countries in the region, the Salvadoran Government negotiated with major pharmaceutical manufacturers and received price reductions on antiretroviral drugs. Currently, 39 percent of people infected with HIV who need ART receive it. In 2003, the country began a national program called Make the Decision to Wait to teach adolescents about safer sexual behaviors and to abstain from sex, and in 2005, two major campaigns were launched to combat stigma against people living with HIV/AIDS (PLWHA).[1] President Elías Antonio Saca González declared June 27, 2007, National HIV Testing Day. With the support of the U.S. Agency for International Development (USAID), the regional NGO Pan American Social Marketing Organization (PASMO) managed the event’s publicity campaign. The campaign resulted in 54,461 tests, exceeding the 40,000 target. Nearly three times the normal monthly average of tests done in all of 2006 were conducted on this one day. The Global Fund to Fight AIDS, Tuberculosis and Malaria is also currently supporting the MOH and the United Nations Development Program to develop a strategy for fighting HIV/AIDS in vulnerable populations to help poverty reduction. Despite these efforts, improved monitoring and surveillance and campaigns to raise awareness are needed.[1] ## See also[edit] * HIV/AIDS in North America ## References[edit] 1. ^ a b c d e f "Health Profile: El Salvador" Archived 2008-09-13 at the Wayback Machine. United States Agency for International Development (June 2008). Accessed September 7, 2008. This article incorporates text from this source, which is in the public domain. * v * t * e HIV/AIDS in North America Sovereign states * Antigua and Barbuda * Bahamas * Barbados * Belize * Canada * Costa Rica * Cuba * Dominica * Dominican Republic * El Salvador * Grenada * Guatemala * Haiti * Honduras * Jamaica * Mexico * Nicaragua * Panama * Saint Kitts and Nevis * Saint Lucia * Saint Vincent and the Grenadines * Trinidad and Tobago * United States Dependencies and other territories * Anguilla * Aruba * Bermuda * Bonaire * British Virgin Islands * Cayman Islands * Curaçao * Greenland * Guadeloupe * Martinique * Montserrat * Puerto Rico * Saint Barthélemy * Saint Martin * Saint Pierre and Miquelon * Saba * Sint Eustatius * Sint Maarten * Turks and Caicos Islands * United States Virgin Islands * 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 * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * 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	HIV/AIDS in El Salvador	None	8,403	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_El_Salvador	2021-01-18T18:43:49	{"wikidata": ["Q5629830"]}
A number sign (#) is used with this entry because primary ciliary dyskinesia-18 (CILD18) with or without situs inversus is caused by homozygous mutation in the HEATR2 gene (DNAAF5; 614864) on chromosome 7p22. For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400. Description Primary ciliary dyskinesia-18 is an autosomal recessive disorder characterized by early infantile onset of recurrent sinopulmonary infections due to ciliary dysfunction and impaired airway clearance. Males are infertile and about half of patients have situs inversus. Electron microscopy of cilia shows a defect of the outer and inner dynein arms and impaired ciliary function (summary by Horani et al., 2012). Clinical Features Lie et al. (2010) reported 9 Amish patients with primary ciliary dyskinesia. Eight of the 9 had neonatal respiratory distress and all had persistent nasal congestion and coughing. Other clinical findings included chronic rhinosinusitis and pneumonia. Only 1 had recurrent otitis media. Five of the 9 patients had laterality defects. Spirometry showed decreased forced vital capacity, and nasal nitric oxide measurements were extremely low. Ciliary ultrastructural analysis showed absent outer dynein arms. Horani et al. (2012) provided follow-up of the 9 Amish patients reported by Lie et al. (2010). Affected individuals presented in early infancy with recurrent sinopulmonary infections resulting in progressive respiratory distress. About half of patients had situs inversus, and males were infertile. Electron microscopy showed absent outer dynein arms and most outer doublets lacked inner dynein arms, suggesting a combined defect. Cultured nasal epithelial cells from a patient showed markedly lower levels of HEATR2 compared to controls, and videomicroscopy showed that patient nasal epithelial cells had virtually immotile cilia. Molecular Genetics In 9 affected members of an Amish community with primary ciliary dyskinesia-18 with or without situs inversus, Horani et al. (2012) identified a homozygous mutation in the HEATR2 gene (L795P; 614864.0001). The mutation was initially found by exome sequencing of 2 affected children. Using a targeted exome panel including 26 primary ciliary dyskinesia-associated genes and 284 selected candidate genes in a study of 74 Dutch CILD patients, Paff et al. (2018) identified 2 sibs (PCD-13147 and PCD-3148) with compound heterozygous mutations in the DNAAF5 gene (614864.0002 and 614864.0003). Clinical features of the sibs were not reported. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Sinusitis, recurrent Ears \- Otitis media, recurrent Nose \- Rhinitis, recurrent RESPIRATORY \- Respiratory insufficiency due to defective ciliary clearance \- Respiratory infections, recurrent Airways \- Chronic bronchitis ABDOMEN \- Situs inversus (in about half of patients) GENITOURINARY Internal Genitalia (Male) \- Infertility due to immotile sperm LABORATORY ABNORMALITIES \- Electron microscopy of patient respiratory cells shows absent outer dynein arms \- Variable defects of inner dynein arms \- Severely impaired ciliary motility MISCELLANEOUS \- Onset in infancy or neonatal period \- Prevalent among the Amish MOLECULAR BASIS \- Caused by mutation in the heat repeat-containing protein-2 gene (HEATR2, 614864.0001 ) ▲ 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	CILIARY DYSKINESIA, PRIMARY, 18	c3543825	8,404	omim	https://www.omim.org/entry/614874	2019-09-22T15:53:54	{"doid": ["0110604"], "omim": ["614874", "244400"], "orphanet": ["244"], "synonyms": ["Alternative titles", "PCD", "CILIARY DYSKINESIA, PRIMARY, 18, WITH OR WITHOUT SITUS INVERSUS"], "genereviews": ["NBK1122"]}
Winchester syndrome is a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. Winchester syndrome used to be considered part of a related condition now called multicentric osteolysis, nodulosis, and arthropathy (MONA). However, because Winchester syndrome and MONA are caused by mutations in different genes, they are now thought to be separate disorders. In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature. Some people with Winchester syndrome have skin abnormalities including patches of dark, thick, and leathery skin. Other features of the condition can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as "coarse." ## Frequency Winchester syndrome is a rare condition whose prevalence is unknown. It has been reported in only a few individuals worldwide. ## Causes Winchester syndrome is caused by mutations in the MMP14 gene (also known as MT1-MMP). This gene provides instructions for making a protein called matrix metallopeptidase 14, which is found on the surface of cells. Matrix metallopeptidase 14 normally helps modify and break down various components of the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. These changes influence many cell activities and functions, including promoting cell growth and stimulating cell movement (migration). Matrix metallopeptidase 14 also turns on (activates) a protein called matrix metallopeptidase 2. The activity of matrix metallopeptidase 2 appears to be important for a variety of body functions, including bone remodeling, which is a normal process in which old bone is broken down and new bone is created to replace it. Mutations in the MMP14 gene alter matrix metallopeptidase 14 so that less of the enzyme is able to reach the cell surface. As a result, not enough of the enzyme is available to break down components of the extracellular matrix and activate matrix metallopeptidase 2. It is unclear how a shortage of this enzyme leads to the signs and symptoms of Winchester syndrome. It is possible that a loss of matrix metallopeptidase 2 activation somehow disrupts the balance of new bone creation and the breakdown of existing bone during bone remodeling, causing a progressive loss of bone tissue. How a reduced amount of matrix metallopeptidase 14 leads to the other features of Winchester syndrome is unknown. ### Learn more about the gene associated with Winchester syndrome * MMP14 ## 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	Winchester syndrome	c0432289	8,405	medlineplus	https://medlineplus.gov/genetics/condition/winchester-syndrome/	2021-01-27T08:24:38	{"gard": ["7894"], "mesh": ["C536709"], "omim": ["277950"], "synonyms": []}
This page will be copied to Wiktionary using the transwiki process. The information in this article appears to be suited for inclusion in a dictionary, and this article's topic meets Wiktionary's criteria for inclusion, has not been transwikied, and is not already represented. It will be copied into Wiktionary's transwiki space from which it can be formatted appropriately. If this page does not meet the criteria, please remove this notice. Otherwise, the notice will be automatically removed after transwiki completes. If this template is placed on a glossary article, it should be removed immediately after the transwiki is completed, and not replaced with {{TWCleanup}}, as there is no consensus for the deletion of glossary articles. Aquaphilia (literally "water lover" from the Latin aqua and Greek φιλειν (philein)) is a form of sexual fetishism that involves images of people swimming or posing underwater, and sexual activity in or under water.[1][2][3][4][5] ## References[edit] 1. ^ Ramsland, Katherine M.; McGrain, Patrick Norman (2010). Inside the Minds of Sexual Predators. ABC-CLIO. pp. 61–62. ISBN 978-0-313-37960-4. 2. ^ Ågmo, Anders (2007). Functional and dysfunctional sexual behavior: a synthesis of neuroscience and comparative psychology. Academic Press. p. 454. ISBN 978-0-12-370590-7. 3. ^ Swami, Viren; Furnham, Adrian (2008). The psychology of physical attraction. Routledge. p. 134. ISBN 978-0-415-42250-5. 4. ^ Sivaloganathan, S. (1984). "Aqua-eroticum – A case of auto-erotic drowning. Medicine, Science and the Law, 24, 300-302". Medicine, Science and the Law. 24 (4): 300–302. doi:10.1177/002580248402400413. PMID 6503665. 5. ^ A., S, Sauvageau, Racette (2006). "Aqua-eroticum: An unusual autoerotic fatality in a lake involving a home-made diving apparatus". Journal of Forensic Sciences. 51 (1): 137–139. doi:10.1111/j.1556-4029.2005.00031.x. PMID 16423240. * v * t * e Paraphilias List * Abasiophilia * Acrotomophilia * Agalmatophilia * Algolagnia * Apotemnophilia * Autassassinophilia * Biastophilia * Capnolagnia * Chremastistophilia * Chronophilia * Coprophagia * Coprophilia * Crurophilia * Crush fetish * Dacryphilia * Dendrophilia * Emetophilia * Eproctophilia * Erotic asphyxiation * Erotic hypnosis * Erotophonophilia * Exhibitionism * Formicophilia * Frotteurism * Gerontophilia * Homeovestism * Hybristophilia * Infantophilia * Kleptolagnia * Klismaphilia * Lactaphilia * Macrophilia * Masochism * Mechanophilia * Microphilia * Narratophilia * Nasophilia * Necrophilia * Object sexuality * Odaxelagnia * Olfactophilia * Omorashi * Paraphilic infantilism * Partialism * Pedophilia * Podophilia * Plushophilia * Pyrophilia * Sadism * Salirophilia * Scopophilia * Somnophilia * Sthenolagnia * Tamakeri * Telephone scatologia * Transvestic fetishism * Trichophilia * Troilism * Urolagnia * Urophagia * Vorarephilia * Voyeurism * Zoophilia * Zoosadism See also * Other specified paraphilic disorder * Erotic target location error * Courtship disorder * Polymorphous perversity * Sexual fetishism * Human sexual activity * Perversion * Sexology * Book * Category * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Aquaphilia (fetish)	None	8,406	wikipedia	https://en.wikipedia.org/wiki/Aquaphilia_(fetish)	2021-01-18T19:05:58	{"wikidata": ["Q2859168"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) Granular myringitis Other namesGM SpecialtyOtorhinolaryngology Granular myringitis is a long term condition in which there is inflammation of the tympanic membrane in the ear and formation of granulation tissue within the tympanic membrane.[1] It is a type of otitis externa.[2] Without treatment it can lead to narrowing of the ear canal.[1] A number of treatment options exist including putting vinegar in the ear, using antibiotic drops, and surgery.[1] ## References[edit] 1. ^ a b c Neilson, LJ; Hussain, SS (January 2008). "Management of granular myringitis: a systematic review". The Journal of Laryngology and Otology. 122 (1): 3–10. doi:10.1017/S0022215107008924. PMID 17592657. 2. ^ Alper, Cuneyt M. (2004). Advanced Therapy of Otitis Media. PMPH-USA. p. 49. ISBN 9781550092011. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Granular myringitis	c0395848	8,407	wikipedia	https://en.wikipedia.org/wiki/Granular_myringitis	2021-01-18T18:50:37	{"umls": ["C0395848"], "wikidata": ["Q30314113"]}
## Clinical Features Perry et al. (1967) described 2 unrelated children with a progressive neurologic disorder characterized by severe mental defect and myoclonic seizures. Both excreted carnosine (see 609064) in the urine, even when all source of the dipeptide was excluded from the diet. Both had unusually high concentrations of homocarnosine in the cerebrospinal fluid. When fed a dietary source of anserine, the children excreted anserine in the urine but not its hydrolysis product, methylhistidine. Perry et al. (1967) suggested that one, and perhaps both, had a defect in carnosinase (see 609064) activity. One child, of German and Dutch ancestry, was the offspring of first-cousin parents. The other child was of Chinese ancestry. Perry et al. (1968) found that the enzyme of normal human serum that hydrolyzes the dipeptides carnosine and anserine into their constituent amino acids was almost absent in the 2 patients. No comment was made on the level of enzyme in the parents. Carnosine is a dipeptide of alanine and histidine. Scriver et al. (1968) commented on the possible relationship of the mental retardation that occurs with hyper-beta-carnosinemia and phenylketonuria (261600). In the case of the affected Dutch child reported by Heeswijk et al. (1969), the parents were consanguineous and showed decreased serum carnosinase activity. Terplan and Cares (1972) reported another family with this rare anomaly. Two brothers, aged 7 and 4, had died. A 6-year-old sister was normal but had chemical changes. The parents have low carnosinase activity. Autopsy on the older boy showed severe axonal degeneration, numerous 'spheroids' in the gray matter, demyelinization, fibrosis, and loss of Purkinje fibers. Willi et al. (1997) reported the case of a 30-month-old girl with hypotonia, developmental delay, and tremor who, although consuming nominal quantities of meat, excreted large amounts of carnosine and anserine. A strict meat-free diet ameliorated, but did not eliminate, these abnormalities. Serum carnosinase activity was found to be extremely low. Cytogenetics Willi et al. (1997) identified a terminal deletion of chromosome 18 with a breakpoint at q21.3 in their patient with carnosinase deficiency. Inheritance Willi et al. (1997) found that neither parent of their patient with carnosinase deficiency exhibited the chromosome 18 deletion, suggesting it was generated de novo in the patient or in a parental germ cell. Molecular studies showed that the patient's paternal chromosome 18 was deleted. Urinary carnosine excretion and serum carnosinase activity were normal in the patient's father. The mother, on the other hand, had low carnosinase activity. The patient's brother exhibited moderate hypercarnosinuria and intermediate enzyme activity, consistent with the carrier state. Cumulatively, these findings suggested to Willi et al. (1997) that the locus for carnosinase resides on the distal long arm of chromosome 18, and they were considered consistent with an unusual mechanism for the inheritance of this typically autosomal recessive condition. Willi et al. (1997) concluded that the patient was probably hemizygous for the defect, having received the deficiency allele from her mother and, by virtue of the chromosomal deletion, no allele from her father. Neuro \- Mental retardation \- Myoclonic seizures Lab \- Carosinase deficiency \- Carnosinemia \- Carnosinuria 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	CARNOSINEMIA	c0268632	8,408	omim	https://www.omim.org/entry/212200	2019-09-22T16:30:04	{"mesh": ["C535328"], "omim": ["212200"], "orphanet": ["1361"], "synonyms": ["Alternative titles", "CARNOSINASE DEFICIENCY"]}
IgG4-related prostatitis Low power view of IgG4-related prostatitis. The prostatic stroma shows a dense inflammatory infiltrate and fibrosis (H&E, 100x) SpecialtyUrology/Immunology IgG4-related prostatitis is prostate involvement in men with IgG4-related disease (IgG4-RD), which is an emerging fibroinflammatory disease entity which is characterised (i) by a tendency to mass forming lesions in multiple sites of the body and (ii) by usually a prompt response to steroid therapy.[1][2] Men with IgG4-related prostatitis may also present with manifestations of IgG4-RD at other sites anywhere in the body; involvement of different areas of the body can occur either at the same time (synchronously) or at different periods of time (metachronously).[3] ## Contents * 1 Symptoms * 2 Histology * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Symptoms[edit] Several case studies on IgG4-related prostatitis have been reported. Patients have been noted to commonly present with lower urinary tract symptoms such as dysuria, pollakisuria, urinary urgency, and a feeling of incomplete emptying.[4][5] The clinical presentation is similar to that in benign prostatic hyperplasia or chronic prostatitis, although pain, as occurs in CP/CPPS, does not usually appear to be significant. ## Histology[edit] The diagnosis of IgG4-related prostatitis could be made from histological examination if prostate biopsy or surgery has been performed.[6] The hallmark histopathological features of established IgG4-related disease are storiform fibrosis, a dense lymphoplasmacytic (lymphocytes and plasma cells) infiltrate rich in IgG4-positive plasma cells, and obliterative phlebitis.[7] However, identification depends on whether or not urologists and pathologists are aware of IgG4-related prostatitis/disease, as special immunostaining is required to identify the characteristic IgG4-positive plasma cells infiltration in prostatic tissue.[3] ## Diagnosis[edit] Men with IgG4-related prostatitis may have similar findings to those that are frequently, but not always, seen in other organ manifestations of IgG4-related disease, such as elevated blood levels of IgG4, IgE and eosinophils. FDG-PET scans have been reported to be useful as a diagnostic modality for detecting IgG4-related prostatitis in men with IgG4-RD.[6][8] ## Treatment[edit] IgG4-related disease responds well, and often dramatically, to glucocorticoid therapy, provided that advanced fibrotic lesions have not resulted in irreversible damage, and this has included resolution of radiologic findings.[1] Men given glucocorticoids to treat IgG4-related disease at other anatomical sites sometimes report relief of their lower urinary tract symptoms, suggesting that IgG4-related prostatitis may be underdiagnosed.[6] Cases are however likely to get misdiagnosed as benign prostatic hyperplasia and to get treated alternatively with medications such as alpha blockers. The efficacy of alpha blockers in IgG4-related prostatitis remains unclear.[3] ## See also[edit] * IgG4-related disease ## References[edit] 1. ^ a b Rodolfo Montironi; Marina Scarpelli; Liang Cheng; Antonio Lopez-Beltran; Maurizio Burattini; Ziya Kirkali; Francesco Montorsi (December 2013). "Immunoglobulin G4-related disease in genitourinary organs: an emerging fibroinflammatory entity often misdiagnosed preoperatively as cancer". European Urology. 64 (1): 865–872. doi:10.1016/j.eururo.2012.11.056. PMID 23266239. 2. ^ John H. Stone; Arezou Khosroshahi; Vikram Deshpande; John K. C. Chan; J. Godfrey Heathcote; Rob Aalberse; Atsushi Azumi; Donald B. Bloch; William R. Brugge; Mollie N. Carruthers; Wah Cheuk; Lynn Cornell; Carlos Fernandez-Del Castillo; Judith A. Ferry; David Forcione; Günter Klöppe; Daniel L. Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Yasufumi Masaki; Kenji Notohara; Kazuichi Okazaki; Ji Kon Ryu; Takako Saeki; Dushyant Sahani; Yasuharu Sato; Thomas Smyrk; James R. Stone; Masayuki Takahira; Hisanori Umehara; George Webster; Motohisa Yamamoto; Eunhee Yi; Tadashi Yoshino; Giuseppe Zamboni; Yoh Zen; Suresh Chari (October 2012). "Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations". Arthritis & Rheumatism. 64 (10): 3061–3067. doi:10.1002/art.34593. PMC 5963880. PMID 22736240. 3. ^ a b c Noboru Hara; Makoto Kawaguchi; Keisuke Takeda; Yoh Zen (28 Nov 2014). "Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis". World Journal of Gastroenterology. 20 (44): 16550–16558. doi:10.3748/wjg.v20.i44.16550. PMC 4248198. PMID 25469023. 4. ^ Yukihiro Yoshimura; Shin-ichi Takeda; Yasuhiko Ieki; Eisuke Takazakura; Hisashi Koizumi; Kiyoshi Takagawa (1 Sep 2006). "IgG4-associated prostatitis complicating autoimmune pancreatitis". Internal Medicine. 45 (15): 897–901. doi:10.2169/internalmedicine.45.1752. PMID 16946571. 5. ^ Isao Nishimori; Takuhiro Kohsaki; Saburo Onishi; Taro Shuin; Shino Kohsaki; Yasuhiro Ogawa; Manabu Matsumoto; Makoto Hiroi; Hideaki Hamano; Shigeyuki Kawa (17 Dec 2007). "IgG4-related autoimmune prostatitis: two cases with or without autoimmune pancreatitis". Internal Medicine. 46 (24): 1983–1989. doi:10.2169/internalmedicine.46.0452. PMID 18084121. 6. ^ a b c Mohamad Zaidan; Julien Adam; Pascale Cervera-Pierot; Dominique Joly (Dec 2011). "The Case \| A 69-year-old man with a 10-year history of idiopathic retroperitoneal fibrosis". Kidney International. 80 (12): 1379–1380. doi:10.1038/ki.2011.357. PMID 22126986. 7. ^ John H. Stone; Yoh Zen; Vikram Deshpande (February 2012). "IgG4-Related Disease". The New England Journal of Medicine. 366 (6): 539–51. doi:10.1056/NEJMra1104650. PMID 22316447. 8. ^ Hiroyuki Takahashi; Hiroto Tsuboi; Hiroshi Ogishima; Masahiro Yokosawa; Hidenori Takahashi; Mizuki Yagishita; Saori Abe; Shinya Hagiwara; Hiromitsu Asashima; Tomoya Hirota; Naoto Umeda; Yuya Kondo; Takeshi Suzuki; Isao Matsumoto; Takayuki Sumida (June 2015). "[18F]fluorodeoxyglucose positron emission tomography/computed tomography can reveal subclinical prostatitis in a patient with IgG4-related disease". Rheumatology. 54 (6): 1113. doi:10.1093/rheumatology/kev099. PMID 25863043. ## External links[edit] Classification D * ICD-10: N41.8 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	IgG4-related prostatitis	None	8,409	wikipedia	https://en.wikipedia.org/wiki/IgG4-related_prostatitis	2021-01-18T18:33:30	{"wikidata": ["Q25091337"]}
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by distal weakness primarily and predominantly occurring in the upper limbs and tendon reflexes absent or reduced in the arms and decreased in the legs. Progression is slow. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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 Charcot-Marie-Tooth disease type 2D	c1832274	8,410	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99938	2021-01-23T17:30:16	{"gard": ["1251"], "mesh": ["C537993"], "omim": ["601472"], "umls": ["C1832274"], "icd-10": ["G60.0"], "synonyms": ["CMT2D"]}
## Description Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002). For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750. For a discussion of autoimmunity, see 109100. Mapping A susceptibility to celiac disease (CELIAC6) and to autoimmunity (AIS5) has been mapped to the 4q27 region, within a linkage disequilibrium (LD) block encompassing the KIAA1109 (611565), TENR (ADAD1), IL2 (147680), and IL21 (605384) genes. ### Celiac Disease Susceptibility In a genomewide study to identify predisposing factors in celiac disease (CD), Van Heel et al. (2007) identified genetic variation in a linkage disequilibrium (LD) block encompassing the KIAA1109, TENR (ADAD1), IL2, and IL21 genes as a susceptibility factor for CD. Using 310,605 genomewide SNPs in 778 individuals from the United Kingdom (UK) with CD and 1,422 UK controls, they achieved the most significant linkage outside the HLA region (see 146880) at rs13119723 (P = 2.0 x 10(-7)) in the KIAA1109 gene (611565) on chromosome 4q27. The association was confirmed in 2 further collections, 508 Dutch CD patients and 929 controls and 483 Irish CD patients and 560 controls (metaanalysis P = 4.8 x 10(-11)). The strongest association overall was achieved at rs6822844 (metaanalysis P = 1.3 x 10(-14)) located 25 kb 5-prime of the IL21 gene. Van Heel et al. (2007) concluded that genetic variation at chromosome 4q27, in an LD block spanning the KIAA1109, TENR (ADAD1), IL2, and IL21 genes, predisposes to CD. The authors stated that because of extensive LD the causal variant associated with CD in the 4q27 region could not be determined. In a separate replication sample comprising 1,643 celiac cases and 3,406 controls from 3 independent European celiac disease collections, Hunt et al. (2008) found that rs6822844 showed a strong association with celiac disease (P overall = 2.82 x 10(-13)). In an Italian cohort involving 538 patients with celiac disease and 593 healthy controls, Romanos et al. (2009) confirmed association at rs6822844 (p = 0.0253). ### Autoimmune Disease Susceptibility Zhernakova et al. (2007) hypothesized that the KIAA1109/TENR/IL2/IL21 CD susceptibility region reported by van Heel et al. (2007) may represent a general risk locus for multiple autoimmune diseases. They tested rs6822844 for association with disease in 350 type 1 diabetes (T1D; see 222100)-affected and 1,047 rheumatoid arthritis (RA; 180300)-affected Dutch patients and 929 controls. A decrease in the frequency of the T allele was observed in both T1D (12.7%) and RA (14.1%) groups compared with controls (18.5%). The association was significant in both T1D (P = 0.0006, OR = 0.64, 95% CI 0.50-0.83) and RA (P = 0.0002, OR = 0.72, 95% CI 0.61-0.86). The Wellcome Trust Case Control Consortium (2007) had reported a locus on 4q27 containing the KIAA1109/TENR/IL2/IL21 region in a genomewide association study of T1D; the follow-up replication study of Todd et al. (2007) indicated moderate association of SNPs in the KIAA1109/TENR/IL2/IL21 region with T1D. Zhernakova et al. (2007) found that the most T1D-associated SNP in the Wellcome Trust Case Control Consortium (2007) study, rs3136534, was in complete LD with one of the SNPs identified by van Heel et al. (2007), rs4505848. Zhernakova et al. (2007) found a slight increase in the G allele of rs4505848 in patients with T1D and RA compared with controls. Overall, Zhernakova et al. (2007) found that the T allele of the rs6822844 SNP was a perfect proxy for a haplotype, AATGG, that showed consistent association with the majority of the decreased risk for CD, T1D, and RA and was therefore the best proxy for the disease variant, which could not be determined because of extensive linkage disequilibrium. ### Psoriatic Arthritis Susceptibility In a genomewide association study of 223 U.S. patients with psoriasis, including 91 with psoriatic arthritis, and 519 European controls, followed by replication in a U.K. cohort of 576 patients with psoriatic arthritis and 480 controls, Liu et al. (2008) found evidence for a locus on chromosome 4q27, which harbors the IL2 (147680) and IL21 (605384) genes. The most significant association in the discovery set was with rs13151961 (p = 4 x 10(-5)); rs13151961, rs7684187, and rs6822844 showed association with psoriatic arthritis in the replication cohort (p values from 0.001 to 0.008). Liu et al. (2008) noted that this region overlaps with the PSORS3 locus (601454) and the CELIAC6 locus. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	CELIAC DISEASE, SUSCEPTIBILITY TO, 6	c1969030	8,411	omim	https://www.omim.org/entry/611598	2019-09-22T16:03:05	{"omim": ["611598"], "synonyms": ["Alternative titles", "GLUTEN-SENSITIVE ENTEROPATHY, SUSCEPTIBILITY TO, 6"]}
For a phenotypic description and discussion of genetic heterogeneity of migraine headaches, see MGR1 (157300). Mapping By linkage studies in Australian pedigrees, Lea et al. (2002) pursued the possibility of a gene for susceptibility to migraine with (MA) or without (MO) aura in the 1q31 region. Initial multipoint analysis provided strong evidence for linkage of 1q31 markers to typical migraine in a large multigenerational pedigree. Subsequent analysis of an independent sample of 82 affected pedigrees added support to the initial findings, with a maximum lod score of 1.24 (maximum allele sharing lod score of 3.36 at D1S2782). Using the independent sample of 82 pedigrees, they also performed a family-based association test. The results of this analysis indicated distortion of allele transmission at marker D1S249 in these pedigrees. ### Familial Hemiplegic Migraine-4 Familial hemiplegic migraine (FHM) is a subtype of autosomal dominant migraine with aura (MA). For a phenotypic description and discussion of genetic heterogeneity of FHM, see 141500. Gardner et al. (1997) implicated a broad 44-cM region on 1q31 as an additional familial hemiplegic migraine susceptibility locus by family linkage studies. This region is approximately 30 cM telomeric to the region reported by Ducros et al. (1997) for FHM2 (602481). It was not clear whether there is a single locus or 2 distinct loci on the chromosome 1q region. The neuronal calcium channel alpha-1 subunit gene, CACNA1E (601013), has been mapped to the region 1q25-q31. This gene has a sequence highly similar to that of CACNA1A (601011), which is mutated in FHM1 (141500), and is therefore an excellent candidate for a cause of another form of familial hemiplegic migraine and possibly also for typical migraine. INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Nausea \- Vomiting NEUROLOGIC Central Nervous System \- Migraine with aura \- Migraine without aura \- Photophobia \- Phonophobia \- Hemiparesis \- Hemiplegia \- Hemisensory attacks MISCELLANEOUS \- May be triggered by minor head trauma \- Genetic heterogeneity, see FHM1, ( 141500 ) and MGR1, ( 157300 ) ▲ 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	MIGRAINE WITH OR WITHOUT AURA, SUSCEPTIBILITY TO, 6	c1843765	8,412	omim	https://www.omim.org/entry/607516	2019-09-22T16:09:03	{"omim": ["607516"], "orphanet": ["569"], "synonyms": ["MGR6", "Alternative titles"]}
Daneman et al. (1985) reported 3 cases, 2 of them in a brother and sister, of children with multinodular goiter, cystic kidney disease, and digital anomalies (bilateral digitalized thumbs and preaxial polydactyly of the feet). (The 'digitalized' thumb was presumably triphalangeal; see 174500.) In the family with affected sibs, the mother, maternal grandmother, and 2 maternal aunts had digitalized thumbs but no known abnormality of thyroid or kidneys. In the third case, in a 14-year-old boy who presented with goiter, there was postaxial polydactyly of the right hand, and right nephrectomy for 'unilateral polycystic kidney disease' was performed at 2 months of age. A 12-year-old brother had postaxial polydactyly of the left hand and a 19-year-old sister had goiter. This may be a syndrome of variable expression and incomplete penetrance inherited as a dominant. GU \- Cystic kidney disease Inheritance \- Autosomal dominant with variable expression and incomplete penetrance Neck \- Multinodular goiter Limbs \- Bilateral digitalized thumbs \- Preaxial polydactyly of feet \- Postaxial polydactyly of hand ▲ 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	GOITER, MULTINODULAR, CYSTIC RENAL DISEASE, AND DIGITAL ANOMALIES	c1841853	8,413	omim	https://www.omim.org/entry/138790	2019-09-22T16:40:37	{"mesh": ["C535986"], "omim": ["138790"], "orphanet": ["2091"], "synonyms": ["Alternative titles", "MULTINODULAR GOITER/CYSTIC RENAL DISEASE/DIGITAL ANOMALIES", "MNG/CRD/DA"]}
## Description The term 'brachyolmia' was coined to designate a bone dysplasia characterized clinically by short trunk dwarfism and radiographically by generalized platyspondyly without significant long bone abnormalities. The Maroteaux type of brachyolmia is an autosomal recessive form in which there is rounding of the anterior and posterior vertebral borders, with less elongation on lateral view and less lateral extension on anteroposterior view than is seen in the Hobaek type of brachyolmia (271530). Maroteaux brachyolmia may also be associated with precocious calcification of the falx cerebri, and minor facial anomalies (summary by Shohat et al., 1989). For a discussion of genetic heterogeneity of brachyolmia, see 271530. Clinical Features Shohat et al. (1989) reported 4 families with the Maroteaux type of brachyolmia, including 2 brothers whose Israeli parents were first cousins, suggesting autosomal recessive inheritance. Birth length was below normal in 1 patient, and in the other patients short stature was usually evident during the first 2 years of life. After age 2 years, growth curves were 4 to 5 standard deviations below the mean but parallel to the norm. The lower segment was measured in 2 patients and the upper/lower segment ratio was normal. Arm spans were measured in 3 children and found to be longer than corresponding heights in 2 patients. Psychomotor development was normal in all but 1 patient who had mild mental retardation. Other physical findings included wide-spaced nipples, clinodactyly, hypoplastic nails, pectus excavatum, and hyperlaxity of joints. Precocious ossification of the falx cerebri was seen in 1 patient. Metaphyseal irregularity as well as small epiphyses of the proximal femurs were noted in 1 child, but none of the other patients had radiologic changes in the long bones. Facial appearance was normal. Inheritance Consanguinity and occurrence in sibs support autosomal recessive inheritance of this disorder (Shohat et al., 1989). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature SKELETAL Spine \- Platyspondyly \- Vertebral borders rounded anteriorly and posteriorly \- Vertebral borders less elongated on lateral view than in Hobaek type ( 271530 ) \- Vertebral borders show less lateral extension on anteroposterior view than in Hobaek type ( 271530 ) NEUROLOGIC Central Nervous System \- Falx cerebri, precocious calcification of ▲ 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	BRACHYOLMIA TYPE 2	c3159322	8,414	omim	https://www.omim.org/entry/613678	2019-09-22T15:57:52	{"doid": ["0050690"], "mesh": ["C563218"], "omim": ["613678"], "orphanet": ["93302"], "synonyms": ["Alternative titles", "BRACHYOLMIA, MAROTEAUX TYPE"]}
## Clinical Features Anzai et al. (1996) described a Japanese family in which 3 boys in 3 separate sibships related as first cousins through the mother in each case had congenital alopecia or marked hypotrichosis. None of the 3 mothers had alopecia, but the maternal grandfather of the 3 affected boys had alopecia from birth. The eyebrows and eyelashes in all these patients were normal. Apart from the congenital alopecia of the scalp, there were no abnormalities of the skin, nails, or teeth. Sweating, heat tolerance, growth, and development were all normal. Skin biopsy from the scalp of 1 boy revealed a decreased number of atrophic hair follicles but normal eccrine glands. Hair \- Congenital scalp alopecia \- Marked hypotrichosis \- Normal eyebrows and eyelashes Inheritance \- X-linked ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	ALOPECIA, CONGENITAL	c0263504	8,415	omim	https://www.omim.org/entry/300042	2019-09-22T16:20:57	{"omim": ["300042"], "icd-10": ["Q84.0"], "orphanet": ["700"]}
COG5-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case to date by moderate mental retardation with slow and inarticulate speech, truncal ataxia, and mild hypotonia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	COG5-CDG	c3150876	8,416	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=263487	2021-01-23T18:53:02	{"gard": ["12348"], "omim": ["613612"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type IIi", "CDG-IIi", "CDG2I", "Carbohydrate deficient glycoprotein syndrome type IIi", "Congenital disorder of glycosylation type 2i", "Congenital disorder of glycosylation type IIi"]}
Asphyxiating thoracic dysplasia Other namesJeune syndrome, asphyxiating thoracic chondrodystrophy, infantile thoracic dystrophy CXR of a newborn with asphyxiating thoracic dysplasia. Note the short ribs. SpecialtyMedical genetics SymptomsNarrow chest, short ribs, shortened bones of the arms and legs, unusually shaped pelvis, and extra fingers and/or toes TreatmentMechanical ventilation, endotracheal suctioning, postural drainage, Vertical expandable prosthetic titanium rib (VEPTR), Lateral thoracic expansion, or other chest reconstruction surgeries. Frequency1 in 100,000 to 130,000 DeathsMortality of affected: 60-70% Asphyxiating thoracic dysplasia (ATD), also known as Jeune syndrome, is a rare inherited bone growth disorder that primarily affects the thoracic region. It was first described in 1955 by the French pediatrician Mathis Jeune.[1] Common signs and symptoms can include a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (polydactyly). The restricted growth and expansion of the lungs caused by this disorder results in life-threatening breathing difficulties. People who are affected with this disorder live short lives either only into infancy or early childhood. If they live beyond childhood, breathing problems can improve with age, but there is a possibility of developing severe kidney or heart problems. Several mutations in different genes such as IFT80, DYNC2H1, WDR19, IFT140 and TTC21B have been identified in some families with the condition as possible causes of the disorder. Treatment is based on the signs and symptoms present in each person.[2] ## Contents * 1 Types * 2 Signs and symptoms * 3 Diagnosis * 4 Treatment * 4.1 Medical care * 4.2 Surgical care * 5 References * 6 External links ## Types[edit] Type OMIM Gene Locus ATD1 208500 ? 15q13 ATD2 611263 IFT80 3q ATD3 613091 DYNC2H1 11q ## Signs and symptoms[edit] Lateral CXR of the same person above Jeune syndrome is a rare genetic disorder that affects the way a child’s cartilage and bones develop. It begins before the child is born and primarily affects the child's rib cage, pelvis, arms and legs.[3] Usually, problems with the rib cage cause the most serious health problems for children with Jeune syndrome. Their rib cages (thorax) are smaller and narrower than usual, which inhibits the child's lungs from developing fully or expanding when they inhale. The child may breathe rapidly and shallowly. They may have trouble breathing when they have an upper or lower respiratory infection, like pneumonia. Breathing trouble can range from mild to severe. In some children, it is not noticeable, aside from fast breathing; however, in others, breathing problems can be fatal. About 60% to 70% of children with this condition die from respiratory failure as babies or young children. Children with Jeune syndrome who survive often develop problems with their kidneys, and over time they may experience kidney failure. As a result, few children with Jeune syndrome live into their teen years. Children with Jeune syndrome have a form of dwarfism. They are short in stature, and their arms and legs are shorter than most people’s.[4] ## Diagnosis[edit] Jeune syndrome is a rare autosomal recessive ciliopathy.[5] This diagnosis is grouped with other chest problems called thoracic insufficiency syndrome (TIS). Diagnosis of Jeune syndrome can be made as early as before birth if signs and symptoms are apparent on an ultrasound; however, diagnosis after birth usually occurs through X-rays and genetic testing, such as the tests found on the Genetic Testing Registry (GTR).[6] ## Treatment[edit] ### Medical care[edit] In order to help relieve respiratory distress, mechanical ventilation is required in most severe cases; while pulmonary infections that tend to lead to respiratory failure occur in less severe cases. In order to treat these infections, doctors may suggest antibiotics, endotracheal suctioning, or postural drainage. ### Surgical care[edit] In severe cases, surgical action is needed; otherwise, failure to intervene can result in pulmonary damage and eventual fatality. Vertical expandable prosthetic titanium rib (VEPTR) surgery is the most common treatment for severe chest wall deformities. During this procedure, one or more titanium rods are attached to the ribs near the spine, which allow space for the patient’s lungs to develop. Small adjustments are made every four to six months through a small incision in the patient's back.[7] Alternatively, lateral thoracic expansion is used to enlarge the chest wall by separating the ribs from their periosteum and covering them with titanium struts. This procedure is common among patients older than a year due to its safe and effective outcome. Chest reconstruction is another surgical procedure that promotes thoracic cage growth. It can be done as an enlargement of the thoracic cage by sternotomy and fixation with bone grafts, or a methylmethacrylate prostheses plate.[5] ## References[edit] 1. ^ de Vries, J.; Yntema, J. L.; van Die, C. E.; Crama, N.; Cornelissen, E. A. M.; Hamel, B. C. J. (January 2010). "Jeune syndrome: description of 13 cases and a proposal for follow-up protocol". European Journal of Pediatrics. 169 (1): 77–88. doi:10.1007/s00431-009-0991-3. ISSN 0340-6199. PMC 2776156. PMID 19430947. 2. ^ "Jeune syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-11-14. 3. ^ Reference, Genetics Home. "Asphyxiating thoracic dystrophy". Genetics Home Reference. Retrieved 2019-11-14. 4. ^ Jeune, M.; Beraud, C.; Carron, R. (1955). "[Asphyxiating thoracic dystrophy with familial characteristics]". Archives Françaises de Pédiatrie. 12 (8): 886–891. ISSN 0003-9764. PMID 13292988. 5. ^ a b "Asphyxiating Thoracic Dystrophy (Jeune Syndrome) Treatment & Management: Approach Considerations, Medical Care, Surgical Care". 2019-11-10. Cite journal requires `\|journal=` (help) 6. ^ Bianchi, Diana W.; Crombleholme, Timothy M.; D'Alton, Mary E. (2000). Fetology: Diagnosis & Management of the Fetal Patient. McGraw Hill Professional. ISBN 9780838525708. 7. ^ Philadelphia, The Children's Hospital of (2018-07-31). "Jeune Syndrome". www.chop.edu. Retrieved 2019-11-14. ## External links[edit] Classification D * OMIM: 208500 * MeSH: C537571 * DiseasesDB: 32469 External resources * eMedicine: article/945537 * v * t * e Diseases of cilia Structural * receptor: Polycystic kidney disease * cargo: Asphyxiating thoracic dysplasia * basal body: Bardet–Biedl syndrome * mitotic spindle: Meckel syndrome * centrosome: Joubert syndrome Signaling * Nephronophthisis Other/ungrouped * Alström syndrome * Primary ciliary dyskinesia * Senior–Løken syndrome * Orofaciodigital syndrome 1 * McKusick–Kaufman syndrome * Autosomal recessive polycystic kidney See also: ciliary proteins * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Asphyxiating thoracic dysplasia	c0265275	8,417	wikipedia	https://en.wikipedia.org/wiki/Asphyxiating_thoracic_dysplasia	2021-01-18T18:42:05	{"gard": ["3049"], "mesh": ["C537571"], "orphanet": ["474"], "wikidata": ["Q4807981"]}
unexplained chronic eosinophila Hypereosinophilic syndrome Other namesHES[1] SpecialtyHematology Differential diagnosisClonal eosinophilia, Reactive eosinophilia Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.[2] HES is a diagnosis of exclusion, after clonal eosinophilia (such as FIP1L1-PDGFRA-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out.[3][4] There are some associations with chronic eosinophilic leukemia[5] as it shows similar characteristics and genetic defects.[6] If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone.[3] The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.[7] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] As HES affects many organs at the same time, symptoms may be numerous. Some possible symptoms a patient may present with include: * Cardiomyopathy[5] * Skin lesions[5] * Thromboembolic disease[5] * Pulmonary disease[5] * Neuropathy[5] * Hepatosplenomegaly[5] * Reduced ventricular size[5] * Atopic eczema ## Diagnosis[edit] Numerous techniques are used to diagnose hypereosinophilic syndrome, of which the most important is blood testing. In HES, the eosinophil count is greater than 1.5 × 109/L.[6] On some smears the eosinophils may appear normal in appearance, but morphologic abnormalities, such as a lowering of granule numbers and size, can be observed.[6] Roughly 50% of patients with HES also have anaemia.[6] Secondly, various imaging and diagnostic technological methods are utilised to detect defects to the heart and other organs, such as valvular dysfunction and arrhythmias by usage of echocardiography.[6] Chest radiographs may indicate pleural effusions and/or fibrosis,[6] and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.[6] A proportion of patients have a mutation involving the PDGFRA and FIP1L1 genes on the fourth chromosome, leading to a tyrosine kinase fusion protein. Testing for this mutation is now routine practice, as its presence indicates response to imatinib, a tyrosine kinase inhibitor.[8] ## Treatment[edit] Treatment primarily consists of reducing eosinophil levels and preventing further damage to organs.[6] Corticosteroids, such as prednisone, are good for reducing eosinophil levels and antineoplastics are useful for slowing eosinophil production.[6] Surgical therapy is rarely utilised, however splenectomy can reduce the pain due to spleen enlargement.[6] If damage to the heart (in particular the valves), then prosthetic valves can replace the current organic ones.[6] Follow-up care is vital for the survival of the patient, as such the patient should be checked for any signs of deterioration regularly.[6] After promising results in drug trials (95% efficiency in reducing blood eosinophil count to acceptable levels) it is hoped that in the future hypereosinophilic syndrome, and diseases related to eosinophils such as asthma and eosinophilic granulomatosis with polyangiitis, may be treated with the monoclonal antibody mepolizumab currently being developed to treat the disease.[7] If this becomes successful, it may be possible for corticosteroids to be eradicated and thus reduce the amount of side effects encountered.[7] ## Epidemiology[edit] The European Medicines Agency (EMA) estimated the prevalence of HES at the time of granting orphan drug designation for HES in 2004 at 1.5 in 100,000 people, corresponding to a current prevalence of about 8,000 in the EU, 5,000 in the U.S., and 2,000 in Japan.[9] Patients who lack chronic heart failure and those who respond well to prednisone or a similar drug have a good prognosis.[6] However, the mortality rate rises in patients with anaemia, chromosomal abnormalities or a very high white blood cell count.[6] ## History[edit] Hypereosinophilic syndrome was first described as a distinct entity by Hardy and Anderson in 1968.[10] ## References[edit] 1. ^ "OMIM Entry - # 607685 - HYPEREOSINOPHILIC SYNDROME, IDIOPATHIC; HES". omim.org. Retrieved 12 May 2019. 2. ^ Chusid MJ, Dale DC, West BC, Wolff SM (1975). "The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature". Medicine (Baltimore). 54 (1): 1–27. doi:10.1097/00005792-197501000-00001. PMID 1090795. S2CID 39212252. 3. ^ a b Fazel R, Dhaliwal G, Saint S, Nallamothu BK (May 2009). "Clinical problem-solving. A red flag". N. Engl. J. Med. 360 (19): 2005–10. doi:10.1056/NEJMcps0802754. PMID 19420370. 4. ^ Reiter A, Gotlib J (2017). "Myeloid neoplasms with eosinophilia". Blood. 129 (6): 704–714. doi:10.1182/blood-2016-10-695973. PMID 28028030. 5. ^ a b c d e f g h Longmore, Murray; Ian Wilkinson; Tom Turmezei; Chee Kay Cheung (2007). Oxford Handbook of Clinical Medicine. Oxford. p. 316. ISBN 978-0-19-856837-7. 6. ^ a b c d e f g h i j k l m n Rothenberg, Marc E (2008). "Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab". The New England Journal of Medicine. 358 (12): 1215–28. doi:10.1056/NEJMoa070812. PMID 18344568. Retrieved 2008-03-17. Last updated: Updated: Oct 4, 2009 by Venkata Samavedi and Emmanuel C Besa 7. ^ a b c Rothenberg ME, Klion AD, Roufosse FE, et al. (March 2008). "Treatment of patients with the hypereosinophilic syndrome with mepolizumab". N. Engl. J. Med. 358 (12): 1215–28. doi:10.1056/NEJMoa070812. PMID 18344568. 8. ^ Cools J, DeAngelo DJ, Gotlib J, et al. (2003). "A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome". N. Engl. J. Med. 348 (13): 1201–14. doi:10.1056/NEJMoa025217. PMID 12660384. 9. ^ European Medicines Agency, Committee for Orphan Medicinal Products. Public summary of opinion on orphan designation: mepolizumab for the treatment of hypereosinophilic syndrome. August 2010. 10. ^ Hardy, William R.; Anderson, Robert E. (1 June 1968). "The Hypereosinophilic syndromes". Annals of Internal Medicine. 68 (6): 1220–9. doi:10.7326/0003-4819-68-6-1220. eISSN 1539-3704. ISSN 0003-4819. PMID 5653621. ## External links[edit] * Hypereosinophilic Syndrome on patient.info * Hypereosinophilic Syndrome on eMedicine Classification D * ICD-10: D72.1 (ILDS D72.12) * ICD-9-CM: 288.3 * ICD-O: 9964/3 * OMIM: 607685 * MeSH: D017681 * DiseasesDB: 34939 External resources * eMedicine: article/202030 article/1051555 article/886861 * 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 * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Hypereosinophilic syndrome	c1540912	8,418	wikipedia	https://en.wikipedia.org/wiki/Hypereosinophilic_syndrome	2021-01-18T18:40:05	{"gard": ["2804"], "mesh": ["D017681"], "icd-9": ["288.3"], "icd-10": ["D72.1"], "orphanet": ["168956"], "wikidata": ["Q2551272"]}
Some of those who are attracted to the female armpit prefer it to be unshaven Shaved armpit with little amounts of stubble are also popular among the people who are attracted to the female armpit Armpit fetishism (also known as maschalagnia) is a type of partialism in which a person is sexually attracted to armpits[1] \- something which may lead to axillism, or armpit intercourse (sexual activity with one or both armpits).[2] ## Contents * 1 Smell * 2 Fetish * 2.1 Axillism * 3 Literary associations * 4 See also * 5 References ## Smell[edit] The natural body smell is a powerful force in sexual attraction,[3] and can be focused by the strong pungent odor of the armpit: Alex Comfort considered that for a woman to shave her armpits was “simply ignorant vandalism”, obliterating a powerful sexual tool, and praised the French for greater sexual awareness than American deodorant culture in this regard.[4] A woman's armpits, armpit hair, and secretions can be seen as essential components of her femininity, whether this is positively[5] or negatively valued.[6] Havelock Ellis found evidence that (in a non-sexual context) smelling one's own armpit could act as a temporary energy boost.[7] ## Fetish[edit] Those who have a mild fetish for armpits often enjoy kissing, tasting, tickling and smelling their partner's armpits during sexual foreplay, perhaps asking partners not to shower or wash their armpits nor wear deodorant for a period of hours. The symbolic equation of armpit and vagina may underpin the fetish, as also the odor.[8] Sigmund Freud however saw such fetishism as becoming problematic only when such preparatory acts substituted totally for intercourse as a final goal.[9] ### Axillism[edit] Stressing the importance in axillism of the (unlubricated) friction being confined to the penile shaft, Alex Comfort saw armpit intercourse as "Not an outstandingly rewarding trick but worth trying if you like the idea".[10] Problems may, however, arise in a relationship when penis to armpit contact (axillism) becomes an exclusive sexual necessity for the man – something which can produce long-term sexual desire disorder in a couple.[11] ## Literary associations[edit] * The French novelist Huysmans wrote an essay 'Le Gousset' on the various smells of what he called the "spice-boxes" that were women's armpits.[12] * Havelock Ellis quotes a Chinese poet writing to his lover of "your odorous armpit...that embalsamed nest".[13] * The folk-tale motif of vagina in armpit is known from Ohio to the East Indies.[14] ## See also[edit] * List of paraphilias * Non-penetrative sex * Petting * Trichophilia ## References[edit] 1. ^ Aggrawal, Anil (2008). Forensic and Medico-Legal Aspects of Sexual Crimes and Unusual Sexual Practices. CRC Press. p. 376. ISBN 978-1-4200-4308-2. 2. ^ D. A. Voorhees, Quickies (2004) p. 122 3. ^ Alex Comfort, The Joy of Sex (1974) p. 71 4. ^ Alex Comfort, The Joy of Sex (1974) pp. 71-3 and p. 98 5. ^ Nancy Friday, Women on Top (1991) p. 195 6. ^ Doris Lessing, The Golden Notebook (1972) p. 590 7. ^ Ellis, Havelock (1905). "Sexual Selection in Man". Studies in the Psychology of Sex. 4: 64–67. ISBN 978-1-55445-828-8. 8. ^ Otto Fenichel, The Psychoanalytic Theory of Neurosis (1946) pp. 342-3 9. ^ Sigmund Freud, On Sexuality (PFL 7) pp. 68-70 10. ^ Alex Comfort, The Joy of Sex (1974) p. 119 11. ^ L. C. Long et al., Sexuality Counselling (2005) p. 222 12. ^ Havelock Ellis, Studies in the Psychology of Sex (2004) vol. 4, p. 65 13. ^ Havelock Ellis, Studies in the Psychology of Sex (2004) vol. 4, p. 65 14. ^ G. Legman, Rationale of the Dirty Joke Vol. II (1973) pp. 148-9 * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Armpit fetishism	None	8,419	wikipedia	https://en.wikipedia.org/wiki/Armpit_fetishism	2021-01-18T18:54:54	{"wikidata": ["Q12230347"]}
MAN1B1-CDG is a form of congenital disorders of N-linked glycosylation characterized by intellectual disability, delayed motor development, hypotonia and truncal obesity. Additional features include slight facial dysmorphism (hypertelorism, downslanting palpebral fissures, large, low-set ears, hypoplastic nasolabial fold, thin upper lip), hypermobility of the joints and skin laxity. The disease is caused by mutations in the gene MAN1B1 (9q34.3). [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	MAN1B1-CDG	c4518783	8,420	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397941	2021-01-23T18:53:10	{"gard": ["12417"], "icd-10": ["E77.8"], "synonyms": ["Carbohydrate deficient glycoprotein syndrome type II due to MAN1B1 deficiency", "Congenital disorder of glycosylation type 2 due to MAN1B1 deficiency", "Congenital disorder of glycosylation type II due to MAN1B1 deficiency", "Intellectual disability-truncal obesity syndrome"]}
Hepatic encephalopathy Other namesPortosystemic encephalopathy, hepatic coma,[1] coma hepaticum Micrograph of Alzheimer type II astrocytes, as may be seen in hepatic encephalopathy. SpecialtyGastroenterology SymptomsAltered level of consciousness, mood changes, personality changes, movement problems[2] TypesAcute, recurrent, persistent[3] CausesLiver failure[2] Risk factorsInfections, GI bleeding, constipation, electrolyte problems, certain medications[4] Diagnostic methodBased on symptoms after ruling out other possible causes[2][5] Differential diagnosisWernicke–Korsakoff’s syndrome, delirium tremens, hypoglycemia, subdural hematoma, hyponatremia[1] TreatmentSupportive care, treating triggers, lactulose, liver transplant[1][3] PrognosisAverage life expectancy less than a year in those with severe disease[1] FrequencyAffects >40% with cirrhosis[6] Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure.[2] Its onset may be gradual or sudden.[2] Other symptoms may include movement problems, changes in mood, or changes in personality.[2] In the advanced stages it can result in a coma.[3] Hepatic encephalopathy can occur in those with acute or chronic liver disease.[3] Episodes can be triggered by infections, GI bleeding, constipation, electrolyte problems, or certain medications.[4] The underlying mechanism is believed to involve the buildup of ammonia in the blood, a substance that is normally removed by the liver.[2] The diagnosis is typically based on symptoms after ruling out other potential causes.[2][5] It may be supported by blood ammonia levels, an electroencephalogram, or a CT scan of the brain.[3][5] Hepatic encephalopathy is possibly reversible with treatment.[1] This typically involves supportive care and addressing the triggers of the event.[3] Lactulose is frequently used to decrease ammonia levels.[1] Certain antibiotics (such as rifaximin) and probiotics are other potential options.[1] A liver transplant may improve outcomes in those with severe disease.[1] More than 40% of people with cirrhosis develop hepatic encephalopathy.[6] More than half of those with cirrhosis and significant HE live less than a year.[1] In those who are able to get a liver transplant, the risk of death is less than 30% over the subsequent five years.[1] The condition has been described since at least 1860.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathogenesis * 4 Diagnosis * 4.1 Investigations * 4.2 Classification * 4.2.1 West Haven criteria * 4.2.2 Types * 4.2.3 Minimal HE * 5 Treatment * 5.1 Diet * 5.2 Lactulose/lactitol * 5.3 Antibiotics * 5.4 L-ornithine and L-aspartate * 6 Epidemiology and prognosis * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] The mildest form of hepatic encephalopathy is difficult to detect clinically, but may be demonstrated on neuropsychological testing. It is experienced as forgetfulness, mild confusion, and irritability. The first stage of hepatic encephalopathy is characterised by an inverted sleep-wake pattern (sleeping by day, being awake at night). The second stage is marked by lethargy and personality changes. The third stage is marked by worsened confusion. The fourth stage is marked by a progression to coma.[3] More severe forms of hepatic encephalopathy lead to a worsening level of consciousness, from lethargy to somnolence and eventually coma. In the intermediate stages, a characteristic jerking movement of the limbs is observed (asterixis, "liver flap" due to its flapping character); this disappears as the somnolence worsens. There is disorientation and amnesia, and uninhibited behaviour may occur. In the third stage, neurological examination may reveal clonus and positive Babinski sign. Coma and seizures represent the most advanced stage; cerebral oedema (swelling of the brain tissue) leads to death.[3] Encephalopathy often occurs together with other symptoms and signs of liver failure. These may include jaundice (yellow discolouration of the skin and the whites of the eyes), ascites (fluid accumulation in the abdominal cavity), and peripheral oedema (swelling of the legs due to fluid build-up in the skin). The tendon reflexes may be exaggerated, and the plantar reflex may be abnormal, namely extending rather than flexing (Babinski's sign) in severe encephalopathy. A particular smell on an affected person's breath (foetor hepaticus) may be detected.[7] ## Causes[edit] In a small proportion of cases, the encephalopathy is caused directly by liver failure; this is more likely in acute liver failure. More commonly, especially in chronic liver disease, hepatic encephalopathy is triggered by an additional cause, and identifying these triggers can be important to treat the episode effectively.[3] Type Causes[3][7][8] Excessive nitrogen load Consumption of large amounts of protein, gastrointestinal bleeding e.g. from esophageal varices (blood is high in protein, which is reabsorbed from the bowel), kidney failure (inability to excrete nitrogen-containing waste products such as urea), constipation Electrolyte or metabolic disturbance Hyponatraemia (low sodium level in the blood) and hypokalaemia (low potassium levels)—these are both common in those taking diuretics, often used for the treatment of ascites; furthermore alkalosis (decreased acid level), hypoxia (insufficient oxygen levels), dehydration Drugs and medications Sedatives such as benzodiazepines (often used to suppress alcohol withdrawal or anxiety disorder), narcotics (used as painkillers or drugs of abuse), antipsychotics, alcohol intoxication Infection Pneumonia, urinary tract infection, spontaneous bacterial peritonitis, other infections Others Surgery, progression of the liver disease, additional cause for liver damage (e.g. alcoholic hepatitis, hepatitis A) Unknown In 20–30% of cases, no clear cause for an attack can be found Hepatic encephalopathy may also occur after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). This is used in the treatment of refractory ascites, bleeding from oesophageal varices and hepatorenal syndrome.[9][10] TIPS-related encephalopathy occurs in about 30% of cases, with the risk being higher in those with previous episodes of encephalopathy, higher age, female sex, and liver disease due to causes other than alcohol.[8] ## Pathogenesis[edit] Ball and stick model of ammonia; one nitrogen atom with three hydrogen atoms. Accumulation of ammonia in the bloodstream is associated with hepatic encephalopathy. There are various explanations why liver dysfunction or portosystemic shunting might lead to encephalopathy. In healthy subjects, nitrogen-containing compounds from the intestine, generated by gut bacteria from food, are transported by the portal vein to the liver, where 80–90% are metabolised through the urea cycle and/or excreted immediately. This process is impaired in all subtypes of hepatic encephalopathy, either because the hepatocytes (liver cells) are incapable of metabolising the waste products or because portal venous blood bypasses the liver through collateral circulation or a medically constructed shunt. Nitrogenous waste products accumulate in the systemic circulation (hence the older term "portosystemic encephalopathy"). The most important waste product is ammonia (NH3). This small molecule crosses the blood–brain barrier and is absorbed and metabolised by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesising glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory γ-aminobutyric acid (GABA) system, and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema of the "cytotoxic" type.[11] Despite numerous studies demonstrating the central role of ammonia, ammonia levels do not always correlate with the severity of the encephalopathy; it is suspected that this means that more ammonia has already been absorbed into the brain in those with severe symptoms whose serum levels are relatively low.[3][7] Other waste products implicated in hepatic encephalopathy include mercaptans (substances containing a thiol group), short-chain fatty acids, and phenol.[7] Numerous other abnormalities have been described in hepatic encephalopathy, although their relative contribution to the disease state is uncertain. Loss of glutamate transporter gene expression (especially EAAT 2) has been attributed to acute liver failure.[12] Benzodiazepine-like compounds have been detected at increased levels as well as abnormalities in the GABA neurotransmission system. An imbalance between aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) has been described; this would lead to the generation of false neurotransmitters (such octopamine and 2-hydroxyphenethylamine). Dysregulation of the serotonin system, too, has been reported. Depletion of zinc and accumulation of manganese may play a role.[3][7] Inflammation elsewhere in the body may precipitate encephalopathy through the action of cytokines and bacterial lipopolysaccharide on astrocytes.[8] ## Diagnosis[edit] Micrograph of Alzheimer type II astrocytes, as may be seen in hepatic encephalopathy. ### Investigations[edit] The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease (types A and C) or a portosystemic shunt (type B), as its symptoms are similar to those encountered in other encephalopathies. To make the distinction, abnormal liver function tests and/or ultrasound suggesting liver disease are required, and ideally a liver biopsy.[3][7] The symptoms of hepatic encephalopathy may also arise from other conditions, such as bleeding in the brain and seizures (both of which are more common in chronic liver disease). A CT scan of the brain may be required to exclude bleeding in the brain, and if seizure activity is suspected an electroencephalograph (EEG) study may be performed.[3] Rarer mimics of encephalopathy are meningitis, encephalitis, Wernicke's encephalopathy and Wilson's disease; these may be suspected on clinical grounds and confirmed with investigations.[7][13] The diagnosis of hepatic encephalopathy is a clinical one, once other causes for confusion or coma have been excluded; no test fully diagnoses or excludes it. Serum ammonia levels are elevated in 90% of people, but not all hyperammonaemia (high ammonia levels in the blood) is associated with encephalopathy.[3][7] A CT scan of the brain usually shows no abnormality except in stage IV encephalopathy, when brain swelling (cerebral oedema) may be visible.[7] Other neuroimaging modalities, such as magnetic resonance imaging (MRI), are not currently regarded as useful, although they may show abnormalities.[13] Electroencephalography shows no clear abnormalities in stage 0, even if minimal HE is present; in stages I, II and III there are triphasic waves over the frontal lobes that oscillate at 5 Hz, and in stage IV there is slow delta wave activity.[3] However, the changes in EEG are not typical enough to be useful in distinguishing hepatic encephalopathy from other conditions.[13] Once the diagnosis of encephalopathy has been made, efforts are made to exclude underlying causes (such as listed above in "causes"). This requires blood tests (urea and electrolytes, full blood count, liver function tests), usually a chest X-ray, and urinalysis. If there is ascites, a diagnostic paracentesis (removal of a fluid sample with a needle) may be required to identify spontaneous bacterial peritonitis (SBP).[3] ### Classification[edit] #### West Haven criteria[edit] The severity of hepatic encephalopathy is graded with the West Haven Criteria; this is based on the level of impairment of autonomy, changes in consciousness, intellectual function, behavior, and the dependence on therapy.[3][13] * Grade 0 - No obvious changes other than potentially mild decrease in intellectual ability and coordination * Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction * Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour * Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation * Grade 4 - Coma #### Types[edit] Micrograph showing liver cirrhosis, a condition that often precedes hepatic encephalopathy. Trichrome stain. A classification of hepatic encephalopathy was introduced at the World Congress of Gastroenterology 1998 in Vienna. According to this classification, hepatic encephalopathy is subdivided in type A, B and C depending on the underlying cause.[13] * Type A (=acute) describes hepatic encephalopathy associated with acute liver failure, typically associated with cerebral oedema * Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease * Type C (=cirrhosis) occurs in people with cirrhosis \- this type is subdivided in episodic, persistent and minimal encephalopathy The term minimal encephalopathy (MHE) is defined as encephalopathy that does not lead to clinically overt cognitive dysfunction, but can be demonstrated with neuropsychological studies.[13][14] This is still an important finding, as minimal encephalopathy has been demonstrated to impair quality of life and increase the risk of involvement in road traffic accidents.[15] #### Minimal HE[edit] The diagnosis of minimal hepatic encephalopathy requires neuropsychological testing by definition. Older tests include the "numbers connecting test" A and B (measuring the speed at which one could connect randomly dispersed numbers 1–20), the "block design test" and the "digit-symbol test".[13] In 2009 an expert panel concluded that neuropsychological test batteries aimed at measuring multiple domains of cognitive function are generally more reliable than single tests, and tend to be more strongly correlated with functional status. Both the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)[16] and PSE-Syndrom-Test[17] may be used for this purpose.[14] The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test.[13][14][15][17] ## Treatment[edit] Those with severe encephalopathy (stages 3 and 4) are at risk of obstructing their airway due to decreased protective reflexes such as the gag reflex. This can lead to respiratory arrest. Transferring the person to a higher level of nursing care, such as an intensive care unit, is required and intubation of the airway is often necessary to prevent life-threatening complications (e.g., aspiration or respiratory failure).[7][18] Placement of a nasogastric tube permits the safe administration of nutrients and medication.[3] The treatment of hepatic encephalopathy depends on the suspected underlying cause (types A, B or C) and the presence or absence of underlying causes. If encephalopathy develops in acute liver failure (type A), even in a mild form (grade 1–2), it indicates that a liver transplant may be required, and transfer to a specialist centre is advised.[18] Hepatic encephalopathy type B may arise in those who have undergone a TIPS procedure; in most cases this resolves spontaneously or with the medical treatments discussed below, but in a small proportion of about 5%, occlusion of the shunt is required to address the symptoms.[8] In hepatic encephalopathy type C, the identification and treatment of alternative or underlying causes is central to the initial management.[3][7][8][15] Given the frequency of infection as the underlying cause, antibiotics are often administered empirically (without knowledge of the exact source and nature of the infection).[3][8] Once an episode of encephalopathy has been effectively treated, a decision may need to be made on whether to prepare for a liver transplant.[15] ### Diet[edit] In the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy. This has been shown to be incorrect. Furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight. A diet with adequate protein and energy is therefore recommended.[3][8] Dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis.[3][8] Some studies have shown benefit of administration of probiotics ("healthy bacteria").[8] ### Lactulose/lactitol[edit] Lactulose and lactitol are disaccharides that are not absorbed from the digestive tract. They are thought to decrease the generation of ammonia by bacteria, render the ammonia inabsorbable by converting it to ammonium (NH4+) ions, and increase transit of bowel content through the gut. Doses of 15-30 ml are typically administered three times a day; the result is aimed to be 3–5 soft stools a day, or (in some settings) a stool pH of <6.0.[3][7][8][15] Lactulose may also be given by enema, especially if encephalopathy is severe.[15] More commonly, phosphate enemas are used. This may relieve constipation, one of the causes of encephalopathy, and increase bowel transit.[3] Lactulose and lactitol are beneficial for treating hepatic encephalopathy, and are the recommended first-line treatment.[3][19] Lactulose does not appear to be more effective than lactitol for treating people with hepatic encephalopathy.[19] Side effects of lactulose and lactitol include the possibility of diarrhea, abdominal bloating, gassiness, and nausea.[19] In acute liver failure, it is unclear whether lactulose is beneficial. The possible side effect of bloating may interfere with a liver transplant procedure if required.[18] ### Antibiotics[edit] The antibiotic rifaximin may be recommended in addition to lactulose for those with recurrent disease.[1] It is a nonabsorbable antibiotic from the rifamycin class. This is thought to work in a similar way to other antibiotics, but without the complications attached to neomycin or metronidazole. Due to the long history and lower cost of lactulose use, rifaximin is generally only used as a second-line treatment if lactulose is poorly tolerated or not effective. When rifaximin is added to lactulose, the combination of the two may be more effective than each component separately.[3] Rifaximin is more expensive than lactulose, but the cost may be offset by fewer hospital admissions for encephalopathy.[15] The antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy.[20] The rationale of their use was the fact that ammonia and other waste products are generated and converted by intestinal bacteria, and killing these bacteria would reduce the generation of these waste products. Neomycin was chosen because of its low intestinal absorption, as neomycin and similar aminoglycoside antibiotics may cause hearing loss and kidney failure if used by injection. Later studies showed that neomycin was indeed absorbed when taken by mouth, with resultant complications. Metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage, in addition to gastrointestinal side effects.[3] ### L-ornithine and L-aspartate[edit] The combination of L-ornithine and L-aspartate (LOLA) lowers the level of ammonia in a person's blood.[21] Very weak evidence from clinical trials indicates that LOLA treatment may benefit people with hepatic encephalopathy.[21] LOLA lowers ammonia levels by increasing the generation of urea through the urea cycle, a metabolic pathway that removes ammonia by turning it into the neutral substance urea.[citation needed] LOLA may be combined with lactulose and/or rifaximin if these alone are ineffective at controlling symptoms.[3] ## Epidemiology and prognosis[edit] In those with cirrhosis, the risk of developing hepatic encephalopathy is 20% per year, and at any time about 30–45% of people with cirrhosis exhibit evidence of overt encephalopathy. The prevalence of minimal hepatic encephalopathy detectable on formal neuropsychological testing is 60–80%; this increases the likelihood of developing overt encephalopathy in the future.[15] Once hepatic encephalopathy has developed, the prognosis is determined largely by other markers of liver failure, such as the levels of albumin (a protein produced by the liver), the prothrombin time (a test of coagulation, which relies on proteins produced in the liver), the presence of ascites and the level of bilirubin (a breakdown product of hemoglobin which is conjugated and excreted by the liver). Together with the severity of encephalopathy, these markers have been incorporated into the Child-Pugh score; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation.[13] In acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality, and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis. Historically, widely used criteria for offering liver transplantation, such as King's College Criteria, are of limited use and recent guidelines discourage excessive reliance on these criteria. The occurrence of hepatic encephalopathy in people with Wilson's disease (hereditary copper accumulation) and mushroom poisoning indicates an urgent need for a liver transplant.[18] ## History[edit] The occurrence of disturbed behaviour in people with jaundice may have been described in antiquity by Hippocrates of Cos (ca. 460–370 BCE).[17][22] Celsus and Galen (first and third century respectively) both recognised the condition. Many modern descriptions of the link between liver disease and neuropsychiatric symptoms were made in the eighteenth and nineteenth century; for instance, Giovanni Battista Morgagni (1682–1771) reported in 1761 that it was a progressive condition.[22] In the 1950s, several reports enumerated the numerous abnormalities reported previously, and confirmed the previously enunciated theory that metabolic impairment and portosystemic shunting are the underlying mechanisms behind hepatic encephalopathy, and that the nitrogen-rich compounds originate from the intestine.[17][23] Professor Dame Sheila Sherlock (1918–2001) performed many of these studies at the Royal Postgraduate Medical School in London and subsequently at the Royal Free Hospital. The same group investigated protein restriction[22] and neomycin.[24] The West Haven classification was formulated by Professor Harold Conn (1925–2011) and colleagues at Yale University while investigating the therapeutic efficacy of lactulose.[13][25][26] ## References[edit] 1. ^ a b c d e f g h i j k l Wijdicks, EF (27 October 2016). "Hepatic Encephalopathy". The New England Journal of Medicine. 375 (17): 1660–1670. doi:10.1056/NEJMra1600561. PMID 27783916. 2. ^ a b c d e f g h "Hepatic encephalopathy". GARD. 2016. Archived from the original on 5 July 2017. Retrieved 30 July 2017. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac Cash WJ, McConville P, McDermott E, McCormick PA, Callender ME, McDougall NI (January 2010). "Current concepts in the assessment and treatment of hepatic encephalopathy". QJM. 103 (1): 9–16. doi:10.1093/qjmed/hcp152. PMID 19903725. 4. ^ a b Starr, SP; Raines, D (15 December 2011). "Cirrhosis: diagnosis, management, and prevention". American Family Physician. 84 (12): 1353–9. PMID 22230269. 5. ^ a b c "Portosystemic Encephalopathy - Hepatic and Biliary Disorders". Merck Manuals Professional Edition. Retrieved 25 September 2019. 6. ^ a b Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 577. ISBN 9780323529570. Archived from the original on 2017-07-30. 7. ^ a b c d e f g h i j k l Chung RT, Podolsky DK (2005). "Cirrhosis and its complications". In Kasper DL, Braunwald E, Fauci AS, et al. (eds.). Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 1858–69. ISBN 978-0-07-139140-5. 8. ^ a b c d e f g h i j Sundaram V, Shaikh OS (July 2009). "Hepatic encephalopathy: pathophysiology and emerging therapies". Med. Clin. North Am. 93 (4): 819–36, vii. doi:10.1016/j.mcna.2009.03.009. PMID 19577116. 9. ^ Khan S, Tudur Smith C, Williamson P, Sutton R (2006). "Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis". Cochrane Database Syst Rev (4): CD000553. doi:10.1002/14651858.CD000553.pub2. PMC 7045742. PMID 17054131. 10. ^ Saab S, Nieto JM, Lewis SK, Runyon BA (2006). "TIPS versus paracentesis for cirrhotic patients with refractory ascites". Cochrane Database Syst Rev (4): CD004889. doi:10.1002/14651858.CD004889.pub2. PMID 17054221. 11. ^ Ryan JM, Shawcross DL (2011). "Hepatic encephalopathy". Medicine. 39 (10): 617–620. doi:10.1016/j.mpmed.2011.07.008. 12. ^ Thumburu, KK; Dhiman, RK; Vasishta, RK; Chakraborti, A; Butterworth, RF; Beauchesne, E; Desjardins, P; Goyal, S; Sharma, N; Duseja, A; Chawla, Y (Mar 2014). "Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure". Journal of Neurochemistry. 128 (5): 617–27. doi:10.1111/jnc.12511. PMID 24164438. S2CID 21367707. 13. ^ a b c d e f g h i j Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei A (2002). "Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998". Hepatology. 35 (3): 716–21. doi:10.1053/jhep.2002.31250. PMID 11870389. S2CID 7929620.[dead link] 14. ^ a b c Randolph C, Hilsabeck R, Kato A, et al. (May 2009). "Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines". Liver Int. 29 (5): 629–35. doi:10.1111/j.1478-3231.2009.02009.x. PMID 19302444. S2CID 30313260. Archived from the original on 2012-12-10. 15. ^ a b c d e f g h Bajaj JS (March 2010). "Review article: the modern management of hepatic encephalopathy". Aliment. Pharmacol. Ther. 31 (5): 537–47. doi:10.1111/j.1365-2036.2009.04211.x. PMID 20002027. S2CID 10976362. 16. ^ Randolph C, Tierney MC, Mohr E, Chase TN (June 1998). "The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity". J Clin Exp Neuropsychol. 20 (3): 310–9. doi:10.1076/jcen.20.3.310.823. PMID 9845158. 17. ^ a b c d Weissenborn K, Ennen JC, Schomerus H, Rückert N, Hecker H (May 2001). "Neuropsychological characterization of hepatic encephalopathy". J. Hepatol. 34 (5): 768–73. doi:10.1016/S0168-8278(01)00026-5. PMID 11434627. 18. ^ a b c d Polson J, Lee WM (May 2005). "AASLD position paper: the management of acute liver failure". Hepatology. 41 (5): 1179–97. doi:10.1002/hep.20703. PMID 15841455. S2CID 6216605. Archived from the original on 2012-12-16. 19. ^ a b c Gluud, Lise Lotte; Vilstrup, Hendrik; Morgan, Marsha Y. (2016-05-06). "Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis". The Cochrane Database of Systematic Reviews (5): CD003044. doi:10.1002/14651858.CD003044.pub4. ISSN 1469-493X. PMC 7004252. PMID 27153247. 20. ^ Ferenci, P (May 2017). "Hepatic encephalopathy". Gastroenterology Report. 5 (2): 138–147. doi:10.1093/gastro/gox013. PMC 5421503. PMID 28533911. 21. ^ a b Goh, Ee Teng; Stokes, Caroline S.; Sidhu, Sandeep S.; Vilstrup, Hendrik; Gluud, Lise Lotte; Morgan, Marsha Y. (2018-05-15). "L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis" (PDF). The Cochrane Database of Systematic Reviews. 5: CD012410. doi:10.1002/14651858.CD012410.pub2. ISSN 1469-493X. PMC 6494563. PMID 29762873. 22. ^ a b c Summerskill WH, Davidson EA, Sherlock S, Steiner RE (April 1956). "The neuropsychiatric syndrome associated with hepatic cirrhosis and an extensive portal collateral circulation". Q. J. Med. 25 (98): 245–66. PMID 13323252. 23. ^ Sherlock S, Summerskill WH, White LP, Phear EA (September 1954). "Portal-systemic encephalopathy; neurological complications of liver disease". Lancet. 264 (6836): 453–7. doi:10.1016/S0140-6736(54)91874-7. PMID 13193045. 24. ^ Last PM, Sherlock S (February 1960). "Systemic absorption of orally administered neomycin in liver disease". N. Engl. J. Med. 262 (8): 385–9. doi:10.1056/NEJM196002252620803. PMID 14414396. 25. ^ Conn HO, Leevy CM, Vlahcevic ZR, et al. (1977). "Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial". Gastroenterology. 72 (4 Pt 1): 573–83. doi:10.1016/S0016-5085(77)80135-2. PMID 14049. 26. ^ Boyer JL, Garcia-Tsao G, Groszmann RJ (February 2012). "In Memoriam: Harold O. Conn, M.D." Hepatology. 55 (2): 658–9. doi:10.1002/hep.25550. S2CID 85090164. ## External links[edit] Classification D * ICD-10: K72 * ICD-9-CM: 572.2 * MeSH: D006501 External resources * MedlinePlus: 000302 * eMedicine: med/3185 article/182208 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Hepatic encephalopathy	c0019151	8,421	wikipedia	https://en.wikipedia.org/wiki/Hepatic_encephalopathy	2021-01-18T18:28:10	{"gard": ["10452"], "mesh": ["D006501"], "umls": ["C0019151"], "wikidata": ["Q642548"]}
Heritable pulmonary arterial hypertension (HPAH) is a form of pulmonary arterial hypertension (PAH, see this term), occurring due to mutations in PAH predisposing genes or in a familial context. HPAH is characterized by elevated pulmonary arterial resistance leading to right heart failure. HPAH is progressive and potentially fatal. ## Epidemiology HPAH represent less than 4% of PAH. Prevalence is estimated at < 1/million people. ## Clinical description HPAH develop usually in adults, and rarely in children; women are twice as likely as men to be affected. Usual age at diagnosis is mid thirties. Initial symptoms include dyspnea, fatigue, syncope, chest pain, palpitations and pedal edema. Precordial signs include loud and palpable second heart sound, right ventricular heave, pulmonary ejection click and murmurs of pulmonary and tricuspid regurgitation.70% of patients present heart failure (classed as New York heart association functional classification (NYHA FC) III or IV).Rarely, clubbing and Raynaud phenomenon (mostly in females) have been observed. Hemoptysis has also been reported. HPAH patients have a severe clinical with less response to acute vasodilator challenge, lower cardiac index, and higher pulmonary vascular resistance. HPAH due to ACVRL1or TBX4gene mutations occurs more commonly in children with rapid progression and poor prognosis. ## Etiology HPAH has been linked to mutations in BMPR2 ((2q33) in majority of cases. However, other genes implicated in HPAH have been described in few cases, and include ACVRL1 ((12q13)), KCNK3 (2p23),CAV1(7q31), TBX4 (17q21) and SMAD9(13q12) . ## Genetic counseling Patients displaying a sporadic PAH or a PAH occurring in a familial context, should be tested in priority for mutations in BMPR2 gene. If no mutations in BMPR2gene were identified in a patient displaying a familial form of PAH, mutations in all other PAH predisposing genes have to searched successively. All PAH predisposing genes are transmitted in an autosomal dominant manner with an incomplete penetrance. In the cases ofBMPR2 mutations the penetrance is estimated to be 42% in female mutation carriers and 14% in male mutation carriers. Prenatal genetic testing and preimplantation diagnosis are considered in patients and asymptomatic relatives carriers of a mutation in PAH predisposing genes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Heritable pulmonary arterial hypertension	c0340543	8,422	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=275777	2021-01-23T18:42:38	{"mesh": ["D065627"], "omim": ["178600", "615342"], "umls": ["C0340543", "C1701939"], "icd-10": ["I27.0"], "synonyms": ["FPAH", "Familial pulmonary arterial hypertension", "HPAH", "Hereditary pulmonary arterial hypertension"]}
Diaphragmatic defect-limb deficiency-skull defect syndrome is characterized by the association of classical diaphragmatic hernia (Bochdalek type) with severe lung hypoplasia, and variable associated malformations. ## Epidemiology It has been reported only once in four successive foetuses (two females and two males) born to a nonconsanguineous couple. ## Clinical description The spectrum of malformations is wide and includes, besides diaphragmatic hernia and hypoplastic lungs (present in the four foetuses), omphalocele (one case), severe limb hypoplasia (two cases), syndactyly of the toes (two cases), extra spleen (one case), and an ossification defect of the skull (one case). ## Antenatal diagnosis Prenatal diagnosis of diaphragmatic hernia and severe lung hypoplasia detected on ultrasonography made the parents opt for termination of the four pregnancies. ## Genetic counseling Inheritance seems either to be autosomal recessive or due to a gonadal mosaicism in one parent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Diaphragmatic defect-limb deficiency-skull defect syndrome	c1832668	8,423	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2141	2021-01-23T18:41:23	{"gard": ["2397"], "mesh": ["C563380"], "omim": ["601163"], "umls": ["C1832668"], "icd-10": ["Q87.8"], "synonyms": ["Froster-Huch syndrome"]}
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, to stresses such as vigorous exercise and heat. ## Epidemiology The incidence of MH reactions ranges from 1/5000 to 1/50,000-100,000 anesthesias. However, the genetic prevalence of the genetic abnormalities may be as great as 1/400 individuals. A significant male preponderance has been reported. ## Clinical description Clinical symptoms of MH are highly variable, ranging from self limiting courses with mild or moderate symptoms to fulminant MH crises. The classic signs of MH include marked hyperthermia, tachycardia, supraventricular and ventricular arrhythmia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, isolated masseter spasm or generalized muscle rigidity and rhabdomyolysis, all of which are related to a hypermetabolic response. In untreated patients, multiorgan failure (including acute renal failure) and circulatory collapse are the end-stage of the disease. ## Etiology In most cases, MH is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the ryanodine receptor gene (RYR1), located on chromosome 19q13.1, and at least 34 are causal for MH. The pathophysiologic changes of MH are due to an uncontrolled rise in myoplasmic calcium, which activates biochemical processes related to muscle activation. As a result of ATP depletion, muscle membrane integrity is compromised, leading to hyperkalemia and rhabdomyolysis. MH events are mainly triggered by volatile anesthetics and succinylcholine. Extremely rarely stresses such as exercise, emotion and heat may trigger a reaction. ## Diagnostic methods An early diagnostic clue is elevation of end-expired carbon dioxide. Arterial blood gas analyses reveal a combination of respiratory and metabolic acidosis with negative base excess, lactemia, hypercapnia, and hypoxemia. Diagnostic testing relies on assessing the in-vitro contracture response of biopsied muscle to halothane and caffeine. Other drugs such as ryanodine and 4-chloro-m-cresol have also been used but are not part of a standard protocol. A diagnosis of MH is given when contracture forces exceed the given threshold after exposure to these substances. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be increasing useful for identifying those at risk. ## Differential diagnosis The differential diagnosis of a fulminant MH crisis includes sporadic pheochromocytoma, serotonin syndrome, neuroleptic malignant syndrome (see these terms), anaphylactic reaction, thyroid crisis and sepsis. ## Genetic counseling MH is inherited autosomal dominantly. Genetic counseling is possible in families with a known disease causing mutation. ## Management and treatment Dantrolene sodium is a specific antagonist of the pathophysiologic changes in MH and should be available wherever general anesthesia is administered. When MH is suspected, administration of triggering agents should be ceased immediately and anesthesia continued with intravenous propofol, opiods and/or sedatives. During an MH crisis, dantrolene should be administered at a dosage of 2.5 mg/kg, every 5-10 minutes until patient is stabilized. Volume resuscitation and administration of vasopressors might be needed to stabilize hemodynamics. Cooling (with cold intravenous fluids, topical ice or special cooling blankets) is essential as high temperatures exacerbate an established MH reaction. ## Prognosis The syndrome is likely to be fatal if untreated but thanks to the dramatic progress in understanding the clinical manifestations and pathophysiology of the syndrome, the mortality from MH has dropped from over 80%, thirty years ago, to less than 5% at present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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 hyperthermia of anesthesia	c0024591	8,424	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=423	2021-01-23T18:17:55	{"gard": ["6964"], "mesh": ["D008305"], "omim": ["145600", "154275", "154276", "600467", "601887", "601888"], "umls": ["C0024591"], "icd-10": ["T88.3"], "synonyms": ["Hyperthermia of anesthesia"]}
A rare autosomal recessive primary immunodeficiency characterized by susceptibility to Epstein-Barr virus (EBV)-associated lymphoproliferative disorders such as malignant B-cell proliferation, Hodgkin lymphoma, B-cell lymphoma, lymphoid granulomatosis, hemophagocytic lymphohistiocytosis, and smooth muscle tumor. Patients present persistent symptoms of infectious mononucleosis including recurrent febrile episodes, lymphadenopathies, and hepatosplenomegaly, accompanied by high EBV viral load in the blood. Additional manifestations are autoimmune diseases like hemolytic anemia or renal 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	Combined immunodeficiency due to ITK deficiency	c3552634	8,425	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=538963	2021-01-23T17:18:51	{"omim": ["613011"], "icd-10": ["D81.1"], "synonyms": ["Autosomal recessive lymphoproliferative disease due to ITK deficiency", "ITK deficiency"]}
Pyruvate dehydrogenase E3 deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by either early-onset lactic acidosis and delayed development, later-onset neurological dysfunction or liver disease. ## Epidemiology Prevalence is unknown. About 20 cases have been reported to date. ## Clinical description The majority of patients have presented with neonatal lactic acidosis or with lactic acidosis, delayed development and hypotonia during infancy. A few patients have presented later in childhood with ataxia and dystonia with normal cognitive development. A separate group of patients, essentially all of Ashkenazi Jewish origin and many homozygous for a common G229C missense mutation, present with episodic vomiting, abdominal pain, encephalopathy and liver cell dysfunction. In some patients, there is evidence of branched chain alpha-ketoacid dehydrogenase deficiency, with elevated concentrations of the branched chain amino acids and their metabolites. However, clinical manifestations in most cases appear to be related to the pyruvate dehydrogenase deficiency. ## Etiology The disorder is caused by mutations in the DLD gene (7q31-q32). ## Genetic counseling The pattern of inheritance is autosomal recessive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Pyruvate dehydrogenase E3 deficiency	c0268193	8,426	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2394	2021-01-23T19:08:02	{"gard": ["3263"], "mesh": ["C537841"], "omim": ["246900"], "icd-10": ["E74.4"], "synonyms": ["DLD deficiency", "Dihydrolipoamide dehydrogenase deficiency", "E3-deficient maple syrup urine disease"]}
Terrien's marginal degeneration SpecialtyOphthalmology Terrien marginal degeneration is a noninflammatory, unilateral or asymmetrically bilateral, slowly progressive thinning of the peripheral corneal stroma.[1][2] ## Contents * 1 Cause * 2 Diagnosis * 3 Treatments * 4 References * 5 External links ## Cause[edit] The cause of Terrien marginal degeneration is unknown, its prevalence is roughly equal between males and females, and it usually occurs in the second or third decade of life.[2] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatments[edit] Spectacles or RGP contact lenses can be used to manage the astigmatism. when the condition worsens, surgical correction may be required.[3] ## References[edit] 1. ^ Risma, Justin. "Terrien Marginal Degeneration". EyeRounds Online Atlas of Ophthalmology. University of Iowa. 2. ^ a b "Terrien marginal degeneration". American Academy of Ophthalmology. 3. ^ Mihlstin, Melanie Lynn; Hwang, Frank S. "Terrien's Marginal Degeneration". EyeWiki. American Academy of Ophthalmology. ## External links[edit] Classification D * ICD-9-CM: 371.48 * DiseasesDB: 33142 * 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	Terrien's marginal degeneration	c0271283	8,427	wikipedia	https://en.wikipedia.org/wiki/Terrien%27s_marginal_degeneration	2021-01-18T18:50:57	{"umls": ["C0271283"], "wikidata": ["Q25098815"]}
## Summary The purpose of this overview is to increase the awareness of clinicians regarding the FGFR craniosynostosis syndromes and their management. Goal 1 Describe the clinical characteristics of FGFR craniosynostosis syndromes. Goal 2 Review the genetic causes of FGFR craniosynostosis syndromes. Goal 3 Provide an evaluation strategy to identify the genetic cause of an FGFR craniosynostosis syndrome in a proband. Goal 4 Inform risk assessment and surveillance of at-risk relatives for early detection and treatment of FGFR craniosynostosis syndromes. Goal 5 Summarize current management recommendations for individuals with an FGFR craniosynostosis syndrome. ## Diagnosis ## Clinical Characteristics ## Differential Diagnosis Craniosynostosis can be primary or secondary. In primary craniosynostosis, abnormal biology of the suture causes premature suture closure, as in FGFR craniosynostosis syndromes. Primary craniosynostosis can be isolated or part of a syndrome. In secondary craniosynostosis, the suture biology is normal, but abnormal external forces result in premature suture closure. #### Isolated Primary Craniosynostosis Single-suture craniosynostosis results in recognizable head shapes: metopic (trigonocephaly), sagittal (scaphocephaly), lambdoid (posterior asymmetric flattening with vertical displacement of one ear and tilt of skull base), unicoronal (asymmetric forehead with nasal twist and harlequin eye deformity), and bicoronal (turribrachycephaly). Among 204 individuals with apparently nonsyndromic and nonfamilial single-suture craniosynostosis, the likelihood of finding an underlying genetic difference varied by suture involvement [Wilkie et al 2010, Mathijssen 2015]. * Isolated unicoronal craniosynostosis. Among individuals with apparently nonsyndromic unicoronal craniosynostosis the prevalence of any syndrome was 17%; Muenke syndrome was identified in 10%. * Isolated bicoronal craniosynostosis. Among individuals with apparently isolated bicoronal craniosynostosis, Muenke syndrome was diagnosed in 38%; no other syndromes were identified. Note: (1) Those with apparently isolated synostosis of the lambdoid, sagittal, or metopic sutures had no pathogenic variants identified [Wilkie et al 2010, Mathijssen 2015]. (2) A study in individuals with either syndromic or nonsyndromic metopic craniosynostosis found no pathogenic variants in FGFR1, CER1, or CDON, suggesting that analysis of these genes is not warranted in persons with metopic craniosynostosis [Jehee et al 2006]. #### Syndromic Primary Craniosynostosis Craniosynostosis is a finding in more than 150 genetic disorders. Additional syndromes that should be considered are included in Table 2. ### Table 2. Syndromes of Interest in the Differential Diagnosis of FGFR Craniosynostosis Syndromes View in own window Gene(s)DisorderMOIClinical Features of Differential Disorder CraniosynostosisFacial featuresHand & foot findings CD96Opitz trigonocephaly syndrome (C syndrome) (OMIM 211750)ADTrigonocephalyMicrognathia, epicanthal folds, upslanted palpebral fissures, strabismus, anteverted nares, broad nasal bridge, short nose, macrostomiaPostaxial polydactyly, clinodactyly, ulnar deviation of fingers, terminal transverse limb reduction, metacarpal hypoplasia, syndactyly EFNB1Craniofrontonasal syndrome (OMIM 304110)XLCoronalAsymmetric frontal bossing, low posterior hairline, widow's peak, hypertelorism, broad bifid nose, ± cleft lip & palateHands/feet: splitting nails, fingers & toes deviated distally or hypoplastic FLNAX-linked otopalatodigital spectrum disordersXLVariableVariableVariable, hypoplasia of 1st digit of hands & feet GLI3Greig cephalopolysyndactyly syndromeADMacrocephalyFrontal bossing, hypertelorism, wide nasal bridgePolydactyly of the hands (often postaxial), & feet w/syndactyly of toes 1-3 & often a duplicated hallux IHH 1Philadelphia-type craniosynostosis 2ADSagittalProminent foreheadHands/feet: cutaneous syndactyly MSX2Boston-type craniosynostosis (OMIM 604757)ADCoronal; cloverleaf skullFronto-orbital recession or frontal bossingFeet: short 1st metatarsals PORAntley-Bixler syndrome (See Cytochrome P450 Oxidoreductase Deficiency.)ARBrachycephaly or turricephalyMidface retrusionHands: arachnodactyly, clinodactyly, camptodactyly, metacarpal synostoses, wrist deviation Feet: rocker-bottom, metatarsal synostoses, talipes RAB23Carpenter syndrome (OMIM 201000)ARVariable sagittal, lambdoid & coronal; acrocephalyMidface retrusion, flat nasal bridge, epicanthal folds, corneal opacityHands: brachydactyly, syndactyly, aplasia/hypoplasia of middle phalanges Feet: preaxial polydactyly RECQL4Baller-Gerold syndromeARCoronal or lambdoid; brachycephalyProptosis, prominent foreheadHands: radial ray defect (thumb aplasia/hypoplasia, radius aplasia/hypoplasia) SKIShprintzen-Goldberg syndromeADCoronal, sagittal, or lambdoidTall or prominent forehead, proptosis, hypertelorism, downslanted palpebral fissures, malar flatteningHands: arachnodactyly; camptodactyly Feet: malposition, pes planus SOX9Campomelic dysplasiaADNot observedMicrognathia, midface hypoplasia, macrocephaly, Robin sequenceShortening of phalanges in hands & feet, talipes equinovarus TGFBR1 TGFBR2Loeys-Dietz SyndromeADSagittal; dolichocephalyHypertelorism, bifid uvula ± cleft palatePes planus TWIST1Saethre-Chotzen syndromeADCoronal (uni- or bilateral)Low frontal hairline, ptosis, strabismus, facial asymmetryHands: ± 2/3 syndactyly AD = autosomal dominant; AR = autosomal recessive; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked 1\. Klopocki et al [2011] 2\. Robin et al [1996] See Craniosynostosis: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. Secondary craniosynostosis. In children with deficient brain growth, all cranial sutures fuse prematurely and the head is symmetric and microcephalic. Abnormal head positioning in utero or in infancy may also produce an abnormal head shape (plagiocephaly); the abnormality often resolves with appropriate head positioning but occasionally results in craniosynostosis [Hunt & Puczynski 1996, Kane et al 1996]. ## Management [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	FGFR Craniosynostosis Syndromes Overview	None	8,428	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1455/	2021-01-18T21:27:32	{"synonyms": ["FGFR Acrocephalosyndactyly"]}
Abortion in Cuba is legal and available upon request,[1] which is rare in Latin America because of widespread Catholic influence. It is unlikely that the rest of Latin America will soon follow the Cuban model as politicians, social commentators, and church officials all tend to oppose abortion, citing reasons of religion and "morality".[2] Dr. Sosa Marin of the National Commission for Family Planning has stated that "the right to abort is the right of women and their partners."[3] ## Contents * 1 History * 2 Current legal status * 3 Methods * 4 Society and culture * 5 See also * 6 References ## History[edit] Abortion in Cuba used to be limited to cases of harm to the mother or fetus and to cases of pregnancy because of rape. While the nature of this law was highly restrictive, the law itself was not strictly enforced, which meant that abortion was still accessible even before its legalization.[4] Furthermore, prior to full legalization, which covered costs of abortion, private fees were relatively low, allowing most middle- and upper-class women to afford private abortions despite the law. However, as private abortions climbed in numbers, so did mortality rates among women seeking then-illegal abortions. It was the spike in mortality rates that sparked the 1965 liberalization of legal abortion, which was no longer restricted to extreme cases and was to be carried out by public doctors free of charge, rather than by private practitioners.[4] The pre-revolutionary fertility rate in Cuba was extremely low, compared to its Latin American peers, and dropped as low as 26 per 1,000 people in 1958. Post-revolutionary Cuba experienced a significant baby boom, which peaked in the mid-1960s. Following the increased fertility rate alongside the 1965 decriminalization of abortion, legal abortion rates in Cuba rose dramatically. By 1977, the Cuban population reached 420 legal abortions per 1,000 people, the highest legal abortion rate in the world during the 1970s.[4] ## Current legal status[edit] In the hope of curbing high mortality rates among Cuban women attempting self-abortions, the Cuban government decriminalized abortion in 1965.[5] The fight for legalization was furthered in 1979, when legislation was passed to make abortion more easily accessible by Cuban women. Since then, abortion in Cuba has remained easily accessible as well as free countrywide from Cuba's national public healthcare system.[5] Late-term abortions, after 10-weeks, require a formal evaluation that is conducted by a committee of gynecologists and a psychologist.[6] Contrary to other countries in Latin America, government restrictions on abortion are not rooted in reasons of morality or Catholic obligation but are instead based on risk factors for the woman seeking pregnancy termination. It is believed that aside from physical complications and death, women who have multiple abortions risk infertility.[6] ## Methods[edit] Throughout history, naturally-occurring herbs and plants have been used to induce abortion and end unwanted pregnancies in Latin America. Other common practices of inducing illegal abortions include the insertion of objects such as sticks and catheters into the uterus in order to rupture the amniotic sac to trigger termination. However, such methods of abortion are highly unsafe and often result in serious complications for the woman.[2] Cuba's data shows a lack of correlation between the use of contraception and the abortion rate. Other Latin American countries, such as Chile, have observed decreased hospitalization rates related to unsafe abortion complications after the popularization of contraceptive use. Cuba, however, simultaneously sees high contraception use and high rates of abortion.[2] One possible explanation for this lack of correlation could be the high failure rates of contraceptives in Cuba, which rose as high as 20%, in 1987.[2] ## Society and culture[edit] Other contraceptives and methods of birth control are still very commonly used in Cuba, in addition to abortion, as means of fertility regulation.[5] While abortion remains a highly popular method for fertility regulation in Cuba, the IUD and oral contraceptives are the most popular preventative measures against pregnancy for Cuban women.[4] In Cuba, low birth rates are commonly associated with the idea of modernity, and they have been made possible by the availability of safe abortion throughout the country.[6] ## See also[edit] * Reproductive Rights in Latin America * Abortion law * UN document on Cuban abortion policy ## References[edit] 1. ^ "Cuba". United Nations. 2. ^ a b c d Paxman, John M.; Rizo, Alberto; Brown, Laura; Benson, Janie (1993-01-01). "The Clandestine Epidemic: The Practice of Unsafe Abortion in Latin America". Studies in Family Planning. 24 (4): 205–226. doi:10.2307/2939189. JSTOR 2939189. 3. ^ Marti, Jose. "Abortion and Infanticide in Cuba". pop.org. Archived from the original on 2014-10-14. 4. ^ a b c d Hollerbach, Paula E. (1980-01-01). "Recent Trends in Fertility, Abortion and Contraception in Cuba". International Family Planning Perspectives. 6 (3): 97–106. doi:10.2307/2947598. JSTOR 2947598. 5. ^ a b c Bélanger, Danièle; Flynn, Andrea (2009-01-01). "The Persistence of Induced Abortion in Cuba: Exploring the Notion of an "Abortion Culture"". Studies in Family Planning. 40 (1): 13–26. doi:10.1111/j.1728-4465.2009.00183.x. JSTOR 25593932. PMID 19397182. 6. ^ a b c Andaya, Elise (2014). Conceiving Cuba: Reproduction, Women, and the State in the Post-Soviet Era. Rutgers University Press. ISBN 9780813565200. * v * t * e Abortion in North America Sovereign states * Antigua and Barbuda * Bahamas * Barbados * Belize * Canada * Costa Rica * Cuba * Dominica * Dominican Republic * El Salvador * Grenada * Guatemala * Haiti * Honduras * Jamaica * Mexico * Nicaragua * Panama * Saint Kitts and Nevis * Saint Lucia * Saint Vincent and the Grenadines * Trinidad and Tobago * United States Dependencies and other territories * Anguilla * Aruba * Bermuda * Bonaire * British Virgin Islands * Cayman Islands * Curaçao * Greenland * Guadeloupe * Martinique * Montserrat * Puerto Rico * Saint Barthélemy * Saint Martin * Saint Pierre and Miquelon * Saba * Sint Eustatius * Sint Maarten * Turks and Caicos Islands * United States Virgin Islands * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Abortion in Cuba	None	8,429	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Cuba	2021-01-18T19:10:45	{"wikidata": ["Q4668448"]}
A rare genetic neurodevelopmental syndrome characterized by mild intellectual disability, developmental delay, dysmorphic facial features, growth- and feeding problems, hypotonia, epilepsy, behavioral problems and a variety of congenital abnormalities. ## Epidemiology Approximately 40 individuals with mutations in SIN3A have been reported. Males and females are equally affected. ## Clinical description Individuals may present with growth or feeding difficulties, developmental delay and/or intellectual disability. Overall intellectual disability is mild (no cognitive impairment in 25%). Intelligence testing typically shows a disharmonic profile favoring verbal IQ. Facial features include a tall, broad forehead, down-slanting palpebral fissures, triangular face with a pointed chin and a thin upper lip. Half of the patients show epilepsy and/or hypotonia. A third have a psychiatric or behavioral condition, including attention deficit and hyperactivity disorder, autism spectrum disorder, aggressive behavior, obsessive compulsory disorder, depression, psychosis, anxiety and schizoaffective disorder. Other reported manifestations are microcephaly, short stature, palatal defect, hearing loss, ocular abnormalities, and hyperlaxity. Brain abnormalities including ventriculomegaly, anomalies of the corpus callosum, cerebellar atrophy, or Chiari 1 malformation are present in a minority. In a minority of patients, congenital anomalies such as pelvic kidney, atrial/ventricular septal defects (ASD/VSD), cystocele, urethrocele, thickened aortic valve Individuals with 15q24 microdeletion syndrome have a more heterogeneous phenotype with moderate to severe intellectual disability and additional features depending on the other genes involved in the deletion. ## Etiology The disorder is either caused by mutations in Switch-insensitive 3 transcription regulator family member A (SIN3A; 15q24.2) or microdeletions, of various sizes, in the chromosome region 15q24 (15q24 microdeletion syndrome). The microdeletions often, but not always, encompass SIN3A. ## Diagnostic methods Most cases will be identified by unbiased genetic testing including chromosomal microarray, intellectual disability gene panels, whole exome or whole genome sequencing. Targeted genetic testing is possible. ## Differential diagnosis Most cases are identified using an unbiased diagnostic approach for syndromic forms of neurodevelopmental delay or intellectual disability. ## Antenatal diagnosis Prenatal diagnosis is possible where the pathogenic variant has previously been identified in a family member. ## Genetic counseling Transmission is autosomal dominant. Genetic counseling should be offered to parents of affected individuals. The majority of cases are sporadic and thus in these cases the sibling recurrence risk is low. If one of the parents is affected, recurrence risk is 50%. ## Management and treatment A multidisciplinary team approach should be considered including a pediatrician, clinical geneticist, and psychiatrist. Referral to other specialists (e.g. neurologist, ophthalmologist) is indicated when specific problems are suspected. Development should be closely monitored and physical and speech therapy should be considered. Early intervention for psychiatric or behavioral conditions is important to ensure optimal treatment and outcome. Clinicians should be aware that affected individuals will likely have a disharmonic intelligence profile; this easily leads to overestimating of the self-management capabilities of patients. Screening of congenital defects (pelvic kidney, ASD/VSD, cystocele, urethrocele, thickened aortic valve) is recommended after diagnosis. Imaging (e.g MRI) should not be performed routinely, but considered on clinical indication, for instance in the occurrence of seizures. ## Prognosis There is insufficient longitudinal follow-up data to determine life expectancy, although survival into adulthood is typical. Individuals will likely require some degree of support throughout life. Quality of life is greatly influenced by the occurrence of psychiatric and/or neurological conditions. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Witteveen-Kolk syndrome	c4310804	8,430	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=500163	2021-01-23T17:06:39	{"synonyms": ["SIN3A-related intellectual disability syndrome", "WITKOS"]}
Karn et al. (1985) identified a new polymorphism, Pc, in human salivary proteins. Two proteins, Pc1 and Pc2, determined by alleles Pc(1) and Pc(2), showed autosomal codominant inheritance. The 2 alleles showed gene frequencies of 0.670 and 0.330 in blacks and 0.461 and 0.539 in whites. Segregation analysis did not suggest the presence of a null allele in either population. Azen et al. (1985) assigned the proline-rich protein (PRP) genes to chromosome 12 by means of a DNA probe derived from one of these and human-mouse somatic cell hybrids. There was complete concordance between this marker and an RFLP in the 12q14-q22 region. By in situ hybridization, Mamula et al. (1985) regionalized the salivary protein gene complex to 12p13.2. Although Pc is clearly a proline-rich salivary protein coded by the gene cluster on 12p, its relation to the 6 gene loci identified there is not known (Azen, 1990). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	PAROTID PROLINE-RICH SALIVARY PROTEIN Pc	c1868593	8,431	omim	https://www.omim.org/entry/168710	2019-09-22T16:36:33	{"omim": ["168710"]}
A rare, medium or small vessel vasculitis characterized by focal and/or diffuse neurologic symptoms due to a documented arteritic process in the central nervous system, in the absence of other identified underlying cause (infectious, systemic, other neurologic diseases, etc.). It presents with non-specific symptoms of headache, stroke or transient ischemic attacks with cognitive impairment, hemiplegia, weakness, and rarely, with cranial nerve involvement, seizures and ataxia. ## Epidemiology The prevalence is unknown, but it is estimated to account for 1% of the systemic vasculitides. ## Clinical description Primary angiitis of the central nervous system (PACNS) usually affects middle-aged adults (mean age 51 years). Clinical presentation is variable, ranging from hyper acute to chronic and insidious, but typically has a progressive clinical evolution. The most common symptom is headache, variable in description but very rarely a thunderclap headache. Other symptoms include cognitive impairment (usually insidious), stroke (typically multiple, occurring over a (long) period and affecting different areas of the vascular bed) and transient ischemic attacks. Rarely, cranial nerve involvement, myelopathy, seizures or ataxia are observed. Associated angiographic abnormalities are common, cerebral MRI is almost invariably abnormal with nonspecific findings (including, rarely, solitary mass lesion), and cerebrospinal fluid (CSF) examination shows aseptic inflammatory abnormalities. Constitutional symptoms such as fever, weight loss and visceral organ involvement are rare and if present, should raise the suspicion of more systemic illnesses. ## Etiology The primary defect is unknown. Pathological inflammation process affecting the small and medium-sized cerebral vessels causes them to become narrowed, occluded and thrombosed, leading to tissue ischemia and necrosis of the territories of the involved vessels. ## Diagnostic methods Diagnosis of PACNS is established in a patient who: (i) has a history of unexplained neurologic deficit after thorough clinical and laboratory evaluation, (ii) has a documented (by cerebral angiography and/or tissue examination) of an arteritic process within the central nervous system, and (iii) no evidence of systemic vasculitis or any other condition to which the angiographic or pathological features could be secondary. Angiography abnormalities encountered in PACNS are characterized by irregular eccentric notched appearance with distal cutoffs and neovascularization, and typically asymmetric involvement. CSF findings resemble those of an aseptic meningitis with modest lymphocytic pleocytosis, normal glucose levels, elevated protein levels and, occasionally, the presence of oligoclonal bands and elevated IgG synthesis. ## Differential diagnosis Differential diagnosis of PACNS is extensive and challenging, and comprises a range of systemic inflammatory conditions, infections, conditions with cerebral angiographic abnormalities (in particular, reversible vasoconstriction syndrome (RCVS) has highly similar clinical presentation; however, the associated headache is predominantly thunderclap by quality), and other neoplastic, genetic or neurological conditions. ## Management and treatment Glucocorticoids combined with immunosuppressive agents, i.e. cyclophosphamide, has been successful in most cases. Accompanying prophylaxis for P. jirovecii and osteoporosis is necessary. ## Prognosis The disease is chronic and relapses are not uncommon. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Primary angiitis of the central nervous system	c2930862	8,432	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=140989	2021-01-23T18:10:43	{"gard": ["8703"], "mesh": ["C535276", "D020293"], "umls": ["C0751881", "C2930862"], "icd-10": ["I67.7"], "synonyms": ["Isolated angiitis of the central nervous system", "PACNS", "PCNSV", "Primary central nervous system vasculitis", "Primary vasculitis of the central nervous system"]}
A number sign (#) is used with this entry because Charcot-Marie-Tooth (CMT) disease type 4C is caused by homozygous or compound heterozygous mutation in the SH3TC2 gene (608206). Mild mononeuropathy of the median nerve (MNMN; 613353) is a less severe allelic disorder caused by heterozygous mutation in the SH3TC2 gene. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400). Clinical Features Kessali et al. (1997) reported 2 large consanguineous Algerian families with autosomal recessive demyelinating CMT. Mean age at onset was 5.2 years (range 2 to 10 years). All patients had foot deformities and scoliosis, often requiring surgery. Motor nerve conduction velocities were severely decreased, and sural nerve biopsy of 1 patient showed concentric Schwann cell proliferation with multiple small onion bulbs. Linkage analysis excluded known CMT loci. Gabreels-Festen et al. (1999) reported the phenotypic findings in 5 Dutch families, a Turkish family, and a sporadic patient with a unique type of autosomal recessive demyelinating CMT. In addition to classic CMT features, such as distal muscle atrophy and weakness, areflexia, foot deformities, and distal sensory impairment, many patients had early onset of a severe scoliosis, often requiring surgery. Nerve biopsy findings were characterized by an increase of basal membranes around myelinated, demyelinated, and unmyelinated axons, relatively few onion bulbs, and, most typically, large cytoplasmic extensions of Schwann cells. Senderek et al. (2003) reported phenotypic and molecular characterization of 17 patients from 11 families, as well as 1 sporadic case, with autosomal recessive demyelinating CMT linked to chromosome 5. Age at onset ranged from infancy to 12 years, and many patients had a delay in learning to walk. Prominent scoliosis was observed in 11 patients. Mean median motor nerve conduction velocity (NCV) was 22.6 m/s, and nerve biopsy, when obtained, showed demyelination, onion bulb formation, and extended Schwann cell processes. Other classic CMT features included foot deformities, distal muscle weakness and atrophy, mild distal sensory loss, and decreased reflexes. Colomer et al. (2006) reported detailed clinical features of 15 individuals from European Gypsy families with CMT4C and homozygous for the R1109X mutation (608206.0006). Nine patients were members of a large consanguineous Spanish Gypsy kindred (Gooding et al., 2005), with 3 patients each from 3 branches of the family. Within each branch, affected individuals were sibs or first cousins, whereas the relation between branches was as first cousins once removed or second cousins. In the first branch, patients had a relatively late onset at ages 16, 26, and 37 years, respectively, with mild foot deformities, lower limb weakness and walking difficulties. One patient could walk with crutches, 1 could stand with support, and the youngest remained ambulatory. All 3 eventually developed mild upper limb involvement. All also had cranial nerve involvement with deafness, slow pupillary light reflexes, and lingual fasciculations. None had scoliosis. Three patients in the second branch of the family had a more severe disease with onset at ages 6, 6, and 7 years, foot deformities, and distal lower limb weakness and areflexia; 1 had severe scoliosis. There was no evidence of cranial nerve involvement. Affected members of the third branch of the family were the most severely affected. Two boys were hypotonic from birth, never achieved ambulation, had severe scoliosis, and remained wheelchair-bound and totally disabled with generalized muscle weakness and wasting. One died at age 22 years. An affected sister had delayed motor development and severe sensory ataxia, but no scoliosis. Two patients showed prolonged brainstem auditory evoked potentials (BAEP), but no other cranial nerve findings. Six additional patients with the R1109X mutation from 5 different families showed variable features, including 4 with delayed motor development, 3 with scoliosis, and 4 with abnormal BAEP recordings. Common features included foot deformities, distal muscle weakness and atrophy, and difficulty walking. Colomer et al. (2006) noted the highly variable phenotype associated with the same homozygous mutation, especially in the large Spanish Gypsy kindred, and suggested that genetic modifiers may play a role in the manifestation of CMT4C. Azzedine et al. (2006) reported 10 families with CMT4C from Europe and North Africa. Onset occurred between ages 2 and 10 years, and almost all patients presented with scoliosis, kyphoscoliosis, and foot deformities. The functional disability was low, and most patients could walk without help. Median motor nerve conduction velocities were decreased but not associated with disease duration. Azzedine et al. (2006) emphasized that spine deformities are a hallmark of this disorder. Mapping LeGuern et al. (1996) reported results of linkage analysis and homozygosity mapping in 2 large consanguineous Algerian pedigrees with Charcot-Marie-Tooth disease. Affected individuals had peripheral motor and sensory neuropathy in at least the lower limbs and reduced median nerve conduction (mean, 24 +/- 5.1 m/s), consistent with a demyelinating process. LeGuern et al. (1996) excluded linkage of CMT in these families to 17p (CMT1A; 118220), 1q (CMT1B; 118200), and 8q (CMT4A). In 1 family, the 8 affected sibs were homozygous for the markers D5S643 and D5S436. When these 2 loci were considered as 1 marker, a lod score of 4.81 at theta = 0.00 was calculated. In the second family, the 3 affected individuals were homozygous for 5 markers overlapping the region of homozygosity in the first family. The authors determined that the minimal overlapping region of homozygosity in the 2 families restricted the locus to a 4-cM interval between D5S658 and D5S402 (or D5S638, which maps to the same position). Guilbot et al. (1999) constructed a physical map of the candidate region by screening YACs for microsatellites that had been used for the genetic analysis. Combined genetic, cytogenetic, and physical mapping restricted the locus to a region of less than 2 Mb on 5q32. They found probable linkage to 5q31-q33 in 3 of 17 consanguineous affected families, suggesting that the 5q locus may account for almost 20% of demyelinating autosomal recessive CMT. Guilbot et al. (1999) excluded several candidate genes in the region on the basis of their position on the contig and/or by sequence analysis, including EGR1 (128990), which is expressed specifically in Schwann cells. Gabreels-Festen et al. (1999) refined the locus for autosomal recessive demyelinating CMT to a 7-cM region between D5S643 and D5S670 on chromosome 5q23-q33. A maximum lod score of 3.10 was obtained for marker D5S413. By homozygosity mapping and allele-sharing analysis in 5 families with autosomal recessive demyelinating CMT that mapped to chromosome 5, Senderek et al. (2003) refined the CMT4C locus to a 1.7-Mb region on 5q32. Molecular Genetics In affected members of 11 families and a sporadic patient with CMT4C, Senderek et al. (2003) identified 11 different mutations in the SH3TC2 gene (see 608206.0001-608206.0005), of which 8 were protein-truncating and 3 missense. Segregation analyses were consistent with autosomal recessive inheritance. In 8 affected members of a large Spanish Gypsy kindred with CMT4C, Gooding et al. (2005) identified a homozygous mutation in the SH3TC2 gene (R1109X; 608206.0006). Four additional European Gypsy patients also had the mutation. Haplotype analysis indicated a founder effect. In affected members of 10 families with CMT4C, Azzedine et al. (2006) identified compound heterozygous or homozygous mutations in the SH3TC2 gene. The authors identified a total of 10 different mutations, including 8 novel ones. R954X (608206.0005) was a recurrent mutation, occurring in 4 Dutch families and 1 Algerian family. Some of the families had been reported by Kessali et al. (1997) and Gabreels-Festen et al. (1999). Lupski et al. (2010) reported 4 sibs with CMT4C caused by compound heterozygous mutations in the SH3TC2 gene: R954X (608206.0005) and Y169H (608206.0008). Three additional family members who were heterozygous for the R954X mutation, resulting in loss of function, had a mild mononeuropathy of the median nerve, and 2 additional family members heterozygous for the Y169H mutation had an apparently autosomal dominant axonal neuropathy with definite median nerve involvement, as shown by electrophysiologic studies. These findings suggested a toxic gain of function for the Y169H-mutant protein. Lupski et al. (2010) commented on the subtle autosomal dominant phenotypes segregating independently with the respective mutations. Population Genetics Gooding et al. (2005) found that CMT4C occurs across European Gypsy populations, with prevalence among Spanish Gypsies. Other inherited conditions associated with peripheral neuropathy common in the European Gypsy population include HMSNL (601455), HMSNR (605285), and CCFDN (604168). Claramunt et al. (2007) found that 10 of 20 Spanish Gypsy families with autosomal recessive demyelinating neuropathy had CMT4C. The most common mutation was R1109X, which was identified in 20 of 21 mutation-carrying chromosomes. Haplotype analysis indicated a founder effect that likely arose about 225 years ago, probably as a result of a bottleneck. Among the cohort of 20 families, 4 had HMSNL, and 3 had HMSNR. In a French Canadian cluster of 17 CMT4C patients from Quebec, Canada, Gosselin et al. (2008) identified the R954X mutation in homozygosity in 12 patients from 7 families and in compound heterozygosity with an unidentified mutation in 2 patients from 1 family. In total, the R954X mutation was identified in 26 (76%) of 34 alleles from 10 families. Thirteen patients, including 10 homozygous for R954X, originated from a series of coastal villages in the Gaspesie, a sparsely populated peninsular region of Quebec, near the Maine/U.S. border. The villages are distributed along a 150-km stretch of the western shore of Chaleur Bay. Haplotype analysis demonstrated that at least 2 distinct CMT4C mutations are present in the French Canadian population and indicated a founder effect for the R954X mutation. Houlden et al. (2009) identified a homozygous R954X mutation in affected members of 4 English families with CMT4C. A fifth English family was compound heterozygous for R954X and E657K (608206.0007). There was significant phenotypic variability between these families: some presented with severe childhood onset, respiratory and cranial nerve involvement, and became wheelchair-bound, whereas others had only mild scoliosis and foot deformity. One patient homozygous for the R954X mutation had a superimposed inflammatory neuropathy associated with steroid treatment for ulcerative colitis. By screening of the SH3TC2 gene in 60 unrelated Czech patients with CMT, Lassuthova et al. (2011) found that 13 (21.7%) carried at least 1 pathogenic mutation and 7 (11.6%) had 2 pathogenic mutations. Nine novel mutations were identified. Screening for only the R954X mutation showed that 8 (1.94%) of 412 additional patients carried this variant; overall, R954X accounted for 63% of the mutant alleles. Lassuthova et al. (2011) concluded that CMT4C is relatively common in the Czech population. Animal Model Arnaud et al. (2009) found that Sh3tc2-null mice developed a progressive peripheral neuropathy manifest by decreased motor and sensory nerve conduction velocity and hypomyelination. Murine Sh3tc2 was specifically expressed in Schwann cells and localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and/or in regions of axoglial interactions. Analysis of myelin in the peripheral nerve of mutant mice showed abnormal organization of the node of Ranvier, a phenotype that was confirmed in CMT4C patient nerve biopsies. The findings suggested a role for the SH3TC2 gene product in myelination and in the integrity of the node of Ranvier. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial weakness \- Cranial nerve involvement Ears \- Deafness \- Prolonged brainstem auditory evoked potentials (BAEP) Eyes \- Abnormal pupillary light reflexes \- Nystagmus Mouth \- Tongue fasciculations \- Tongue weakness \- Tongue atrophy SKELETAL Spine \- Scoliosis, early-onset, severe Feet \- Pes cavus \- Foot deformities NEUROLOGIC Central Nervous System \- Delayed motor development Peripheral Nervous System \- Distal lower limb muscle weakness due to peripheral neuropathy \- Distal lower limb muscle atrophy due to peripheral neuropathy \- Difficulty walking \- Distal upper limb involvement may occur later \- Proximal lower limb involvement \- Distal sensory impairment of touch, vibration, proprioception \- Cranial nerve involvement \- Decreased motor nerve conduction velocity (NCV) (less than 38 m/s) \- Segmental demyelination \- Secondary axonal degeneration and regeneration \- Basal lamina 'onion bulb' formations on nerve biopsy \- Large cytoplasmic Schwann cell extensions around axons \- Loss of large myelinated fibers MISCELLANEOUS \- Highly variable phenotype, even within families \- Onset usually in first or second decades \- Later onset has been reported (third or fourth decades) \- Usually begins in feet and legs (peroneal distribution) \- Patients may become wheelchair-bound \- Genetic heterogeneity (see CMT4A 214400 ) \- Prevalent among European, particularly Spanish, Gypsies (R1109X, 608206.0006 ) MOLECULAR BASIS \- Caused by mutation in the SH3 domain and tetratricopeptide repeat domain 2 gene (SH3TC2, 608206.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	CHARCOT-MARIE-TOOTH DISEASE, TYPE 4C	c1866636	8,433	omim	https://www.omim.org/entry/601596	2019-09-22T16:14:33	{"doid": ["0110183"], "mesh": ["C535423"], "omim": ["601596"], "orphanet": ["99949"], "synonyms": ["Alternative titles", "CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, AUTOSOMAL RECESSIVE, TYPE 4C", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 4C"], "genereviews": ["NBK1358", "NBK1340"]}
A number sign (#) is used with this entry because Nijmegen breakage syndrome (NBS) is caused by homozygous or compound heterozygous mutation in the NBS1 gene (NBN; 602667) on chromosome 8q21. Description The Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2 is the designation for the Berlin breakage syndrome, which differ only in complementation studies. Cells from NBS/BBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from those of ataxia-telangiectasia (AT; 208900), but NBS/BBS patients have a distinct clinical phenotype. The clinical features of LIG4 syndrome (606593), caused by mutation in the LIG4 gene (601837), resemble those of NBS. Clinical Features Patients with AT variant-1 are clinically indistinguishable from those with AT variant-2. These patients share mitogenic features with AT, such as spontaneous chromosomal instability, clonal occurrence of rearrangements involving, in particular, chromosomes 7 and 14, chromosomal and cellular hypersensitivity to irradiation, and radioresistant DNA synthesis. However, patients with AT-V have neither ataxia nor telangiectasia, and are characterized by pronounced microcephaly, microgenia, 'bird-like' facies, immunodeficiency, and normal serum levels of alpha-fetoprotein. V1 and V2 are distinguished from one another only by complementation analysis (Wegner et al., 1988; Saar et al., 1997). Weemaes et al. (1981) described 2 sons of second-cousin parents who had microcephaly, stunted growth, mental retardation, cafe-au-lait spots, and immunodeficiency. Cytogenetic studies showed a typical form of chromosome instability with multiple rearrangements of chromosomes 7 and 14. A lower frequency of the same chromosome abnormalities was found in the father and 3 of the phenotypically normal sibs. Seemanova et al. (1985) described 9 patients in 6 families with a 'new' disorder characterized by low birth weight for dates, microcephaly with normal intelligence, receding mandibula, cellular and humoral immune defects, and increased risk of lymphoreticular malignancies. No evidence of chromosomal instability was found, but chromosome analysis was difficult because the rate of blastic transformation with phytohemagglutinin was low. Even sex ratio, consanguinity in 1 family and grandparental isonymy in a second, and the occurrence of 2 affected sibs in 3 families supported autosomal recessive inheritance. Bronchiectasis, pneumonia, otitis media, mastoiditis, and sinusitis occurred. Immunoglobulin levels were reduced. In 2 sibs, acute lymphoblastic leukemia developed at ages 9 years and 12 months, respectively. Generalized malignancies, apparently originating in the mediastinum and variously identified as malignant lymphogranuloma, acute undifferentiated hemoblastoma and mediastinal blastoma (probably neuroblastoma) was the cause of death in several. The oldest surviving patient of 4 was 12.5 years old. Conley et al. (1986) described a 21-year-old woman with growth failure, immunodeficiency, and chromosomal breakage syndrome involving chromosomes 7 and 14. Maraschio et al. (1986) described the case of a 31-year-old woman with primary amenorrhea, microcephaly and immunodeficiency. Her healthy parents were related as first cousins once removed. A younger sister, who also had primary amenorrhea, had died at age 20 years with a malignant lymphoma. Chromosome studies revealed a high proportion of metaphases with multiple chromosome aberrations. The same unbalanced translocation, t(8q;21q), was present in about 59% of metaphases. A few rearrangements involving chromosomes 7 and 14, similar to those described in patients with ataxia-telangiectasia, were found. Sister chromatid exchanges were not increased. Teebi et al. (1987) reported a large inbred Arab kindred in which 8 individuals in 5 sibships had microcephaly and normal intelligence. Two died of acute lymphoreticular malignancy or bronchial pneumonia. Immunologic and chromosomal studies carried out in 3 affected living sibs yielded normal results. Taalman et al. (1989) reported the findings in 5 families, 2 from the Netherlands and 3 from Czechoslovakia, containing a total of 8 patients with NBS. The patients had microcephaly, short stature, a 'bird-like' face, and immunologic defects. The basic karyotype in these patients was normal, but in a fifth or more of metaphases, rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all 5 living patients were very sensitive to ionizing radiation. Chrzanowska et al. (1995) reported 11 patients with Nijmegen breakage syndrome from 8 independent Polish families, with a total of 3 pairs of affected sibs. The clinical pattern included microcephaly, particular 'bird-like' face, growth retardation, and, in some cases, mild to moderate mental deficiency. Most of the patients had recurrent respiratory tract infections. One girl developed B-cell lymphoma. Chromosome studies showed structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14, in a proportion of metaphase in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were studied from this point of view. The clinical, immunologic, chromosomal, and cell-biologic findings in 42 patients in the NBS Registry in Nijmegen were reviewed by van der Burgt et al. (1996). Although the immunologic, chromosomal, and cell-biologic findings resembled those in AT, the clinical findings were quite different. The authors stated that NBS appears to be a separate entity that is not allelic to AT, as indicated by the fact that linkage studies exclude 11q22-q23, where the gene for ataxia-telangiectasia is located, as the site of the NBS gene. None of the patients had signs of cerebellar ataxia, apraxic eye movements, or other neurologic abnormalities except for twin girls described by Curry et al. (1989) who had clinical symptoms of both NBS and AT (see 607585.0014). Complementation studies assigned these cases to NBS complementation group V1. Subtle scleral telangiectasia was noted in 10 of 25 patients. The patients did not have raised serum AFP levels, as in ataxia-telangiectasia. Twelve patients varying in age from 1 to 22 years had developed lymphoma. One patient developed a glioma at the age of 12 years, 1 patient a medulloblastoma at 15 years, and 1 patient a rhabdomyosarcoma at 4 years. Der Kaloustian et al. (1996) described a boy who in addition to typical manifestations had penoscrotal hypospadias. He had lymphopenia with low percentage of B and T cells, absence of IgE, and low response to mitogen stimulation. At the age of 4 years he developed rhabdomyosarcoma. Cytogenetic study showed multiple chromatid and chromosome breaks, structural rearrangements involving mainly chromosomes 7 and 14, and different monosomies in 57 to 58% of cells. Nijmegen breakage syndrome was diagnosed, although hypospadias and a high percentage of monosomic cells led the authors to suggest he represented a specific variant of this syndrome. Der Kaloustian et al. (1996) suggested that the boy described by Woods et al. (1995) as a patient with Seckel syndrome might have the same variant of Nijmegen breakage syndrome. Meyer et al. (2004) described a 7-year-old girl with NBS who was homozygous for the NBS1 698del4 mutation (602667.0002). She had been diagnosed with perianal rhabdomyosarcoma (RMS) and experienced severe toxicity from chemotherapy. RMS arising perianally is exceedingly uncommon but had previously been described in 2 cases of NBS (Der Kaloustian et al., 1996; Tekin et al., 2002). Thus, association with NBS should be considered when a perianal RMS is encountered. Tupler et al. (1997) provided the first report of an Italian case of Nijmegen breakage syndrome. The proband was an immunodeficient, microcephalic, 11-year-old boy with a 'bird-like' face. He developed a T-cell-rich B-cell lymphoma. Spontaneous chromosomal instability was detected in T- and B-lymphocytes and in fibroblasts; chromosomes 7 and 14 were only sporadically involved in the rearrangements and no clonal abnormality was present. The patient appeared to be sensitive both to ionizing radiation and to bleomycin, although his sensitivity did not reach the level of ataxia-telangiectasia reference cells. Although the clinical evaluation suggested to Tupler et al. (1997) a diagnosis of NBS, differences in the cytogenetic and cell-biologic data suggested that the patient might have an allelic form of the disorder. To evaluate the possibility of carrier detection, Tanzarella et al. (2003) studied heterozygous individuals from 3 unrelated NBS families with distinct gene deletion mutations for the frequency of spontaneous chromosome abnormalities in blood lymphocytes, x-ray G2 sensitivity in lymphoblastoid cell lines, and the ability to detect nibrin variants by immunoprecipitation and immunoblotting. All 13 heterozygotes showed chromosomal instability (chromatid and chromosomal breaks as well as rearrangements), but 7 of 8 tested were similar to controls in radiosensitivity. Immunoprecipitation of nibrin detected the normal and variant proteins in carriers from all 3 families, but immunoblotting was not as discriminating. ### Complementation Groups Jaspers et al. (1988) studied fibroblast cultures from 6 unrelated patients with immunodeficiency, developmental delay, microcephaly, and chromosomal instability; 1 of the patients had been described by Weemaes et al. (1981), 1 by Sperling (1983), 3 by Seemanova et al. (1985), and 1 by Conley et al. (1986). The cells showed radiosensitivity, clonogenic cell survival, and abnormal inhibition of DNA synthesis. Fibroblasts from all cases showed complementation with the 5 complementation groups of AT. Cross-complementation studies within the group indicated the existence of 2 separate complementation groups, designated V1 and V2, that were genetically distinct from AT. The case of Conley et al. (1986) and 1 case of Sperling (1983) showed complementation with the other cases, and were therefore classified as having V2. The patient of Sperling (1983) was further studied by Wegner et al. (1988). Wegner et al. (1988) reported 2 sibs with a syndrome identical to that in the patient reported by Conley et al. (1986), as shown by complementation studies. These patients had V2. Jaspers et al. (1988) performed complementation studies on fibroblast strains from 50 patients with either AT or NBS. Using the radioresistant DNA replication characteristic as a marker, they demonstrated 6 different genetic complementation groups, 2 of which, groups V1 and V2, involved patients with NBS. An individual with clinical symptoms of both AT and NBS was found in group V2, indicating that the 2 disorders are closely related. Clinical Management In the treatment of malignancies in patients with NBS, van der Burgt et al. (1996) stated that cytostatics are the first choice; however, radiomimetics (for example, bleomycin) should be avoided, and the chemotherapy doses should be reduced. Radiation therapy should be avoided, since x-irradiation can induce malignancies in NBS patients. Cytogenetics Kleier et al. (2000) pointed out that rearrangements involving chromosomes 7 and 14 occur in both ataxia-telangiectasia and NBS. However, NBS patients show characteristic microcephaly, which is rare in ataxia-telangiectasia, and they do not develop ataxia and telangiectasia. Mapping In 6 of the affected Polish families reported by Chrzanowska et al. (1995), Stumm et al. (1995) performed haplotype studies and sib-pair analysis and demonstrated lack of linkage to the 11q22-q23 region where the AT locus maps. One of these families had been assigned to complementation group AT-V1 and a second to complementation group AT-V2 by cell-fusion studies. No complementation studies had been done in the other 4 families. Komatsu et al. (1996) likewise excluded the ATM locus on chromosome 11 as the site of the mutation in AT-V2. They found that the sensitivity of V2 cells to radiation is unchanged after the transfer of an extra copy of a normal chromosome 11 into the cells. Saar et al. (1997) performed a whole-genome screen in 14 NBS/BBS families and localized the causative gene to a 1-cM interval on 8q21, between markers D8S271 and D8S270, with a peak lod score of 6.86 at D8S1811. This marker also showed strong allelic association to both Slavic NBS and German BBS patients, suggesting the existence of one major mutation of Slavic origin. The authors stated that since the same allele is seen in both complementation groups, genetic homogeneity of NBS/BBS can be considered as proved. Matsuura et al. (1997) used microcell-mediated chromosome transfer followed by complementation assays based on radiosensitivity to demonstrate that only chromosome 8 complements the sensitivity to ionizing radiation in NBS cell lines. In complementation assays performed after the transfer of a reduced chromosome, merely the long arm of chromosome 8 was sufficient for restoring the defect. The results supported the suggestion that NBS is a homogeneous disorder and that the gene for NBS is located at 8q21-q24. In a geographically diverse group of NBS patients, Cerosaletti et al. (1998) reported linkage to 8q21 in 6 of 7 families, with a maximum lod score of 3.58. Significant linkage disequilibrium was detected for 8 of 13 markers tested in the 8q21 region, including D8S1811. To localize the gene for NBS further, they generated a radiation hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that placed the NBS gene between D8S1757 and D8S270. A common founder haplotype was present in 15 of 18 disease chromosomes from 9 of 11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggested that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88. Pathogenesis The similarity of cellular and chromosomal symptoms between AT and variant AT suggests that the NBS gene is a radiosensitivity gene and that both the AT and the NBS genes may be part of the same protein complex or pathway. Stumm et al. (1997) found noncomplementation of radiation-induced chromosome aberrations in heterodikaryons between ataxia-telangiectasia and ataxia-telangiectasia variant cells. They suggested that the results of noncomplementation in AT/AT-V cell hybrids could be explained best by genes whose products contribute to a multisubunit protein involved in the damage response of radiation-induced chromosome aberrations. The data supported the assumption that the AT-V disorders represent a homogeneous genetic trait. Molecular Genetics Varon et al. (1998) and Carney et al. (1998) isolated the gene responsible for the Nijmegen breakage syndrome. In patients with NBS, Varon et al. (1998) identified mutations in the nibrin/p95 gene (see, e.g., 657del5; 602667.0001). In the patient reported by Maraschio et al. (1986), Varon et al. (2006) identified a homozygous hypomorphic mutation in the NBN gene (602667.0010). In monozygotic twin brothers with a severe form of NBS without chromosomal instability, Seemanova et al. (2006) identified compound heterozygosity for the major 657del5 mutation and a missense mutation (R215W; 602667.0009) in the NBS1 gene. The infants were small for gestational age and microcephalic; ultrasound revealed enlarged, mildly asymmetric lateral ventricles, enlarged subarachnoid areas, and poor gyrification of the brain. Psychomotor development was severely retarded in both boys. Seemanova et al. (2006) postulated that the severity of the phenotype was due to the R215W mutation. ### Genetic Heterogeneity Maraschio et al. (2003) confirmed genetic heterogeneity for NBS by demonstrating lack of mutation in either the NBS1 or the LIG4 gene in a patient with a typical NBS phenotype. The patient showed intrauterine growth retardation and was born with bilateral inguinal hernia, right cryptorchidism, and curved penis with hypospadias, all of which required surgical treatment. He was seen at the age of 9 months for growth and developmental delay and facial dysmorphism. Facial features included upslanted palpebral fissures, prominent nasal bridge, large mouth with thin upper lip and everted lower lip, and micrognathia. In the proband's blood samples, the frequency of abnormal metaphases was found to vary between 5% and 22%, with a mean value of 10.4%, on a total of 501 observed metaphases. Aberrations consisted mainly of chromatid breaks and chromosome breaks. A slightly increased frequency of chromatid breaks was observed in both parents. ### Heterozygosity Cheung and Ewens (2006) found 520 genes with expression levels that differed significantly (p less than 0.001) between heterozygous NBS mutation carriers and controls. By linear discrimination analysis, they identified a combination of 16 genes that allowed 100% correct classification of individuals as either carriers or noncarriers. Cheung and Ewens (2006) concluded that NBS carriers have a specific gene expression phenotype, and suggested that heterozygous mutations can contribute significantly to natural variation in gene expression. Population Genetics Some of the patients studied by Saar et al. (1997) were Germans in whom the Berlin breakage syndrome had been described and others were Slavic patients in whom the Seemanova syndrome (a synonym for NBS) had been described. Saar et al. (1997) noted that it would be interesting to investigate whether Dutch patients also showed an allelic association at D8S1811, similar to what they had found in Slavic and German patients. In the first half of the 17th century, after the battle of Weissenberg in the Thirty Years War, a considerable number of Bohemian Protestants emigrated to the Netherlands from an area presently part of Poland and the Czech Republic. A major NBS mutation may have found its way to the Netherlands by migration. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, most below 3rd percentile for height Other \- Prenatal growth retardation HEAD & NECK Head \- Microcephaly \- Mastoiditis Face \- Sloping forehead \- Micrognathia \- Prominent midface \- Upward slanting of palpebral fissures Ears \- Large dysplastic ears \- Otitis media Nose \- Choanal atresia \- Long nose (beaked or upturned) Mouth \- Cleft lip \- Cleft palate RESPIRATORY Nasopharynx \- Sinusitis Airways \- Bronchitis \- Bronchiectasis Lung \- Recurrent pneumonia ABDOMEN Gastrointestinal \- Diarrhea and recurrent GI infections \- Anal stenosis \- Anal atresia GENITOURINARY Kidneys \- Hydronephrosis \- Recurrent urinary tract infections SKIN, NAILS, & HAIR Skin \- Cafe au lait spots \- Depigmented spots \- Progressive vitiligo NEUROLOGIC Central Nervous System \- Normal IQ in infancy, then IQ drops with age \- Mental retardation by the age of 7 years \- Hyperactivity \- Neurodegeneration ENDOCRINE FEATURES \- Primary ovarian failure HEMATOLOGY \- Autoimmune hemolytic anemia \- Thrombocytopenia post hemolytic anemia IMMUNOLOGY \- Dysgammaglobulinemia \- Mild to moderately reduced T cell count \- Relatively increased number of natural killer cells NEOPLASIA \- Lymphoma \- Glioma \- Medulloblastoma \- Rhabdomyosarcoma LABORATORY ABNORMALITIES \- Normal alpha fetoprotein \- Low T cell count \- Low B cell count \- Low CD4+ count \- Low CD4+/CD8+ ratio MISCELLANEOUS \- Premature death \- Spontaneous chromosomal instability with multiple rearrangements, especially chromosome 7 and 14 \- Chromosomal hypersensitivity to ionizing radiation and alkylating agents \- Radioresistant DNA synthesis MOLECULAR BASIS \- Caused by mutations in the Nijmegen breakage syndrome gene (NBS1, 602667.0001 ) ▲ 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	NIJMEGEN BREAKAGE SYNDROME	c0398791	8,434	omim	https://www.omim.org/entry/251260	2019-09-22T16:25:11	{"doid": ["7400"], "mesh": ["D049932"], "omim": ["251260"], "orphanet": ["647"], "synonyms": ["Alternative titles", "ATAXIA-TELANGIECTASIA VARIANT V1", "MICROCEPHALY WITH NORMAL INTELLIGENCE, IMMUNODEFICIENCY, AND LYMPHORETICULAR MALIGNANCIES", "SEEMANOVA SYNDROME II", "NONSYNDROMAL MICROCEPHALY, AUTOSOMAL RECESSIVE, WITH NORMAL INTELLIGENCE", "IMMUNODEFICIENCY, MICROCEPHALY, AND CHROMOSOMAL INSTABILITY"], "genereviews": ["NBK1176"]}
For other uses, see Tunnel vision (disambiguation). Tunnel vision Tunnel vision imitation SpecialtyOphthalmology Tunnel vision is the loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision.[1] ## Contents * 1 Causes * 2 Eyeglass users * 3 Mask, goggle, and helmet users * 4 Optical instruments * 5 See also * 6 References * 7 External links ## Causes[edit] Tunnel vision can be caused by: * Glaucoma, a disease of the eye.[2] * Retinitis pigmentosa, a disease of the eye.[3] * Blood loss (hypovolemia) * Alcohol consumption.[4] In addition, the vision becomes blurred or double since eye muscles lose their precision causing them to be unable to focus on the same object. * Sustained (1 second or more) high accelerations.[5] Typically, flying an airplane with a centripetal acceleration of up to or over 39 m/s2 (about 4g) with the head towards the center of curvature, common in aerobatic or fighter pilots. In these cases, tunnel vision and greyout may proceed to a g-force induced Loss Of Consciousness (g-LOC). * Hallucinogenic drugs, in particular the dissociatives. * Stimulant drugs that release and/or prevent the reuptake of dopamine and norepinephrine, in particular amphetamines.[6] * Extreme fear or distress, most often in the context of a panic attack. * Excitement or extreme pleasure such as on a roller-coaster, causing a surge of adrenaline in the body. * During periods of high adrenaline production, such as an intense physical fight. * Altitude sickness, hypoxia in passenger aircraft[7] * Exposure to oxygen at a partial pressure above 1.5-2 atmospheres, producing central nervous system oxygen toxicity, called narcosis.[8] Other symptoms can include dizziness, nausea, blindness, fatigue, anxiety, confusion and lack of coordination. * Pituitary tumours (or other brain tumours that compress the optic chiasm) * Prolonged exposure to air contaminated with heated hydraulic fluids and oils, as can sometimes happen in passenger aircraft.[7] * Severe cataracts, causing a removal of most of the field of vision * During the aura phase of a migraine * Intense anger, due to the body being rapidly flooded with adrenaline and oxygen * A bite from a black mamba and other snakes with the same strength venom. * Mercury poisoning (especially methylmercury) * Sleep deprivation * Syncope (fainting)[9] ## Eyeglass users[edit] Eyeglass users experience tunnel vision to varying degrees due to the corrective lens only providing a small area of proper focus, with the rest of the field of view beyond the lenses being unfocused and blurry. Where a naturally sighted person only needs to move their eyes to see an object far to the side or far down, the eyeglass wearer may need to move their whole head to point the eyeglasses towards the target object.[citation needed] The eyeglass frame also blocks the view of the world with a thin opaque boundary separating the lens area from the rest of the field of view. The eyeglass frame is capable of obscuring small objects and details in the peripheral field.[citation needed] ## Mask, goggle, and helmet users[edit] Wide-field, wrap-around diving mask Diving mask with narrow field of view Extremely large wide-field binoculars that would not be practical to carry Activities which require a protective mask, safety goggles, or fully enclosing protective helmet can also result in an experience approximating tunnel vision. Underwater diving masks using a single flat transparent lens usually have the lens surface several centimeters from the eyes. The lens is typically enclosed with an opaque black rubber sealing shell to keep out water. For this type of mask the peripheral field of the diver is extremely limited. Generally, the peripheral field of a diving mask is improved if the lenses are as close to the eye as possible, or if the lenses are large, multi-window, or is a curved wrap-around design.[citation needed] Protective helmets such as a welding helmet restrict vision to an extremely small slot or hole, with no peripheral perception at all. This is done out of necessity so that ultraviolet radiation emitted from the welding arc does not damage the welder's eyes due to reflections off shiny objects in the peripheral field.[citation needed] ## Optical instruments[edit] Binoculars, telescopes, and microscopes induce an experience of extreme tunnel vision due to the design of the optical components. A wide field microscope or telescope generally requires much larger diameter and thicker lenses, or complex parabolic mirror assemblies, either of which results in significantly greater cost for construction of the optical device.[citation needed] Wide-field binoculars are possible, but require bulkier, heavier, and more complex eyepieces. The diameter of the objective lenses is unimportant for field of view.[10] The widest-angle eyepieces used in telescopes are so large that two would not fit side-by-side for use in binoculars.[citation needed] ## See also[edit] * Target fixation ## References[edit] 1. ^ "Definition of Tunnel vision". MedicineNet. 2. ^ "Glaucoma: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2016-02-21. 3. ^ "Retinitis pigmentosa". Genetics Home Reference. 2016-02-15. Retrieved 2016-02-21. 4. ^ Effects of Alcohol on Vision Archived 2006-10-08 at the Wayback Machine 5. ^ "Virtual Naval Hospital: United States Naval Flight Surgeon Manual: Third Edition 1991: Chapter 2: Acceleration and Vibration: Sustained Acceleration". 23 November 2005. Archived from the original on 2005-11-23. 6. ^ Mills, Kenneth C.; Spruill, Susan E.; Kanne, Roy W.; Parkman, Katherine M.; Zhang, Ying (5 September 2016). "The Influence of Stimulants, Sedatives, and Fatigue on Tunnel Vision: Risk Factors for Driving and Piloting". Human Factors: The Journal of the Human Factors and Ergonomics Society. 43 (2): 310–327. doi:10.1518/001872001775900878. PMID 11592671. S2CID 6852335. 7. ^ a b "Friend Statement". 5 October 2006. Archived from the original on 2006-10-05. 8. ^ "Virtual Naval Hospital: United States Naval Flight Surgeon Manual: Third Edition 1991: Chapter 1: Oxygen Toxicity". 22 November 2005. Archived from the original on 2005-11-22. 9. ^ "Vasovagal syncope". www.mayoclinic.org. Retrieved 2020-08-28. 10. ^ "Meade Sports Optics - How to Select the Right Binocular". www.meade.com. ## External links[edit] * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Tunnel vision	c2937228	8,435	wikipedia	https://en.wikipedia.org/wiki/Tunnel_vision	2021-01-18T18:47:39	{"umls": ["C2937228"], "wikidata": ["Q2460147"]}
Mandibuloacral dysplasia Other namesMAD[1] Mandibuloacral dysplasia (MAD) is a rare autosomal recessive syndrome characterized by mandibular hypoplasia, delayed cranial suture closure, dysplastic clavicles, abbreviated and club-shaped terminal phalanges, acroosteolysis, atrophy of the skin of the hands and feet, and typical facial changes.[2]:576 ## Contents * 1 Types * 2 See also * 3 References * 4 External links ## Types[edit] Type OMIM Gene Locus MADA 248370 LMNA[3] 1q21.2 MADB 608612 ZMPSTE24[4] 1p34 ## See also[edit] * Hereditary sclerosing poikiloderma * Skin lesion ## References[edit] 1. ^ "Mandibuloacral dysplasia". Genetic and Rare Diseases. NIH. Retrieved 19 March 2019. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 3. ^ Al-Haggar M, Madej-Pilarczyk A, Kozlowski L, Bujnicki JM, Yahia S, Abdel-Hadi D, Shams A, Ahmad N, Hamed S, Puzianowska-Kuznicka M (2012). "A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome". Eur J Hum Genet. 20 (11): 1134–40. doi:10.1038/ejhg.2012.77. PMC 3476705. PMID 22549407. 4. ^ Barrowman J, Wiley PA, Hudon-Miller SE, Hrycyna CA, Michaelis S (2012). "Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity". Hum Mol Genet. 21 (18): 4084–93. doi:10.1093/hmg/dds233. PMC 3428156. PMID 22718200. ## External links[edit] Classification D * OMIM: 248370 * DiseasesDB: 33029 * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins This Genodermatoses article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Mandibuloacral dysplasia	c0432291	8,436	wikipedia	https://en.wikipedia.org/wiki/Mandibuloacral_dysplasia	2021-01-18T19:06:26	{"gard": ["11893"], "mesh": ["C535705"], "umls": ["C0432291"], "orphanet": ["2457"], "wikidata": ["Q16968886"]}
Mosaic trisomy 20 is a rare chromosomal anomaly syndrome with a highly variable phenotype ranging from normal (in the majority of cases) to a mild, subtle phenotype principally characterized by spinal abnormalities (i.e. stenosis, vertebral fusion, and kyphosis), hypotonia, lifelong constipation, sloped shoulders, skin pigmentation abnormalities (i.e. linear and whorled nevoid hypermelanosis) and significant learning disabilities despite normal intelligence. More severe phenotypes, with patients presenting psychomotor and speech delay, mild facial dysmorphism, cardiac (i.e. ventricular septal defect, dysplastic tricuspid mitral valve) and renal anomalies (e.g. horseshoe kidneys), have 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	Mosaic trisomy 20	c0265479	8,437	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1724	2021-01-23T17:19:39	{"mesh": ["C535372"], "icd-10": ["Q92.1"], "synonyms": ["Mosaic trisomy chromosome 20", "Trisomy 20 mosaicism"]}
A number sign (#) is used with this entry because it represents a gene cluster on chromosome 5q31 containing 16 tandemly arranged single-exon genes: PCDHB1 (606327), PCDHB2 (606328), PCDHB3 (606329), PCDHB4 (606330), PCDHB5 (606331), PCDHB6 (606332), PCDHB7 (606333), PCDHB8 (606334), PCDHB9 (606335), PCDHB10 (606336), PCDHB11 (606337), PCDHB12 (606338), PCDHB13 (606339), PCDHB14 (606340), PCDHB15 (606341), and PCDHB16 (606345). Description Cadherins are calcium-dependent cell-cell adhesion molecules, and protocadherins constitute a subfamily of nonclassic cadherins. The PCDHB gene cluster encodes a family of protocadherins. Unlike the PCDHA (604966) and PCDHG (604968) gene clusters, in which mRNAs are produced by splicing a single upstream variable exon to 3 downstream constant region exons, PCDHB mRNAs are encoded by single-exon genes. Thus, each PCDHB gene encodes the extracellular, transmembrane, and short cytoplasmic domains of the protein (Wu et al., 2001). Cloning and Expression By EST database searching for cadherin-like sequences, Wu and Maniatis (1999) identified 52 novel genes organized into 3 closely linked tandem clusters, alpha, beta, and gamma, on human chromosome 5q31. A distinct large, uninterrupted exon of approximately 2,400 nucleotides encodes the 6 N-terminal extracellular domains and the transmembrane domain of each protocadherin. The C termini of the PCDHA and PCDHG proteins are identical within each cluster and are encoded by 3 small exons located downstream from the array of N-terminal exons. Each large exon is independently spliced to the first exon encoding the intracellular domain. Wu and Maniatis (1999) denoted the extracellular portion as the variable region and the cytoplasmic portion as the constant region. They could not determine the cytoplasmic sequence of the PCDHB genes. Wu and Maniatis (1999) proposed 4 models to explain protocadherin gene regulation and noted that several neurologic disorders map to chromosome 5q31. Wu and Maniatis (1999) determined that the PCDHB cluster contains at least 15 genes that encode proteins whose sequences most closely resemble those of the rat brain Pcdh3 protein. They identified numerous EST database matches from human brain tissue. Vanhalst et al. (2001) and Wu et al. (2001) showed that in contrast to the PCDHA and PCDHG clusters, the PCDHB gene cluster does not have a downstream constant region. The C-terminal cytoplasmic domains of PCDHB proteins are therefore encoded by the single-exon PCDHB genes. By sequence analysis, Vanhalst et al. (2001) determined that the N-terminal regions of PCDHB proteins (ectodomains 1, 2, and 3) are variable, while the 3 membrane proximal ectodomains (4, 5, and 6) are more conserved. The single transmembrane domain and the cytoplasmic domain are highly conserved in PCDHB proteins, except for the last 20 amino acids. Most PCDHB proteins have a PXXP motif, a putative SH3 protein-binding site, at the end of the conserved region of the cytoplasmic domain. Vanhalst et al. (2001) concluded that the PCDHB genes arose by repeated gene duplication events. ### PCDHG Antisense Transcripts A cis-antisense gene pair is defined as a pair of genes residing on opposite strands in the same locus with at least 1 exon of one gene overlapping at least 1 exon of the other gene. Cis-antisense transcripts function in gene regulation at both the transcriptional and posttranscriptional levels. By in silico analysis of the PCDH gene clusters, Lipovich et al. (2006) identified 12 cis-antisense transcriptional units. Those with greatest EST support were anti-PCDHA12 (606318), anti-PCDHB3, and anti-PCDH5 pseudogene, all of which appeared to be noncoding. These antisense transcripts were conserved in chimpanzee and rhesus, but not in mouse. PCR analysis verified expression of these antisense transcripts in adult and fetal human brain and in rhesus brain, and the presence of antisense transcripts was associated with significantly reduced sense expression levels across all orthologs. Gene Function Mountoufaris et al. (2017) showed that the PCDH-alpha (604966), PCDH-beta, and PCDH-gamma (604968) gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb. Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all 3 clusters led to a severe axonal arborization defect and loss of self-avoidance. By contrast, when endogenous Pcdh diversity is overridden by the expression of a single-tricluster gene repertoire (alpha and beta and gamma), olfactory sensory neuron axons fail to converge to form glomeruli, likely owing to contact-mediated repulsion between axons expressing identical combinations of Pcdh isoforms. Gene Structure Wu et al. (2001) determined that the PCDHB gene cluster spans about 200 kb and contains 16 genes. Unlike the PCDHA and PCDHG gene clusters, the PCDHB cluster has no constant region exons. The mouse Pcdhb gene cluster is larger and contains 6 more genes than the human PCDHB gene cluster. Comparative sequence analysis of human and mouse PCDHB gene clusters showed that there are high ratios of CpG dinucleotide islands near the 5-prime ends of each PCDHB gene. The results indicated that each PCDHB gene has its own promoter, which is highly conserved between orthologous genes in mouse and human. Tasic et al. (2002) showed that each PCDHB gene is preceded by a promoter. Furthermore, each PCDHB exon contains a conserved 5-prime splice site, and each transcript terminates near a polyadenylation signal in the intergenic region downstream of the corresponding 5-prime splice site. Mapping By genomic sequence analysis, Wu and Maniatis (1999) mapped the PCDHB gene cluster to chromosome 5q31. They mapped the mouse Pcdhb gene cluster to a region of chromosome 18 that shows homology of synteny to human chromosome 5q31. Molecular Genetics Miki et al. (2005) identified numerous SNPs in the PCDHB gene cluster in 104 Japanese individuals. A relatively high number of amino acid changes due to coding SNPs were identified in ectodomains 5 and 6. They also identified SNPs that appeared to represent gene conversions of PCDHB9 to PCDHB7. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	PROTOCADHERIN-BETA GENE CLUSTER	None	8,438	omim	https://www.omim.org/entry/604967	2019-09-22T16:11:41	{"omim": ["604967"], "synonyms": ["Alternative titles", "PCDH-BETA GENE CLUSTER"]}
Abortion in Alabama is legal. Several legal challenges are blocking the recent abortion ban legislation.[1] Abortion is a divisive issue in the state, with 37% of adults believing it should be legal in all or most cases and 58% believing it should be illegal in all or most cases.[2] Recent support to restrict abortions in the state has come from white evangelical Christian women. There have been laws about abortion in Alabama dating back to the 1800s, when the state legislature banned the practice out of a desire to protect women's health because of the number of deaths linked to the practice. In 1972, a year before the US Supreme Court's Roe v. Wade ruling, abortion was legal only in cases where the woman's physical health was endangered. Women have gotten around restrictions by traveling to other states. The state legislature was active in trying to pass cardiogenesis or "fetal heartbeat" detection date abortion bans starting in 2014, and continuing unsuccessfully for the next few years. After the confirmation of Brett Kavanaugh to the US Supreme Court, the state legislature passed new legislation with the hope of challenging and overturning Roe v. Wade. The number of abortion clinics in Alabama has been on the decline for years, going from 45 in 1982 to three in 2019. Abortion rights activism takes place in the state. One organization involved with this is the Yellowhammer Fund. Women have also protested the denial of access to abortion as part of the #StoptheBans movement in 2019 in Montgomery and Birmingham. There is also a pro-life movement in the state that opposes abortion. ## Contents * 1 Terminology * 2 Context * 3 History * 3.1 Legislative history * 3.2 Judicial history * 3.3 Clinic history * 4 Statistics * 5 Women's abortion experiences * 6 Abortion rights views and activities * 6.1 Views * 6.2 Organizations * 6.3 Donations * 6.4 Protests * 6.5 Political support * 7 Anti-abortion views and activities * 7.1 Activities * 7.2 Violence * 8 Footnotes * 9 References ## Terminology[edit] Main article: Abortion The abortion debate most commonly relates to the "induced abortion" of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[note 1] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[3] Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[4][5] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[6][7] Both "pro-choice" and "pro-life" are examples of terms labeled as political framing: they are terms which purposely try to define their philosophies in the best possible light, while by definition attempting to describe their opposition in the worst possible light. "Pro-choice" implies that the alternative viewpoint is "anti-choice", while "pro-life" implies the alternative viewpoint is "pro-death" or "anti-life".[8] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[9] ## Context[edit] Free birth control correlates to teenage girls having fewer pregnancies and fewer abortions. A 2014 New England Journal of Medicine study found such a link. At the same time, a 2011 study by Center for Reproductive Rights and Ibis Reproductive Health also found that states with more abortion restrictions have higher rates of maternal death, higher rates of uninsured pregnant women, higher rates of infant and child deaths, higher rates of teen drug and alcohol abuse, and lower rates of cancer screening.[10] The study singled out Oklahoma, Mississippi and Kansas as being the most restrictive states that year, followed by Arkansas and Indiana for second in terms of abortion restrictions, and Florida, Arizona and Alabama in third for most restrictive state abortion requirements.[10] According to a 2017 report from the Center for Reproductive Rights and Ibis Reproductive Health, states that tried to pass additional constraints on a women's ability to access legal abortions had fewer policies supporting women's health, maternal health and children's health. These states also tended to resist expanding Medicaid, family leave, medical leave, and sex education in public schools.[11] In 2017, Georgia, Ohio, Missouri, Louisiana, Alabama and Mississippi have among the highest rates of infant mortality in the United States.[11] In 2017, Alabama had an infant mortality rate of 7.4 deaths per 1,000 births.[11] Medicaid expansion under the Affordable Care Act was rejected by Alabama, Georgia, Mississippi and Missouri. Consequently, poor women in the typical age range to become mothers had a gap in coverage for prenatal care. According to Georgetown University Center for Children and Families research professor Adam Searing, "The uninsured rate for women of childbearing age is nearly twice as high in states that have not expanded Medicaid. [...] That means a lot more women who don't have health coverage before they get pregnant or after they have their children. [...] If states would expand Medicaid coverage, they would improve the health of mothers and babies and save lives."[11] According to the 2018 Premature Birth Report Cards, Louisiana, Mississippi and Alabama were all given an F.[11] According to the 2018 America's Health Rankings produced by United Health Foundation, Alabama ranked 7th in the country when it came to maternal mortality.[11] A 2018 March of Dimes report said the preterm birth rate among African American women in Alabama and Louisiana was much higher, 51% higher, than women of all other races in the state.[11] Poor women in the United States had problems paying for menstrual pads and tampons in 2018 and 2019. Almost two-thirds of American women could not pay for them. These were not available through the federal Women, Infants, and Children Program (WIC).[12] Lack of menstrual supplies has an economic impact on poor women. A study in St. Louis found that 36% had to miss days of work because they lacked adequate menstrual hygiene supplies during their period. This was on top of the fact that many had other menstrual issues including bleeding, cramps and other menstrual induced health issues.[12] This state was one of a majority that taxed essential hygiene products like tampons and menstrual pads as of November 2018.[13][14][15][16] Alabama was one of only two states in the US (along with Minnesota) in 2019 that did not have a law that terminated parental rights of men who produced a child via rape or incest.[17][18] In 2019, an effort was made to pass legislation doing so in the case of rape, but it did not pass as such. It was changed to allow courts to terminate parental rights of parents who sexually abused their own children.[18] ## History[edit] Between 1892 and 1935, there were 40 prosecutions and five convictions in Alabama for women having abortions.[19] In 2014, 37% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[20] 58% of people in Alabama said abortion should be “illegal in all or most cases.”[21] According to a 2014 Public Religion Research Institute (PRRI) study, 60% of white women, the same percentage as white men, in the state believed that abortion be illegal in all or most cases.[22] In recent years, white women have played a major role in helping Republican male anti-abortion rights candidates get elected. In 2017, around 63% of white women voted for Republican Roy Moore and not for Democratic senatorial candidate Democrat Doug Jones. 98% of black women voted for Jones.[22] One of the biggest groups of women who oppose legalized abortion in the United States are southern white evangelical Christians. These women voted overwhelming for Donald Trump, with 80% of these voters supporting him at the ballot box in 2016. In November 2018, during US House exit polling, 75% of white evangelical Christian women indicated they supported Trump and only 20% said they voted for Democratic candidates. 75% of white evangelical Christian women voted for Moore in 2017.[22] With states like Alabama and Georgia passing restrictive abortion laws in early 2019, some businesses announced they would boycott these states. Birmingham, Alabama Mayor Randall Woodfin said that these boycotts would likely mean two tech companies would not base themselves in the city. Other states moved to try to take advantage of this political situation, including New Jersey where Governor Phil Murphy related a statement that said, “New Jersey is open for business for any company that, given the assault on a woman’s right to choose perpetrated by states like Alabama and Georgia, is seeking a home that recognizes basic constitutional rights. [...] New Jersey offers not only a hospitable business climate, but also maintains its progressive values, which include defending a woman’s right to choose. “[23] ### Legislative history[edit] Fetal heartbeat bills by state, including time limit without exceptions marked: Heartbeat bill passed (to go into effect) Law partially passed by state legislature Law blocked by court order By the end of the 1800s, all states in the Union except Louisiana had therapeutic exceptions in their legislative bans on abortions.[19] In the 19th century, bans by state legislatures on abortion were about protecting the life of the mother given the number of deaths caused by abortions; state governments saw themselves as looking out for the lives of their citizens.[19] By the end of 1972, Mississippi allowed abortion in cases of rape or incest only and Alabama and Massachusetts allowed abortions only in cases where the woman's physical health was endangered. In order to obtain abortions during this period, women would often travel from a state where abortion was illegal to states where it was legal.[24] emergency), was introduced into the Lower House. The bill passed the Lower House on April 30 (74-3),[25] the Senate on 14 May,[26] and was signed into law by Governor Kay Ivey on 16 May.[27] The state was one of 23 states in 2007 to have a detailed abortion-specific informed consent requirement.[28] By law, abortion providers in Alabama, Louisiana and Mississippi were required to perform ultrasounds before providing women with ultrasounds, even in situations like in the first trimester where an ultrasound has no medical necessity.[29] In 2013, state Targeted Regulation of Abortion Providers (TRAP) law applied to medication induced abortions and private doctor offices in addition to abortion clinics.[30] Dates of when heartbeat laws come into effect (as of May 25, 2019) The state legislature was one of five states nationwide that tried, and failed, to pass a fetal heartbeat bill in 2014.[31] House Bill 490 prohibiting abortions once a cardiogenesis or "fetal heartbeat" is detected passed the Lower House (73-29) on 4 March 2014.[32] The bill later died in committee. [33] Despite this, Alabama's Lower House was the first state in the nation to pass such a bill.[32] The state legislature tried and failed again in 2015 to pass similar legislation where they were one of three states, again in 206 when they were one of four states, and again in 2017 when they were one of eight states to attempt to pass a fetal heartbeat bill.[31] The law as of March 2019 required women wait 24 hours after their initial appointment for an abortion before they could have a second appointment for the actual procedure.[34] State law at the time prohibited health insurance companies on public exchanges from offering abortion services unless the life of the woman was at risk, or the pregnancy was a result of rape or incest.[34] Nationally, 2019 was one of the most active years for state legislatures in terms of trying to pass abortion rights restrictions. State governments with Republican majorities started to push these bills after Brett Kavanaugh was confirmed as a US Supreme Court judge, replacing the more liberal Anthony Kennedy. These state governments generally saw this as a positive sign that new moves to restrict abortion rights would less likely face resistance by the courts.[35] Then, House Bill 314 banning abortions at every stage of pregnancy and criminalizing the procedure for doctors (except in the case of medical emergency), was introduced into the Lower House on 2 Apr 2019. The bill passed the Lower House on 30 Apr (74-3),[8] the Senate on 14 May,[9] and was signed into law by Governor Kay Ivey on 16 May.[10] In mid-2019, the state legislature passed a law that would make abortion illegal in almost all cases after 8 weeks. It was one of several states passing such laws in May 2019 alongside Missouri, Louisiana, and Georgia.[36][37][35] The Republican Governor Kay Ivey signed the bill into law in mid-May.[35] At the time that the legislation passed, only 16% of the state legislators were female.[38] ### Judicial history[edit] The US Supreme Court's decision in 1973's Roe v. Wade ruling meant the state could no longer regulate abortion in the first trimester.[19] In August 2018, the dilation & evacuation (D & E) legislation passed by Texas and Alabama were working their way through the federal courts appeal process.[39] The Eleventh Circuit ruled the D&E legislation to be unconstitutional, blocking it from being enforced, and the Supreme Court of the United States denied to hear its appeal in its 2019 term. On February 6, 2019, Ryan Magers filed a wrongful death lawsuit against an abortion clinic, Alabama Women's Center, after his girlfriend had a legal abortion there in January 2017 as she did not want to continue her pregnancy. He also sued three employees of the clinic and the pharmaceutical company that made the drug for the medication induced abortion. Madison County Probate Judge Frank Barger recognized the status of the unborn fetus as a person on March 4, 2019 in accepting the case.[40] In May 2019, Planned Parenthood and the American Civil Liberties Union said they would challenge Alabama's recently enacted abortion ban in the federal courts.[11] In June 2019, it was reported that a woman Marshae Jones; whose pregnancy was terminated after she was shot in the stomach in 2018 during a fight, was arrested on grounds of manslaughter of the fetus. The case is still on going.[41] ### Clinic history[edit] Total abortion clinics in Alabama by year. Between 1982 and 1992, the number of abortion clinics in the state decreased by 25, going from 45 in 1982 to 20 in 1992.[42] In 2014, there were five abortion clinics in the state.[39] In 2014, 93% of the counties in the state did not have an abortion clinic.[43] That year, 59% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[43] In 2017, there were two Planned Parenthood clinics in a state with a population of 1,117,288 women aged 15 – 49 of which two offered abortion services.[44] Alabama Women's Center was a clinic operating in the state in 2017.[40] There were five abortion clinics in Alabama in March 2019, and all were located in metro areas. They were located in Birmingham, Huntsville, Tuscaloosa, Mobile and Montgomery.[34] Of the five clinics operating in March 2019, one was only one on weekends.[34] In 2019, the Yellowhammer Fund assisted women at three abortion clinics in Alabama in paying to have an abortion.[45] In May and June 2019, Alabama's abortion clinics were regularly getting calls from women trying to find out if they could still use their services to get a legal abortion; legislative changes had resulted in a lot of confusion from pregnant women about their abortion rights in the state.[46] ## Statistics[edit] In the period between 1972 and 1974, the state had an illegal abortion mortality rate per million women aged 15 – 44 of between 0.1 and 0.9.[47] In 1990, 456,000 women in the state faced the risk of an unintended pregnancy.[42] In 2010, the state had nine publicly funded abortions, none of which were federally or state funded.[48] 59% of Alabama women lived in a county without an abortion clinic in 2014. There was an average of one abortion clinic every 10,483 square miles that year.[34] Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[49] Census division and state Number Rate % change 1992–1996 1992 1995 1996 1992 1995 1996 Total 1,528,930 1,363,690 1,365,730 25.9 22.9 22.9 –12 East South Central 54,060 44,010 46,100 14.9 12 12.5 –17 Alabama 17,450 14,580 15,150 18.2 15 15.6 –15 Kentucky 10,000 7,770 8,470 11.4 8.8 9.6 –16 Mississippi 7,550 3,420 4,490 12.4 5.5 7.2 –42 Tennessee 19,060 18,240 17,990 16.2 15.2 14.8 –8 Number, rate, and ratio of reported abortions, by reporting area of residence and occurrence and by percentage of abortions obtained by out-of-state residents, US CDC Estimates Location Residence Occurrence % obtained by out-of-state residents Year Ref No. Rate^ Ratio^^ No. Rate^ Ratio^^ Alabama \-- \-- \-- 13,358 14 215 9.3 1992 [50] Alabama \-- \-- \-- 14,221 15 236 12.3 1995 [51] Alabama \-- \-- \-- 13,826 14 229 14,6 1996 [52] Alabama 7,893 8.2 133 8,080 8.4 136 17.7 2014 [53] Alabama 6,618 6.9 111 5,899 6.2 99 13.1 2015 [54] Alabama 6,986 7.3 118 6,642 7.0 112 16.8 2016 [55] ^number of abortions per 1000 women aged 15–44; ^^number of abortions per 1000 live births ## Women's abortion experiences[edit] Jenna King-Shepherd had an abortion when she was a 17-year-old. While her father is a pastor at a Southern Baptist church and while he opposed abortion and read her Biblical verses to explain why abortion was wrong, King-Shepherd's father accompanied her to a clinic to get an abortion. According to King-Shepherd, "I think that just speaks to the incredibly complex decision, not even just the decision to have an abortion, but the incredibly complicated beliefs surrounding abortion even."[46] ## Abortion rights views and activities[edit] ### Views[edit] Yellowhammer Fund President Amanda Reyes said in 2019, "Republicans don't have fewer abortions than Democrats or liberals or anarchists or communists. It's that our political rhetoric paints people who have abortions as largely the same — poor women, young women, irresponsible women, women who hate children. [...] It's gotten us to a point where we can't see the fact that we're all having abortions, and we're doing it for reasons we personally think matters — and that's all that matters. Pro-life women are having abortions, too."[45] ### Organizations[edit] The Yellowhammer Fund is an organization that financially assists women in Alabama who are seeking an abortion but have difficulty paying for one.[45] ### Donations[edit] After Alabama passed its restrictive abortion legislation in 2019, The National Network of Abortion Funds got more than US$262,000 in donations from more than 12,000 total people.[56] Yellowhammer Fund also saw a huge surge. Thanks largely in response to fundraising efforts by one activist, the organization got close to US$30,000 in donations in a three-hour period.[56] ### Protests[edit] On May 19, 2019, women from Montgomery participated in an abortion rights march outside the Alabama Capitol building as part of a #StoptheBans rally.[57][58] Another protest took place in Birmingham, Alabama on May 19, 2019. Women participating included Liz Satterfield.[45] ### Political support[edit] California Senator Kamala Harris held a 2020 Democratic Party Primary campaign rally in Birmingham on June 7, 2019. One of the messages she talked about during her rally was abortion rights in the state. During the rally, she said that if she were president, she would require the Department of Justice to review any state law restriction abortion access “if it’s coming from a state that has a history of limiting those rights.” This way, the US Government could make sure that such laws were constitutional before going into effect and prevent states like Alabama from continually trying to challenge established precedent that has legalized abortion through cases like Roe v. Wade.[59] ## Anti-abortion views and activities[edit] ### Activities[edit] North Jefferson Women's Center is a non-profit family planning clinic in Fultondale that opposes abortions. In 2019, they were seeking funding for a new ultrasound machine to assist pregnant women that use their services. Unable to pay for it on their own, the Southern Baptist organization The Psalm 139 Project donated the funds to support a clinic that teaches life begins at conception. The North Jefferson Women's Center will never refer women to an abortion provider, even if the pregnant woman desires such information.[46] The Southern Baptist Convention held their annual convention in Birmingham in June 2019. The timing was coincidental with the efforts in the state to restrict legal abortion access, but opposing legal abortions was part of their planned two-day discussion.[46] This van was parked outside of the Women's Clinic that was bombed by Eric Rudolph in the mid-1990s. It's still open, and obviously still draws protesters. It had broken down though, and the woman who owned it, couldn't get anyone to let her use their phone to call for a tow. ### Violence[edit] On May 12, 1984, two men entered a Birmingham, Alabama clinic on Mother's Day weekend shortly after a lone woman opened the doors at 7:25 A.M. Forcing their way into the clinic, one of the men threatened the woman if she tried to prevent the attack while the other, wielding a sledgehammer, did between $7,500 and $8,500 of damage to suction equipment. The man who damaged the equipment was later identified as Father Edward Markley. Markley is a Benedictine priest who was the Birmingham diocesan "Coordinator for Pro-Life Activities". Markley was convicted of first-degree criminal mischief and second-degree burglary. His accomplice has never been identified. The following month (near Father's Day), Markley entered a women's health center in Huntsville, Alabama.[60] On June 15, 1984, a month after he destroyed suction equipment at a Birmingham clinic, Father Edward Markley, a Benedictine priest who was the Birmingham diocesan "Coordinator for Pro-Life Activities".[I 1][I 2] Kathryn Wood, one of the workers, received back injuries and a broken neck vertebrae while preventing Markley from splashing red paint on the clinic's equipment. Markley was convicted of first-degree criminal mischief, one count of third-degree assault, and one count of harassment in the Huntsville attack.[61] Between 1993 and 2015, 11 people were killed at American abortion clinics.[62] The Army of God claimed responsibility for Eric Robert Rudolph's 1997 shrapnel bombing of abortion clinics in Atlanta and Birmingham.[63][62] The organization embraces its description as terrorist.[64] On January 29, 1998, Robert Sanderson, an off-duty police officer who worked as a security guard at an abortion clinic in Birmingham, Alabama, was killed when his workplace was bombed. Eric Rudolph admitted responsibility; he was also charged with three Atlanta bombings: the 1997 bombing of an abortion center, the 1996 Centennial Olympic Park bombing, and another of a lesbian nightclub. He was charged with the crimes and received two life sentences as a result.[65][66][62][67] Nurse Emily Lyons was permanently injured as a result of it.[62] ## Footnotes[edit] 1. ^ According to the Supreme Court's decision in Roe v. Wade: > (a) For the stage prior to approximately the end of the first trimester, the abortion decision and its effectuation must be left to the medical judgement of the pregnant woman's attending physician. (b) For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. (c) For the stage subsequent to viability, the State in promoting its interest in the potentiality of human life may, if it chooses, regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgement, for the preservation of the life or health of the mother. Likewise, Black's Law Dictionary defines abortion as "knowing destruction" or "intentional expulsion or removal". 1. ^ "Priest convicted on assault charges". The Tuscaloosa News. July 11, 1984. 2. ^ Blanchard, Dallas (1993). Religious Violence and Abortion: The Gideon Project. Gainesville, Florida: University Press of Florida. pp. 191–193. ISBN 0-8130-1194-9. "markley." ## References[edit] 1. ^ https://www.guttmacher.org/fact-sheet/state-facts-about-abortion-alabama 2. ^ "Public Opinion on Abortion". Pew Research Center. Retrieved October 30, 2019. 3. ^ Watson, Katie (December 20, 2019). "Why We Should Stop Using the Term "Elective Abortion"". AMA Journal of Ethics. 20: E1175-1180. doi:10.1001/amajethics.2018.1175. PMID 30585581. Retrieved May 17, 2019. 4. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1). 5. ^ "The Roberts Court Takes on Abortion". New York Times. November 5, 2006. Retrieved January 18, 2008. 6. ^ Brennan 'Dehumanizing the vulnerable' 2000 7. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review. 8. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on July 27, 2011. Retrieved November 16, 2011. 9. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007. 10. ^ a b Castillo, Stephanie (October 3, 2014). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Retrieved May 27, 2019. 11. ^ a b c d e f g h "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved May 25, 2019. 12. ^ a b Mundell, E.J. (January 16, 2019). "Two-Thirds of Poor U.S. Women Can't Afford Menstrual Pads, Tampons: Study". US News & World Report. Retrieved May 26, 2019. 13. ^ Larimer, Sarah (January 8, 2016). "The 'tampon tax,' explained". The Washington Post. Archived from the original on December 11, 2016. Retrieved December 10, 2016. 14. ^ Bowerman, Mary (July 25, 2016). "The 'tampon tax' and what it means for you". USA Today. Archived from the original on December 11, 2016. Retrieved December 10, 2016. 15. ^ Hillin, Taryn. "These are the U.S. states that tax women for having periods". Splinter. Retrieved December 15, 2017. 16. ^ "Election Results 2018: Nevada Ballot Questions 1-6". KNTV. Retrieved November 7, 2018. 17. ^ Wax-Thibodeaux, Emily (June 9, 2019). "In Alabama — where lawmakers banned abortion for rape victims — rapists' parental rights are protected". The Washington Post. Retrieved June 10, 2019. 18. ^ a b Michaels, Samantha. "Alabama banned abortions. Then its lawmakers remembered rapists can get parental rights". Mother Jones. Retrieved June 8, 2019. 19. ^ a b c d Buell, Samuel (1991). "Criminal Abortion Revisited". New York University Law Review. 66: 1774–1831. 20. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics". Pew Research Center. Retrieved May 23, 2019. 21. ^ Jr, Perry Bacon (May 16, 2019). "Three Reasons There's A New Push To Limit Abortion In State Legislatures". FiveThirtyEight. Retrieved May 26, 2019. 22. ^ a b c Brownstein, Ronald (May 23, 2019). "White Women Are Helping States Pass Abortion Restrictions". The Atlantic. Retrieved May 26, 2019. 23. ^ Gore, Leada (May 24, 2019). "New Jersey governor blasts Alabama, invites business to relocate over abortion law". al.com. Retrieved June 2, 2019. 24. ^ Kliff, Sarah (January 22, 2013). "CHARTS: How Roe v. Wade changed abortion rights". The Washington Post. 25. ^ "Alabama HB314 \| 2019 \| Regular Session". LegiScan. Retrieved May 15, 2019. 26. ^ Williams, Timothy; Blinder, Alan (May 14, 2019). "Alabama Lawmakers Vote to Effectively Ban Abortion in the State". The New York Times. ISSN 0362-4331. Retrieved May 15, 2019. 27. ^ Ivey, Kay [@GovernorKayIvey] (May 15, 2019). "Today, I signed into law the Alabama Human Life Protection Act. To the bill's many supporters, this legislation stands as a powerful testament to Alabamians' deeply held belief that every life is precious & that every life is a sacred gift from God" (Tweet). Retrieved May 22, 2019 – via Twitter. 28. ^ "State Policy On Informed Consent for Abortion" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019. 29. ^ "State Abortion Counseling Policies and the Fundamental Principles of Informed Consent". Guttmacher Institute. November 12, 2007. Retrieved May 22, 2019. 30. ^ "TRAP Laws Gain Political Traction While Abortion Clinics—and the Women They Serve—Pay the Price". Guttmacher Institute. June 27, 2013. Retrieved May 27, 2019. 31. ^ a b Lai, K. K. Rebecca (May 15, 2019). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved May 24, 2019. 32. ^ a b Mitra, A. G.; Laurent, S. L.; Moore, J. E.; Blanchard, G. F.; Chescheir, N. C. (July 1996). "Transvaginal versus transabdominal Doppler auscultation of fetal heart activity: a comparative study". American Journal of Obstetrics and Gynecology. 175 (1): 41–44. doi:10.1016/s0002-9378(96)70248-x. ISSN 0002-9378. PMID 8694073. 33. ^ Cason, Mike (April 6, 2014). "Bills that passed and died during the Alabama Legislature's 2014 session". Al.com. Retrieved September 20, 2014. 34. ^ a b c d e Emanuella Grinberg. "The reality for women seeking abortions in Alabama and Georgia". CNN. Retrieved June 8, 2019. 35. ^ a b c Tavernise, Sabrina (May 15, 2019). "'The Time Is Now': States Are Rushing to Restrict Abortion, or to Protect It". The New York Times. ISSN 0362-4331. Retrieved May 24, 2019. 36. ^ Lartey, Jamiles (May 22, 2019). "Louisiana senate passes anti-abortion bill in latest attack on women's rights". The Guardian. ISSN 0261-3077. Retrieved May 22, 2019. 37. ^ "National Debate Over Abortion Laws Comes To Rhode Island". www.wbur.org. Retrieved May 23, 2019. 38. ^ "Yes, you can blame the patriarchy for these horrible abortion laws. We did the math". Mother Jones. Retrieved May 26, 2019. 39. ^ a b Gould, Rebecca Harrington, Skye. "The number of abortion clinics in the US has plunged in the last decade — here's how many are in each state". Business Insider. Retrieved May 23, 2019. 40. ^ a b Arnold, Amanda (March 7, 2019). "A Man Is Suing an Abortion Clinic on Behalf of a Fetus". The Cut. Retrieved May 25, 2019. 41. ^ Romo, Vanessa (June 28, 2019). "Woman Indicted For Manslaughter After Death Of Her Fetus, May Avoid Prosecution". NPR.org. Retrieved June 29, 2019. 42. ^ a b Arndorfer, Elizabeth; Michael, Jodi; Moskowitz, Laura; Grant, Juli A.; Siebel, Liza (December 1998). A State-By-State Review of Abortion and Reproductive Rights. DIANE Publishing. ISBN 9780788174810. 43. ^ a b businessinsider (August 4, 2018). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved May 24, 2019. 44. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved May 23, 2019. 45. ^ a b c d "When it comes to abortion, conservative women aren't a monolith". USA TODAY. Retrieved May 26, 2019. 46. ^ a b c d "Southern Baptists descend on Alabama, epicenter of abortion debate". The Tennessean. Retrieved June 8, 2019. 47. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687. 48. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved May 24, 2019. 49. ^ "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. June 15, 2005. Retrieved June 2, 2019. 50. ^ "Abortion Surveillance -- United States, 1992". www.cdc.gov. Retrieved May 11, 2020. 51. ^ "Abortion Surveillance -- United States, 1995". www.cdc.gov. Retrieved May 11, 2020. 52. ^ "Abortion Surveillance -- United States, 1996". www.cdc.gov. Retrieved May 11, 2020. 53. ^ Jatlaoui, Tara C. (2017). "Abortion Surveillance — United States, 2014". MMWR. Surveillance Summaries. 66 (24): 1–48. doi:10.15585/mmwr.ss6624a1. ISSN 1546-0738. PMID 29166366. 54. ^ Jatlaoui, Tara C. (2018). "Abortion Surveillance — United States, 2015". MMWR. Surveillance Summaries. 67 (13): 1–45. doi:10.15585/mmwr.ss6713a1. ISSN 1546-0738. PMC 6289084. PMID 30462632. 55. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738. 56. ^ a b Pesce, Nicole Lyn. "Abortion bans are spurring donations to Planned Parenthood, the National Organization for Women, and more". MarketWatch. Retrieved May 27, 2019. 57. ^ Kilpatrick, Mary (May 20, 2019). "Abortion rights #StoptheBans rally set for Tuesday". cleveland.com. Retrieved May 25, 2019. 58. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA TODAY. Retrieved May 25, 2019. 59. ^ Koplowitz, Howard (June 8, 2019). "Kamala Harris in Alabama: 'Legitimate fear' that women will die from abortion ban". al.com. Retrieved June 8, 2019. 60. ^ Blanchard, Dallas A. (1993). Religious violence and abortion : the Gideon Project. Prewitt, Terry J. (Terry James), 1945-. Gainesville: University Press of Florida. ISBN 0813020654. OCLC 45728628. 61. ^ Turner, Winford (February 9, 1985). "Jurors convict Markley". TimesDaily (116–40). pp. 1, 3. Retrieved December 11, 2015. 62. ^ a b c d Stack, Liam (November 29, 2015). "A Brief History of Deadly Attacks on Abortion Providers". The New York Times. ISSN 0362-4331. Retrieved May 23, 2019. 63. ^ "Army of God letters claim responsibility for clinic bombing". CNN. February 2, 1998. Archived from the original on March 25, 2012. Retrieved May 22, 2019. 64. ^ Jefferis, Jennifer (2011). Armed for Life: The Army of God and Anti-Abortion Terror in the United States. ABC-CLIO. p. 40. ISBN 9780313387548. 65. ^ "CNN.com - Rudolph gets life for Birmingham clinic attack - Jul 18, 2005". www.cnn.com. Retrieved May 22, 2019. 66. ^ Jacobson, Mireille; Royer, Heather (December 2010). "Aftershocks: The Impact of Clinic Violence on Abortion Services". American Economic Journal: Applied Economics. 3: 189–223. doi:10.1257/app.3.1.189. 67. ^ Larson, Jordan. "Timeline: The 200-Year Fight for Abortion Access". The Cut. Retrieved May 25, 2019. Abortion in the United States by state States * Alabama * Alaska * Arizona * Arkansas * California * Colorado * Connecticut * Delaware * Florida * Georgia * Hawaii * Idaho * Illinois * Indiana * Iowa * Kansas * Kentucky * Louisiana * Maine * Maryland * Massachusetts * Michigan * Minnesota * Mississippi * Missouri * Montana * Nebraska * Nevada * New Hampshire * New Jersey * New Mexico * New York * North Carolina * North Dakota * Ohio * Oklahoma * Oregon * Pennsylvania * Rhode Island * South Carolina * South Dakota * Tennessee * Texas * Utah * Vermont * Virginia * Washington * West Virginia * Wisconsin * Wyoming Federal district Washington, D.C. Insular areas * American Samoa * Guam * Northern Mariana Islands * Puerto Rico * U.S. Virgin Islands [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Abortion in Alabama	None	8,439	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Alabama	2021-01-18T18:57:59	{"wikidata": ["Q64876900"]}
Pinealoma Pineocytoma SpecialtyOncology TreatmentSurgical resection, radiation therapy A pinealoma is a tumor of the pineal gland, a part of the brain that produces melatonin. If a pinealoma destroys the cells of the pineal gland in a child, it can cause precocious puberty. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 References * 7 External links ## Signs and symptoms[edit] The pineal gland produces the hormone melatonin which plays a role in regulating circadian rhythms. A pinealoma may disrupt production of this hormone, and insomnia may result.[citation needed] Frequently, paralysis of upward gaze along with several ocular findings such as convergence retraction nystagmus and eyelid retraction also known as Collier's sign and Light Near Dissociation (pupil accommodates but doesn't react to light) are known collectively as Parinaud's syndrome [1] or Dorsal Mid-brain syndrome, are the only physical symptoms seen. This is caused by the compression of the vertical gaze center in the midbrain tectum at the level of the superior colliculus and cranial nerve III. Work-up usually includes Neuro-imaging as seen on the right.[citation needed] A pinealoma may cause interruption of hypothalamic inhibiting pathways, sometimes leading to beta-hCG secretion and consequent Leydig's cell stimulation (endocrine syndrome).[citation needed] Other symptoms may include hydrocephalus, gait disturbances, and precocious puberty.[citation needed] ## Cause[edit] Pinealomas can be due to proliferation of primary pineocytes (pineocytomas, pineoblastomas), astrocytes (astrocytoma), or germ cells (germinoma).[2] Germinomas are the most common tumor in the pineal gland.[citation needed] * * ## Diagnosis[edit] This section is empty. You can help by adding to it. (November 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (November 2017) ## Prognosis[edit] Of the different types of pinealomas, the type with the most favorable prognosis is the pineocytoma.[3] ## References[edit] 1. ^ Gaspar N, Verschuur A, Mercier G, Couanet D, Sainte-Rose C, Brugières L (September 2003). "Reversible hearing loss associated with a malignant pineal germ cell tumor. Case report". J. Neurosurg. 99 (3): 587–90. doi:10.3171/jns.2003.99.3.0587. PMID 12959450. 2. ^ "eMedicine - Germinoma, Central Nervous System : Article by Daniel D Mais, MD". Retrieved 2007-12-03. 3. ^ Deshmukh VR, Smith KA, Rekate HL, Coons S, Spetzler RF (2004). "Diagnosis and management of pineocytomas". Neurosurgery. 55 (2): 349–55, discussion 355–7. doi:10.1227/01.NEU.0000129479.70696.D2. PMID 15271241. ## External links[edit] * 00322 at CHORUS Classification D * ICD-10: D44.5, C75.3 * ICD-9-CM: 237.1, 194.4 * ICD-O: M9360/1-9362/3 * MeSH: D010871 * DiseasesDB: 10044 * SNOMED CT: 359619007 External resources * eMedicine: med/2911 * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). * v * t * e Tumours of endocrine glands Pancreas * Pancreatic cancer * Pancreatic neuroendocrine tumor * α: Glucagonoma * β: Insulinoma * δ: Somatostatinoma * G: Gastrinoma * VIPoma Pituitary * Pituitary adenoma: Prolactinoma * ACTH-secreting pituitary adenoma * GH-secreting pituitary adenoma * Craniopharyngioma * Pituicytoma Thyroid * Thyroid cancer (malignant): epithelial-cell carcinoma * Papillary * Follicular/Hurthle cell * Parafollicular cell * Medullary * Anaplastic * Lymphoma * Squamous-cell carcinoma * Benign * Thyroid adenoma * Struma ovarii Adrenal tumor * Cortex * Adrenocortical adenoma * Adrenocortical carcinoma * Medulla * Pheochromocytoma * Neuroblastoma * Paraganglioma Parathyroid * Parathyroid neoplasm * Adenoma * Carcinoma Pineal gland * Pinealoma * Pinealoblastoma * Pineocytoma MEN * 1 * 2A * 2B [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Pinealoma	c0031941	8,440	wikipedia	https://en.wikipedia.org/wiki/Pinealoma	2021-01-18T19:01:48	{"mesh": ["D010871"], "umls": ["C0153655", "C1412004", "C0031941"], "wikidata": ["Q1047551"]}
## Description SERPINA2P is part of a cluster of structurally related serine protease inhibitor (SERPIN) genes on chromosome 14. However, SERPINA2P appears to be a pseudogene (Rollini and Fournier, 1997). Cloning and Expression Kelsey et al. (1988) identified, 10 kb downstream of the authentic alpha-1-antitrypsin gene (AAT or PI; 107400), a genomic sequence with considerable homology to the AAT gene. They designated this sequence the alpha-1-antitrypsin-related gene (ATR). They introduced the AAT and ATR genes separately into L-cells by transfection in order to establish a method for distinguishing between expression of the 2 genes. RNA probes from the cloned ATR region were then used in a ribonuclease protection assay against RNA from a range of human adult and fetal tissues. No evidence of expression of ATR was found, indicating that this gene is probably a pseudogene. Bao et al. (1988) cloned a 7.7-kb EcoRI genomic DNA fragment highly homologous to the human AAT gene. The nucleotide sequence of the ATR gene showed extensive homology with the authentic AAT gene in the introns as well as exons. The conservation of all RNA splice sites and lack of internal termination codons in the exons suggested that it may not be a classic pseudogene. If expressed, it would result in a protein of 420 amino acid residues, exhibiting a 70% overall homology with AAT. The signal peptide sequence was well conserved, but the active site of protease inhibition (met-ser) in AAT had been changed to trp-ser. The findings suggested that the putative protein is a secretory serine protease inhibitor with an altered substrate specificity. Since even the introns showed 65% nucleotide sequence homology with the authentic AAT gene, ATR appears to have been derived from a recent duplication of the AAT gene. It presumably represents a new member of the serine protease inhibitor superfamily. Gene Structure Kelsey et al. (1988) determined that the ATR pseudogene spans about 5 kb. Mapping Kelsey et al. (1988) mapped the SERPINA2P pseudogene about 10 kb downstream of the SERPINA1 gene. Bao et al. (1988) determined that the SERPINA2P pseudogene is located about 8 kb downstream of the SERPINA1 gene. Kalsheker and Watkins (1988) and others before them demonstrated RFLPs in the ATR sequence. Rollini and Fournier (1997) presented a detailed restriction map of a 110-kb region of genomic DNA that includes the genes PI, PIL, and CDG (122500). They found that the 3 genes were in this order from telomere to centromere and that all 3 genes lie in a distal-to-proximal orientation. The PIL gene is approximately 12 kb downstream of the PI gene, which maps to 14q32.1, and CBG is approximately 57 kb downstream of PI. Earlier work on the mapping of these loci includes that of Sefton et al. (1990), Billingsley et al. (1993), and Byth et al. (1994). Rollini and Fournier (1997) stated that PIL is generally thought to be a pseudogene because it seems to lack promoter sequences and exon I, but that this issue was not clearly resolved. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	SERPIN PEPTIDASE INHIBITOR, CLADE A, MEMBER 2, PSEUDOGENE	c3888213	8,441	omim	https://www.omim.org/entry/107410	2019-09-22T16:44:56	{"omim": ["107410"], "synonyms": ["Alternative titles", "PROTEASE INHIBITOR 1-LIKE", "ANTITRYPSIN-RELATED PROTEIN", "ALPHA-1-ANTITRYPSIN-RELATED GENE SEQUENCE", "SERPINA2"]}
For a general phenotypic description and a discussion of genetic heterogeneity of vesicoureteral reflux (VUR), see 193000. Clinical Features Weng et al. (2009) identified 16 families with primary vesicoureteral reflux. The families were of various origins, including Caucasian American, Italian, and Hasidic Jewish. Among the 184 relatives of the probands, 56 individuals (30%) had primary VUR based on a positive VCUG without other renal or urologic defects, and 11 individuals (6%) had urinary tract abnormalities other than VUR. The prevalence of VUR and other urinary tract abnormalities among relatives was approximately 30-fold and 60-fold higher, respectively, than the reported prevalence in the general population, suggesting familial aggregation. Mapping By genomewide linkage analysis of 12 informative families with primary VUR, Weng et al. (2009) identified a locus on chromosome 12p11-q13 using a recessive model. Multipoint analysis yielded an hlod score of 3.6 at marker D12S1048, defining a 22.7-Mb interval between rs1388659 and D12S361. The lod score increased to 4.5 when 2 large pedigrees that failed to link across the entire genome were excluded. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	VESICOURETERAL REFLUX 7	c3809337	8,442	omim	https://www.omim.org/entry/615390	2019-09-22T15:52:23	{"doid": ["9620"], "omim": ["615390"], "orphanet": ["289365"], "synonyms": ["Familial VUR"]}
In a family of Portuguese extraction, Antinolo et al. (1992) described 7 individuals in 4 sibships in 3 generations with a disorder comprising spastic paraplegia, demyelinating peripheral neuropathy, and poikiloderma, manifested by 'delicate, smooth, and wasted' skin from an early age and loss of eyebrows and eyelashes at age 3 years. Electroneurophysiologic studies demonstrated motor and sensory neuropathy. Sural nerve biopsy showed onion bulb formations, indicating demyelination of peripheral nerves. Distal amyotrophy was evident after puberty. There were 2 affected males but no male-to-male transmission. Neuro \- Spastic paraplegia \- Demyelinating peripheral neuropathy Inheritance \- Autosomal dominant Lab \- Motor and sensory neuropathy on electroneurophysiologic studies \- Onion bulb formations on sural nerve biopsy Hair \- Loss of eyebrows and eyelashes by age 3 years Skin \- Poikiloderma \- Delicate, smooth, wasted skin Muscle \- Distal amyotrophy ▲ 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	SPASTIC PARAPLEGIA WITH NEUROPATHY AND POIKILODERMA	c1866851	8,443	omim	https://www.omim.org/entry/182815	2019-09-22T16:34:39	{"mesh": ["C536870"], "omim": ["182815"], "orphanet": ["2821"]}
Bietti's crystalline dystrophy (BCD) is a rare progressive autosomal recessive tapetoretinal degeneration disease, occurring in the third decade of life, characterized by small sparkling crystalline deposits in the posterior retina and corneal limbus in addition to sclerosis of the choroidal vessels and manifesting as nightblindness, decreased vision, paracentral scotoma, and, in the end stages of the disease, legal blindness. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Bietti crystalline dystrophy	c1859486	8,444	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=41751	2021-01-23T19:07:25	{"gard": ["10050"], "mesh": ["C535440"], "omim": ["210370"], "umls": ["C1859486"], "icd-10": ["H15.5"], "synonyms": ["BCD", "Bietti crystalline corneoretinal dystrophy", "Bietti crystalline retinopathy"]}
Craniosynostosis, Herrmann-Opitz type is a rare bone development disorder characterized by intellectual disability, short stature, turribrachycephaly, facial dysmorphism (i.e. severe hypertelorism, hypoplasia of supraorbital ridges, abnormal ears, and micrognathia), bony defects of the occiput, and digital anomalies (incl. syndactyly, oligodactyly, and/or brachydactyly). Urethral atresia has also been reported. There have been no further descriptions in the literature since 1987. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Craniosynostosis, Herrmann-Opitz type	None	8,445	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2145	2021-01-23T16:56:05	{"icd-10": ["Q75.0"]}
Juvenile xanthogranuloma is the most common type of non-Langerhans cell histiocytosis (see this term) characterized by the occurrence of one or more reddish or yellowish self-limiting and benign papules or nodules of several millimeters in diameter, usually appearing on the head and neck (but sometimes on the extremities and trunk) during the first year of life (or rarely in adulthood) and usually regressing spontaneously. Extracutaneous involvement has also been reported, involving most commonly the eye (uveal tract) but with other locations including the central nervous system, lung, liver, bones and endocrine glands, and may be associated with considerable morbidity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Juvenile xanthogranuloma	c0043324	8,446	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=158000	2021-01-23T18:13:43	{"mesh": ["D014972"], "umls": ["C0043324"], "icd-10": ["D76.3"]}
## Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss. For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900). Clinical Features Ahmed et al. (2009) reported a consanguineous Pakistani family (PKDF125) with Usher syndrome type I. All affected individuals were reported to be deaf from birth, showed delayed motor development consistent with vestibular dysfunction, and showed variable severity of retinitis pigmentosa related to age. Mapping By genomewide linkage analysis of 2 consanguineous Pakistani families with autosomal recessive Usher syndrome, Ahmed et al. (2009) identified a novel locus, which they termed USH1H, on chromosome 15q22-q23 (maximum 2-point lod score of 4.21 at marker ZA840/841 and 5.67 at marker D15S980, respectively). The shared 4.2-cM interval between markers D15S988 and D15S967 overlapped with DFNB48 (609439). The overlapping interval of USH1H and DFNB48 contains only the TLE3 gene (600190), and sequence analysis did not reveal any pathogenic alleles. Sequence analysis of genes in a 3.36-Mb candidate region, including ITGA11 (604789), CORO2B (605002), and KIF23 (605064), did not reveal any pathogenic mutations. Molecular Genetics ### Exclusion Studies In 1 of the Pakistani families with Usher syndrome (PKDF125) reported by Ahmed et al. (2009), Riazuddin et al. (2012) excluded mutations in the CIB2 gene (605564). The other family (PKDF117) was found to carry a homozygous mutation in the CIB2 gene (605564.0004); see USH1J (614869). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	USHER SYNDROME, TYPE IH	c0271097	8,447	omim	https://www.omim.org/entry/612632	2019-09-22T16:00:57	{"doid": ["0110835"], "mesh": ["D052245"], "omim": ["612632"], "orphanet": ["886", "231169"], "genereviews": ["NBK1265"]}
Increase in the amount of organic tissue that results from cell proliferation Hyperplasia Whereas hypertrophy stems from an increase in cell size, hyperplasia results from an increase in cell number. SpecialtyPathology TypesBenign prostatic hyperplasia, Hyperplasia of the breast(many more)[1][2] Diagnostic methodBiopsy[3] TreatmentDepends which type (see types) Hyperplasia (from ancient Greek ὑπέρ huper, "over" + πλάσις plasis, "formation"), or hypergenesis, is an increase in the amount of organic tissue that results from cell proliferation.[4] It may lead to the gross enlargement of an organ, and the term is sometimes confused with benign neoplasia or benign tumor.[5] Hyperplasia is a common preneoplastic response to stimulus.[6] Microscopically, cells resemble normal cells but are increased in numbers. Sometimes cells may also be increased in size (hypertrophy).[7] Hyperplasia is different from hypertrophy in that the adaptive cell change in hypertrophy is an increase in the size of cells, whereas hyperplasia involves an increase in the number of cells.[8] -plasia and -trophy * Anaplasia (structural differentiation loss within a cell or group of cells). * Aplasia (organ or part of organ missing) * Desmoplasia (connective tissue growth) * Dysplasia (change in cell or tissue phenotype) * Hyperplasia (proliferation of cells) * Hypoplasia (congenital below-average number of cells, especially when inadequate) * Metaplasia (conversion in cell type) * Neoplasia (abnormal proliferation) * Prosoplasia (development of new cell function) * Abiotrophy (loss in vitality of organ or tissue) * Atrophy (reduced functionality of an organ, with decrease in the number or volume of cells) * Hypertrophy (increase in the volume of cells or tissues) * Hypotrophy (decrease in the volume of cells or tissues) * Dystrophy (any degenerative disorder resulting from improper or faulty nutrition) * v * t * e ## Contents * 1 Causes * 2 Mechanism * 3 Diagnosis * 3.1 Types * 4 Treatment * 5 See also * 6 References * 7 Further reading * 8 External links ## Causes[edit] Hyperplasia may be due to any number of causes, including proliferation of basal layer of epidermis to compensate skin loss, chronic inflammatory response, hormonal dysfunctions, or compensation for damage or disease elsewhere.[9] Hyperplasia may be harmless and occur on a particular tissue. An example of a normal hyperplastic response would be the growth and multiplication of milk-secreting glandular cells in the breast as a response to pregnancy, thus preparing for future breast feeding.[10] Perhaps the most interesting and potent effect IGF has on the human body is its ability to cause hyperplasia, which is an actual splitting of cells.[11] By contrast, hypertrophy is what occurs, for example, to skeletal muscle cells during weight training and is simply an increase in the size of the cells.[12] With IGF use, one is able to cause hyperplasia which actually increases the number of muscle cells present in the tissue.[13] Weight training enables these new cells to mature in size and strength. It is theorized that hyperplasia may also be induced through specific power output training for athletic performance, thus increasing the number of muscle fibers instead of increasing the size of a single fiber.[14] ## Mechanism[edit] Hyperplasia is considered to be a physiological (normal) response to a specific stimulus, and the cells of a hyperplastic growth remain subject to normal regulatory control mechanisms.[5] However, hyperplasia can also occur as a pathological response, if an excess of hormone or growth factor is responsible for the stimuli. Similarly to physiological hyperplasia, cells that undergo pathologic hyperplasia are controlled by growth hormones, and cease to proliferate if such stimuli are removed.[15] This differs from neoplasia (the process underlying cancer and benign tumors), in which genetically abnormal cells manage to proliferate in a non-physiological manner which is unresponsive to normal stimuli.[16] That being said, the effects caused by pathologic hyperplasia can provide a suitable foundation from which neoplastic cells may develop.[15] ## Diagnosis[edit] In the case of endometrial hyperplasia usually a Pap smear is done, also a biopsy during the pelvic examination, may be done of the individuals endometrial tissue. You may want to consult your doctor for further examination.[3] In regards to Cushing's disease, the diagnosis of salivary cortisol in an elevated level around "late-night" is a way to detect it in many patients.[17] ### Types[edit] Patient with hemihyperplasia involving the upper and lower left extremities. The leg length discrepancy can be noted by the pelvic tilt. Some of the more commonly known clinical forms of hyperplasia, or conditions leading to hyperplasia, are: * Benign prostatic hyperplasia, also known as prostate enlargement.[1] * Cushing's disease – Physiopathology of hyperplasia of adrenal cortex due to increased circulating level of ACTH (adrenocorticotropic hormone).[18] * Congenital adrenal hyperplasia – Inherited disorder of gland (adrenal).[19] * Endometrial hyperplasia – Hyperproliferation of the endometrium, usually in response to unopposed estrogen stimulation in the setting of polycystic ovary syndrome or exogenous administration of hormones. Atypical endometrial hyperplasia may represent an early neoplastic process which can lead to endometrial adenocarcinoma.[20] The development of endometrial adenocarcinoma from endometrial hyperplasia is a typical example of how the effects of pathologic hyperplasia can lead to neoplasia, and females who exhibit hyperplasia of the endometrium are indeed more likely to develop cancer of these cells.[15] * Hemihyperplasia when only half (or one side) of the body is affected, sometimes generating limbs of different lengths.[21] * Hyperplasia of the breast – "Hyperplastic" lesions of the breast include usual ductal hyperplasia, a focal expansion of the number of cells in a terminal breast duct, and atypical ductal hyperplasia, in which a more abnormal pattern of growth is seen, and which is associated with an increased risk of developing breast cancer.[2] * Intimal hyperplasia – The thickening of the tunica intima of a blood vessel as a complication of a reconstruction procedure or endarterectomy. Intimal hyperplasia is the universal response of a vessel to injury and is an important reason of late bypass graft failure, particularly in vein and synthetic vascular grafts.[22] * Focal epithelial hyperplasia (also known as Heck's disease) – This is a wart-like growth in the mucous tissues of the mouth or, rarely, throat that is caused by certain sub-types of the human papillomavirus (HPV). Heck's disease has not been known to cause cancer.[23] * Sebaceous hyperplasia – In this condition, small yellowish growths develop on the skin, usually on the face. This condition is neither contagious nor dangerous.[24] * Compensatory liver hyperplasia – The liver undergoes cellular division after acute injury, resulting in new cells that restore liver function back to baseline. Approximately 75% of the liver can be acutely damaged or resected with seemingly full regeneration through hepatocyte division, i.e., hyperplasia. This is what makes living-donor liver transplants possible.[25] * Epidermal hyperplasia of the skin[citation needed] ## Treatment[edit] The treatment of hyperplasia would consist upon which; in the case of benign prostate hyperplasia the combination of alpha-1-receptor blockers and 5-alpha-reductase inhibitors are effective.[26] ## See also[edit] * List of biological development disorders ## References[edit] 1. ^ a b "Prostate Enlargement: Benign Prostatic Hyperplasia". www.niddk.nih.gov. Retrieved 2015-05-30. 2. ^ a b Koerner, Frederick C. (2009). Diagnostic Problems in Breast Pathology. Elsevier Health Sciences. ISBN 978-1416026129. 3. ^ a b Dunphy, Lynne M.; Winland-Brown, Jill E. (2011-04-06). Primary Care: The Art and Science of Advanced Practice Nursing. F.A. Davis. ISBN 9780803626478. 4. ^ "Hyperplasia: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-05-30. 5. ^ a b Sembulingam, K.; Sembulingam, Prema (2012-09-01). Essentials of Medical Physiology. JP Medical Ltd. ISBN 9789350259368. 6. ^ Zachary, James F.; McGavin, M. Donald (2013-12-11). Pathologic Basis of Veterinary Disease. Elsevier Health Sciences. ISBN 9780323291729. 7. ^ Braun, Carie Ann; Anderson, Cindy Miller (2007). Pathophysiology: Functional Alterations in Human Health. Lippincott Williams & Wilkins. p. 17. ISBN 9780781762502. 8. ^ Rubin, Emanuel; Reisner, Howard M. (2009). Essentials of Rubin's Pathology. Lippincott Williams & Wilkins. ISBN 9780781773249. 9. ^ Porth, Carol (2011). Essentials of Pathophysiology: Concepts of Altered Health States. Lippincott Williams & Wilkins. ISBN 9781582557243. 10. ^ Dirbas, Frederick; Scott-Conner, Carol (2011-01-15). Breast Surgical Techniques and Interdisciplinary Management. Springer Science & Business Media. ISBN 9781441960764. 11. ^ Gardiner, Phillip. Advanced Neuromuscular Exercise Physiology. Human Kinetics. ISBN 9781450412278. 12. ^ Metzl, Jordan D.; Shookhoff, Carol (2009-10-31). The Young Athlete: A Sports Doctor's Complete Guide for Parents. Little, Brown. ISBN 9780316086738. 13. ^ Publishing, Britannica Educational (2011-11-01). The Endocrine System. Britannica Educational Publishing. ISBN 9781615307319. 14. ^ Kisner, Carolyn; Colby, Lynn Allen (2012-10-08). Therapeutic Exercise: Foundations and Techniques. F.A. Davis. ISBN 9780803638976. 15. ^ a b c Kumar, V., Abbas, A., Aster, J. (2013). Robbins Basic Pathology. Philadelphia, USA: Elsevier. p. 4. ISBN 9780808924326.CS1 maint: multiple names: authors list (link) 16. ^ Hong, Waun Ki; Hait, William N. (2010). Holland Frei Cancer Medicine Eight. PMPH-USA. ISBN 9781607950141. 17. ^ Cushing's Syndrome: New Insights for the Healthcare Professional: 2013 Edition: ScholarlyBrief. ScholarlyEditions. 2013-07-22. ISBN 9781481651837. 18. ^ "Cushing disease: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-05-30. 19. ^ "Congenital adrenal hyperplasia: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-05-30. 20. ^ "Endometrial Hyperplasia - ACOG". www.acog.org. Retrieved 2015-05-30. 21. ^ "Hemihyperplasia - Glossary Entry". Genetics Home Reference. Retrieved 2015-05-30. 22. ^ Subbotin, Vladimir M (2007-10-31). "Analysis of arterial intimal hyperplasia: review and hypothesis". Theoretical Biology & Medical Modelling. 4: 41. doi:10.1186/1742-4682-4-41. ISSN 1742-4682. PMC 2169223. PMID 17974015. 23. ^ Purkait, Swapan Kumar (2011). Essentials of Oral Pathology. JP Medical Ltd. ISBN 9789350252147. 24. ^ Evans, Colby Craig; High, Whitney A. (2011-10-01). Skin Diseases in the Elderly: A Color Handbook. CRC Press. ISBN 9781840766158. 25. ^ Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2014-09-05). Robbins & Cotran Pathologic Basis of Disease. Elsevier Health Sciences. ISBN 9780323296359. 26. ^ "Benign Prostatic Hypertrophy Treatment & Management: Approach Considerations, Combination Therapy, Minimally Invasive Treatment". Medscape. eMedicine. Retrieved 3 September 2016. ## Further reading[edit] * Bachmann, Alexander; Rosette, Jean de la (2011-11-24). Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms in Men. OUP Oxford. ISBN 9780199572779. ## External links[edit] Classification D * MeSH: D006965 * SNOMED CT: 76197007 External resources * MedlinePlus: 003441 Scholia has a topic profile for Hyperplasia. * v * t * e Overview of tumors, cancer and oncology Conditions Benign tumors * Hyperplasia * Cyst * Pseudocyst * Hamartoma Malignant progression * Dysplasia * Carcinoma in situ * Cancer * Metastasis * Primary tumor * Sentinel lymph node Topography * Head and neck (oral, nasopharyngeal) * Digestive system * Respiratory system * Bone * Skin * Blood * Urogenital * Nervous system * Endocrine system Histology * Carcinoma * Sarcoma * Blastoma * Papilloma * Adenoma Other * Precancerous condition * Paraneoplastic syndrome Staging/grading * TNM * Ann Arbor * Prostate cancer staging * Gleason grading system * Dukes classification Carcinogenesis * Cancer cell * Carcinogen * Tumor suppressor genes/oncogenes * Clonally transmissible cancer * Oncovirus * Carcinogenic bacteria Misc. * Research * Index of oncology articles * History * Cancer pain * Cancer and nausea * v * t * e Pathology Principles of pathology * Disease * Infection * Neoplasia * Cause * Pathogenesis * Hemodynamics * Ischemia * Inflammation * Cell damage * Wound healing Cellular adaptation Atrophy Hypertrophy Hyperplasia Dysplasia Metaplasia Squamous Glandular Cell death Necrosis Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis Myocytolysis Programmed cell death Apoptosis Pyknosis Karyorrhexis Karyolysis Accumulations pigment Hemosiderin Lipochrome/Lipofuscin Melanin Steatosis Anatomical pathology * Surgical pathology * Cytopathology * Autopsy * Molecular pathology * Forensic pathology * Oral and maxillofacial pathology * Gross examination * Histopathology * Immunohistochemistry * Electron microscopy * Immunofluorescence * Fluorescence in situ hybridization Clinical pathology * Clinical chemistry * Hematopathology * Transfusion medicine * Medical microbiology * Diagnostic immunology * Immunopathology * Enzyme assay * Mass spectrometry * Chromatography * Flow cytometry * Blood bank * Microbiological culture * Serology [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Hyperplasia	c0020507	8,448	wikipedia	https://en.wikipedia.org/wiki/Hyperplasia	2021-01-18T18:29:37	{"mesh": ["D006965"], "umls": ["C0020507"], "wikidata": ["Q835051"]}
A number sign (#) is used with this entry because autosomal recessive cone-rod dystrophy-13 (CORD13) is caused by mutation in the RPGRIP1 gene (605446). For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970. Clinical Features Hameed et al. (2003) reported 4 consanguineous Pakistani families with cone-rod dystrophy. Two of the families were large: 1 had 8 affected members over 2 generations, and the other had 8 affected members over 3 generations. The other 2 families had 2 affected sibs each. In all affected patients, there was deterioration in central vision and colorblindness from an early age, and rapid loss of vision between ages 14 and 16 years (visual acuity 1/60). Patients also had severe photophobia from childhood. Funduscopy showed a variable degree of fundus granularity and macular degeneration, and ERG showed involvement of both cones and rods. Mapping Exclusion studies on the 2 large families with cone-rod dystrophy reported by Hameed et al. (2003) showed linkage to chromosome 14q11 (maximum lod = 5.17 and 4.21 for the 2 families, respectively, at marker D14S1023). Molecular Genetics In a large Pakistani family with cone-rod dystrophy, Hameed et al. (2003) identified a homozygous mutation in the RPGRIP1 gene (605446.0005). Three additional affected Pakistani families had a different homozygous mutation in the RPGRIP1 gene (605446.0006). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	CONE-ROD DYSTROPHY 13	c2750720	8,449	omim	https://www.omim.org/entry/608194	2019-09-22T16:08:11	{"doid": ["0111016"], "mesh": ["C567698"], "omim": ["608194", "120970"], "orphanet": ["1872"], "synonyms": []}
Haney and Falls (1961) described affected brother and sister with associated manifestations in the form of retarded mental and physical growth, hypertelorism, corneal nebulae, short 'bull neck,' and stubby limbs and digits. They quoted the following description of the corneal lesion: '...the appearance one might expect if into the posterior surface of a plastic cornea one had excavated a subsidiary small basin-like depression by pressing into it a marble of much smaller curvature than that of the corneal surface itself.' The parents denied consanguinity. Curiously, the authors suggested autosomal dominant inheritance with poor penetrance. It is true that Jacobs (1957) reported keratoconus posticus in father and son. He made no mention of associated manifestations. Although they stated that they had 'been unable to trace any former reports of an identical condition,' Young et al. (1982) seem to have observed a brother and sister with the same disorder as that reported by Haney and Falls (1961). The brother was 20 and the sister 14 years of age at the time of report. At birth, bilateral cleft lip and cleft palate and bilateral central posterior corneal opacities were noted; the lenses, which were clear, appeared to lie in juxtaposition to the posterior surface of the cornea. Both had a short webbed neck, limitation of extension and supination of the elbows, and brachydactyly, with fifth finger clinodactyly. Both had had bilateral heel cord lengthening and the sister had frequent urinary tract infections and radiographically proven bilateral ureteric reflux. Both had multiple errors of segmentation and fusion in the thoracic vertebrae. Chromosomes were normal in the sibs; the mother had a triple-X karyotype 'in all cells analysed.' Young et al. (1982) considered this coincidental. GU \- Frequent urinary tract infections \- Ureteric reflux Neuro \- Retarded mental development Inheritance \- Autosomal recessive Skel \- Short 'bull' neck \- Webbed neck \- Stubby limbs \- Limited elbow extension and supination \- Brachydactyly \- Fifth finger clinodactyly \- Abnormal vertebral segmentation and fusion Growth \- Retarded growth HEENT \- Hypertelorism \- Corneal nebulae \- Posterior corneal depression \- Central posterior corneal opacities \- Cleft lip/palate ▲ 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	KERATOCONUS POSTICUS CIRCUMSCRIPTUS	c1855646	8,450	omim	https://www.omim.org/entry/244600	2019-09-22T16:26:06	{"mesh": ["C565455"], "omim": ["244600"]}
Spondylometaphyseal dysplasia, Schmidt type is characterized by short stature, myopia, ,small pelvis, progressive kypho-scoliosis, wrist deformity, severe genu valgum, short long bones, and severe metaphyseal dysplasia with moderate spinal changes and minimal changes in the hands and feet. ## Epidemiology This condition has been reported in five members of an Algerian family and one Polish boy; the patient reported by Schmidt et al. possibly had this disorder. ## Etiology Autosomal dominant inheritance has been suggested, but the causative gene has not yet been identified. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Spondylometaphyseal dysplasia, Schmidt type	c1866688	8,451	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93316	2021-01-23T16:58:13	{"gard": ["504"], "mesh": ["C535794"], "omim": ["184253"], "umls": ["C1866688"], "icd-10": ["Q77.8"], "synonyms": ["Spondylometaphyseal dysplasia with severe genu valgum", "Spondylometaphyseal dysplasia, Algerian type"]}
Toxic effects of breathing in oxygen at high concentrations Oxygen toxicity Other namesOxygen toxicity syndrome, oxygen intoxication, oxygen poisoning In 1942–43 the UK Government carried out extensive testing for oxygen toxicity in divers. The chamber is pressurised with air to 3.7 bar. The subject in the centre is breathing 100% oxygen from a mask.[1] SpecialtyEmergency medicine Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen (O 2) at increased partial pressures. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lungs, and eyes. Historically, the central nervous system condition was called the Paul Bert effect, and the pulmonary condition the Lorrain Smith effect, after the researchers who pioneered the discoveries and descriptions in the late 19th century. Oxygen toxicity is a concern for underwater divers, those on high concentrations of supplemental oxygen (particularly premature babies), and those undergoing hyperbaric oxygen therapy. The result of breathing increased partial pressures of oxygen is hyperoxia, an excess of oxygen in body tissues. The body is affected in different ways depending on the type of exposure. Central nervous system toxicity is caused by short exposure to high partial pressures of oxygen at greater than atmospheric pressure. Pulmonary and ocular toxicity result from longer exposure to increased oxygen levels at normal pressure. Symptoms may include disorientation, breathing problems, and vision changes such as myopia. Prolonged exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause oxidative damage to cell membranes, collapse of the alveoli in the lungs, retinal detachment, and seizures. Oxygen toxicity is managed by reducing the exposure to increased oxygen levels. Studies show that, in the long term, a robust recovery from most types of oxygen toxicity is possible. Protocols for avoidance of the effects of hyperoxia exist in fields where oxygen is breathed at higher-than-normal partial pressures, including underwater diving using compressed breathing gases, hyperbaric medicine, neonatal care and human spaceflight. These protocols have resulted in the increasing rarity of seizures due to oxygen toxicity, with pulmonary and ocular damage being mainly confined to the problems of managing premature infants. In recent years, oxygen has become available for recreational use in oxygen bars. The US Food and Drug Administration has warned those suffering from problems such as heart or lung disease not to use oxygen bars. Scuba divers use breathing gases containing up to 100% oxygen, and should have specific training in using such gases. ## Contents * 1 Classification * 2 Signs and symptoms * 2.1 Central nervous system * 2.2 Lungs * 2.3 Eyes * 3 Causes * 3.1 Central nervous system toxicity * 3.2 Lung toxicity * 3.3 Ocular toxicity * 4 Mechanism * 5 Diagnosis * 6 Prevention * 6.1 Underwater * 6.2 Hyperbaric setting * 6.3 Normobaric setting * 6.4 Hypobaric setting * 7 Management * 8 Prognosis * 9 Epidemiology * 10 History * 11 Society and culture * 12 See also * 13 References * 14 Sources * 15 Further reading * 16 External links ## Classification[edit] The effects of oxygen toxicity may be classified by the organs affected, producing three principal forms:[2][3][4] * Central nervous system, characterised by convulsions followed by unconsciousness, occurring under hyperbaric conditions; * Pulmonary (lungs), characterised by difficulty in breathing and pain within the chest, occurring when breathing increased pressures of oxygen for extended periods; * Ocular (retinopathic conditions), characterised by alterations to the eyes, occurring when breathing increased pressures of oxygen for extended periods. Central nervous system oxygen toxicity can cause seizures, brief periods of rigidity followed by convulsions and unconsciousness, and is of concern to divers who encounter greater than atmospheric pressures. Pulmonary oxygen toxicity results in damage to the lungs, causing pain and difficulty in breathing. Oxidative damage to the eye may lead to myopia or partial detachment of the retina. Pulmonary and ocular damage are most likely to occur when supplemental oxygen is administered as part of a treatment, particularly to newborn infants, but are also a concern during hyperbaric oxygen therapy. Oxidative damage may occur in any cell in the body but the effects on the three most susceptible organs will be the primary concern. It may also be implicated in damage to red blood cells (haemolysis),[5][6] the liver,[7] heart,[8] endocrine glands (adrenal glands, gonads, and thyroid),[9][10][11] or kidneys,[12] and general damage to cells.[2][13] In unusual circumstances, effects on other tissues may be observed: it is suspected that during spaceflight, high oxygen concentrations may contribute to bone damage.[14] Hyperoxia can also indirectly cause carbon dioxide narcosis in patients with lung ailments such as chronic obstructive pulmonary disease or with central respiratory depression.[14] Hyperventilation of atmospheric air at atmospheric pressures does not cause oxygen toxicity, because sea-level air has a partial pressure of oxygen of 0.21 bar (21 kPa) whereas toxicity does not occur below 0.3 bar (30 kPa).[15] ## Signs and symptoms[edit] Oxygen poisoning at 90 feet (27 m) in the dry in 36 subjects in order of performance[1] Exposure (mins.) Num. of subjects Symptoms 96 1 Prolonged dazzle; severe spasmodic vomiting 60–69 3 Severe lip-twitching; Euphoria; Nausea and vertigo; arm twitch 50–55 4 Severe lip-twitching; Dazzle; Blubbering of lips; fell asleep; Dazed 31–35 4 Nausea, vertigo, lip-twitching; Convulsed 21–30 6 Convulsed; Drowsiness; Severe lip-twitching; epigastric aura; twitch L arm; amnesia 16–20 8 Convulsed; Vertigo and severe lip twitching; epigastric aura; spasmodic respiration; 11–15 4 Inspiratory predominance; lip-twitching and syncope; Nausea and confusion 6–10 6 Dazed and lip-twitching; paraesthesiae; vertigo; "Diaphragmatic spasm"; Severe nausea ### Central nervous system[edit] Central nervous system oxygen toxicity manifests as symptoms such as visual changes (especially tunnel vision), ringing in the ears (tinnitus), nausea, twitching (especially of the face), behavioural changes (irritability, anxiety, confusion), and dizziness. This may be followed by a tonic–clonic seizure consisting of two phases: intense muscle contraction occurs for several seconds (tonic phase); followed by rapid spasms of alternate muscle relaxation and contraction producing convulsive jerking (clonic phase). The seizure ends with a period of unconsciousness (the postictal state).[16][17] The onset of seizure depends upon the partial pressure of oxygen in the breathing gas and exposure duration. However, exposure time before onset is unpredictable, as tests have shown a wide variation, both amongst individuals, and in the same individual from day to day.[16][18][19] In addition, many external factors, such as underwater immersion, exposure to cold, and exercise will decrease the time to onset of central nervous system symptoms.[1] Decrease of tolerance is closely linked to retention of carbon dioxide.[20][21][22] Other factors, such as darkness and caffeine, increase tolerance in test animals, but these effects have not been proven in humans.[23][24] ### Lungs[edit] Pulmonary toxicity symptoms result from an inflammation that starts in the airways leading to the lungs and then spreads into the lungs (tracheobronchial tree). The symptoms appear in the upper chest region (substernal and carinal regions).[25][26][27] This begins as a mild tickle on inhalation and progresses to frequent coughing.[25] If breathing increased partial pressures of oxygen continues, patients experience a mild burning on inhalation along with uncontrollable coughing and occasional shortness of breath (dyspnoea).[25] Physical findings related to pulmonary toxicity have included bubbling sounds heard through a stethoscope (bubbling rales), fever, and increased blood flow to the lining of the nose (hyperaemia of the nasal mucosa).[27] X-rays of the lungs show little change in the short term, but extended exposure leads to increasing diffuse shadowing throughout both lungs.[25] Pulmonary function measurements are reduced, as noted by a reduction in the amount of air that the lungs can hold (vital capacity) and changes in expiratory function and lung elasticity.[27][28] Tests in animals have indicated a variation in tolerance similar to that found in central nervous system toxicity, as well as significant variations between species. When the exposure to oxygen above 0.5 bar (50 kPa) is intermittent, it permits the lungs to recover and delays the onset of toxicity.[29] ### Eyes[edit] In premature babies, signs of damage to the eye (retinopathy of prematurity, or ROP) are observed via an ophthalmoscope as a demarcation between the vascularised and non-vascularised regions of an infant's retina. The degree of this demarcation is used to designate four stages: (I) the demarcation is a line; (II) the demarcation becomes a ridge; (III) growth of new blood vessels occurs around the ridge; (IV) the retina begins to detach from the inner wall of the eye (choroid).[30] ## Causes[edit] Oxygen toxicity is caused by exposure to oxygen at partial pressures greater than those to which the body is normally exposed. This occurs in three principal settings: underwater diving, hyperbaric oxygen therapy, and the provision of supplemental oxygen, particularly to premature infants. In each case, the risk factors are markedly different. ### Central nervous system toxicity[edit] See also: Technical diving Exposures, from minutes to a few hours, to partial pressures of oxygen above 1.6 bars (160 kPa)—about eight times normal atmospheric partial pressure—are usually associated with central nervous system oxygen toxicity and are most likely to occur among patients undergoing hyperbaric oxygen therapy and divers. Since sea level atmospheric pressure is about 1 bar (100 kPa), central nervous system toxicity can only occur under hyperbaric conditions, where ambient pressure is above normal.[31][32] Divers breathing air at depths beyond 60 m (200 ft) face an increasing risk of an oxygen toxicity "hit" (seizure). Divers breathing a gas mixture enriched with oxygen, such as nitrox, can similarly suffer a seizure at shallower depths, should they descend below the maximum operating depth allowed for the mixture.[33] ### Lung toxicity[edit] The curves show typical decrement in lung vital capacity when breathing oxygen. Lambertsen concluded in 1987 that 0.5 bar could be tolerated indefinitely. The lungs and the remainder of the respiratory tract are exposed to the highest concentration of oxygen in the human body and are therefore the first organs to show toxicity. Pulmonary toxicity occurs only with exposure to partial pressures of oxygen greater than 0.5 bar (50 kPa), corresponding to an oxygen fraction of 50% at normal atmospheric pressure. The earliest signs of pulmonary toxicity begin with evidence of tracheobronchitis, or inflammation of the upper airways, after an asymptomatic period between 4 and 22 hours at greater than 95% oxygen,[34] with some studies suggesting symptoms usually begin after approximately 14 hours at this level of oxygen.[35] At partial pressures of oxygen of 2 to 3 bar (200 to 300 kPa)—100% oxygen at 2 to 3 times atmospheric pressure—these symptoms may begin as early as 3 hours after exposure to oxygen.[34] Experiments on rats breathing oxygen at pressures between 1 and 3 bars (100 and 300 kPa) suggest that pulmonary manifestations of oxygen toxicity may not be the same for normobaric conditions as they are for hyperbaric conditions.[36] Evidence of decline in lung function as measured by pulmonary function testing can occur as quickly as 24 hours of continuous exposure to 100% oxygen,[35] with evidence of diffuse alveolar damage and the onset of acute respiratory distress syndrome usually occurring after 48 hours on 100% oxygen.[34] Breathing 100% oxygen also eventually leads to collapse of the alveoli (atelectasis), while—at the same partial pressure of oxygen—the presence of significant partial pressures of inert gases, typically nitrogen, will prevent this effect.[37] Preterm newborns are known to be at higher risk for bronchopulmonary dysplasia with extended exposure to high concentrations of oxygen.[38] Other groups at higher risk for oxygen toxicity are patients on mechanical ventilation with exposure to levels of oxygen greater than 50%, and patients exposed to chemicals that increase risk for oxygen toxicity such the chemotherapeutic agent bleomycin.[35] Therefore, current guidelines for patients on mechanical ventilation in intensive care recommends keeping oxygen concentration less than 60%.[34] Likewise, divers who undergo treatment of decompression sickness are at increased risk of oxygen toxicity as treatment entails exposure to long periods of oxygen breathing under hyperbaric conditions, in addition to any oxygen exposure during the dive.[31] ### Ocular toxicity[edit] See also: Retinopathy of prematurity Prolonged exposure to high inspired fractions of oxygen causes damage to the retina.[39][40][41] Damage to the developing eye of infants exposed to high oxygen fraction at normal pressure has a different mechanism and effect from the eye damage experienced by adult divers under hyperbaric conditions.[42][43] Hyperoxia may be a contributing factor for the disorder called retrolental fibroplasia or retinopathy of prematurity (ROP) in infants.[42][44] In preterm infants, the retina is often not fully vascularised. Retinopathy of prematurity occurs when the development of the retinal vasculature is arrested and then proceeds abnormally. Associated with the growth of these new vessels is fibrous tissue (scar tissue) that may contract to cause retinal detachment. Supplemental oxygen exposure, while a risk factor, is not the main risk factor for development of this disease. Restricting supplemental oxygen use does not necessarily reduce the rate of retinopathy of prematurity, and may raise the risk of hypoxia-related systemic complications.[42] Hyperoxic myopia has occurred in closed circuit oxygen rebreather divers with prolonged exposures.[43][45][46] It also occurs frequently in those undergoing repeated hyperbaric oxygen therapy.[40][47] This is due to an increase in the refractive power of the lens, since axial length and keratometry readings do not reveal a corneal or length basis for a myopic shift.[47][48] It is usually reversible with time.[40][47] ## Mechanism[edit] Main articles: Reactive oxygen species and Oxidative stress The lipid peroxidation mechanism shows a single radical initiating a chain reaction which converts unsaturated lipids to lipid peroxides, The biochemical basis for the toxicity of oxygen is the partial reduction of oxygen by one or two electrons to form reactive oxygen species,[49] which are natural by-products of the normal metabolism of oxygen and have important roles in cell signalling.[50] One species produced by the body, the superoxide anion (O 2−),[51] is possibly involved in iron acquisition.[52] Higher than normal concentrations of oxygen lead to increased levels of reactive oxygen species.[53] Oxygen is necessary for cell metabolism, and the blood supplies it to all parts of the body. When oxygen is breathed at high partial pressures, a hyperoxic condition will rapidly spread, with the most vascularised tissues being most vulnerable. During times of environmental stress, levels of reactive oxygen species can increase dramatically, which can damage cell structures and produce oxidative stress.[19][54] While all the reaction mechanisms of these species within the body are not yet fully understood,[55] one of the most reactive products of oxidative stress is the hydroxyl radical (·OH), which can initiate a damaging chain reaction of lipid peroxidation in the unsaturated lipids within cell membranes.[56] High concentrations of oxygen also increase the formation of other free radicals, such as nitric oxide, peroxynitrite, and trioxidane, which harm DNA and other biomolecules.[19][57] Although the body has many antioxidant systems such as glutathione that guard against oxidative stress, these systems are eventually overwhelmed at very high concentrations of free oxygen, and the rate of cell damage exceeds the capacity of the systems that prevent or repair it.[58][59][60] Cell damage and cell death then result.[61] ## Diagnosis[edit] Diagnosis of central nervous system oxygen toxicity in divers prior to seizure is difficult as the symptoms of visual disturbance, ear problems, dizziness, confusion and nausea can be due to many factors common to the underwater environment such as narcosis, congestion and coldness. However, these symptoms may be helpful in diagnosing the first stages of oxygen toxicity in patients undergoing hyperbaric oxygen therapy. In either case, unless there is a prior history of epilepsy or tests indicate hypoglycaemia, a seizure occurring in the setting of breathing oxygen at partial pressures greater than 1.4 bar (140 kPa) suggests a diagnosis of oxygen toxicity.[62] Diagnosis of bronchopulmonary dysplasia in newborn infants with breathing difficulties is difficult in the first few weeks. However, if the infant's breathing does not improve during this time, blood tests and x-rays may be used to confirm bronchopulmonary dysplasia. In addition, an echocardiogram can help to eliminate other possible causes such as congenital heart defects or pulmonary arterial hypertension.[63] The diagnosis of retinopathy of prematurity in infants is typically suggested by the clinical setting. Prematurity, low birth weight and a history of oxygen exposure are the principal indicators, while no hereditary factors have been shown to yield a pattern.[64] ## Prevention[edit] The label on the diving cylinder shows that it contains oxygen-rich gas (36%) and is boldly marked with a maximum operating depth of 28 metres. The prevention of oxygen toxicity depends entirely on the setting. Both underwater and in space, proper precautions can eliminate the most pernicious effects. Premature infants commonly require supplemental oxygen to treat complications of preterm birth. In this case prevention of bronchopulmonary dysplasia and retinopathy of prematurity must be carried out without compromising a supply of oxygen adequate to preserve the infant's life. ### Underwater[edit] See also: Maximum operating depth Oxygen toxicity is a catastrophic hazard in diving, because a seizure results in near certain death by drowning.[33] The seizure may occur suddenly and with no warning symptoms.[17] The effects are sudden convulsions and unconsciousness, during which victims can lose their regulator and drown.[65][66] One of the advantages of a full-face diving mask is prevention of regulator loss in the event of a seizure. As there is an increased risk of central nervous system oxygen toxicity on deep dives, long dives and dives where oxygen-rich breathing gases are used, divers are taught to calculate a maximum operating depth for oxygen-rich breathing gases, and cylinders containing such mixtures must be clearly marked with that depth.[22][67] In some diver training courses for these types of diving, divers are taught to plan and monitor what is called the oxygen clock of their dives.[67] This is a notional alarm clock, which ticks more quickly at increased oxygen pressure and is set to activate at the maximum single exposure limit recommended in the National Oceanic and Atmospheric Administration Diving Manual.[22][67] For the following partial pressures of oxygen the limits are: 45 minutes at 1.6 bar (160 kPa), 120 minutes at 1.5 bar (150 kPa), 150 minutes at 1.4 bar (140 kPa), 180 minutes at 1.3 bar (130 kPa) and 210 minutes at 1.2 bar (120 kPa), but it is impossible to predict with any reliability whether or when toxicity symptoms will occur.[68][69] Many nitrox-capable dive computers calculate an oxygen loading and can track it across multiple dives. The aim is to avoid activating the alarm by reducing the partial pressure of oxygen in the breathing gas or by reducing the time spent breathing gas of greater oxygen partial pressure. As the partial pressure of oxygen increases with the fraction of oxygen in the breathing gas and the depth of the dive, the diver obtains more time on the oxygen clock by diving at a shallower depth, by breathing a less oxygen-rich gas, or by shortening the duration of exposure to oxygen-rich gases.[70][71] Diving below 56 m (184 ft) on air would expose a diver to increasing danger of oxygen toxicity as the partial pressure of oxygen exceeds 1.4 bar (140 kPa), so a gas mixture must be used which contains less than 21% oxygen (a hypoxic mixture). Increasing the proportion of nitrogen is not viable, since it would produce a strongly narcotic mixture. However, helium is not narcotic, and a usable mixture may be blended either by completely replacing nitrogen with helium (the resulting mix is called heliox), or by replacing part of the nitrogen with helium, producing a trimix.[72] Pulmonary oxygen toxicity is an entirely avoidable event while diving. The limited duration and naturally intermittent nature of most diving makes this a relatively rare (and even then, reversible) complication for divers.[73] Established guidelines enable divers to calculate when they are at risk of pulmonary toxicity.[74][75][76] ### Hyperbaric setting[edit] The presence of a fever or a history of seizure is a relative contraindication to hyperbaric oxygen treatment.[77] The schedules used for treatment of decompression illness allow for periods of breathing air rather than 100% oxygen (oxygen breaks) to reduce the chance of seizure or lung damage. The U.S. Navy uses treatment tables based on periods alternating between 100% oxygen and air. For example, USN table 6 requires 75 minutes (three periods of 20 minutes oxygen/5 minutes air) at an ambient pressure of 2.8 standard atmospheres (280 kPa), equivalent to a depth of 18 metres (60 ft). This is followed by a slow reduction in pressure to 1.9 atm (190 kPa) over 30 minutes on oxygen. The patient then remains at that pressure for a further 150 minutes, consisting of two periods of 15 minutes air/60 minutes oxygen, before the pressure is reduced to atmospheric over 30 minutes on oxygen.[78] Vitamin E and selenium were proposed and later rejected as a potential method of protection against pulmonary oxygen toxicity.[79][80][81] There is however some experimental evidence in rats that vitamin E and selenium aid in preventing in vivo lipid peroxidation and free radical damage, and therefore prevent retinal changes following repetitive hyperbaric oxygen exposures.[82] ### Normobaric setting[edit] Bronchopulmonary dysplasia is reversible in the early stages by use of break periods on lower pressures of oxygen, but it may eventually result in irreversible lung injury if allowed to progress to severe damage. One or two days of exposure without oxygen breaks are needed to cause such damage.[14] Retinopathy of prematurity is largely preventable by screening. Current guidelines require that all babies of less than 32 weeks gestational age or having a birth weight less than 1.5 kg (3.3 lb) should be screened for retinopathy of prematurity at least every two weeks.[83] The National Cooperative Study in 1954 showed a causal link between supplemental oxygen and retinopathy of prematurity, but subsequent curtailment of supplemental oxygen caused an increase in infant mortality. To balance the risks of hypoxia and retinopathy of prematurity, modern protocols now require monitoring of blood oxygen levels in premature infants receiving oxygen.[84] ### Hypobaric setting[edit] In low-pressure environments oxygen toxicity may be avoided since the toxicity is caused by high partial pressure of oxygen, not merely by high oxygen fraction. This is illustrated by modern pure oxygen use in spacesuits, which must operate at low pressure (also historically, very high percentage oxygen and lower than normal atmospheric pressure was used in early spacecraft, for example, the Gemini and Apollo spacecraft).[85] In such applications as extra-vehicular activity, high-fraction oxygen is non-toxic, even at breathing mixture fractions approaching 100%, because the oxygen partial pressure is not allowed to chronically exceed 0.3 bar (4.4 psi).[85] ## Management[edit] The retina (red) is detached at the top of the eye. The silicone band (scleral buckle, blue) is placed around the eye. This brings the wall of the eye into contact with the detached retina, allowing the retina to re-attach. During hyperbaric oxygen therapy, the patient will usually breathe 100% oxygen from a mask while inside a hyperbaric chamber pressurised with air to about 2.8 bar (280 kPa). Seizures during the therapy are managed by removing the mask from the patient, thereby dropping the partial pressure of oxygen inspired below 0.6 bar (60 kPa).[17] A seizure underwater requires that the diver be brought to the surface as soon as practicable. Although for many years the recommendation has been not to raise the diver during the seizure itself, owing to the danger of arterial gas embolism (AGE),[86] there is some evidence that the glottis does not fully obstruct the airway.[87] This has led to the current recommendation by the Diving Committee of the Undersea and Hyperbaric Medical Society that a diver should be raised during the seizure's clonic (convulsive) phase if the regulator is not in the diver's mouth – as the danger of drowning is then greater than that of AGE – but the ascent should be delayed until the end of the clonic phase otherwise.[65] Rescuers ensure that their own safety is not compromised during the convulsive phase. They then ensure that where the victim's air supply is established it is maintained, and carry out a controlled buoyant lift. Lifting an unconscious body is taught by most diver training agencies. Upon reaching the surface, emergency services are always contacted as there is a possibility of further complications requiring medical attention.[88] The U.S. Navy has procedures for completing the decompression stops where a recompression chamber is not immediately available.[89] The occurrence of symptoms of bronchopulmonary dysplasia or acute respiratory distress syndrome is treated by lowering the fraction of oxygen administered, along with a reduction in the periods of exposure and an increase in the break periods where normal air is supplied. Where supplemental oxygen is required for treatment of another disease (particularly in infants), a ventilator may be needed to ensure that the lung tissue remains inflated. Reductions in pressure and exposure will be made progressively, and medications such as bronchodilators and pulmonary surfactants may be used.[90] Retinopathy of prematurity may regress spontaneously, but should the disease progress beyond a threshold (defined as five contiguous or eight cumulative hours of stage 3 retinopathy of prematurity), both cryosurgery and laser surgery have been shown to reduce the risk of blindness as an outcome. Where the disease has progressed further, techniques such as scleral buckling and vitrectomy surgery may assist in re-attaching the retina.[91] ## Prognosis[edit] Although the convulsions caused by central nervous system oxygen toxicity may lead to incidental injury to the victim, it remained uncertain for many years whether damage to the nervous system following the seizure could occur and several studies searched for evidence of such damage. An overview of these studies by Bitterman in 2004 concluded that following removal of breathing gas containing high fractions of oxygen, no long-term neurological damage from the seizure remains.[19][92] The majority of infants who have survived following an incidence of bronchopulmonary dysplasia will eventually recover near-normal lung function, since lungs continue to grow during the first 5–7 years and the damage caused by bronchopulmonary dysplasia is to some extent reversible (even in adults). However, they are likely to be more susceptible to respiratory infections for the rest of their lives and the severity of later infections is often greater than that in their peers.[93][94] Retinopathy of prematurity (ROP) in infants frequently regresses without intervention and eyesight may be normal in later years. Where the disease has progressed to the stages requiring surgery, the outcomes are generally good for the treatment of stage 3 ROP, but are much worse for the later stages. Although surgery is usually successful in restoring the anatomy of the eye, damage to the nervous system by the progression of the disease leads to comparatively poorer results in restoring vision. The presence of other complicating diseases also reduces the likelihood of a favourable outcome.[95] ## Epidemiology[edit] Retinopathy of prematurity (ROP) in 1997 was more common in middle income countries where neonatal intensive care services were increasing; but greater awareness of the problem, leading to preventive measures, had not yet occurred.[96] The incidence of central nervous system toxicity among divers has decreased since the Second World War, as protocols have developed to limit exposure and partial pressure of oxygen inspired. In 1947, Donald recommended limiting the depth allowed for breathing pure oxygen to 7.6 m (25 ft), which equates to an oxygen partial pressure of 1.8 bar (180 kPa).[97] Over time this limit has been reduced, until today a limit of 1.4 bar (140 kPa) during a recreational dive and 1.6 bar (160 kPa) during shallow decompression stops is generally recommended.[98] Oxygen toxicity has now become a rare occurrence other than when caused by equipment malfunction and human error. Historically, the U.S. Navy has refined its Navy Diving Manual Tables to reduce oxygen toxicity incidents. Between 1995 and 1999, reports showed 405 surface-supported dives using the helium–oxygen tables; of these, oxygen toxicity symptoms were observed on 6 dives (1.5%). As a result, the U.S. Navy in 2000 modified the schedules and conducted field tests of 150 dives, none of which produced symptoms of oxygen toxicity. Revised tables were published in 2001.[99] The variability in tolerance and other variable factors such as workload have resulted in the U.S. Navy abandoning screening for oxygen tolerance. Of the 6,250 oxygen-tolerance tests performed between 1976 and 1997, only 6 episodes of oxygen toxicity were observed (0.1%).[100][101] Central nervous system oxygen toxicity among patients undergoing hyperbaric oxygen therapy is rare, and is influenced by a number of a factors: individual sensitivity and treatment protocol; and probably therapy indication and equipment used. A study by Welslau in 1996 reported 16 incidents out of a population of 107,264 patients (0.015%), while Hampson and Atik in 2003 found a rate of 0.03%.[102][103] Yildiz, Ay and Qyrdedi, in a summary of 36,500 patient treatments between 1996 and 2003, reported only 3 oxygen toxicity incidents, giving a rate of 0.008%.[102] A later review of over 80,000 patient treatments revealed an even lower rate: 0.0024%. The reduction in incidence may be partly due to use of a mask (rather than a hood) to deliver oxygen.[104] Bronchopulmonary dysplasia is among the most common complications of prematurely born infants and its incidence has grown as the survival of extremely premature infants has increased. Nevertheless, the severity has decreased as better management of supplemental oxygen has resulted in the disease now being related mainly to factors other than hyperoxia.[38] In 1997 a summary of studies of neonatal intensive care units in industrialised countries showed that up to 60% of low birth weight babies developed retinopathy of prematurity, which rose to 72% in extremely low birth weight babies, defined as less than 1 kg (2.2 lb) at birth. However, severe outcomes are much less frequent: for very low birth weight babies—those less than 1.5 kg (3.3 lb) at birth—the incidence of blindness was found to be no more than 8%.[96] ## History[edit] Paul Bert, a French physiologist, first described oxygen toxicity in 1878. Central nervous system toxicity was first described by Paul Bert in 1878.[105][106] He showed that oxygen was toxic to insects, arachnids, myriapods, molluscs, earthworms, fungi, germinating seeds, birds, and other animals. Central nervous system toxicity may be referred to as the "Paul Bert effect".[14] Pulmonary oxygen toxicity was first described by J. Lorrain Smith in 1899 when he noted central nervous system toxicity and discovered in experiments in mice and birds that 0.43 bar (43 kPa) had no effect but 0.75 bar (75 kPa) of oxygen was a pulmonary irritant.[29] Pulmonary toxicity may be referred to as the "Lorrain Smith effect".[14] The first recorded human exposure was undertaken in 1910 by Bornstein when two men breathed oxygen at 2.8 bar (280 kPa) for 30 minutes while he went on to 48 minutes with no symptoms. In 1912, Bornstein developed cramps in his hands and legs while breathing oxygen at 2.8 bar (280 kPa) for 51 minutes.[3] Smith then went on to show that intermittent exposure to a breathing gas with less oxygen permitted the lungs to recover and delayed the onset of pulmonary toxicity.[29] Albert R. Behnke et al. in 1935 were the first to observe visual field contraction (tunnel vision) on dives between 1.0 bar (100 kPa) and 4.1 bar (410 kPa).[107][108] During World War II, Donald and Yarbrough et al. performed over 2,000 experiments on oxygen toxicity to support the initial use of closed circuit oxygen rebreathers.[39][109] Naval divers in the early years of oxygen rebreather diving developed a mythology about a monster called "Oxygen Pete", who lurked in the bottom of the Admiralty Experimental Diving Unit "wet pot" (a water-filled hyperbaric chamber) to catch unwary divers. They called having an oxygen toxicity attack "getting a Pete".[110][111] In the decade following World War II, Lambertsen et al. made further discoveries on the effects of breathing oxygen under pressure and methods of prevention.[112][113] Their work on intermittent exposures for extension of oxygen tolerance and on a model for prediction of pulmonary oxygen toxicity based on pulmonary function are key documents in the development of standard operating procedures when breathing increased pressures of oxygen.[114] Lambertsen's work showing the effect of carbon dioxide in decreasing time to onset of central nervous system symptoms has influenced work from current exposure guidelines to future breathing apparatus design.[21][22][115] Retinopathy of prematurity was not observed before World War II, but with the availability of supplemental oxygen in the decade following, it rapidly became one of the principal causes of infant blindness in developed countries. By 1960 the use of oxygen had become identified as a risk factor and its administration restricted. The resulting fall in retinopathy of prematurity was accompanied by a rise in infant mortality and hypoxia-related complications. Since then, more sophisticated monitoring and diagnosis have established protocols for oxygen use which aim to balance between hypoxic conditions and problems of retinopathy of prematurity.[96] Bronchopulmonary dysplasia was first described by Northway in 1967, who outlined the conditions that would lead to the diagnosis.[116] This was later expanded by Bancalari and in 1988 by Shennan, who suggested the need for supplemental oxygen at 36 weeks could predict long-term outcomes.[117] Nevertheless, Palta et al. in 1998 concluded that radiographic evidence was the most accurate predictor of long-term effects.[118] Bitterman et al. in 1986 and 1995 showed that darkness and caffeine would delay the onset of changes to brain electrical activity in rats.[23][24] In the years since, research on central nervous system toxicity has centred on methods of prevention and safe extension of tolerance.[119] Sensitivity to central nervous system oxygen toxicity has been shown to be affected by factors such as circadian rhythm, drugs, age, and gender.[120][121][122][123] In 1988, Hamilton et al. wrote procedures for the National Oceanic and Atmospheric Administration to establish oxygen exposure limits for habitat operations.[74][75][76] Even today, models for the prediction of pulmonary oxygen toxicity do not explain all the results of exposure to high partial pressures of oxygen.[124] ## Society and culture[edit] See also: Nitrox and Oxygen bar Recreational scuba divers commonly breathe nitrox containing up to 40% oxygen, while technical divers use pure oxygen or nitrox containing up to 80% oxygen. Divers who breathe oxygen fractions greater than of air (21%) need to be trained in the dangers of oxygen toxicity and how to prevent them.[67] In order to buy nitrox, a diver has to show evidence of such qualification.[125] Since the late 1990s the recreational use of oxygen has been promoted by oxygen bars, where customers breathe oxygen through a nasal cannula. Claims have been made that this reduces stress, increases energy, and lessens the effects of hangovers and headaches, despite the lack of any scientific evidence to support them.[126] There are also devices on sale that offer "oxygen massage" and "oxygen detoxification" with claims of removing body toxins and reducing body fat.[127] The American Lung Association has stated "there is no evidence that oxygen at the low flow levels used in bars can be dangerous to a normal person's health", but the U.S. Center for Drug Evaluation and Research cautions that people with heart or lung disease need their supplementary oxygen carefully regulated and should not use oxygen bars.[126] Victorian society had a fascination for the rapidly expanding field of science. In "Dr. Ox's Experiment", a short story written by Jules Verne in 1872, the eponymous doctor uses electrolysis of water to separate oxygen and hydrogen. He then pumps the pure oxygen throughout the town of Quiquendone, causing the normally tranquil inhabitants and their animals to become aggressive and plants to grow rapidly. An explosion of the hydrogen and oxygen in Dr Ox's factory brings his experiment to an end. Verne summarised his story by explaining that the effects of oxygen described in the tale were his own invention.[128] There is also a brief episode of oxygen intoxication in his "From the Earth to the Moon".[129] ## See also[edit] * Effect of oxygen on chronic obstructive pulmonary disease * Nitrogen narcosis – Reversible narcotic effects of respiratory nitrogen at elevated partial pressures ## References[edit] 1. ^ a b c Donald, Part I 1947. 2. ^ a b Clark & Thom 2003, pp. 358–360. 3. ^ a b Acott, Chris (1999). "Oxygen toxicity: A brief history of oxygen in diving". South Pacific Underwater Medicine Society Journal. 29 (3): 150–5. ISSN 0813-1988. OCLC 16986801. Retrieved 29 April 2008. 4. ^ Beehler, CC (1964). 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Columbus, OH: College Book Company. Translated by: Hitchcock, Mary Alice; Hitchcock, Fred A 106. ^ British Sub-aqua Club (1985). Sport diving : the British Sub-Aqua Club diving manual. London: Stanley Paul. p. 110. ISBN 0-09-163831-3. OCLC 12807848. 107. ^ Behnke, Alfred R; Johnson, FS; Poppen, JR; Motley, EP (1935). "The effect of oxygen on man at pressures from 1 to 4 atmospheres". American Journal of Physiology. 110 (3): 565–572. doi:10.1152/ajplegacy.1934.110.3.565. Note: 1 atmosphere (atm) is 1.013 bars. 108. ^ Behnke, Alfred R; Forbes, HS; Motley, EP (1935). "Circulatory and visual effects of oxygen at 3 atmospheres pressure". American Journal of Physiology. 114 (2): 436–442. doi:10.1152/ajplegacy.1935.114.2.436. Note: 1 atmosphere (atm) is 1.013 bars. 109. ^ Donald 1992. 110. ^ Taylor, Larry "Harris" (1993). "Oxygen Enriched Air: A New Breathing Mix?". IANTD Journal. Retrieved 29 May 2008. 111. ^ Davis, Robert H (1955). Deep Diving and Submarine Operations (6th ed.). Tolworth, Surbiton, Surrey: Siebe Gorman & Company Ltd. p. 291. 112. ^ Lambertsen, Christian J; Clark, John M; Gelfand, R (2000). "The Oxygen research program, University of Pennsylvania: Physiologic interactions of oxygen and carbon dioxide effects and relations to hyperoxic toxicity, therapy, and decompression. Summation: 1940 to 1999". EBSDC-IFEM Report No. 3-1-2000. Philadelphia, PA: Environmental Biomedical Stress Data Center, Institute for Environmental Medicine, University of Pennsylvania Medical Center. 113. ^ Vann, Richard D (2004). "Lambertsen and O2: Beginnings of operational physiology". Undersea and Hyperbaric Medicine. 31 (1): 21–31. PMID 15233157. Retrieved 29 April 2008. 114. ^ Clark & Lambertsen 1970. 115. ^ Lang 2001, pp. 81–6. 116. ^ Northway, WH; Rosan, RC; Porter, DY (1967). "Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia". New England Journal of Medicine. 276 (7): 357–68. doi:10.1056/NEJM196702162760701. PMID 5334613. 117. ^ Shennan, AT; Dunn, MS; Ohlsson, A; Lennox, K; Hoskins, EM (1988). "Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period". Pediatrics. 82 (4): 527–32. PMID 3174313. 118. ^ Palta, Mari; Sadek, Mona; Barnet, Jodi H; et al. (January 1998). "Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project". Journal of Pediatrics. 132 (1): 57–63. doi:10.1016/S0022-3476(98)70485-8. PMID 9470001. 119. ^ Natoli, MJ; Vann, Richard D (1996). "Factors Affecting CNS Oxygen Toxicity in Humans". Report to the U.S. Office of Naval Research. Durham, NC: Duke University. Retrieved 29 April 2008. 120. ^ Hof, DG; Dexter, JD; Mengel, CE (1971). "Effect of circadian rhythm on CNS oxygen toxicity". Aerospace Medicine. 42 (12): 1293–6. PMID 5130131. 121. ^ Torley, LW; Weiss, HS (1975). "Effects of age and magnesium ions on oxygen toxicity in the neonate chicken". Undersea Biomedical Research. 2 (3): 223–7. PMID 15622741. Retrieved 20 September 2008. 122. ^ Troy, SS; Ford, DH (1972). "Hormonal protection of rats breathing oxygen at high pressure". Acta Neurologica Scandinavica. 48 (2): 231–42. doi:10.1111/j.1600-0404.1972.tb07544.x. PMID 5061633. S2CID 28618515. 123. ^ Hart, George B; Strauss, Michael B (2007). "Gender differences in human skeletal muscle and subcutaneous tissue gases under ambient and hyperbaric oxygen conditions". Undersea and Hyperbaric Medicine. 34 (3): 147–61. PMID 17672171. Retrieved 20 September 2008. 124. ^ Shykoff, Barbara E (2007). "Performance of various models in predicting vital capacity changes caused by breathing high oxygen partial pressures". Nedu-Tr-07-13. Panama City, FL: U.S. Naval Experimental Diving Unit Technical Report. Retrieved 6 June 2008. 125. ^ British Sub-Aqua Club (2006). "The Ocean Diver Nitrox Workshop" (PDF). British Sub-Aqua Club. p. 6. Archived from the original (PDF) on 16 July 2011. Retrieved 15 September 2010. 126. ^ a b Bren, Linda (November–December 2002). "Oxygen Bars: Is a Breath of Fresh Air Worth It?". FDA Consumer. Vol. 36 no. 6. pp. 9–11. PMID 12523293. Retrieved 25 March 2020. 127. ^ "O2 Planet – Exercise and Fitness Equipment". O2Planet LLC. 2006. Archived from the original on 15 April 2006. Retrieved 21 October 2008. 128. ^ Verne, Jules (2004) [1872]. A Fantasy of Dr Ox. Hesperus Press. ISBN 978-1-84391-067-1. Retrieved 8 May 2009. Translated from French 129. ^ Verne, Jules (1877) [1870]. "VIII" [At seventy-eight thousand one hundred and fourteen leagues]. Autour de la Lune [Round the Moon]. London: Ward Lock. ISBN 2-253-00587-8. Retrieved 2 September 2009. Translated from French ## Sources[edit] * Clark, James M; Thom, Stephen R (2003). "Oxygen under pressure". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett and Elliott's physiology and medicine of diving (5th ed.). United States: Saunders. pp. 358–418. ISBN 978-0-7020-2571-6. OCLC 51607923.CS1 maint: ref=harv (link) * Clark, John M; Lambertsen, Christian J (1970). "Pulmonary oxygen tolerance in man and derivation of pulmonary oxygen tolerance curves". IFEM Report No. 1-70. Philadelphia, PA: Environmental Biomedical Stress Data Center, Institute for Environmental Medicine, University of Pennsylvania Medical Center. Archived from the original on 7 October 2008. Retrieved 29 April 2008.CS1 maint: ref=harv (link) * Donald, Kenneth W (1947). "Oxygen Poisoning in Man: Part I". British Medical Journal. 1 (4506): 667–672. doi:10.1136/bmj.1.4506.667. PMC 2053251. PMID 20248086. * Donald, Kenneth W (1947). "Oxygen Poisoning in Man: Part II". British Medical Journal. 1 (4507): 712–717. doi:10.1136/bmj.1.4507.712. PMC 2053400. PMID 20248096. * Revised version of Donald's articles also available as: * Donald, Kenneth W (1992). Oxygen and the diver. UK: Harley Swan, 237 pages. ISBN 1-85421-176-5. OCLC 26894235.CS1 maint: ref=harv (link) * Hamilton, Robert W; Thalmann, Edward D (2003). "Decompression practice". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett and Elliott's physiology and medicine of diving (5th ed.). United States: Saunders. pp. 475–479. ISBN 978-0-7020-2571-6. OCLC 51607923.CS1 maint: ref=harv (link) * Lang, Michael A, ed. (2001). DAN nitrox workshop proceedings. Durham, NC: Divers Alert Network, 197 pages. Archived from the original on 16 September 2011. Retrieved 20 September 2008.CS1 maint: ref=harv (link) * Regillo, Carl D; Brown, Gary C; Flynn, Harry W (1998). Vitreoretinal Disease: The Essentials. New York: Thieme, 693 pages. ISBN 978-0-86577-761-3. OCLC 39170393.CS1 maint: ref=harv (link) * U.S. Navy Supervisor of Diving (2011). U.S. Navy Diving Manual (PDF). SS521-AG-PRO-010 0910-LP-106-0957, revision 6 with Change A entered. U.S. Naval Sea Systems Command. Archived from the original (PDF) on 10 December 2014. Retrieved 29 January 2015. ## Further reading[edit] * Lamb, John S. (1999). The Practice of Oxygen Measurement for Divers. Flagstaff: Best Publishing, 120 pages. ISBN 0-941332-68-3. OCLC 44018369. * Lippmann, John; Bugg, Stan (1993). The Diving Emergency Handbook. Teddington, UK: Underwater World Publications. ISBN 0-946020-18-3. OCLC 52056845. * Lippmann, John; Mitchell, Simon (2005). "Oxygen". Deeper into Diving (2nd ed.). Victoria, Australia: J.L. Publications. pp. 121–4. ISBN 0-9752290-1-X. OCLC 66524750. ## External links[edit] General The following external site is a compendium of resources: * Rubicon Research Repository. – Online collection of the oxygen toxicity research Specialised The following external sites contain resources specific to particular topics: * 2008 Divers Alert Network Technical Diving Conference. – Video of "Oxygen Toxicity" lecture by Dr. Richard Vann (free download, mp4, 86MB). * Nosek, Thomas M. "Section 4/4ch7/s4ch7_7". Essentials of Human Physiology. Archived from the original on 24 March 2016.. – Wide and detailed discussion of the effects of breathing oxygen on the respiratory system. * Rajiah, Prabhakar (11 March 2009). "Bronchopulmonary Dysplasia". eMedicine. WebMD. Retrieved 29 June 2009. – Concise clinical overview with extensive references. Classification D * ICD-10: T59.8 * ICD-9-CM: 987.8 * MeSH: D018496 * v * t * e Respiratory physiology Respiration * breath * inhalation * exhalation * obligate nasal breathing * respiratory rate * respirometer * pulmonary surfactant * compliance * elastic recoil * hysteresivity * airway resistance * bronchial * hyperresponsiveness * constriction * dilatation * mechanical ventilation Control * pons * pneumotaxic center * apneustic center * medulla * dorsal respiratory group * ventral respiratory group * chemoreceptors * central * peripheral * pulmonary stretch receptors * Hering–Breuer reflex Lung volumes * VC * FRC * Vt * dead space * CC * PEF calculations respiratory minute volume FEV1/FVC ratio Lung function tests spirometry body plethysmography peak flow meter nitrogen washout Circulation * pulmonary circulation * hypoxic pulmonary vasoconstriction * pulmonary shunt Interactions * ventilation (V) * Perfusion (Q) * Ventilation/perfusion ratio * V/Q scan * zones of the lung * gas 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stage * Downline * Jackstay * Launch and recovery system * Messenger line * Moon pool Breathing gas handling * Air filtration * Activated carbon * Hopcalite * Molecular sieve * Silica gel * Booster pump * Carbon dioxide scrubber * Cascade filling system * Diver's pump * Diving air compressor * Diving air filter * Water separator * High pressure breathing air compressor * Low pressure breathing air compressor * Gas blending * Gas blending for scuba diving * Gas panel * Gas reclaim system * Gas storage bank * Gas storage quad * Gas storage tube * Helium analyzer * Nitrox production * Membrane gas separation * Pressure swing adsorption * Oxygen analyser * Oxygen compatibility Decompression equipment * Built-in breathing system * Decompression tables * Diving bell * Bell cursor * Closed bell * Clump weight * Launch and recovery system * Wet bell * Diving chamber * Diving stage * Recreational Dive Planner * Saturation system Platforms * Dive boat * Canoe and kayak diving * Combat Rubber Raiding Craft * Liveaboard * Subskimmer * Diving support vessel * HMS Challenger (K07) Underwater habitat * Aquarius Reef Base * Continental Shelf Station Two * Helgoland Habitat * Jules' Undersea Lodge * Scott Carpenter Space Analog Station * SEALAB * Tektite habitat Remotely operated underwater vehicles * 8A4-class ROUV * ABISMO * Atlantis ROV Team * CURV * Deep Drone * Épaulard * Global Explorer ROV * Goldfish-class ROUV * Kaikō ROV * Kaşif ROUV * Long-Term Mine Reconnaissance System * Mini Rover ROV * OpenROV * ROV KIEL 6000 * ROV PHOCA * Scorpio ROV * Sea Dragon-class ROV * Seabed tractor * Seafox drone * Seahorse ROUV * SeaPerch * SJT-class ROUV * T1200 Trenching Unit * VideoRay UROVs Safety equipment * Diver down flag * Diving shot * Hyperbaric lifeboat * Hyperbaric stretcher * Jackstay * Jonline * Reserve gas supply General * Diving spread * Air spread * Saturation spread * Hot water system * Sonar * Underwater acoustic positioning system * Underwater acoustic communication Freediving Activities * Aquathlon * Apnoea finswimming * Freediving * Haenyeo * Pearl hunting * Ama * Snorkeling * Spearfishing * Underwater football * Underwater hockey * Underwater ice hockey * Underwater rugby * Underwater target shooting Competitions * Nordic Deep * Vertical Blue * Disciplines * Constant weight (CWT) * Constant weight without fins (CNF) * Dynamic apnea (DYN) * Dynamic apnea without fins (DNF) * Free immersion (FIM) * No-limits apnea (NLT) * Static apnea (STA) * Skandalopetra diving * Variable weight apnea (VWT) * Variable weight apnea without fins Equipment * Diving mask * Diving suit * Hawaiian sling * Polespear * Snorkel (swimming) * Speargun * Swimfins * Monofin * Water polo cap Freedivers * Deborah Andollo * Peppo Biscarini * Sara Campbell * Derya Can Göçen * Goran Čolak * Carlos Coste * Robert Croft * Mandy-Rae Cruickshank * Yasemin Dalkılıç * Leonardo D'Imporzano * Flavia Eberhard * Şahika Ercümen * Emma Farrell * Francisco Ferreras * Pierre Frolla * Flavia Eberhard * Mehgan Heaney-Grier * Elisabeth Kristoffersen * Loïc Leferme * Enzo Maiorca * Jacques Mayol * Audrey Mestre * Karol Meyer * Stéphane Mifsud * Alexey Molchanov * Natalia Molchanova * Dave Mullins * Patrick Musimu * Guillaume Néry * Herbert Nitsch * Umberto Pelizzari * Annelie Pompe * Michal Risian * Stig Severinsen * Tom Sietas * Aharon Solomons * Martin Štěpánek * Walter Steyn * Tanya Streeter * William Trubridge * Devrim Cenk Ulusoy * Danai Varveri * Alessia Zecchini * Nataliia Zharkova Hazards * Barotrauma * Drowning * Freediving blackout * Deep-water blackout * Shallow-water blackout * Hypercapnia * Hypothermia Historical * Ama * Octopus wrestling * Swimming at the 1900 Summer Olympics – Men's underwater swimming Organisations * AIDA International * Scuba Schools International * Australian Underwater Federation * British Freediving Association * Confédération Mondiale des Activités Subaquatiques * Fédération Française d'Études et de Sports Sous-Marins * Performance Freediving International Professional diving Occupations * Ama * Commercial diver * Commercial offshore diver * Hazmat diver * Divemaster * Diving instructor * Diving safety officer * Diving superintendent * Diving supervisor * Haenyeo * Media diver * Police diver * Public safety diver * Scientific diver * Underwater archaeologist Military diving * Army engineer diver * Clearance diver * Frogman * List of military diving units * Royal Navy ships diver * Special Boat Service * United States military divers * U.S. Navy diver * U.S.Navy master diver * United States Navy SEALs * Underwater Demolition Team Underwater work * Commercial offshore diving * Dive leader * Diver training * Recreational diver training * Hyperbaric welding * Media diving * Nondestructive testing * Pearl hunting * Police diving * Potable water diving * Public safety diving * Scientific diving * Ships husbandry * Sponge diving * Submarine pipeline * Underwater archaeology * Archaeology of shipwrecks * Underwater construction * Offshore construction * Underwater demolition * Underwater photography * Underwater search and recovery * Underwater videography Salvage diving * SS Egypt * Kronan * La Belle * SS Laurentic * RMS Lusitania * Mars * Mary Rose * USS Monitor * HMS Royal George * Vasa Diving contractors * COMEX * Helix Energy Solutions Group Tools & equipment * Abrasive waterjet * Airlift * Baited remote underwater video * In-water surface cleaning * Brush cart * Cavitation cleaning * Pressure washing * Pigging * Lifting bag * Remotely operated underwater vehicle * Thermal lance * Tremie * Water jetting Underwater weapons * Limpet mine * Speargun * Hawaiian sling * Polespear Underwater firearm * Gyrojet * Mk 1 Underwater Defense Gun * Powerhead * Underwater pistols * Heckler & Koch P11 * SPP-1 underwater pistol * Underwater revolvers * AAI underwater revolver * Underwater rifles * ADS amphibious rifle * APS underwater rifle * ASM-DT amphibious rifle Recreational diving Specialties * Altitude diving * Cave diving * Deep diving * Ice diving * Muck diving * Open-water diving * Rebreather diving * Sidemount diving * Solo diving * Technical diving * Underwater photography * Wreck diving Diver organisations * British Sub-Aqua Club (BSAC) * Cave Divers Association of Australia (CDAA) * Cave Diving Group (CDG) * Comhairle Fo-Thuinn (CFT) * Confédération Mondiale des Activités Subaquatiques (CMAS) * Federación Española de Actividades Subacuáticas (FEDAS) * Fédération Française d'Études et de Sports Sous-Marins (FFESSM) * International Association for Handicapped Divers (IAHD) * National Association for Cave Diving (NACD) * Woodville Karst Plain Project (WKPP) Diving tourism industry * Dive center * Environmental impact of recreational diving * Scuba diving tourism * Shark tourism * Sinking ships for wreck diving sites Diving events and festivals * Diversnight * Underwater Bike Race Recreational dive sites Reef diving regions * Aliwal Shoal Marine Protected Area * Arrecifes de Cozumel National Park * Edmonds Underwater Park * Great Barrier Reef * iSimangaliso Marine Protected Area * Poor Knights Islands * Table Mountain National Park Marine Protected Area Reef dive sites * Artificial reef * Gibraltar Artificial Reef * Shark River Reef * Osborne Reef * Fanadir * Gamul Kebir * Palancar Reef * Underwater artworks * Cancún Underwater Museum * Christ of the Abyss * Molinere Underwater Sculpture Park Wreck diving regions * Chuuk Lagoon * Edmonds Underwater Park * Finger Lakes Underwater Preserve Association * Maritime Heritage Trail – Battle of Saipan * Michigan Underwater Preserves * Robben Island Marine Protected Area * Table Mountain National Park Marine Protected Area * Tulagi * Tulamben * Whitefish Point Underwater Preserve * Wreck Alley, San Diego Wreck dive sites * HMS A1 * HMS A3 * USS Aaron Ward * Abessinia * Aeolian Sky * Albert C. Field * Andrea Doria * Antilla * Antilles * Aquila * USS Arkansas * Bianca C. * SS Binnendijk * HMS Boadicea * Booya * HMSAS Bloemfontein * Breda * HMAS Brisbane * HMHS Britannic * Bungsberg * HMAS Canberra * Carl D. Bradley * Carnatic * SMS Dresden * Dunraven * Eastfield * HMT Elk * Ellengowan * RMS Empress of Ireland * HMS Falmouth * Fifi * SS Francisco Morazan * Fujikawa Maru * Fumizuki * SATS General Botha * USNS General Hoyt S. Vandenberg * HMS Ghurka * Glen Strathallan * SAS Good Hope * Gothenburg * Herzogin Cecilie * Hilma Hooker * Hispania * HMS Hood * HMAS Hobart * Igara * James Eagan Layne * Captain Keith Tibbetts * King Cruiser * SMS Kronprinz * Kyarra * HMS Laforey * USAT Liberty * Louis Sheid * USS LST-507 * SMS Markgraf * Mikhail Lermontov * HMS M2 * Maine * Maloja * HMS Maori * Marguerite * SS Mauna Loa * USAT Meigs * Mendi * USCGC Mohawk * Mohegan * RMS Moldavia * HMS Montagu * MV RMS Mulheim * Nagato * Oceana * USS Oriskany * Oslofjord * P29 * P31 * Pedernales * Persier * HMAS Perth * SAS Pietermaritzburg * Piłsudski * Pool Fisher * HMS Port Napier * Preußen * President Coolidge * PS Queen Victoria * Radaas * Rainbow Warrior * RMS Rhone * Rondo * Rosehill * Rotorua * Royal Adelaide * Royal Charter * Rozi * HMS Safari * Salem Express * USS Saratoga * USS Scuffle * HMS Scylla * HMS Sidon * USS Spiegel Grove * Stanegarth * Stanwood * Stella * HMAS Swan * USS Tarpon * Thesis * Thistlegorm * Toa Maru * Torrey Canyon * SAS Transvaal * U-40 * U-352 * U-1195 * Um El Faroud * Varvassi * Walter L M Russ * Washingtonian (1913) * HMNZS Wellington * USS Yancey * Yongala * Zenobia * Zealandia * Zingara Cave diving sites * Blauhöhle * Chinhoyi Caves * Devil's Throat at Punta Sur * Engelbrecht Cave * Fossil Cave * Jordbrugrotta * Piccaninnie Ponds * Pluragrotta * Pollatoomary * Sistema Ox Bel Ha * Sistema Sac Actun * Sistema Dos Ojos * Sistema Nohoch Nah Chich Freshwater dives * Dutch Springs * Ewens Ponds * Little Blue Lake Training sites * Capernwray Dive Centre * Deepspot * National Diving and Activity Centre * Stoney Cove Open ocean diving * Blue-water diving * Black-water diving Diving safety * Human factors in diving equipment design * Human factors in diving safety * Life-support system * Safety-critical system * Scuba diving fatalities Diving hazards * List of diving hazards and precautions * Environmental * Current * Delta-P * Entanglement hazard * Overhead * Silt out * Wave action * Equipment * Freeflow * Use of breathing equipment in an underwater environment * Failure of diving equipment other than breathing apparatus * Single point of failure * Physiological * Cold shock response * Decompression * Nitrogen narcosis * Oxygen toxicity * Seasickness * Uncontrolled decompression * Diver behaviour and competence * Lack of competence * Overconfidence effect * Panic * Task loading * Trait anxiety * Willful violation Consequences * Barotrauma * Decompression sickness * Drowning * Hypothermia * Hypoxia * Hypercapnia * Hyperthermia Diving procedures * Ascending and descending * Emergency ascent * Boat diving * Canoe and kayak diving * Buddy diving * buddy check * Decompression * Decompression practice * Pyle stop * Ratio decompression * Dive briefing * Dive log * Dive planning * Scuba gas planning * Diver communications * Diving hand signals * Diving line signals * Diver voice communications * Diver rescue * Diver training * Doing It Right * Drift diving * Gas blending for scuba diving * Night diving * Solo diving * Water safety Risk management * Checklist * Hazard identification and risk assessment * Hazard analysis * Job safety analysis * Risk assessment * Risk control * Hierarchy of hazard controls * Incident pit * Lockout–tagout * Permit To Work * Redundancy * Safety data sheet * Situation awareness Diving team * Bellman * Chamber operator * Diver medical technician * Diver's attendant * Diving supervisor * Diving systems technician * Gas man * Life support technician * Stand-by diver Equipment safety * Breathing gas quality * Testing and inspection of diving cylinders * Hydrostatic test * Sustained load cracking * Diving regulator * Breathing performance of regulators Occupational safety and health * Approaches to safety * Job safety analysis * Risk assessment * Toolbox talk * Housekeeping * Association of Diving Contractors International * Code of practice * Contingency plan * Diving regulations * Emergency procedure * Emergency response plan * Evacuation plan * Hazardous Materials Identification System * Hierarchy of hazard controls * Administrative controls * Engineering controls * Hazard elimination * Hazard substitution * Personal protective equipment * International Marine Contractors Association * Occupational hazard * Biological hazard * Chemical hazard * Physical hazard * Psychosocial hazard * Occupational hygiene * Exposure assessment * Occupational exposure limit * Workplace health surveillance * Safety culture * Code of practice * Diving safety officer * Diving superintendent * Health and safety representative * Operations manual * Safety meeting * Standard operating procedure Diving medicine Diving disorders * List of signs and symptoms of diving disorders * Cramp * Motion sickness * Surfer's ear Pressure related * Alternobaric vertigo * Barostriction * Barotrauma * Air embolism * Aerosinusitis * Barodontalgia * Dental barotrauma * Pulmonary barotrauma * Compression arthralgia * Decompression illness * Dysbarism Oxygen * Freediving blackout * Hyperoxia * Hypoxia * Oxygen toxicity Inert gases * Avascular necrosis * Decompression sickness * Isobaric counterdiffusion * Taravana * Dysbaric osteonecrosis * High-pressure nervous syndrome * Hydrogen narcosis * Nitrogen narcosis Carbon dioxide * Hypercapnia * Hypocapnia Breathing gas contaminants * Carbon monoxide poisoning Immersion related * Asphyxia * Drowning * Hypothermia * Immersion diuresis * Instinctive drowning response * Laryngospasm * Salt water aspiration syndrome * Swimming-induced pulmonary edema Treatment * Demand valve oxygen therapy * First aid * Hyperbaric medicine * Hyperbaric treatment schedules * In-water recompression * Oxygen therapy * Therapeutic recompression Personnel * Diving Medical Examiner * Diving Medical Practitioner * Diving Medical Technician * Hyperbaric nursing Screening * Atrial septal defect * Effects of drugs on fitness to dive * Fitness to dive * Psychological fitness to dive Research Researchers in diving physiology and medicine * Arthur J. Bachrach * Albert R. Behnke * Paul Bert * George F. Bond * Robert Boyle * Albert A. Bühlmann * John R. Clarke * Guybon Chesney Castell Damant * Kenneth William Donald * William Paul Fife * John Scott Haldane * Robert William Hamilton Jr. * Leonard Erskine Hill * Brian Andrew Hills * Felix Hoppe-Seyler * Christian J. Lambertsen * Simon Mitchell * Charles Momsen * John Rawlins R.N. * Charles Wesley Shilling * Edward D. Thalmann * Jacques Triger Diving medical research organisations * Aerospace Medical Association * Divers Alert Network (DAN) * Diving Diseases Research Centre (DDRC) * Diving Medical Advisory Council (DMAC) * European Diving Technology Committee (EDTC) * European Underwater and Baromedical Society (EUBS) * National Board of Diving and Hyperbaric Medical Technology * Naval Submarine Medical Research Laboratory * Royal Australian Navy School of Underwater Medicine * Rubicon Foundation * South Pacific Underwater Medicine Society (SPUMS) * Southern African Underwater and Hyperbaric Medical Association (SAUHMA) * Undersea and Hyperbaric Medical Society (UHMS) * United States Navy Experimental Diving Unit (NEDU) Law * Civil liability in recreational diving * Diving regulations * Duty of care * List of legislation regulating underwater diving * Investigation of diving accidents * UNESCO Convention on the Protection of the Underwater Cultural Heritage History of underwater diving * History of decompression research and development * History of scuba diving * List of researchers in underwater diving * Timeline of diving technology * Underwater diving in popular culture Archeological sites * SS Commodore * USS Monitor * Queen Anne's Revenge * Whydah Gally Underwater art and artists * The Diver * Jason deCaires Taylor Engineers and inventors * William Beebe * Georges Beuchat * John R. Clarke * Jacques Cousteau * Charles Anthony Deane * John Deane * Ted Eldred * Henry Fleuss * Émile Gagnan * Joseph-Martin Cabirol * Christian J. Lambertsen * Yves Le Prieur * John Lethbridge * Ernest William Moir * Joseph Salim Peress * Auguste Piccard * Willard Franklyn Searle * Augustus Siebe * Jacques Triger Equipment * Aqua-Lung * RV Calypso * SP-350 Denise * Nikonos * Porpoise regulator * Standard diving dress * Vintage scuba Military and covert operations * Raid on Alexandria (1941) * Sinking of the Rainbow Warrior Scientific projects * 1992 cageless shark-diving expedition * Mission 31 Incidents Dive boat incidents * Sinking of MV Conception * Fire on MV Red Sea Aggressor Diver rescues * Alpazat cave rescue * Tham Luang cave rescue Early diving * John Day (carpenter) * Charles Spalding * Ebenezer Watson Freediving fatalities * Loïc Leferme * Audrey Mestre * Nicholas Mevoli * Natalia Molchanova Offshore diving incidents * Byford Dolphin diving bell accident * Drill Master diving accident * Star Canopus diving accident * Stena Seaspread diving accident * Venture One diving accident * Waage Drill II diving accident * Wildrake diving accident Professional diving fatalities * Roger Baldwin * John Bennett * Victor F. Guiel Jr. * Craig M. Hoffman * Peter Henry Michael Holmes * Johnson Sea Link accident * Edwin Clayton Link * Gerard Anthony Prangley * Pier Skipness * Robert John Smyth * Albert D. Stover * Richard A. Walker * Lothar Michael Ward * Joachim Wendler * Bradley Westell * Arne Zetterström Scuba diving fatalities * Ricardo Armbruster * Allan Bridge * David Bright * Berry L. Cannon * Cotton Coulson * Cláudio Coutinho * E. Yale Dawson * Deon Dreyer * Milan Dufek * Sheck Exley * Maurice Fargues * Fernando Garfella Palmer * Guy Garman * Steve Irwin * Jim Jones * Henry Way Kendall * Artur Kozłowski * Chris and Chrissy Rouse * Kirsty MacColl * Agnes Milowka * François de Roubaix * Dave Shaw * Wesley C. Skiles * Dewey Smith * Rob Stewart * Esbjörn Svensson * Josef Velek Publications Manuals * NOAA Diving Manual * U.S. Navy Diving Manual * Basic Cave Diving: A Blueprint for Survival * Underwater Handbook * Bennett and Elliott's physiology and medicine of diving * Encyclopedia of Recreational Diving * The new science of skin and scuba diving * Professional Diver's Handbook * Basic Scuba Standards and Codes of Practice * Code of Practice for Scientific Diving (UNESCO) * DIN 7876 * IMCA Code of Practice for Offshore Diving * ISO 24801 Recreational diving services — Requirements for the training of recreational scuba divers General non-fiction * The Darkness Beckons * Goldfinder * The Last Dive * Shadow Divers * The Silent World: A Story of Undersea Discovery and Adventure Research * List of Divers Alert Network publications Dive guides * Training and registration Diver training * Competence and assessment * Competency-based learning * Refresher training * Skill assessment * Diver training standard * Diving instructor * Diving school * Occupational diver training * Commercial diver training * Military diver training * Public safety diver training * Scientific diver training * Recreational diver training * Introductory diving * Teaching method * Muscle memory * Overlearning * Stress exposure training Skills * Combat sidestroke * Diver navigation * Diver trim * Ear clearing * Frenzel maneuver * Valsalva maneuver * Finning techniques * Scuba skills * Buddy breathing * Low impact diving * Diamond Reef System * Surface-supplied diving skills * Underwater searches Recreational scuba certification levels Core diving skills * Advanced Open Water Diver * Autonomous diver * CMAS* scuba diver * CMAS** scuba diver * Introductory diving * Low Impact Diver * Master Scuba Diver * Open Water Diver * Supervised diver Leadership skills * Dive leader * Divemaster * Diving instructor * Master Instructor Specialist skills * Rescue Diver * Solo diver Diver training certification and registration organisations * European Underwater Federation (EUF) * International Diving Regulators and Certifiers Forum (IDRCF) * International Diving Schools Association (IDSA) * International Marine Contractors Association (IMCA) * List of diver certification organizations * National Oceanic and Atmospheric Administration (NOAA) * Nautical Archaeology Society * Universal Referral Program * World Recreational Scuba Training Council (WRSTC) Commercial diver certification authorities * Australian Diver Accreditation Scheme (ADAS) * Commercial diver registration in South Africa * Divers Institute of Technology * Health and Safety Executive (HSE) * Department of Employment and Labour Commercial diving schools * Divers Academy International * Norwegian diver school Free-diving certification agencies * AIDA International (AIDA) * Confédération Mondiale des Activités Subaquatiques (CMAS) * Performance Freediving International (PI) * Scuba Schools International (SSI) Recreational scuba certification agencies * American Canadian Underwater Certifications (ACUC) * American Nitrox Divers International (ANDI) * Association nationale des moniteurs de plongée (ANMP) * British Sub-Aqua Club (BSAC) * Comhairle Fo-Thuinn (CFT) * Confédération Mondiale des Activités Subaquatiques (CMAS) * Federación Española de Actividades Subacuáticas (FEDAS) * Fédération Française d'Études et de Sports Sous-Marins (FFESSM) * Federazione Italiana Attività Subacquee (FIAS) * Global Underwater Explorers (GUE) * International Association for Handicapped Divers (IAHD) * International Association of Nitrox and Technical Divers (IANTD) * International Diving Educators Association (IDEA) * Israeli Diving Federation (TIDF) * National Academy of Scuba Educators (NASE) * National Association of Underwater Instructors (NAUI) * Nederlandse Onderwatersport Bond (NOB) * Professional Association of Diving Instructors (PADI) * Professional Diving Instructors Corporation (PDIC) * Sub-Aqua Association (SAA) * Scuba Diving International (SDI) * Scuba Educators International (SEI) * Scottish Sub Aqua Club (ScotSAC) * Scuba Schools International (SSI) * Türkiye Sualtı Sporları Federasyonu (TSSF) * United Diving Instructors (UDI) * YMCA SCUBA Program Scientific diver certification authorities * American Academy of Underwater Sciences (AAUS) * CMAS Scientific Committee Technical certification agencies * American Nitrox Divers International (ANDI) * British Sub-Aqua Club (BSAC) * Confédération Mondiale des Activités Subaquatiques (CMAS) * Diving Science and Technology (DSAT) * Federazione Italiana Attività Subacquee (FIAS) * International Association of Nitrox and Technical Divers (IANTD) * Professional Association of Diving Instructors (PADI) * Professional Diving Instructors Corporation (PDIC) * Trimix Scuba Association (TSA) * Technical Extended Range (TXR) Cave diving * Cave Divers Association of Australia (CDAA) * Cave Diving Group (CDG) * Global Underwater Explorers (GUE) * National Association for Cave Diving (NACD) * National Speleological Society#Cave Diving Group (CDG) * National Association of Underwater Instructors (NAUI) * Technical Diving International (TDI) Underwater sports Surface snorkeling * Finswimming Snorkeling/breath-hold * Spearfishing * Underwater football * Underwater hockey * Australia * Turkey * Underwater rugby * Colombia * United States * Underwater target shooting Breath-hold * Aquathlon * Apnoea finswimming * Freediving * Underwater ice hockey Open Circuit Scuba * Immersion finswimming * Sport diving * Underwater cycling * Underwater orienteering * Underwater photography Rebreather * Underwater photography Sports governing organisations and federations * International * AIDA International * Confédération Mondiale des Activités Subaquatiques) * National * AIDA Hellas * Australian Underwater Federation * British Freediving Association * British Octopush Association * British Underwater Sports Association * Comhairle Fo-Thuinn * Federación Española de Actividades Subacuáticas * Fédération Française d'Études et de Sports Sous-Marins * South African Underwater Sports Federation * Türkiye Sualtı Sporları Federasyonu * Underwater Society of America) Competitions * 14th CMAS Underwater Photography World Championship Underwater divers Pioneers of diving * Eduard Admetlla i Lázaro * Aquanaut * James F. Cahill * Jacques Cousteau * Billy Deans * Dottie Frazier * Hans Hass * Dick Rutkowski * Teseo Tesei * Arne Zetterström Underwater scientists archaeologists and environmentalists * Michael Arbuthnot * Robert Ballard * George Bass * Mensun Bound * Louis Boutan * Hugh Bradner * Cathy Church * Eugenie Clark * James P. Delgado * Sylvia Earle * John Christopher Fine * George R. Fischer * Anders Franzén * Honor Frost * Fernando Garfella Palmer * David Gibbins * Graham Jessop * Swietenia Puspa Lestari * Pilar Luna * Robert F. Marx * Anna Marguerite McCann * Innes McCartney * Charles T. Meide * David Moore * Mark M. Newell * Lyuba Ognenova-Marinova * John Peter Oleson * Mendel L. Peterson * Richard Pyle * William R. Royal * Margaret Rule * Gunter Schöbel * Stephanie Schwabe * Myriam Seco * E. Lee Spence * Robert Sténuit * Peter Throckmorton Scuba record holders * Pascal Bernabé * Jim Bowden * Mark Ellyatt * Sheck Exley * Nuno Gomes * Claudia Serpieri * Krzysztof Starnawski Underwater filmmakers and presenters * Samir Alhafith * David Attenborough * Ramón Bravo * Jean-Michel Cousteau * Richie Kohler * Ivan Tors * Andrew Wight Underwater photographers * Tamara Benitez * Georges Beuchat * Adrian Biddle * Jonathan Bird * Eric Cheng * Neville Coleman * Jacques Cousteau * John D. Craig * Ben Cropp * Bernard Delemotte * David Doubilet * John Christopher Fine * Dermot FitzGerald * Rodney Fox * Ric Frazier * Stephen Frink * Peter Gimbel * Monty Halls * Hans Hass * Henry Way Kendall * Rudie Kuiter * Joseph B. MacInnis * Luis Marden * Agnes Milowka * Noel Monkman * Steve Parish * Zale Parry * Pierre Petit * Leni Riefenstahl * Peter Scoones * Brian Skerry * Wesley C. Skiles * E. Lee Spence * Philippe Tailliez * Ron Taylor * Valerie Taylor * Albert Tillman * John Veltri * Stan Waterman * Michele Westmorland * John Ernest Williamson * J. Lamar Worzel Underwater explorers * Caves * Graham Balcombe * Sheck Exley * Martyn Farr * Jochen Hasenmayer * Jill Heinerth * Jarrod Jablonski * William Hogarth Main * Tom Mount * Jack Sheppard * Bill Stone * Reefs * * Wrecks * Leigh Bishop * John Chatterton * Clive Cussler * Bill Nagle * Aristotelis Zervoudis Aquanauts * Andrew Abercromby * Joseph M. Acaba * Clayton Anderson * Richard R. Arnold * Serena Auñón-Chancellor * Michael Barratt (astronaut) * Robert L. Behnken * Randolph Bresnik * Timothy J. Broderick * Justin Brown * Berry L. Cannon * Scott Carpenter * Gregory Chamitoff * Steve Chappell * Catherine Coleman * Robin Cook * Craig B. Cooper * Fabien Cousteau * Philippe Cousteau * Timothy Creamer * Jonathan Dory * Pedro Duque * Sylvia Earle * Jeanette Epps * Sheck Exley * Albert Falco * Andrew J. Feustel * Michael Fincke * Satoshi Furukawa * Ronald J. Garan Jr. * Michael L. Gernhardt * Christopher E. Gerty * David Gruber * Chris Hadfield * Jeremy Hansen * José M. Hernández * John Herrington * Paul Hill * Akihiko Hoshide * Mark Hulsbeck * Emma Hwang * Norishige Kanai * Les Kaufman * Scott Kelly * Karen Kohanowich * Timothy Kopra * Dominic Landucci * Jon Lindbergh * Kjell N. Lindgren * Michael López-Alegría * Joseph B. MacInnis * Sandra Magnus * Thomas Marshburn * Matthias Maurer * K. Megan McArthur * Craig McKinley * Jessica Meir * Simone Melchior * Dorothy Metcalf-Lindenburger * Andreas Mogensen * Karen Nyberg * John D. Olivas * Takuya Onishi * Luca Parmitano * Nicholas Patrick * Tim Peake * Thomas Pesquet * Marc Reagan * Garrett Reisman * Kathleen Rubins * Dick Rutkowski * Tara Ruttley * David Saint-Jacques * Josef Schmid * Robert Sheats * Dewey Smith * Steve Squyres * Heidemarie Stefanyshyn-Piper * Robert Sténuit * Hervé Stevenin * Nicole Stott * James Talacek * Daniel M. Tani * Robert Thirsk * Bill Todd * Mark T. Vande Hei * Koichi Wakata * Rex J. Walheim * Shannon Walker * John Morgan Wells * Joachim Wendler * Douglas H. Wheelock * Peggy Whitson * Dafydd Williams * Jeffrey Williams * Sunita Williams * Gregory R. Wiseman * Kimiya Yui Writers and journalists * Michael C. Barnette * Victor Berge * Philippe Diolé * Gary Gentile * Bret Gilliam * Bob Halstead * Trevor Jackson * Steve Lewis * John Mattera Rescuers * Craig Challen * Richard Harris * Rick Stanton * John Volanthen Frogmen * Lionel Crabb Commercial salvors * Keith Jessop Science of underwater diving Diving physics * Breathing performance of regulators * Buoyancy * Archimedes' principle * Neutral buoyancy * Concentration * Diffusion * Molecular diffusion * Force * Oxygen fraction * Permeation * Psychrometric constant * Solubility * Henry's law * Saturation * Solution * Supersaturation * Surface tension * Hydrophobe * Surfactant * Temperature * Torricellian chamber * Underwater acoustics * Modulated ultrasound * Underwater vision * Snell's law * Underwater computer vision * Weight * Apparent weight Gas laws * Amontons's law * Boyle's law * Charles's law * Combined gas law * Dalton's law * Gay-Lussac's law * Ideal gas law Pressure * Absolute pressure * Ambient pressure * Atmospheric pressure * Gauge pressure * Hydrostatic pressure * Metre sea water * Partial pressure Diving physiology * Artificial gills * Cold shock response * Diving reflex * Equivalent narcotic depth * Lipid * Maximum operating depth * Metabolism * Physiological response to water immersion * Tissue * Underwater vision Circulatory system * Blood shift * Patent foramen ovale * Perfusion * Pulmonary circulation * Systemic circulation Decompression theory * Decompression models: * Bühlmann decompression algorithm * Haldane's decompression model * Reduced gradient bubble model * Thalmann algorithm * Thermodynamic model of decompression * Varying Permeability Model * Equivalent air depth * Equivalent narcotic depth * Oxygen window in diving decompression * Physiology of decompression Respiration * Blood–air barrier * Breathing * CO₂ retention * Dead space * Gas exchange * Hypocapnia * Respiratory exchange ratio * Respiratory quotient * Respiratory system * Work of breathing Diving environment Classification * List of diving environments by type * Altitude diving * Benign water diving * Confined water diving * Deep diving * Inland diving * Inshore diving * Muck diving * Night diving * Open-water diving * Black-water diving * Blue-water diving * Penetration diving * Cave diving * Ice diving * Wreck diving * Recreational dive sites * Underwater environment Impact * Environmental impact of recreational diving * Low impact diving Environmental factors * Algal bloom * Currents: * Current * Longshore drift * Ocean current * Rip current * Tidal race * Undertow * Upwelling * Ekman transport * Halocline * Reef * Coral reef * Stratification * Thermocline * Tides * Turbidity * Wind wave * Breaking wave * Surf * Surge * Wave shoaling Other * Bathysphere * Defense against swimmer incursions * Diver detection sonar * Offshore survey * Underwater domain awareness Awards and events * Hans Hass Award * International Scuba Diving Hall of Fame * London Diving Chamber Dive Lectures * NOGI Awards Deep-submergence vehicle * Aluminaut * DSV Alvin * American submarine NR-1 * Bathyscaphe * Archimède * FNRS-2 * FNRS-3 * FNRS-4 * Harmony class bathyscaphe * Sea Pole-class bathyscaphe * Trieste II * Deepsea Challenger * Ictineu 3 * JAGO * Jiaolong * Konsul-class submersible * DSV Limiting Factor * Russian submarine Losharik * Mir * Nautile * Pisces-class deep submergence vehicle * DSV Sea Cliff * DSV Shinkai * DSV Shinkai 2000 * DSV Shinkai 6500 * DSV Turtle * DSV-5 Nemo Deep-submergence rescue vehicle * LR5 * LR7 * MSM-1 * Mystic-class deep-submergence rescue vehicle * DSRV-1 Mystic * DSRV-2 Avalon * NATO Submarine Rescue System * Priz-class deep-submergence rescue vehicle * Russian deep submergence rescue vehicle AS-28 * Russian submarine AS-34 * ASRV Remora * SRV-300 * Submarine Rescue Diving Recompression System * Type 7103 DSRV * URF (Swedish Navy) Special interest groups * Artificial Reef Society of British Columbia * CMAS Europe * Coral Reef Alliance * Diving Equipment and Marketing Association * Divers Alert Network * Green Fins * Historical Diving Society * Karst Underwater Research * Nautical Archaeology Program * Nautical Archaeology Society * Naval Air Command Sub Aqua Club * Project AWARE * Reef Check * Reef Life Survey * Rubicon Foundation * Save Ontario Shipwrecks * SeaKeys * Sea Research Society * Society for Underwater Historical Research * Society for Underwater Technology * Underwater Archaeology Branch, Naval History & Heritage Command Submarine escape and rescue * Escape trunk * International Submarine Escape and Rescue Liaison Office * McCann Rescue Chamber * Submarine Escape and Rescue system (Royal Swedish Navy) * Submarine escape training facility * Submarine Escape Training Facility (Australia) * Submarine rescue ship Neutral buoyancy facilities for Astronaut training * Neutral Buoyancy Laboratory * Neutral buoyancy pool * Neutral buoyancy simulation as a training aid * Neutral Buoyancy Simulator * Space Systems Laboratory * Yuri Gagarin Cosmonaut Training Center Other * Nautilus Productions * Category * Commons * * Glossary * Indexes: dive sites * divers * diving * * Outline * Portal * Medicine portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Oxygen toxicity	c0238327	8,452	wikipedia	https://en.wikipedia.org/wiki/Oxygen_toxicity	2021-01-18T18:39:24	{"icd-10": ["T59.8"], "wikidata": ["Q125223"]}
See 153430 for a general discussion of this class of proteins. These proteins were identified by high resolution 2-dimensional gel electrophoresis developed by O'Farrell (1975). Hamaguchi et al. (1982) found in the Japanese population polymorphism of a 49-kD polypeptide, which was demonstrated by Coomassie blue-staining of material from PHA-stimulated peripheral blood lymphocytes. Hamaguchi et al. (1982) demonstrated autosomal dominant inheritance of variants and gave the gene frequency for the genetic polymorphism in the Japanese population. Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	LYMPHOCYTE CYTOSOL POLYPEPTIDE, 49-KD	None	8,453	omim	https://www.omim.org/entry/153290	2019-09-22T16:38:45	{"omim": ["153290"], "synonyms": ["Alternative titles", "LC49P", "LCP49"]}
A number sign (#) is used with this entry because Leber congenital amaurosis-4 (LCA4) is caused by homozygous or compound heterozygous mutation in the gene encoding arylhydrocarbon-interacting protein-like-1 (AIPL1; 604392) on chromosome 17p13. Heterozygous mutation in the AIPL1 gene can cause juvenile retinitis pigmentosa and a form of cone-rod dystrophy. Description Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Various intermediate phenotypes between LCA and retinitis pigmentosa are known and are sometimes described as 'early-onset severe rod-cone dystrophy' or 'early-onset retinal degeneration' (Booij et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000; for cone-rod dystrophy, see 120970. Clinical Features Hameed et al. (2000) studied a consanguineous Pakistani family in which 3 sibs and their cousin had Leber congenital amaurosis and keratoconus. All affected individuals were blind from birth, with absence of rod and cone function as demonstrated by electroretinography (ERG), and the patients also showed bone spicule pigmentation of the retina. In addition, patients developed bilateral ectasia with central thinning of the cornea before age 20 years. On examination, the central cornea had a pronounced cone shape with severe corneal clouding. Sohocki et al. (2000) examined affected members of 4 unrelated LCA families in whom mutations in the AIPL1 gene (604392) were found (see MOLECULAR GENETICS). Affected individuals from a Pakistani family were blind from birth with absence of rod and cone function as demonstrated by ERG, but without keratoconus. Fundus examination indicated pigmentary retinopathy, attenuated blood vessels, and macular degeneration. In 3 unrelated European families, patients had poor central vision from birth, severe night blindness, and pendular nystagmus. ERG testing revealed borderline or nondetectable cone and rod responses by the second decade of life. Fundus examination showed widespread retinal pigment epithelium changes with pigment clumping, attenuated retinal vessels, macular atrophy, and a pale optic disc. Aboshiha et al. (2015) compiled data on 42 patients from 18 countries with molecularly confirmed LCA4. The age of the patients ranged from 0.5 to 43 years (median, 8 years); 24 patients were less than 10 years of age and 10 were less than 5 years of age. The model visual acuity was perception of light, which was found in 21 patients, with a range of visual acuities from no perception of light to a logMAR of 0.90. Posterior pole examination findings, which were available for 39 patients, showed a normal posterior pole appearance in 7 (18%, age range 0.5-5 years), with 18 (46%) having retinal pigmentary changes without macular atrophy, and 13 (33%) exhibiting macular atrophy. The youngest patient with macular atrophy was 6 years old. Of 13 patients in whom good optical coherence tomography (OCT) images could be obtained, 3 (23%; aged 1 year or younger) demonstrated significant outer retinal structure, with relative preservation of the inner segment ellipsoid layer and outer nuclear layer at the fovea, and 1 (aged 3 years) demonstrated qualified evidence of a foveal inner segment ellipsoid layer. Three of the 4 patients were homozygous for the common W278X mutation (604372.0001). Aboshiha et al. (2015) suggested the possibility of gene therapy in young patients with LCA4. Mapping Not all LCA families that showed linkage to 17p13.1 had demonstrable mutations in the GUCY2D gene (600179); Perrault et al. (1996) identified disease-causing GUCY2D mutations in only 8 of 15 families showing mapping to 17p13.1, suggesting that there may be another LCA locus on 17p13.1. Confirming this prediction, Hameed et al. (2000) found that the LCA with keratoconus segregating in an autosomal recessive fashion in a consanguineous Pakistani family mapped to 17p13.1, between D17S849 and D17S960--a region that excluded GUCY2D. They designated the LCA in this family LCA4. Molecular Genetics In affected members of a consanguineous Pakistani family with Leber congenital amaurosis and keratoconus mapping to chromosome 17p13.1, originally studied by Hameed et al. (2000) and found to be negative for mutation in the GUC2D gene (600179), Sohocki et al. (2000) demonstrated homozygosity for a nonsense mutation in the AIPL1 gene (W278X; 604392.0001). Analysis of the AIPL1 gene in 14 additional LCA families revealed 4 more families that were homozygous or compound heterozygous for W278X and/or other mutations in AIPL1 (see 604392.0002-604392.0003), and Sohocki et al. (2000) concluded that mutations in the AIPL1 gene might account for approximately 20% of recessive LCA. Noting that AIPL1 is not expressed in the cornea and that affected members of 2 unrelated families who had LCA without keratoconus were homozygous for the W278X mutation, the authors suggested that the keratoconus present in affected members of the original LCA4 family, who were also homozygous for W278X, was possibly secondary to eye rubbing due to the LCA. To determine more generally the prevalence of AIPL1 mutations in inherited retinal degenerative disease, Sohocki et al. (2000) screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases. They identified 11 LCA families whose retinal disorder was caused by homozygosity or compound heterozygosity for AIPL1 mutations. They also identified affected individuals in 2 apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who were heterozygous for a 12-bp deletion (604392.0004) in the AIPL1 gene. The results suggested that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy. Animal Model Tan et al. (2009) evaluated whether adeno-associated virus (AAV)-mediated gene replacement therapy was able to improve photoreceptor function and survival in retinal degeneration associated with AIPL1 defects. Two mouse models of AIPL1 deficiency were used: the Aipl1-hypomorphic (h/h) mouse (with reduced Aipl1 levels and a relatively slow degeneration), and the Aipl1-null mouse (with no functional Aipl1 and a very rapid retinal degeneration). Two pseudotypes of recombinant AAV exhibiting different transduction kinetics were used for gene transfer. The authors demonstrated restoration of cellular function and preservation of photoreceptor cells and retinal function in Aipl1 h/h mice 28 weeks after subretinal injection of an AAV2/2 vector and in the light-accelerated Aipl1 h/h model and Aipl1-null mice using an AAV2/8 vector. Tan et al. (2009) established the potential of gene replacement therapy in varying rates of degeneration that reflect the clinical spectrum of disease. Kirschman et al. (2010) transgenically expressed human AIPL1 exclusively in the rod photoreceptors of the Aipl1 -/- mouse. Transgenic expression of AIPL1 restored rod morphology and the rod-derived electroretinogram response, but cone photoreceptors were nonfunctional in the absence of AIPL1. Cone photoreceptors degenerated, but at a slower rate compared with Aipl1 -/- mice. This degeneration was linked to the highly reduced levels of cone PDE6 (180071) observed in the AIPL1 transgenic mice. The authors concluded that AIPL1 is needed for the proper functioning and survival of cone photoreceptors. However, rod photoreceptors may also provide support that partially preserves cone photoreceptors from rapid death in the absence of AIPL1. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Poor central vision or blindness from birth \- Keratoconus (in some patients) \- Night blindness, severe \- Pendular nystagmus \- Pigment clumping \- Retinal vessels severely attenuated \- Macular atrophy \- Pale optic disc \- Cone and rod responses borderline or nondetectable on electroretinography (ERG) by the second decade of life MISCELLANEOUS \- Keratoconus, which was observed in 1 family, might be secondary to eye rubbing due to LCA MOLECULAR BASIS \- Caused by mutation in the arylhydrocarbon-interacting receptor protein-like 1 gene (AIPL1, 604392.0001 ) ▲ 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	LEBER CONGENITAL AMAUROSIS 4	c0035334	8,454	omim	https://www.omim.org/entry/604393	2019-09-22T16:11:59	{"doid": ["0110332"], "mesh": ["D012174"], "omim": ["604393", "120970"], "orphanet": ["1872", "791", "65"], "synonyms": [], "genereviews": ["NBK531510"]}
X-linked distal arthrogryposis multiplex congenital (SMAX2) is a rare form of spinal muscular atrophy characterized by the neonatal onset of severe hypotonia, areflexia, profound weakness, multiple congenital contractures, facial dysmorphic features (myopathic face with open, tent-shaped mouth), cryptorchidism, and mild skeletal abnormalities (i.e. kyphosis, scoliosis), that is often preceded by polyhydramnios and reduced fetal movements in utero and followed by bone fractures shortly after birth. SMAX2 patients often have a limited life span, often succumbing to the disease within 2 years, as muscle weakness is progressive and chest muscle involvement eventually leads to ventilatory insufficiency and respiratory failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Infantile-onset X-linked spinal muscular atrophy	c1844934	8,455	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1145	2021-01-23T17:49:42	{"gard": ["8521"], "mesh": ["C535380"], "omim": ["301830"], "umls": ["C1844934"], "icd-10": ["G12.1"], "synonyms": ["SMAX2", "Spinal muscular atrophy with arthrogryposis", "X-linked distal arthrogryposis multiplex congenita", "X-linked spinal muscular atrophy type 2"]}
A rare disorder due to toxic effects characterized by a progressive, permanent affliction of the extrapyramidal system with the globus pallidus and striatum as primary targets of neurotoxic effects. Symptoms include headache, insomnia, memory loss, emotional instability, hyperreflexia, dystonia, tremor, speech disturbances, and gait abnormalities. Individual factors like age, gender, genetics, and pre-existing medical conditions appear to have a profound impact on manganese toxicity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Manganese poisoning	c0677050	8,456	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=306682	2021-01-23T16:52:34	{"mesh": ["D020149"], "umls": ["C0677050"], "icd-10": ["T57.2"], "synonyms": ["Manganese intoxication", "Manganism"]}
## Summary ### Clinical characteristics. Brugada syndrome is characterized by cardiac conduction abnormalities (ST-segment abnormalities in leads V1-V3 on ECG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and the sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. ### Diagnosis/testing. Diagnosis is based on clinical findings and/or by the identification of a heterozygous (or hemizygous in the case of KCNE5 in a male) pathogenic variant in one of 23 genes: ABCC9, CACNA1C, CACNA2D1, CACNB2, FGF12, GPD1L, HCN4, KCND2, KCND3, KCNE5, KCNE3, KCNH2, KCNJ8, PKP2, RANGRF, SCN1B, SCN2B, SCN3B, SCN5A, SCN10A, SEMA3A, SLMAP, and TRPM4. ### Management. Treatment of manifestations: Implantable cardioverter defibrillator (ICD) in individuals with a history of syncope or cardiac arrest; isoproterenol for electrical storms. Prevention of primary manifestations: Quinidine (1-2 g daily). Treatment of asymptomatic individuals is controversial. Prevention of secondary complication: During surgery and in the postsurgical recovery period persons with Brugada syndrome should be monitored by ECG. Surveillance: ECG monitoring every one to two years for at-risk individuals with a family history of Brugada syndrome or who have a known pathogenic variant that can lead to Brugada syndrome. Agents/circumstances to avoid: High fever, anesthetics, antidepressant drugs, and antipsychotic drugs with sodium-blocking effects; class 1 C antiarrhythmic drugs (i.e., flecainide, propafenone) and class 1A agents (i.e., procainamide, disopyramide). Evaluation of relatives at risk: Identification of relatives at risk using ECG or (if the pathogenic variant in the family is known) molecular genetic testing enables use of preventive measures and avoidance of medications that can induce ventricular arrhythmias. ### Genetic counseling. In most cases Brugada syndrome is inherited in an autosomal dominant manner; the exception is KCNE5-related Brugada syndrome, which is inherited in an X-linked manner. Most individuals diagnosed with Brugada syndrome have an affected parent. The proportion of cases caused by a de novo pathogenic variant is estimated at 1%. Each child of an individual with autosomal dominant Brugada syndrome 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 Brugada syndrome is a channelopathy, caused by genetic changes in transmembrane ion channels which create action potentials, in this case leading to an increased risk of cardiac arrhythmia [Benito et al 2009]. ### Suggestive Findings Brugada syndrome should be suspected in individuals with any of the following findings: * Recurrent syncope * Ventricular fibrillation * Self-terminating polymorphic ventricular tachycardia * Cardiac arrest * Family history of sudden cardiac death AND one of the following ECG patterns: * Type 1 ECG (elevation of the J wave ≥2 mm with a negative T wave and ST segment that is coved type and gradually descending) in more than one right precordial lead (V1-V3)* (see Figure 1) with or without administration of a sodium channel blocker (i.e., flecainide, pilsicainide, ajmaline, or procainamide) * No other factor(s) should account for the ECG abnormality. * Type 2 ECG (elevation of the J wave ≥2 mm with a positive or biphasic T wave; ST segment with saddle-back configuration and elevated ≥1 mm) in more than one right precordial lead under baseline conditions with conversion to type 1 ECG following challenge with a sodium channel blocker * Type 3 ECG (elevation of the J wave ≥2 mm with a positive T wave; ST segment with saddle-back configuration and elevated <1 mm) in more than one lead under baseline conditions with conversion to type 1 ECG following challenge with a sodium channel blocker #### Figure 1. Characteristic ECG in Brugada syndrome. Note presence of ST-segment elevation in leads V1-V3, coved type. ### Establishing the Diagnosis The diagnosis of Brugada syndrome is established in a proband with both of following findings and may include identification of a heterozygous (or hemizygous in the case of KCNE5 in a male) pathogenic variant in one of the genes listed in Tables 1a and 1b (see Note). * Type 1 ECG (elevation of the J wave ≥2 mm with a negative T wave and ST segment that is coved type and gradually descending) in more than one right precordial lead (V1-V3)* (see Figure 1) with or without administration of a sodium channel blocker (i.e., flecainide, pilsicainide, ajmaline, or procainamide) * No other factor(s) should account for the ECG abnormality. * At least one of the following: * Documented ventricular fibrillation * Self-terminating polymorphic ventricular tachycardia * A family history of sudden cardiac death * Coved-type ECGs in family members * Electrophysiologic inducibility * Syncope or nocturnal agonal respiration Note: In approximately 75% of persons affected by Brugada syndrome the diagnosis is established based on clinical history and ECG results. Molecular genetic testing confirms the diagnosis and may complement clinical testing [Benito et al 2009]. See Figure 2 for a diagnostic algorithm for Brugada syndrome. #### Figure 2. Diagnostic algorithm for Brugada syndrome From Berne & Brugada [2012]. Used by permission. Molecular genetic testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Serial single-gene testing can be considered starting with SCN5A, heterozygous pathogenic variants in which account for 15%-30% of cases. Alternatively, serial single-gene testing may be considered if factors including clinical findings, laboratory findings, and ancestry indicate that mutation of a particular gene is most likely. Sequence analysis of the gene of interest is performed first, followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. * A multigene panel that includes all current Brugada syndrome-related and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if serial single-gene testing and/or use of a multigene panel fails to confirm a diagnosis in an individual with features of Brugada syndrome. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. See Table 1a for the most common genetic causes (i.e., pathogenic variants of any one of the genes included in this table account for >1% of Brugada syndrome) and Table 1b for less common genetic causes (i.e., pathogenic variants of any one of the genes included in this table are reported in only a few families). ### Table 1a. Molecular Genetics of Brugada Syndrome: Most Common Genetic Causes View in own window Gene 1Phenotype Designation% of Brugada Syndrome Attributed to Pathogenic Variants in This GeneProportion of Pathogenic Variants 2 Detectable by This Method Sequence analysis 3Gene-targeted deletion/duplication analysis 4 SCN5ABrugada syndrome 115%-30% 5>95%Unknown 6 Pathogenic variants of any one of the genes included in this table account for >1% of Brugada syndrome. 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on pathogenic allelic variants detected. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. 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\. Kapplinger et al [2010] 6\. Eastaugh et al [2011], Hertz et al [2015] ### Table 1b. Molecular Genetics of Brugada Syndrome: Less Common Genetic Causes View in own window Gene 1 ,2, 3Phenotype Designation ABCC9 CACNA1CBrugada syndrome 3 CACNA2D1 CACNB2Brugada syndrome 4 FGF12 GPD1LBrugada syndrome 2 HCN4Brugada syndrome 8 KCND2 KCND3 KCNE3Brugada syndrome 6 KCNE5 KCNH2 KCNJ8 PKP2 RANGRF SCN1BBrugada syndrome 5 SCN2B SCN3BBrugada syndrome 7 SCN10A SEMA3A SLMAP TRPM4 Pathogenic variants of any one of the genes listed in this table are reported in only a few families (i.e., <1% of Brugada syndrome) 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. Genes are not described in detail in Molecular Genetics, but may be included here (pdf). ## Clinical Characteristics ### Clinical Description Age at diagnosis. Brugada syndrome manifests primarily during adulthood, with a mean age of sudden death of approximately 40 years. The youngest individual diagnosed with the syndrome was two days old and the oldest age 85 years [Huang & Marcus 2004]. Gender differences. Although Brugada syndrome is more prevalent among males, it affects females as well, and both genders are at a high risk for ventricular arrhythmias and sudden death [Hong et al 2004b]. Presentation. Currently, the most common presentation is that of a person in his/her 40s with malignant arrhythmias and a previous history of syncopal episodes. Syncope is a common presenting symptom [Mills et al 2005, Benito & Brugada 2006, Karaca & Dinckal 2006]. Affected individuals in whom sustained ventricular arrhythmias are easily induced and who have a spontaneously abnormal ECG have a 45% likelihood of having an arrhythmic event at any time during life [Benito et al 2009]. Electrical storms (also known as arrhythmic storms), which are multiple episodes of ventricular arrhythmias that occur over a short period of time, are malignant but rare phenomena in Brugada syndrome. Incessant ventricular tachycardia (VT) is defined as hemodynamically stable VT continuing for hours. Brugada syndrome can occur in conjunction with conduction disease. The presence of first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome in Brugada syndrome is not unusual [Smits et al 2005]. Clinical presentations of Brugada syndrome may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) [Priori et al 2000a, Antzelevitch 2001, Skinner et al 2005, Van Norstrand et al 2007] and sudden unexpected nocturnal death syndrome (SUNDS) [Vatta et al 2002], a syndrome seen in Southeast Asia in which young people die from cardiac arrest with no identifiable cause. The same pathogenic variant in SCN5A was identified in individuals with Brugada syndrome and SUNDS, thus supporting the hypothesis that they are the same disease [Hong et al 2004a]. Precipitating factors for the Brugada ECG pattern and the syndrome of sudden cardiac death (SCD) include fever, cocaine use, electrolyte disturbances, and use of class I antiarrhythmic medications and a number of other non-cardiac medications [Francis & Antzelevitch 2005]. Most importantly, in some (usually young) persons, the presence of the induced ECG pattern has been associated with sudden cardiac death. The pathophysiologic mechanisms behind this association remain largely unknown. Predicting risk of malignant arrhythmias. Several parameters have been investigated to improve stratification of the risk of developing malignant arrhythmias (see Figure 3). #### Figure 3. Proposed risk stratification scheme and recommendations of ICD in individuals with Brugada syndrome From Berne & Brugada [2012]. Used by permission. * Inducibility during electrophysiologic study (EPS) is the only parameter currently used for clinical decision making. During such a study the heart is electrically stimulated using intracardiac catheters. Although the inducibility of arrhythmias in an asymptomatic individual during the EPS is highly predictive of subsequent malignant events (arrhythmias and sudden cardiac death), the data remain controversial. Several groups do not use EPS for risk stratification in asymptomatic individuals; however, no other risk stratification parameter is presently available [Nunn et al 2010]. Thus, decisions regarding timing of implantation of a defibrillator vary widely among physicians and investigators [Eckardt et al 2005, Glatter et al 2005, Ikeda et al 2005, Al-Khatib 2006, Delise et al 2006, Gehi et al 2006, Imaki et al 2006, Ito et al 2006, Ott & Marcus 2006, Tatsumi et al 2006, Benito et al 2009]. * Genotype has been proposed as an additional parameter for risk stratification. Meregalli et al [2009] found that among individuals with an SCN5A pathogenic variant, those who were more symptomatic had more ECG signs of conduction slowing, supporting the notion that conduction slowing, mediated by loss-of-function SCN5A pathogenic variants, was a key pathophysiologic mechanism in Brugada syndrome. This limited study indicates that it may be possible in the future to use genotype information in risk stratification; however, at present this remains an area of investigation. Pathophysiology. Brugada syndrome, caused by a sodium channelopathy, is associated with age-related progressive conduction abnormalities, such as prolongation of the ECG PQ, QRS, and HV intervals [Smits et al 2002, Yokokawa et al 2007]. Sodium current dysfunction contributes to local conduction block in the epicardium, resulting in multiple spikes within the QRS complex and triggering of atrial and ventricular fibrillation [Morita et al 2008]. Sodium channelopathies exhibited typical Brugada-type ECG and frequent arrhythmogenesis during bradycardia [Makiyama et al 2005]; both quinidine and isoproterenol normalized the J-ST elevation and prevented arrhythmias. ### Genotype-Phenotype Correlations Few studies have investigated genotype-phenotype correlations. For SCN5A: * The degree of ST elevation and the occurrence of arrhythmias were similar between persons with Brugada syndrome with and without a heterozygous SCN5A pathogenic variant [Morita et al 2009]. * In general the SCN5A pathogenic variants which cause LQT3 (see Long QT Syndrome) are associated with a gain of function rather than the loss of function associated with Brugada syndrome and progressive conduction system disease; however, pathogenic variants that are associated with both diseases in the same family have been described. * By restoring (at least partially) sodium current defects, the common SCN5A variant p.His558Arg appears to modulate the phenotypic effects of heterozygous SCN5A pathogenic variants [Lizotte et al 2009] such as p.Thr512Ile, which results in clinically significant cardiac conduction disturbances [Viswanathan et al 2003], and p.Arg282His, which results in Brugada syndrome [Poelzing et al 2006]. ### Penetrance Among individuals with an SCN5A pathogenic variant: * Approximately 20%-30% have an ECG diagnostic of Brugada syndrome; * Approximately 80% manifest the characteristic ECG changes when challenged with a sodium channel blocker (ajmaline) [Hong et al 2004b, Benito et al 2009]. ### Nomenclature Vatta et al [2002] and Hong et al [2004a] determined that sudden unexpected nocturnal death syndrome (SUNDS) and Brugada syndrome are phenotypically, genetically, and functionally the same disorder. SUNDS was originally described in individuals from Southeast Asia. Other names for SUNDS include sudden and unexpected death syndrome (SUDS), bangungut (Philippines), non-lai tai (Laos), lai-tai (Thailand), and pokkuri (Japan). ### Prevalence Brugada syndrome was identified relatively recently; thus, it is difficult to determine its prevalence and population distribution. Further, because the ECG is dynamic and may normalize, diagnosis may be problematic, making it difficult to estimate the true incidence of Brugada syndrome in the general population. Data suggest that Brugada syndrome occurs worldwide. The prevalence of the disease in endemic areas is on the order of 1:2,000 persons. In countries in Southeast Asia in which sudden unexpected nocturnal death syndrome (SUNDS) is endemic, it is the second cause (following accidents) of death of men under age 40 years. Data from published studies indicate that Brugada syndrome is responsible for 4%-12% of unexpected sudden deaths and for up to 20% of all sudden death in individuals with an apparently normal heart. As recognition of Brugada syndrome increases in the future, a sizeable increase in the number of identified cases can be expected. A prospective study of an adult Japanese population (22,027 individuals) showed 12 individuals (prevalence of 0.05%) with ECGs compatible with Brugada syndrome [Tohyou et al 1995]. A second study of adults in Awa (Japan) showed a prevalence of 0.6% (66:10,420 individuals) [Namiki et al 1995]. In contrast, a third study in Japanese children showed only a 0.0006% (1:163,110) prevalence of ECGs compatible with Brugada syndrome [Hata et al 1997]. Therefore, in the absence of symptoms and/or molecular genetic testing of SCN5A, these studies provide an estimate of the prevalence of the Brugada syndrome ECG pattern (not of Brugada syndrome) in the population studied. The results suggest that Brugada syndrome manifests primarily during adulthood, a finding in concordance with the mean age of sudden death (age 35-40 years). ## Differential Diagnosis Brugada syndrome should always be considered in the differential diagnosis of: * Sudden cardiac death and syncope in persons with a structurally normal heart * SIDS. Brugada syndrome does not usually cause problems at such a young age; however, pathogenic variants in SCN5A have been previously described in a few SIDS cases. SIDS is believed to be etiologically and genetically heterogeneous [Weese-Mayer et al 2007] with an unknown proportion attributed to Brugada syndrome. * Sick sinus syndrome. Brugada syndrome could be observed in persons with sick sinus syndrome given the defects observed in cardiac conduction [Nakazato et al 2004]. Other conditions that can be associated with ST-segment elevation in right precordial leads include the following (adapted from Wilde et al [2002] with permission). Abnormalities that can lead to ST-segment elevation in the right precordial leads * Right or left bundle branch block, left ventricular hypertrophy * Acute myocardial ischemia or infarction * Acute myocarditis * Hypothermia, causing Osborn wave in ECGs and sometimes resembling Brugada syndrome * Right ventricular ischemia or infarction * Dissecting aortic aneurysm * Acute pulmonary thromboemboli * Various central and autonomic nervous system abnormalities * Heterocyclic antidepressant overdose * Duchenne muscular dystrophy * Friedreich ataxia * Thiamine deficiency * Hypercalcemia * Hyperkalemia * Cocaine intoxication * Mediastinal tumor compressing the right ventricular outflow tract (RVOT) * Arrhythmogenic cardiomyopathy (AC) Other conditions that can lead to ST-segment elevation in the right precordial leads * Early repolarization syndrome * Other normal variants (particularly in males) Most of the conditions listed can give rise to a type 1 ECG, whereas ARVD/C and Brugada syndrome can both give rise to type 2 and type 3 ECGs. Therefore, it is important to distinguish between these two disorders. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Brugada syndrome, the following evaluations are recommended: * Electrocardiogram * Induction with sodium blockers (ajmaline, procainamide, pilsicainide, flecainide) in persons with a type 2 ECG or type 3 ECG and suspicion of the disease * Electrophysiologic study to assess risk of sudden cardiac death. Although the data are controversial, no other risk stratification parameter is presently available for asymptomatic individuals [Nunn et al 2010]. * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Brugada syndrome is characterized by the presence of ST-segment elevation in leads V1 to V3. Implantable cardioverter defibrillators (ICDs) are the only therapy currently known to be effective in persons with Brugada syndrome with syncope or cardiac arrest [Brugada et al 1999, Wilde et al 2002]. See Figure 3 for risk stratification and recommendations of ICD in individuals with Brugada syndrome. Electrical storms respond well to infusion of isoproterenol (1-3 µg/min), the first line of therapy before other antiarrhythmics [Maury et al 2004]. It is important to: * Eliminate/treat agents/circumstances such as fever, cocaine use, electrolyte disturbances, and use of class I antiarrhythmic medications and other non-cardiac medications that can induce acute arrhythmias; AND * Hospitalize the patient at least until the ECG pattern has normalized. Controversy exists regarding the treatment of asymptomatic individuals. Recommendations vary [Benito et al 2009, Escárcega et al 2009, Nunn et al 2010] and include the following: * Observation until the first symptom develops (the first symptom can also be sudden cardiac death) * Placement of an ICD if the family history is positive for sudden cardiac death * Use of electrophysiologic study (EPS) to identify those most likely to experience arrhythmias and thus to benefit the most from placement of an ICD ### Prevention of Primary Manifestations Quinidine (1-2 g daily) has been shown to restore ST segment elevation and decrease the incidence of arrhythmias [Belhassen et al 2004, Hermida et al 2004, Probst et al 2006]. ### Prevention of Secondary Complications During surgery and in the postsurgical recovery period persons with Brugada syndrome should be monitored by ECG. ### Surveillance At-risk individuals with a family history of Brugada syndrome or a known pathogenic variant should undergo ECG monitoring every one to two years beginning at birth [Oe et al 2005]. The presence of type I ECG changes should be further investigated. ### Agents/Circumstances to Avoid The following can unmask the Brugada syndrome ECG [Antzelevitch et al 2002]: * Febrile state * Vagotonic agents * α-adrenergic agonists [Miyazaki et al 1996] * β-adrenergic antagonists * Tricyclic antidepressants * First-generation antihistamines (dimenhydrinate) * Cocaine toxicity The following should be avoided [Antzelevitch et al 2003]: * Class 1C antiarrhythmic drugs including flecainide and propafenone * Class 1A agents including procainamide and disopyramide ### Evaluation of Relatives at Risk If the pathogenic variant has been identified in an affected family member, molecular genetic testing of at-risk relatives is appropriate because: * ECG changes have low sensitivity in establishing the diagnosis [Priori et al 2003]; * Identification of individuals at risk allows preventive measures such as avoidance of medications that can induce ventricular arrhythmias; * Surveillance can then be limited to family members who have the identified pathogenic variant [Benito et al 2009, Escárcega et al 2009, Nunn et al 2010]. If the pathogenic variant has not been identified in the family, relatives should be screened with an ECG. If a type I ECG is identified, further investigation is warranted. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Hormonal changes during pregnancy can precipitate arrhythmic events in women with Brugada syndrome. Recurrent ventricular tachyarrhythmia can be inhibited and the electrocardiographic pattern can normalize following IV infusion of low-dose isoproterenol followed by oral quinidine [Sharif-Kazemi et al 2011]. Quinidine is not known to be teratogenic to the developing fetus and is a preferred drug to treat arrhythmia in pregnancy. See www.mothertobaby.org for more information about medication use during pregnancy. ### 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	Brugada Syndrome	c1142166	8,457	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1517/	2021-01-18T21:38:58	{"mesh": ["D053840"], "synonyms": ["Sudden Unexpected Nocturnal Death Syndrome"]}
## Description Spinocerebellar ataxia-32 (SCA32) is an autosomal dominant neurologic disorder characterized by ataxia, variable mental impairment, and azoospermia in males (summary by Jiang et al., 2010). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). Clinical Features Jiang et al. (2010) reported a Chinese family with an autosomal dominant form of spinocerebellar ataxia. There was a broad range of age at onset, particularly among females. Those with onset of ataxia before age 40 years showed cognitive impairment, and brain MRI showed cerebellar atrophy. All affected males were infertile and had azoospermia with testicular atrophy. Testicular biopsy from 1 male showed complete absence of germ cells and progenitors. Mapping By genomewide linkage analysis of a Chinese family with autosomal dominant SCA and azoospermia, Jiang et al. (2010) found linkage to a locus, termed SCA32, on chromosome 7q32-q33 between rs3847110 and rs2241728. The critical region spanned 0.989 cM (989 kb). INHERITANCE \- Autosomal dominant GENITOURINARY Internal Genitalia (Male) \- Infertility \- Azoospermia \- Testicular atrophy \- Absence of germ cells and progenitors seen on biopsy NEUROLOGIC Central Nervous System \- Cerebellar ataxia \- Cognitive impairment in individuals with onset before age 40 \- Cerebellar atrophy MISCELLANEOUS \- Broad range of onset, particularly among females \- One Chinese family has been reported with limited clinical information (last curated April 2011) ▲ 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	SPINOCEREBELLAR ATAXIA 32	c3151343	8,458	omim	https://www.omim.org/entry/613909	2019-09-22T15:57:02	{"omim": ["613909"], "orphanet": ["276183"], "synonyms": ["Cerebellar ataxia with azoospermia and intellectual disability", "SCA32"]}
A number sign (#) is used with this entry because ethylmalonic encephalopathy (EE) is caused by homozygous or compound heterozygous mutation in the ETHE1 gene (608451), which encodes a mitochondrial matrix protein, on chromosome 19q13. Description Ethylmalonic encephalopathy is an autosomal recessive severe metabolic disorder of infancy affecting the brain, gastrointestinal tract, and peripheral vessels. The disorder is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Brain MRI shows necrotic lesions in deep gray matter structures. Death usually occurs in the first decade of life (summary by Drousiotou et al., 2011). Clinical Features Burlina et al. (1991) first described ethylmalonic encephalopathy as a syndrome characterized by developmental delay, acrocyanosis, petechiae, and chronic diarrhea. Laboratory studies showed ethylmalonic and methylsuccinic aciduria and lactic acidemia. However, in vitro activities of short chain acyl-CoA dehydrogenase (SCAD; 606885) and 2-methyl-branched chain acyl-CoA dehydrogenase, 2 enzymes whose deficiencies could theoretically produce the biochemical findings observed in ethylmalonic encephalopathy, were found to be normal (Burlina et al., 1994). Nowaczyk et al. (1998) reported the cases of 2 sibs with ethylmalonic encephalopathy and central nervous system malformations. The girl had primary tethered cord. Her younger brother, who was evaluated at the age of 4 years because of a similar phenotype (episodic ataxia, chronic diarrhea, and acrocyanosis), had cerebellar tonsillar ectopia (Chiari I malformation). Tiranti et al. (2004) stated that since the initial report no more than 30 cases of ethylmalonic encephalopathy had been described worldwide, leading to the assumption that the disorder is very rare. However, the actual incidence of the condition may be significantly underestimated because the biochemical phenotype may be incorrectly attributed to other metabolic disorders. Drousiotou et al. (2011) reported 3 patients from 2 unrelated families of Greek Cypriot origin with ethylmalonic encephalopathy. The first patient presented at age 2.5 months with feeding difficulties, failure to thrive, petechiae, and ecchymosis. She was floppy with severe head lag and microcephaly, and showed poor responses to auditory and visual stimuli. Deep tendon reflexes were exaggerated, and there was sustained clonus and bilateral Babinski sign. She subsequently developed chronic diarrhea and seizures. Brain MRI revealed multiple bilateral loci of high intensity in the basal ganglia on T2-weighted images. She showed neurologic regression and was 5.5 years old at the time of the report. Her older brother died at age 6 months of a presumably similar disorder. Ultrasound of the brain showed hyperechogenicity of gyri and sulci. No tissues were available for confirmation of diagnosis. A girl from a second family was born prematurely at 36 weeks' gestation and presented at age 6 months with feeding difficulties, hypotonia, and global developmental delay. She later developed diarrhea, petechiae, ecchymosis, and seizures, and brain MRI showed abnormal signals in the basal ganglia and thinning of the corpus callosum. She died at age 8 months from cardiopulmonary arrest. Laboratory studies of all 3 patients showed increased serum lactate and butyrylcarnitine, and increased urinary ethylmalonic acid, methylsuccinate, and thiosulfate. Western blot analysis from 2 patients showed complete absence of the ETHE1 protein. Clinical Management Viscomi et al. (2010) treated a 29-month-old Italian boy with ethylmalonic encephalopathy with metronidazole and N-acetylcysteine, a precursor of sulfide-buffering glutathione. The therapy was designed to act against accumulation of toxic hydrogen sulfide. Over the next 8 months, the patient showed increased body weight, a decrease and then disappearance of diarrhea, petechiae, and acrocyanosis, and marked neurologic improvement, with decreased seizures, less severe hypotonia, reversion of brain atrophy, and a reduction in leukodystrophy, although lesions in the neostriatum become more evident. Biochemical abnormalities also lessened. Treatment of 4 additional patients showed similar clinical, biochemical, and MRI improvements. The clinical treatment was performed after Viscomi et al. (2010) obtained favorable results in an Ethe -/- mouse model. Molecular Genetics By a combination of homozygosity mapping, integration of physical and functional genomic datasets, and mutational screening, Tiranti et al. (2004) identified the ETHE1 gene (608451) as the site of mutations causing EE. They demonstrated that the ETHE1 protein is targeted to mitochondria and internalized into the matrix after energy-dependent cleavage of a short leader peptide. The severe consequences of its malfunctioning indicate an important role of the ETHE1 gene product in mitochondrial homeostasis and energy metabolism. In 14 patients with ethylmalonic encephalopathy, Mineri et al. (2008) identified homozygosity for mutations in the ETHE1 gene (see, e.g., 608451.0006 and 608451.0007). At the time of the report, 11 patients were deceased; age of death ranged from 18 months to 3 years. Three patients were alive at 6 months, 7 years, and 13 years, respectively. In 2 patients from 2 unrelated families of Greek Cypriot origin with ethylmalonic encephalopathy, Drousiotou et al. (2011) identified 2 different mutations in the ETHE1 gene (608451.0007 and 608451.0008). One was compound heterozygous for the mutations, whereas the other was homozygous for 1 of the mutations. Population Genetics With few exceptions, the patients with ethylmalonic encephalopathy have been of Mediterranean (Garcia-Silva et al., 1997; Grosso et al., 2002) or Arabic (Ozand et al., 1994) extraction. Animal Model Tiranti et al. (2009) found that Ethe1-null mice developed the cardinal features of ethylmalonic encephalopathy, including poor growth, reduced motor activity, early death, low cytochrome c oxidase (COX) in muscle and brain, and increased urinary excretion of ethylmalonic acid. Both mutant mice and humans with the disorder excreted massive amounts of thiosulfate in the urine, and there was an accumulation of thiosulfate and hydrogen sulfide (H2S) in mutant mouse tissue. Hydrogen sulfide is powerful inhibitor of COX and short-chain fatty acid oxidation, and has vasoactive and vasotoxic effects. The findings suggested that ethylmalonic encephalopathy is a disease associated with impaired catabolism of inorganic sulfur leading to accumulation of hydrogen sulfide in key tissues. The toxic effects of this accumulation can account for several features, including ethylmalonic aciduria, COX deficiency, microangiopathy, acrocyanosis, and chronic diarrhea. Sulfide is detoxified by a mitochondrial pathway that includes a sulfur dioxygenase. Sulfur dioxygenase activity was absent in Ethe1-null mice, but it was markedly increased by ETHE1 overexpression in HeLa cells and E. coli. These findings indicated that ETHE1 is a mitochondrial sulfur dioxygenase involved in catabolism of sulfide that accumulates to toxic levels in ethylmalonic encephalopathy. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Eyes \- Retinal lesions with tortuous vessels CARDIOVASCULAR Vascular \- Orthostatic acrocyanosis ABDOMEN Gastrointestinal \- Chronic diarrhea SKIN, NAILS, & HAIR Skin \- Petechiae \- Orthostatic acrocyanosis NEUROLOGIC Central Nervous System \- Developmental regression \- Developmental delay \- Mental retardation \- Pyramidal symptoms \- Extrapyramidal symptoms \- Ataxia \- Hypotonia \- Seizures \- Hyperintense lesions in the basal ganglia on MRI LABORATORY ABNORMALITIES \- Lactic acidemia \- Ethylmalonic aciduria \- Methylsuccinic aciduria \- Cytochrome c oxidase deficiency in skeletal muscle and brain \- Increased serum C4 and C5 acylcarnitine esters \- Increased urinary isobutyryl glycine \- Increased urinary 2-methylbutyryl glycine \- Increased urinary thiosulphate MISCELLANEOUS \- Onset in first months of life \- Patients are often of Mediterranean origin \- Death usually occurs in first decade of life MOLECULAR BASIS \- Caused by mutation in the ETHE1 gene (ETHE1, 608451.0001 ) ▲ 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	ENCEPHALOPATHY, ETHYLMALONIC	c1865349	8,459	omim	https://www.omim.org/entry/602473	2019-09-22T16:13:42	{"doid": ["0060640"], "mesh": ["C535737"], "omim": ["602473"], "orphanet": ["51188"], "genereviews": ["NBK453432"]}
A number sign (#) is used with this entry because cardiofaciocutaneous syndrome-1 (CFC1) is caused by heterozygous mutation in the BRAF gene (164757) on chromosome 7q34. Description Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects, and mental retardation (summary by Niihori et al., 2006). The heart defects include pulmonic stenosis, atrial septal defect, and hypertrophic cardiomyopathy. Some patients have ectodermal abnormalities such as sparse and friable hair, hyperkeratotic skin lesions, and a generalized ichthyosis-like condition. Typical facial characteristics include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Most cases occur sporadically, but autosomal dominant transmission has been rarely reported (Linden and Price, 2011). Roberts et al. (2006) provided a detailed review of CFC syndrome, including a discussion of the phenotypic overlap of CFC syndrome with Noonan syndrome (NS1; 163950) and Costello syndrome (218040). ### Genetic Heterogeneity of Cardiofaciocutaneous Syndrome Other forms of cardiofaciocutaneous syndrome include CFC2 (615278), caused by mutation in the KRAS gene (190070); CFC3 (615279), caused by mutation in the MAP2K1 gene (176872); and CFC4 (615280), caused by mutation in the MAP2K2 gene (601263). The protein products of these causative genes, including BRAF, interact in a common RAS/ERK (see 601795) pathway that regulates cell differentiation, proliferation, and apoptosis (summary by Roberts et al., 2006). Clinical Features Reynolds et al. (1986) described 4 males and 4 females, each from a different family, with a previously undefined multiple congenital anomalies/mental retardation syndrome, which they designated the cardiofaciocutaneous syndrome. The manifestations included congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. The most common cardiac defects were pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of the supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis-like condition. There was no history of consanguinity. Neri et al. (1987) reported 2 cases; again, no parental consanguinity was observed. Roberts et al. (2006) provided follow-up on 6 of the patients originally reported by Reynolds et al. (1986). Three had been lost to follow-up, 1 was living independently with family, 1 was in a group home, and 1 had died of heart failure. Verloes et al. (1988) reported 2 cases and pointed out the similarity to Noonan syndrome. They also suggested that the Noonan-like short stature syndrome with sparse hair described by Baraitser and Patton (1986) is the same disorder. The first of their patients had the habitus of Noonan syndrome associated with keratosis plantaris and nystagmus; the second had a somewhat Noonan-like face, macrocephaly, keratosis pilaris, and hypertrophic cardiomyopathy. Chrzanowska et al. (1989) described an affected girl whose twin brother died shortly after birth and may have had the same malformation syndrome. The father and mother, aged 35 and 36 years, respectively, were healthy and nonconsanguineous. Mucklow (1989) described 1 case, and Sorge et al. (1989) described 3 cases. In addition to high cranial vault, bitemporal frontal constriction was noted. Gross-Tsur et al. (1990) described what they alleged to be the sixteenth reported case of CFC. Roberts et al. (2006) noted that this child had Lennox-Gastaut encephalopathy. Fryer et al. (1991) also emphasized the phenotypic overlap between the CFC syndrome and the Noonan syndrome. They presented findings in the patient reported by Navaratnam and Hodgson (1973), published photographs spanning from infancy to age 21 years, and showed the appearance of the pectus carinatum/excavatum and the keratotic skin lesions. Matsuda et al. (1991) described 2 Japanese boys with the CFC syndrome but without hyperkeratosis of the skin. Neri et al. (1991) concluded that the Noonan and CFC syndromes are indeed distinct and separate conditions, both falling within the broad and causally heterogeneous spectrum of the Noonan/congenital lymphedema phenotype; other members of the cluster were listed. Turnpenny et al. (1992) described a 7-year-old girl whose features were thought to satisfy the diagnosis of CFC syndrome. The ectodermal features consisted of fine and sparse hair, thin and opalescent nails, finger tip pads, generalized cutaneous pigmentation, but no hyperkeratosis. Although CFC syndrome is distinguished from Noonan syndrome by the presence of abnormal hair and hyperkeratotic lesions and by its usual sporadic occurrence, Ward et al. (1994) supported the suggestion of Fryer et al. (1991) that it falls 'within the clinical spectrum of the Noonan phenotype.' They described mother and daughter who had features consistent with the CFC syndrome but had other features which have been reported in the Noonan syndrome but not in the CFC syndrome, namely, hemorrhagic diathesis and ocular abnormalities. They were described as having ulerythema ophryogenes (keratosis pilaris affecting the follicles of the eyebrow hairs, associated with erythema, scarring, and atrophy). Krajewska-Walasek et al. (1996) reported 2 unrelated children (a boy and a girl) with CFC syndrome who had 'Noonan-like' face, sparse, thin, curly hair, and severe mental retardation. The girl also had altered sensation of the distal part of the limbs, which has been described in patients with Noonan syndrome but not in patients with CFC syndrome. Leichtman (1996) described a family suggesting that CFC syndrome is a variable expression of Noonan syndrome. He reported a 4-year-old girl with features sufficient to meet the criteria for CFC, including developmental delay, hypotrichosis, eczematic eruption, and characteristic facial and cardiac anomalies, whose mother demonstrated typical manifestations of Noonan syndrome. Manoukian et al. (1996) reported the case of a 25-year-old woman with typical features of CFC syndrome but without mental retardation. She had valvular and infundibular pulmonic stenosis, brittle and woolly hair with patchy alopecia, scant body hair, dry and hypohidrotic skin, and characteristic facial traits. At the age of 3 years the patient had shown fullness of periorbital tissues, ectropion of the lower palpebral fissures, malar hypoplasia, bulbous nose, and hyperplasia of the helix and earlobes. At the age of 25 she showed downslanting palpebral fissures with scant eyebrows and absent eyelashes on the nasal side, edematous eyelids, ectropion of the lower eyelids, posteriorly angulated ears with hyperplastic helix and lobes, and webbed neck. Wieczorek et al. (1997) described 3 patients in whom the diagnosis was considered to be CFC syndrome. They provided a detailed review of previously reported cases and discussed the differences from Noonan and Costello (218040) syndromes. McGaughran (2003) reported the diagnosis of CFC syndrome in a 52-year-old woman who had short stature, a head circumference below the 50th centile, bilateral ptosis, fine, thin hair with frontal balding, posteriorly angulated ears with tipped-up ear lobes, a high, narrow palate, lax skin, and deep palmar creases. Ptosis and lax skin had been present since childhood. McGaughran (2003) stated that this was the oldest person that had been described with CFC syndrome. Armour and Allanson (2008) reported the clinical features of 38 patients with genetically confirmed CFC syndrome. Polyhydramnios (77%) and prematurity (49%) were common perinatal issues. Cardiac anomaly was present in 71% of individuals with the most common being pulmonary valve stenosis (42%), hypertrophic cardiomyopathy (39%), and atrial septal defect (28%). Hair anomalies were also typical: curly hair (92%), sparse hair (84%), and absent or sparse eyebrows (86%). The most frequent cutaneous features were keratosis pilaris (73%), hyperkeratosis (61%), and nevi (76%). Significant and long-lived gastrointestinal dysmotility (71%), seizures (49%), optic nerve hypoplasia (30%), and renal anomalies, chiefly hydronephrosis (20%), were among the less well known issues reported. In 17 (52%) of 33 unrelated patients with a clinical diagnosis of CFCS, Sarkozy et al. (2009) identified heterozygous de novo mutations in the BRAF gene. The most common facial features included prominent forehead, bitemporal narrowing, hypertelorism, downslanting palpebral fissures, epicanthal folds, thick lips, and low-set ears with thick helices. Pulmonary stenosis and hypertrophic cardiomyopathy were the most common cardiac defects, occurring in 90% and 55% of patients, respectively. Ectodermal anomalies included absent or hypoplastic eyebrows, curly, sparse hair, hyperkeratosis, and keratosis pilaris; hyperhidrosis was a common feature (78%). About half of patients had short stature, and most had some degree of neonatal growth failure with poor feeding. Most also had moderate to severe mental retardation, although 2 had normal cognition. Many had hypotonia or seizures. Nine of 17 patients had pigmentary skin changes, including 2 with a high number of lentigines. Goodwin et al. (2013) evaluated the craniofacial features of 32 individuals ranging in age from 2 to 27 years with a clinical diagnosis of CFC who were ascertained from large conferences on the disorder. The most common features included relative macrocephaly (97%), high forehead (84%), bitemporal narrowing (84%), a convex facial profile (74%), and hypertelorism (65%)/telecanthus (100%). About half (52%) had hypoplasia of the superior orbital ridge, and only a few (10%) had micrognathia or a small mandible. Other common features were short nose (71%) and low-set (90%), posteriorly rotated (84%) ears with upturned lobes (52%). The patients also had a recognizable dental phenotype characterized by malocclusion, with open bite in which the anterior teeth were not in contact when the posterior teeth were in occlusion (37%). Many (19%) had a posterior crossbite, in which the maxillary posterior teeth are on the lingual side of the mandibular teeth instead of the buccal side. The majority of patients (80%) had a constricted high-arched palate and many showed tongue thrusting. However, dental development, eruption patterns, and enamel were similar to the general population. Individuals with BRAF mutations had a significantly higher incidence (92%) of high-arched palate compared with MEK1- or MEK2-positive individuals. Inheritance Bottani et al. (1991) reported a patient and reviewed the cases, all sporadic, reported to date. In 20 cases for which information was available, the average age of fathers at the birth of the child was 39 years. This evidence of paternal age effect significantly supports autosomal dominant inheritance. Corsello and Giuffre (1991) reported 2 unrelated boys with CFC syndrome. The parents were nonconsanguineous but the fathers were 45 and 50 years old. Lecora et al. (1996) reported that the mother and younger sister of a patient with CFC, originally described by Ghezzi et al. (1992), also had variable phenotypes consistent with CFC syndrome, thus suggesting autosomal dominant inheritance. Diagnosis Grebe and Clericuzio (2000) described 2 patients with severe manifestations of cardiofaciocutaneous syndrome. Based on these patients, diagnostic criteria for a severe phenotype of CFC syndrome were proposed. These criteria included macrocephaly; characteristic facial features; growth retardation; cardiac defect; sparse, curly hair; neurologic impairment/developmental delay; gastrointestinal dysfunction; ocular abnormalities/dysfunction; history of polyhydramnios; and hyperkeratotic skin lesions. The authors suggested that these stringent diagnostic criteria be used in future studies aimed at identifying a molecular basis for this condition. Kavamura et al. (2002) created a clinical and objective method, called the CFC index, for the diagnosis of CFC syndrome. The method also differentiated CFC from Noonan and Costello (218040) syndromes. Other Features Van Den Berg and Hennekam (1999) reported a child with CFC who developed acute lymphoblastic leukaemia (ALL). The authors noted that malignancy had not been described previously in patients with CFC but had been in those with Noonan syndrome, and that in this group ALL was the most commonly described malignancy. Van Den Berg and Hennekam (1999) cited the report of Legius et al. (1998) and also noted that on the basis of this single case it remained uncertain whether malignancy was a manifestation of CFC or a coincidence in this child. This patient was found to carry a G469E mutation in the BRAF gene (164757.0014) by Niihori et al. (2006). Molecular Genetics The phenotypic overlap among CFC syndrome, Noonan syndrome, and Costello syndrome, and the finding of causative mutations for the latter syndromes in the PTPN11 and HRAS (190020) genes, respectively, suggested to Niihori et al. (2006) that the action of the RAS-MAPK pathway is the common underlying mechanism of Noonan syndrome and Costello syndrome and, hence, possibly of CFC syndrome. To elucidate the molecular basis of CFC syndrome, Niihori et al. (2006) examined the downstream molecules of RAS in the signaling pathway and sequenced the entire 18 codons of BRAF in 40 individuals with CFC. They identified 8 mutations (e.g., 164757.0012) in 16 individuals. Niihori et al. (2006) also sequenced the entire coding regions of 3 Ras genes, HRAS, KRAS, and NRAS (164790), in genomic DNA from 43 individuals with CFC syndrome and identified 2 KRAS mutations: G60R (190070.0009) and D153V (190070.0010). Rodriguez-Viciana et al. (2006) screened 23 CFC patients for mutations in BRAF. Eighteen of 23, or 78% of individuals, had mutations in BRAF; 11 distinct missense mutations clustered in 2 regions. Five individuals had a gln257-to-arg missense mutation (164757.0013) in the cysteine-rich domain of the conserved region 1 (CR1). The other cluster of mutations was in the protein kinase domain and involved exons 11, 12, 14, and 15. Five patients had heterogeneous missense mutations in exon 12. All parents and controls, totaling 40 phenotypically unaffected individuals, had none of these mutations, supporting the hypothesis that occurrence of CFC is sporadic. Rodriguez-Viciana et al. (2006) suggested that although the causative mutations in BRAF were heterogeneous, the distribution of mutations was specific and nonrandom. No frameshift, nonsense, or splice site mutations were detected in the cohort of patients; thus, BRAF haploinsufficiency is not a likely causative mechanism of CFC. In 2 patients originally diagnosed with Costello syndrome but with features overlapping those of CFC, in whom no HRAS mutations were found (Estep et al., 2006), Rauen (2006) identified missense mutations in the BRAF gene (164757.0020 and 164757.0021, respectively). Rauen (2006) stated that Costello syndrome and CFC can be distinguished by mutation analysis of genes in the RAS/MAPK pathway. In 17 (52%) of 33 unrelated patients with a clinical diagnosis of CFCS, Sarkozy et al. (2009) identified heterozygous de novo mutations in the BRAF gene. The mutations clustered in exon 6, encoding the cysteine-rich domain, and in exons 11 to 17, encoding the kinase domain. In vitro functional expression studies of selected variants showed variable gain of function, but little transforming ability; all mutations had less activating potential than the common V600E mutation (164757.0001). ### Exclusion Studies Because CFC syndrome had been considered to be a more severe variant of Noonan syndrome, Ion et al. (2002) screened for PTPN11 mutations in a series of 28 CFC patients using denaturing high-performance liquid chromatography (DHPLC), but found no abnormalities in the coding region of the gene. In an analysis of the PTPN11 gene in 96 Noonan syndrome patients, Musante et al. (2003) also screened 5 sporadic patients with CFC syndrome and found no mutations in the PTPN11 gene. Genotype/Phenotype Correlations Niihori et al. (2006) compared the manifestations of KRAS-positive and BRAF-positive individuals and found similar frequencies of growth and mental retardation, craniofacial appearance, abnormal hair, and heart defects. However, they observed a difference between the 2 groups in manifestations of skin abnormality, including ichthyosis, hyperkeratosis, and hemangioma, which were observed in 13 BRAF-positive individuals but in none of the KRAS-positive individuals (P less than 0.05). That somatic mutations in BRAF have been identified in 60% of malignant melanoma or nevi (Garnett and Marais, 2004) suggested to Niihori et al. (2006) that BRAF has an important role in the skin. Gripp et al. (2007) reported 13 unrelated patients ages 0 to 8 years with a clinical diagnosis of Costello syndrome (218040), Costello-like syndrome, or thought to have either CFC syndrome or Costello syndrome who were negative for mutations in the HRAS gene. De novo heterozygous BRAF or MEK1 mutations were identified in 8 and 5 patients, respectively. In a comparison to a group of previously published patients with HRAS mutations, Gripp et al. (2007) found several significant clinical differences between the 2 groups. Patients with an HRAS mutation and Costello syndrome tended to have polyhydramnios, ulnar deviation, growth hormone deficiency, and tachycardia more frequently than patients with BRAF or MEK1 mutations. Those with BRAF or MEK1 mutations had more cardiovascular malformations. Although the presence of more than 1 papilloma strongly suggested Costello syndrome over CFC, the authors noted that these lesions typically develop over time and thus may not be very helpful in the differential diagnosis of younger children. Gripp et al. (2007) concluded that the 13 patients in their study had CFC syndrome and not Costello syndrome, based on the clinical and molecular findings. The authors noted the phenotypic overlap between the 2 disorders, but suggested that Costello syndrome be reserved for patients with HRAS mutations. Among 51 patients with CFC, Schulz et al. (2008) identified mutations in the BRAF (47%), MAP2K1 (9.8%), MAP2K2 (5.9%), and KRAS (5.9%) genes. Careful assessment of facial features suggested that patients with MAP2K1 mutations showed macrostomia and horizontal shape of the palpebral fissures, whereas those with MAP2K2 mutations had a long, narrow face with a high forehead, low-set ears, severe ptosis, epicanthal folds, and prominent supraorbital ridges. In 6 patients with a clinical diagnosis of CFC, Nystrom et al. (2008) identified mutations in the BRAF (2), KRAS (1), MEK1 (1), and MEK2 (2) genes. A seventh patient with a diagnosis of CFC had a mutation in the SOS1 gene (182530), which is usually associated with Noonan syndrome-4 (NS4; 610733). An eighth patient with a diagnosis of Noonan syndrome was found to have a mutation in the BRAF gene, which is usually associated with CFC. Nystrom et al. (2008) concluded that the molecular and clinical overlap between CFC and Noonan syndrome is complex and suggested that they may even represent allelic disorders. However, Neri et al. (2008) disputed the diagnoses of 2 patients reported by Nystrom et al. (2008). Neri et al. (2008) concluded that the SOS1 mutation-bearing CFC patient actually had typical Noonan syndrome, and that the BRAF-carrying NS patient actually had typical CFC. Neri et al. (2008) stated that NS can be caused by mutations in the PTPN11 (176876), SOS1, and RAF1 genes, that CFC can be caused by mutations in the BRAF, MEK1, and MEK2 genes, and that the diagnosis of Costello syndrome should be restricted to patients with HRAS mutations. History Rauen et al. (2000) reported the case of a 19-month-old girl who presented with the phenotype of CFC syndrome, including characteristic minor facial anomalies, cardiac defect, ectodermal anomalies (keratosis pilaris), and developmental delay. The patient was found to have an interstitial deletion at 12q21.2-q22, proximal to the critical region for Noonan syndrome, suggesting that in this patient CFC is genetically distinct from Noonan syndrome. Rauen et al. (2002) reported an additional patient with an interstitial deletion cytogenetically identical to the one reported by Rauen et al. (2000). The patient was of XYY sex chromosome constitution. Microarray-based comparative genomic hybridization confirmed both the deletion and the second Y chromosome. The deletion on 12q spanned at least 14 Mb as indicated by the genomic positions of the 4 BAC clones included in the deletion. While the proband did not have the classic features of CFC, he had some dysmorphic craniofacial characteristics, ectodermal anomalies, and moderate developmental delay which were suggestive of CFC syndrome. Zollino and Neri (2000) looked for 12q21-q22 deletions in 7 patients with classic CFC syndrome using FISH with the same probe used by Rauen et al. (2000) and found no deletions. Based on phenotypic features, Zollino and Neri (2000) and Neri et al. (2003) argued that the patients presented by Rauen et al. (2000, 2002) did not have CFC. Rauen and Cotter (2003) stated that 'controversy exists as to whether CFC represents a separate entity or if CFC is part of the Noonan syndrome (NS) spectrum.' They pointed out the identification of mutations in the PTPN11 gene on chromosome 12q24.1 in patients with Noonan syndrome, which shares phenotypic features with CFC. In an Editor's Note, Carey (2003) stated that the idea that 12q21.2-q22 is a candidate region for CFC is not a conclusion, but a hypothesis. Animal Model Anastasaki et al. (2009) expressed a panel of 28 BRAF and MEK alleles in zebrafish embryos to assess the function of human disease alleles and available chemical inhibitors of this pathway. Both kinase-activating and kinase-impaired CFC mutant alleles promoted the equivalent developmental outcome when expressed during early development. Treatment of CFC-zebrafish embryos with inhibitors of the FGF-MAPK pathway could restore normal early development. There was a developmental window in which treatment with an MEK inhibitor could restore the normal early development of the embryo without additional unwanted developmental effects of MEK inhibitor. Inoue et al. (2014) created heterozygous knockin mice expressing Braf with a gln241-to-arg (Q241R) mutation, which corresponds to the most frequent mutation in CFC syndrome, gln257 to arg (Q257R; 164757.0013). Braf Q241R/+ mice showed embryonic or neonatal lethality, with liver necrosis, edema, craniofacial abnormalities, and heart defects, including cardiomegaly, enlarged cardiac valves, ventricular noncompaction, and ventricular septal defects. Braf Q241R/+ embryos also showed massively distended jugular lymphatic sacs and subcutaneous lymphatic vessels. Prenatal treatment with a Mek inhibitor partly rescued embryonic lethality in Braf Q241R/+ embryos, with amelioration of craniofacial abnormalities and edema. One surviving pup was obtained following treatment with a histone-3 demethylase inhibitor. Combined treatment with Mek and histone-3 demethylase inhibitors further increased the survival rate in Braf Q241R/+ embryos and ameliorated enlarged cardiac valves. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature, postnatal Other \- Failure to thrive HEAD & NECK Head \- Macrocephaly, relative \- Dolichocephaly Face \- Prominent forehead \- Bitemporal narrowing \- Shallow orbital ridges \- Prominent philtrum \- Coarse facial features \- Micrognathia \- Convex facial profile Ears \- Posteriorly rotated ears \- Low-set ears \- Earlobe creases \- Hearing loss Eyes \- Ptosis \- Nystagmus \- Strabismus \- Downslanting palpebral fissures \- Hypertelorism \- Exophthalmos \- Epicanthal folds \- Myopia \- Optic nerve dysplasia \- Oculomotor apraxia \- Loss of visual acuity \- Absence of eyebrows \- Absence of eyelashes Nose \- Short upturned nose \- Bulbous nasal tip \- Depressed nasal bridge Mouth \- Submucous cleft palate \- High-arched palate \- Open mouth \- Tongue thrusting Teeth \- Malocclusion \- Open bite \- Posterior crossbite CARDIOVASCULAR Heart \- Atrial septal defects \- Pulmonic stenosis \- Hypertrophic cardiomyopathy CHEST External Features \- Pectus excavatum \- Pectus carinatum ABDOMEN Spleen \- Splenomegaly Gastrointestinal \- Poor feeding \- Dysmotility \- Vomiting \- Constipation \- Gastroesophageal reflux GENITOURINARY Kidneys \- Hydronephrosis SKELETAL \- Joint hyperextensibility \- Delayed bone age \- Osteopenia Hands \- Hyperextensible fingers \- Clinodactyly \- Multiple palmar creases Feet \- Multiple plantar creases SKIN, NAILS, & HAIR Skin \- Severe atopic dermatitis \- Ichthyosis \- Hyperkeratosis (especially extensor surfaces) \- Cavernous hemangioma \- Keratosis pilaris \- Multiple palmar creases \- Multiple lentigines Hair \- Sparse, curly hair \- Slow-growing hair \- Absence of eyebrows \- Absence of eyelashes NEUROLOGIC Central Nervous System \- Mild to moderate mental retardation \- Seizures \- Hypotonia \- Hypertonia \- Hydrocephalus \- Cortical atrophy \- Frontal lobe hypoplasia \- Hypoplasia or absence of the corpus callosum \- Brain stem atrophy Peripheral Nervous System \- Peripheral axonal neuropathy (uncommon) PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios Delivery \- Premature delivery MISCELLANEOUS \- Most cases are sporadic \- Associated with advanced paternal age \- Autosomal dominant transmission has been rarely reported \- Phenotypic similarities to Noonan syndrome ( 163950 ) \- Phenotypic similarities to Costello syndrome ( 218040 ) MOLECULAR BASIS \- Caused by mutation in the V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog gene (KRAS, 190070.0009 ) \- Caused by mutation in the V-Raf murine sarcoma viral oncogene homolog B1 gene (BRAF, 164757.0012 ) \- Caused by mutation in the mitogen-activated protein kinase kinase 1 gene (MAP2K1, 176872.0001 ) \- Caused by mutation in the mitogen-activated protein kinase kinase 1 gene (MAP2K2, 601263.0001 ) ▲ 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	CARDIOFACIOCUTANEOUS SYNDROME 1	c1275081	8,460	omim	https://www.omim.org/entry/115150	2019-09-22T16:43:55	{"doid": ["0060233"], "mesh": ["C535579"], "omim": ["115150"], "orphanet": ["1340"], "synonyms": ["Alternative titles", "CFC SYNDROME", "CFCS"], "genereviews": ["NBK1186"]}
Congenital central hypoventilation syndrome (CCHS) is a disorder that affects normal breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This nervous system reaction is impaired in people with CCHS. They must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night. Symptoms of CCHS usually become apparent shortly after birth when affected infants hypoventilate upon falling asleep. In these infants, a lack of oxygen in the blood often causes a bluish appearance of the skin or lips (cyanosis). In some milder cases, CCHS may not become apparent until later in life. In addition to the breathing problem, people with CCHS may have difficulty regulating their heart rate and blood pressure, for example, in response to exercise or changes in body position. They also have decreased perception of pain, low body temperature, and occasional episodes of heavy sweating. People with CCHS may have additional problems affecting the nervous system. About 20 percent of people with CCHS have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. (Some researchers refer to the combination of CCHS and Hirschsprung disease as Haddad syndrome.) Some affected individuals develop learning difficulties or other neurological problems. People with CCHS are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas. Additionally, individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as "box-shaped." In CCHS, life expectancy and the extent of any intellectual disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment. ## Frequency CCHS is a relatively rare disorder. More than 1,000 individuals with this condition have been identified. Researchers believe that some cases of sudden infant death syndrome (SIDS) or sudden unexplained death in children may be caused by undiagnosed CCHS. ## Causes Mutations in a gene called PHOX2B cause CCHS. The PHOX2B gene provides instructions for making a protein that is important during development before birth. The PHOX2B protein helps support the formation of nerve cells (neurons) and regulates the process by which the neurons mature to carry out specific functions (differentiation). The protein is active in the neural crest, which is a group of cells in the early embryo that give rise to many tissues and organs. Neural crest cells migrate to form parts of the autonomic nervous system, many tissues in the face and skull, and other tissue and cell types. PHOX2B gene mutations that cause CCHS are believed to interfere with the PHOX2B protein's role in supporting neuron formation and differentiation, especially in the autonomic nervous system. As a result, bodily functions that are controlled by this system, including regulation of breathing, heart rate, blood pressure, and body temperature, are inconsistent in CCHS. ### Learn more about the gene associated with Congenital central hypoventilation syndrome * PHOX2B ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. More than 90 percent of cases of CCHS result from new mutations in the PHOX2B gene. These cases occur in people with no history of the disorder in their family. Occasionally an affected person inherits the mutation from one affected parent. The number of such cases has been increasing as better treatment has allowed more affected individuals to live into adulthood and start families. About 5 to 10 percent of affected individuals inherit the altered gene from an unaffected parent who has a PHOX2B gene mutation only in their sperm or egg cells. This phenomenon is called germline mosaicism. A parent with mosaicism for a PHOX2B gene mutation may not show any signs or symptoms of CCHS. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Congenital central hypoventilation syndrome	c1859049	8,461	medlineplus	https://medlineplus.gov/genetics/condition/congenital-central-hypoventilation-syndrome/	2021-01-27T08:25:37	{"gard": ["8535"], "mesh": ["C536209"], "omim": ["209880"], "synonyms": []}
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: "Anaplastic oligodendroglioma" – news · newspapers · books · scholar · JSTOR (January 2021) (Learn how and when to remove this template message) Human brain tumor Anaplastic oligodendroglioma Play media Video of tumor growth simulation (anaplastic oligodendroglioma). Simulation was run for 2600 days since tumor onset (one original cell) with a detection level of 1 cell/mm2. SpecialtyOncology SymptomsSeizures[1] Usual onsetpeak years are age 45-50[1] Durationuntil cure or death CausesGenerally unknown[1] Risk factorsGenerally unknown Diagnostic methodBiopsy Differential diagnosisOther gliomas PreventionNot known TreatmentSurgery, radiation, chemotherapy[1] MedicationTemozolomide[1] PrognosisGenerally fatal after 2-6 years[1] Frequency0.07 to 0.18 per 100,000 person-years[1] Anaplastic oligodendroglioma is a neuroepithelial tumor which is believed to originate from oligodendrocytes, a cell type of the glia. In the World Health Organization (WHO) classification of brain tumors, anaplastic oligodendrogliomas are classified as grade III.[2] In the course of the disease, they can degenerate into WHO grade IV glioblastoma.[3] The vast majority of oligodendrogliomas occur sporadically, without a confirmed cause and without inheritance within a family. ## Contents * 1 Pathogenesis * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 Research * 6 References ## Pathogenesis[edit] The (malignant) anaplastic oligodendroglioma belongs to the group of diffuse glioma and arises in the central nervous system (brain and spinal cord) from precursor stem cells of the oligodendrocytes. This tumor occurs primarily in middle adulthood with a frequency peak in the 4th and 5th decade of life.[3] ## Diagnosis[edit] The most important diagnostic procedure is magnetic resonance imaging (MRI).[3] Occasionally, outside of routine diagnostics, the metabolism in the tissue is shown using positron emission tomography (PET). The diagnosis is confirmed by a fine tissue examination following an operation. Anaplastic oligodendrogliomas often show a loss of genetic material. About 50 to 70%[4] of WHO grade III anaplastic oligodendrogliomas have combined allele losses on the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q). This change is mostly referred to as "1p / 19q Co Deletion". It can be seen as favorable for the patient and makes a response to radiation or chemotherapy more likely.[3] The designation of grade III oligodendroglioma (high grade) generally subsumes the previous diagnoses of anaplastic or malignant oligodendroglioma.[2] * Histopathological image of anaplastic oligodendroglioma in cerebrum. Hematoxylin & eosin stain. * Zooming, note the irregular cell- and nucleus-shapes ## Treatment[edit] Surgery can help reduce symptoms caused by the tumor. As complete as possible removal of the tumor visible on the MRI is preferred, provided the location of the tumor allows this. Since the cells of an anaplastic oligodendroglioma have already migrated into the surrounding healthy brain tissue at the time of diagnosis, a complete surgical removal of all tumor cells is not possible. The "1p / 19q Codeletion" marker plays an increasingly important role in the selection of therapy and therapy combinations. Because of the indolent nature of this tumor and the potential morbidity associated with neurosurgery, chemotherapy and radiation therapy, most neurooncologists will initially pursue a course of watchful waiting and treat patients symptomatically. Symptomatic treatment often includes the use of anticonvulsants for seizures and steroids for brain swelling. For further treatment, radiation or chemotherapy with temozolomide or a chemotherapy with Procarbazine, CCNU and Vincristine (PCV) has been shown to be effective and was the most commonly used chemotherapy regimen used for treating anaplastic oligodendrogliomas.[3][5] ## Prognosis[edit] 5–Year relative survival rate: Age 20–44, 76%. Age 45–54, 67%. Age 55–64, 45%.[6][7] Procarbazine, lomustine and vincristine have been used since May 1975. For 46 years, new therapeutic options have been regularly tested as part of therapy studies to improve the treatment of anaplastic oligodendroglioma.[8] ## Research[edit] As of 2021[update], a definitive cure is not possible with anaplastic oligodendrogliomas of WHO grade III. A retrospective study on 1054 patients with anaplastic oligodendroglioma, presented during the 2009 ASCO Annual Meeting, suggests that PCV therapy may be effective. Median time to progression for patients with 1p19q co-deletion was longer following PCV alone (7.6 years) than with temozolomide alone (3.3 years); median overall survival was also longer with PCV treatment versus temozolomide treatment (not reached, vs. 7.1 years).[9] A recent long-term study does affirm that radiation combined with adjuvant chemotherapy is significantly more efficacious for anaplastic oligodendroglioma patients with 1p 19q co-deleted tumors and has become the new standard of care.[10] It is possible that radiotherapy may prolong the overall time to progression for non-deleted tumors. If the tumor mass compresses adjacent brain structures, a neurosurgeon will typically remove as much of the tumor as he or she can without damaging other critical, healthy brain structures. Recent studies suggest that radiation does not improve overall survival (even when age, clinical data, histological grading, and type of surgery are considered).[11][12] ## References[edit] 1. ^ a b c d e f g Anderson, Mark D.; Gilbert, Mark R. (April 14, 2013). "Treatment Recommendations for Anaplastic Oligodendrogliomas That Are Codeleted". Oncology. 27 (4). Retrieved 4 January 2021. 2. ^ a b Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (August 2007). "The 2007 WHO classification of tumours of the central nervous system". Acta Neuropathol. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. PMC 1929165. PMID 17618441. 3. ^ a b c d e Schweizerische Hirntumor Stiftung. "Anaplastisches Oligodendrogliom". www.swissbraintumorfoundation.com/ (in German). 4. ^ administrador (5 February 2020). "Anaplastic oligodendroglioma, IDH-mutant & 1p/19q-codeleted". 5. ^ Engelhard HH, Stelea A, Mundt A (November 2003). "Oligodendroglioma and anaplastic oligodendroglioma: clinical features, treatment, and prognosis". Surg Neurol. 60 (5): 443–56. doi:10.1016/s0090-3019(03)00167-8. PMID 14572971. 6. ^ "Survival Rates for Selected Adult Brain and Spinal Cord Tumors". American Cancer Society. Retrieved 8 January 2021. 7. ^ Ostrom QT, Gittleman H, Xu J, et al. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013. Neuro Oncol. 2016;18 Suppl 5:v1−v75. (November 7, 2017). "Survival Rates for Selected Adult Brain and Spinal Cord Tumors". Cite journal requires `\|journal=` (help)CS1 maint: uses authors parameter (link) 8. ^ Gutin PH, Wilson CB, Kumar AR, Boldrey EB, Levin V, Powell M, Enot KJ (May 1975). "Phase II study of procarbazine, CCNU, and vincristine combination chemotherapy in the treatment of malignant brain tumors". Cancer. 35 (5): 1398–404. doi:10.1002/1097-0142(197505)35:5<1398::aid-cncr2820350524>3.0.co;2-c. PMID 1122488. 9. ^ Lassman, A. B. (20 May 2009). "Retrospective analysis of outcomes among more than 1,000 patients with newly diagnosed anaplastic oligodendroglial tumors". Journal of Clinical Oncology. 27 (15S): 2014. doi:10.1200/jco.2009.27.15_suppl.2014. ISSN 0732-183X. 10. ^ "New Standard of Care for Anaplastic Oligodendroglial Tumors with 1p/19q Codeletions – the ASCO Post". 11. ^ Sunyach MP, Jouvet A, Perol D, et al. (December 2007). "Role of exclusive chemotherapy as first line treatment in oligodendroglioma". J. Neurooncol. 85 (3): 319–28. doi:10.1007/s11060-007-9422-3. PMID 17568995. 12. ^ Mohile NA, Forsyth P, Stewart D, et al. (September 2008). "A phase II study of intensified chemotherapy alone as initial treatment for newly diagnosed anaplastic oligodendroglioma: an interim analysis". J. Neurooncol. 89 (2): 187–93. doi:10.1007/s11060-008-9603-8. PMID 18458821. * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Anaplastic oligodendroglioma	c0334590	8,462	wikipedia	https://en.wikipedia.org/wiki/Anaplastic_oligodendroglioma	2021-01-18T18:40:41	{"gard": ["9472"], "mesh": ["D009837"], "umls": ["C0334590"], "orphanet": ["251630"], "wikidata": ["Q84955701"]}
A number sign (#) is used with this entry because of evidence that lipoyltransferase-1 deficiency (LIPT1D) is caused by compound heterozygous mutation in the LIPT1 gene (610284) on chromosome 2q11. Clinical Features Soreze et al. (2013) reported a boy, born of unrelated French parents, who presented at age 15 months with delayed psychomotor development and hypotonia. At age 18 months, he had acute metabolic decompensation associated with gastroenteritis. Symptoms included increased serum lactate, metabolic acidosis, abnormal liver enzymes, and psychomotor regression manifest as severe hypotonia, dystonia, loss of head control, and coma. After a few days, he had spastic tetraparesis and extrapyramidal signs as well as inability to speak, but he was otherwise fully conscious and alert. Brain imaging showed cerebellar atrophy, cortical atrophy, bilateral thalamic abnormalities, bifrontal white matter abnormalities, and delayed myelination. The findings were consistent with a clinical diagnosis of Leigh syndrome (256000). Laboratory studies showed increased glutamine and proline and were consistent with decreased activities of the pyruvate dehydrogenase complex (PDHC) and alpha-ketoglutarate dehydrogenase (KGDH), as demonstrated in patient fibroblasts. Branched-chain alpha-keto acid dehydrogenase (BCKDH) activity was also decreased. Glycine was not increased. Carbon dioxide production by the Krebs cycle and mitochondrial respiratory chain activity were decreased with pyruvate as a substrate compared to controls. Tort et al. (2014) reported a female infant, born of unrelated parents, who presented with sudden clinical deterioration and bradycardia on the second day of life. She had moderate jaundice, hypoactivity, and weak cry, and a perinatal infection was suspected. Physical examination showed generalized hypertonia and dystonic movements of the hands and feet. She developed pulmonary hypertension and further clinical deterioration, resulting in cardiorespiratory arrest and death at age 9 days. Laboratory studies showed severe lactic acidosis, liver dysfunction, and increased 2-ketoglutarate. There was no evidence of increased glycine. Overall PDHC activity was decreased compared to controls, but partial reactions catalyzed by the E1 (PDHA1, 300502 and PDHB, 179060) and E3 (DLD; 238331) subunits were normal; E2 (DLAT; 608770) activity was not measured, but sequence analysis of DLAT was normal. Muscle samples from the patient showed normal mitochondrial respiratory chain activities. Inheritance The transmission pattern of LIPT1 deficiency in the family reported by Soreze et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In a boy with early-onset encephalopathy due to LIPT1 deficiency, Soreze et al. (2013) identified compound heterozygous mutations in the LIPT1 gene (S292X, 610284.0001 and T179A, 610284.0002). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Immunoblot analysis of patient fibroblasts showed absence of the LIPT1 protein and absence of the expected lipoylated E2 proteins of KGDH, PDHC, and BCKDH. In a female infant with fatal LIPT1 deficiency, Tort et al. (2014) identified compound heterozygous missense mutations in the LIPT1 gene (S71F, 610284.0003 and R98G, 610284.0004). Immunostaining analysis of patient cells showed decreased levels of lipoylated E2-PDH and E2-KGDH. There was normal lipoylation of the H protein (GCSH; 238330) of the glycine cleavage system (GCS) and normal activity of the GCS, suggesting that the LIPT1 mutations caused a defect of lipoic acid transfer to particular proteins rather than a general impairment of lipoic acid biosynthesis. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Bradycardia (patient B) Vascular \- Pulmonary hypertension (patient B) ABDOMEN Liver \- Liver dysfunction NEUROLOGIC Central Nervous System \- Delayed psychomotor development (patient A) \- j Hypertonia \- Dystonic movements \- Truncal hypotonia (patient A) \- Spastic tetraparesis (patient A) \- Extrapyramidal symptoms (patient A) \- Cerebellar atrophy (patient A) \- Thalamic abnormalities (patient A) \- White matter abnormalities (patient A) \- Delayed myelination (patient A) \- Leigh syndrome (patient A) METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Abnormal liver enzymes \- Increased bilirubin (patient B) \- Increased serum alpha-ketoglutarate \- Increased serum lactate \- Increased serum alpha-alanine (patient B) \- Increased serum glutamine (patient A) \- Increased serum proline \- Normal serum glycine \- Absence of protein-bound lipoic acid \- Decreased activity of branched-chain ketoacid dehydrogenase (BCKDH) \- Decreased activity of alpha-ketoglutarate dehydrogenase (alpha-KGDH) \- Decreased activity of pyruvate dehydrogenase complex (PDH) MISCELLANEOUS \- Onset in infancy \- Symptoms present as acute metabolic and clinical decompensation associated with infection \- Death in infancy (patient B) \- Two unrelated patients have been reported (last curated April 2015) MOLECULAR BASIS \- Caused by mutation in the lipoyltransferase 1 gene (LIPT1, 610284.0001 ) ▲ 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	LIPOYLTRANSFERASE 1 DEFICIENCY	c4225379	8,463	omim	https://www.omim.org/entry/616299	2019-09-22T15:49:20	{"omim": ["616299"], "orphanet": ["401862"], "synonyms": []}
A rare small vessel vasculitis associated with rapidly progressive glomerulonephritis (GN) and clinically characterized by renal manifestations such as urinary abonormalities (hematuria and/or proteinuria) and hypertension leading to renal failure within days or weeks, and the absence of distinguished by the absence of immune depositis on immunofluorescent microscopy. The disease can occur as a renal-limited disease or as a component of systemic necrotizing small-vessel vasculitis. ## Epidemiology Pauci-immune GN is the most common cause of rapidly progressive glomerulonephritis. The incidence of pauci-immune GN in the United States is estimated at 3.1/1,000,000, with significantly higher rates for Caucasians, males and individuals over 65. In the European population, the incidence is estimated between 1-2/100,000, with an increasing trend in recent years. ## Clinical description Patients with pauci-immune GN may present with different clinical pictures, and predominantly occurs in patients over 55 years of age, although rarely it may occur earlier. Most patients report a prodromal 'flu-like' illness preceding the overt vasculitic syndrome. Pauci-immune GN can occur as a renal-limited disease or as a component of systemic vasculitis. Systemic symptoms including fever, asthenia, arthralgias, weight loss, and myalgias can precede the renal presentation of the disease. Clinically, it is characterized by renal manifestations such as urinary abonormalities (hematuria and/or proteinuria) and hypertension leading to renal failure within days or weeks. It can also be associated with extrarenal manifestations depending on the disease process and may involve the upper and lower respiratory tract, nerves, skin, and musculoskeletal system. Risk factors for progression to end stage renal disease (ESRD) include increased initial serum creatinine or decreased estimated glomerular filtration rate (eGFR) at baseline, older age, presence of pulmonary hemorrhage, and dialysis-dependent acute kidney injury. ## Diagnostic methods The disease is associated with the presence of serum anti-neutrophil cytoplasmic antibodies (ANCAs) in a high percentage of subjects. Renal biopsy is essential for the diagnosis and subsequent management of pauci-immune GN, and is used to to determine the activity and chronicity of the renal lesions as well as the risk associated with immunotherapy of ANCA pauci-immune necrotizing glomerulonephritis. The histological hallmarks of the disease are the presence of extracapillary proliferation and segmental necrosis on light microscopy, and the absence of immune deposits on immunofluorescence microscopy. Immunologic classification is based on the presence or absence of circulating ANCAs, namely pauci-immune-GN with ANCAs and pauci-immune GN without ANCAs. Other laboratory data such as erythrocyte sedimentation rate, C-reactive protein (CRP) and urine test are not specific but can help with the diagnosis. ## Differential diagnosis Differential diagnosis includes other forms of crescentic GN. ## Management and treatment Conventional induction therapies for pauci-immune GN have been defined and include Cyclophosphamide (CYC) for at least 3 months, with a corticosteroid taper followed by maintenance immunosuppression for up to 2 years with azathioprine or mycophenolate mofetil. Clinical trials have shown that rituximab (RTX) is an effective induction therapy for pauci-immune ANCA-associated GN. Since preventing relapses and maintaining remission are critical to slowing chronic kidney disease (CKD) progression to ESRD in this group of patients, a number of trials have focused on repeat doses of RTX at 4/6 month intervals. As with other forms of CKD, patients with stable but decreased eGFR usually benefit from blood pressure control with long-term inhibition of RAAS axis to reduce glomerular hyperfiltration, a low-sodium diet, and moderation and moderate protein intake. ## Prognosis Despite the substantial progress in treatment, pauci-immune glomerulonephritis remain a group of diseases with significant morbidity and mortality related to the disease itself. Renal involvement is one of the most threatening aspects * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Pauci-immune glomerulonephritis	c4324689	8,464	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93126	2021-01-23T17:22:34	{"icd-10": ["N05.7"]}
This article is about the human medical condition. For animals that walk on their toes, see Digitigrade. For the posture where a human consciously lifts their heels off the ground, see Tiptoe. Toe walking Toe walking in an autistic young woman SpecialtyPediatrics Toe walking refers to a condition where a person walks on their toes without putting much weight on the heel or any other part of the foot. Toe walking in toddlers is common. These children usually adopt a normal walking pattern as they grow older. If a child continues to walk on their toes past the age of three, they should be evaluated by a doctor.[1] Toe walking can be caused by different factors. One type of toe walking is also called "habitual" or "idiopathic" toe walking, where the cause is unknown.[2] Other causes include a congenital short Achilles tendon, muscle spasticity (especially as associated with cerebral palsy) and paralytic muscle disease such as Duchenne muscular dystrophy.[3] A congenital shortening of the Achilles tendon can be hereditary, can take place over time as the result of abnormal foot structure which shortens the tendon, or can shorten over time if its full length is not being used. Toe walking is sometimes caused by a bone block located at the ankle which prevents the antagonist movement, dorsiflexion. This cause is often associated with trauma or arthritis.[4] It may also be one way of accommodating a separate condition, foot drop. Persistent toe walking in children has been identified as a potential early sign of autism.[5][6] Toe walking has been found to be more prevalent in males than females when tested with very large numbers of children. This study looked for family history of toe walking and the connection to children demonstrating idiopathic toe walking (ITW). 64.2% of the subjects with ITW were males showing a relationship between ITW and males. Of 348 subjects with positive family history of toe walking, about 60% had family history on the paternal side showing it may be genetically related to paternal genes. [7] In 30–42% of idiopathic toe walkers, a family link has been observed.[8] ## Contents * 1 Cause * 1.1 Unknown * 1.2 Cerebral palsy * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Cause[edit] ### Unknown[edit] Idiopathic toe walking can be described as bilateral toe walking with no orthopedic or neurological cause past the age of two. [9] In this condition, children are able to voluntarily walk with the normal heel-toe pattern, but prefer to walk with the toe-toe pattern. In order for it to be considered idiopathic, the child's medical history should be clear of any neurological, orthopedic, or neuro-psychiatric conditions including other gait abnormalities. [10] [11] Two classifications of idiopathic toe walking have been established. The Alvarez's classification identifies the severity of the dysfunction based upon kinematics and ankle rockers. The Pomarino classification identifies the toe walking according to the individual's specific characteristics and characterizes them into three types based on the signs presented. [12] Diagnosis includes a spin test, walking, heel walking, dorsiflexion range of motion, and lumbar lordosis. [13] Some treatment options include serial casting and surgery for ankle motion. [14] ### Cerebral palsy[edit] Studies have been performed to determine the source of the association between toe walking and cerebral palsy patients. One study suggests that the toe walking—sometimes called an equinus gait—associated with cerebral palsy presents with an abnormally short medial and lateral gastrocnemius and soleus—the primary muscles involved in plantarflexion. A separate study found that the gait could be a compensatory movement due to weakened plantarflexion muscles.[15] The study performed clinical studies to determine that a greater plantarflexion force is required for normal heel-to-toe walking than for toe walking. Able bodied children were tasked to perform gaits at different levels of toe walking and the study discovered that their toe walking could not reduce the force to the levels that cerebral palsy patients indicated in their walk. This suggests that cerebral palsy in which an equinus gait is present may be due to abnormally weakened plantarflexion that can only manage toe walking.[16] ## Diagnosis[edit] A doctor will typically evaluate whether there is bilateral (both legs) toe walking, what the child's range of motion is (how far they can flex their feet) and perform a basic neurological exam. Treatment will depend on the cause of the condition.[17] ## Treatment[edit] For idiopathic toe walking in young children, doctors may prefer to watch and wait: the child may "outgrow" the condition.[18] If there is a reduction in the child's range of motion, there are several options.[3] * Wearing a brace or splint either during the day, night or both which limits the ability of the child to walk on their toes and stretches the Achilles tendon. One type of brace used is an AFO (ankle-foot orthosis). * Serial casting where the foot is cast with the tendon stretched, and the cast is changed weekly with progressive stretching. However, these casts may not be changed weekly and instead every 2–3 weeks. * Botox therapy is used to paralyze the calf muscles to reduce the opposition of the muscles to stretching the Achilles tendon, usually together with serial casting or splinting. * If conservative measures fail to correct the toe walking after about 12–24 months, surgical lengthening of the tendon is an option. The surgery is typically done under full anesthesia but if there are no issues, the child is released the same day. After the surgery, a below-the-knee walking cast is worn for six weeks and then an AFO is worn to protect the tendon for several months. For toe walking which results from more serious neuro-muscular conditions, additional specialists may need to be consulted. ## References[edit] 1. ^ "Toe Walking". Mayo Clinic. Archived from the original on 2007-06-03. Retrieved 2007-06-24. 2. ^ Babb A, Carlson WO (2008). "Idiopathic toe-walking". South Dakota Medicine. 61 (2): 53, 55–7. PMID 18432151. 3. ^ a b "Toe Walking". emedecine.com. Archived from the original on 2007-06-01. Retrieved 2007-06-07. 4. ^ "Equinus Deformity at Foot Associates of Central Texas, LLC". 2009. Archived from the original on 2013-12-08. Retrieved 2013-12-11. 5. ^ Sala DA, Shulman LH, Kennedy RF, Grant AD, Chu ML (1999). "Idiopathic toe-walking: a review" (PDF). Developmental Medicine & Child Neurology. 41 (12): 846–8. doi:10.1017/S0012162299001681. PMID 10619285. 6. ^ Geschwind DH (2009). "Advances in autism". Annual Review of Medicine. 60 (1): 367–80. doi:10.1146/annurev.med.60.053107.121225. PMC 3645857. PMID 19630577. 7. ^ Pomarino, David; Ramírez Llamas, Juliana; Pomarino, Andrea (2016). "Idiopathic Toe Walking Family Predisposition and Gender Distribution". Foot & Ankle Specialist. 9 (5): 417–422. doi:10.1177/1938640016656780. PMID 27370652. S2CID 1160638. 8. ^ Pomarino, David; Ramírez Llamas, Juliana; Martin, Stephan; Pomarino, Andrea (16 January 2017). "Literature Review of Idiopathic Toe Walking: Etiology, Prevalence, Classification, and Treatment". Foot & Ankle Specialist. 10 (4): 337–342. doi:10.1177/1938640016687370. PMID 28092971. S2CID 3389265. 9. ^ Pomarino, David; Ramírez Llamas, Juliana; Martin, Stephan; Pomarino, Andrea (16 January 2017). "Literature Review of Idiopathic Toe Walking: Etiology, Prevalence, Classification, and Treatment". Foot & Ankle Specialist. 10 (4): 337–342. doi:10.1177/1938640016687370. PMID 28092971. S2CID 3389265. 10. ^ Pomarino, David; Ramírez Llamas, Juliana; Martin, Stephan; Pomarino, Andrea (16 January 2017). "Literature Review of Idiopathic Toe Walking: Etiology, Prevalence, Classification, and Treatment". Foot & Ankle Specialist. 10 (4): 337–342. doi:10.1177/1938640016687370. PMID 28092971. S2CID 3389265. 11. ^ Kuijk, A; Kosters, R; Vugts, M; Geurts, A (2014). "Treatment for idiopathic toe walking: A systematic review of the literature". Journal of Rehabilitation Medicine. 46 (10): 945–957. doi:10.2340/16501977-1881. PMID 25223807. 12. ^ Pomarino, David; Ramírez Llamas, Juliana; Martin, Stephan; Pomarino, Andrea (16 January 2017). "Literature Review of Idiopathic Toe Walking: Etiology, Prevalence, Classification, and Treatment". Foot & Ankle Specialist. 10 (4): 337–342. doi:10.1177/1938640016687370. PMID 28092971. S2CID 3389265. 13. ^ Pomarino, David; Ramírez Llamas, Juliana; Martin, Stephan; Pomarino, Andrea (16 January 2017). "Literature Review of Idiopathic Toe Walking: Etiology, Prevalence, Classification, and Treatment". Foot & Ankle Specialist. 10 (4): 337–342. doi:10.1177/1938640016687370. PMID 28092971. S2CID 3389265. 14. ^ Kuijk, A; Kosters, R; Vugts, M; Geurts, A (2014). "Treatment for idiopathic toe walking: A systematic review of the literature". Journal of Rehabilitation Medicine. 46 (10): 945–957. doi:10.2340/16501977-1881. PMID 25223807. 15. ^ Hampton, DA, Hollander, Kw, Engsberg, JR (2003). "Equinus Deformity as a Compensatory Mechanism for Ankle Plantarflexor Weakness in Cerebral Palsy" (PDF). Journal of Applied Biomechanics. 19 (4): 325–339. doi:10.1123/jab.19.4.325. Retrieved 2013-12-11.CS1 maint: multiple names: authors list (link) 16. ^ Wren, T. A.; Do, K. P.; Kay, R. M. (2004). "Gastrocnemius and soleus lengths in cerebral palsy equinus gait: differences between children with and without static contracture and effects of gastrocnemius recession". Journal of Biomechanics. 37 (9): 1321–7. doi:10.1016/j.jbiomech.2003.12.035. PMID 15275839. 17. ^ "Toe Walking". orthoseek.com. Archived from the original on 2007-09-19. Retrieved 2007-06-07. 18. ^ "Toe Walking". mastersofpediatrics.com. Archived from the original on 2007-06-08. Retrieved 2007-06-24. ## External links[edit] Classification D * ICD-10: R26.8 * ICD-9-CM: 781.2 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Toe walking	c0427144	8,465	wikipedia	https://en.wikipedia.org/wiki/Toe_walking	2021-01-18T18:52:31	{"wikidata": ["Q1097541"]}
Holoprosencephaly is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. There are 4 types of holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disability and pituitary gland problems. Holoprosencephaly can be caused by mutations in any of at least 14 different genes; chromosome abnormalities; or agents that can cause birth defects (teratogens). It may also be a feature of several unique genetic syndromes. In many cases, the exact cause is unknown. Life expectancy for people with this condition varies, and treatment depends on the symptoms and severity in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Holoprosencephaly	c0079541	8,466	gard	https://rarediseases.info.nih.gov/diseases/6665/holoprosencephaly	2021-01-18T18:00:00	{"mesh": ["D016142"], "umls": ["C0079541"], "orphanet": ["2162"], "synonyms": ["HPE"]}
Ewing's sarcoma Other namesEwing sarcoma, peripheral primitive neuroectodermal tumor, Askin tumor, and Ewing sarcoma family of tumors[1] Micrograph of metastatic Ewing sarcoma (right of image) in normal lung (left of image). PAS stain. Pronunciation * /ˈjuːɪŋ/ YOO-ing SpecialtyOncology SymptomsSwell and pain near the tumor[1] ComplicationsPleural effusion, paraplegia[2] Usual onset10 to 20 years old[3][2] CausesUnknown[2] Diagnostic methodTissue biopsy[1] Differential diagnosisOsteosarcoma, neuroblastoma, osteomyelitis, eosinophilic granuloma[2] TreatmentChemotherapy, radiation therapy, surgery, stem cell transplant[1] PrognosisFive year survival ~ 70%[3] Frequency1 per million people (US)[3] Ewing sarcoma is a type of cancer that may be a bone sarcoma or a soft-tissue sarcoma.[1] Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture.[1] The most common areas where it begins are the legs, pelvis, and chest wall.[3] In about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis.[3] Complications may include a pleural effusion or paraplegia.[2] The cause of Ewing sarcoma is unknown.[2] Most cases appear to occur randomly.[2] It is sometimes grouped together with primitive neuroectodermal tumors, in a category known as the Ewing family of tumors.[2] The underlying mechanism often involves a genetic change known as a reciprocal translocation.[2] Diagnosis is based on biopsy of the tumor.[1] Treatment often includes chemotherapy, radiation therapy, surgery, and stem cell transplant.[1] Targeted therapy and immunotherapy are being studied.[1] Five year survival is about 70%.[3] A number of factors, however, affect this estimate.[3] James Ewing in 1920 established that the tumor is a distinct type of cancer.[4][5] It affects about one in a million people per year in the United States.[3] Ewing sarcoma occurs most often in teenagers and young adults and represents 2% of childhood cancers.[1][2] Caucasians are affected more often than African Americans or Asians.[3] Males are affected more often than females.[3] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 3.1 Medical imaging * 3.2 Differential diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] Distribution of Ewing sarcoma: The most frequent locations are the large long bones and the pelvis. Ewing sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. It can occur anywhere in the body but most commonly in the pelvis and proximal long tubular bones, especially around the growth plates. The diaphyses of the femur are the most common sites, followed by the tibia and the humerus. Thirty percent are overtly metastatic at presentation. People usually experience extreme bone pain. Rarely, it can develop in the vagina.[6][7] Signs and symptoms include intermittent fevers, anemia, leukocytosis, increased sedimentation rate, and other symptoms of inflammatory systemic illness.[8] According to the Bone Cancer Research Trust (BCRT), the most common symptoms are localized pain, swelling, and sporadic bone pain with variable intensity. The swelling is most likely to be visible if the sarcoma is located on a bone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may not be visible.[9] ## Genetics[edit] Genetic exchange between chromosomes can cause cells to become cancerous. Most cases of Ewing sarcoma (85%) are the result of a translocation between chromosomes 11 and 22, which fuses the EWSR1 gene of chromosome 22 to the FLI1 gene of chromosome 11.[8] A genome-wide association study (GWAS) identified three susceptibility loci located on chromosomes 1, 10 and 15.[10] A continuative study discovered that the Ewing sarcoma susceptibility gene EGR2, which is located within the chromosome 10 susceptibility locus, is regulated by the EWSR1-FLI1 fusion oncogene via a GGAA-microsatellite.[11][12] EWS/FLI functions as the master regulator.[13] Other translocations are at t(21;22)[14] and t(7;22).[15] Ewing sarcoma cells are positive for CD99 and MIC2,[8] and negative for CD45.[16] ## Diagnosis[edit] Micrograph of a metastatic Ewing sarcoma with the characteristic cytoplasmic clearing on H&E staining, which was showing to be PAS positive The definitive diagnosis is based on histomorphologic findings, immunohistochemistry and molecular pathology. Ewing sarcoma is a small-blue-round-cell tumor that typically has a clear cytoplasm on H&E staining, due to glycogen. The presence of the glycogen can be demonstrated with positive PAS staining and negative PAS diastase staining. The characteristic immunostain is CD99, which diffusely marks the cell membrane. However, as CD99 is not specific for Ewing sarcoma, several auxiliary immunohistochemical markers can be employed to support the histological diagnosis.[17] Morphologic and immunohistochemical findings are corroborated with an associated chromosomal translocation, of which several occur. The most common translocation, present in about 90% of Ewing sarcoma cases, is t(11;22)(q24;q12),[18][19] which generates an aberrant transcription factor through fusion of the EWSR1 gene with the FLI1 gene.[20] The pathologic differential diagnosis is the grouping of small-blue-round-cell tumors, which includes lymphoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor, among others.[citation needed] ### Medical imaging[edit] This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (February 2019) (Learn how and when to remove this template message) X-ray of a child with Ewing sarcoma of the tibia On conventional radiographs, the most common osseous presentation is a permeative lytic lesion with periosteal reaction. The classic description of lamellated or "onion-skin" type periosteal reaction is often associated with this lesion. Plain films add valuable information in the initial evaluation or screening. The wide zone of transition (e.g. permeative) is the most useful plain film characteristic in differentiation of benign versus aggressive or malignant lytic lesions. Magnetic resonance imaging slice showing Ewing sarcoma of the left hip (white area shown right) Magnetic resonance imaging (MRI) should be routinely used in the work-up of malignant tumors. It will show the full bony and soft tissue extent and relate the tumor to other nearby anatomic structures (e.g. vessels). Gadolinium contrast is not necessary as it does not give additional information over noncontrast studies, though some current researchers argue that dynamic, contrast-enhanced MRI may help determine the amount of necrosis within the tumor, thus help in determining response to treatment prior to surgery. Computed axial tomography (CT) can also be used to define the extraosseous extent of the tumor, especially in the skull, spine, ribs, and pelvis. Both CT and MRI can be used to follow response to radiation and/or chemotherapy. Bone scintigraphy can also be used to follow tumor response to therapy. In the group of malignant small round cell tumors that includes Ewing sarcoma, bone lymphoma, and small cell osteosarcoma, the cortex may appear almost normal radiographically, while permeative growth occurs throughout the Haversian channels. These tumors may be accompanied by a large soft-tissue mass while almost no bone destruction is visible. The radiographs frequently do not shown any signs of cortical destruction. Radiographically, Ewing sarcoma presents as "moth-eaten" destructive radiolucencies of the medulla and erosion of the cortex with expansion. ### Differential diagnosis[edit] Other entities with similar clinical presentations include osteomyelitis, osteosarcoma (especially telangiectatic osteosarcoma), and eosinophilic granuloma. Soft-tissue neoplasms such as pleomorphic undifferentiated sarcoma (malignant fibrous histiocytoma) that erode into adjacent bone may also have a similar appearance. Accumulating evidence suggests that EWSR1-NFATc2 positive sarcomas, which were previously considered to possibly belong to the Ewing family of tumors, differ from Ewing sarcoma in their genetics, transcriptomes, and epigentic and epidemiological profiles, indicating that they might represent a distinct tumor entity.[21][22][23][24] ## Treatment[edit] Almost all people receive multidrug chemotherapy (most often vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide),[25] as well as local disease control with surgery and/or radiation.[26] An aggressive approach is necessary because almost all people with apparently localized disease at the time of diagnosis actually have asymptomatic metastatic disease.[citation needed] The surgical resection may involve limb salvage or amputation. Complete excision at the time of biopsy may be performed if malignancy is confirmed at the time it is examined.[citation needed] Treatment lengths vary depending on location and stage of the disease at diagnosis. Radical chemotherapy may be as short as six treatments at three-week cycles, but most people undergo chemotherapy for 6–12 months and radiation therapy for 5–8 weeks.[citation needed] Radiotherapy has been used for localized disease. The tumor has a unique property of being highly sensitive to radiation, sometimes acknowledged by the phrase "melting like snow", but the main drawback is that it recurs dramatically after some time.[citation needed] Antisense oligodeoxynucleotides have been proposed as possible treatment by down-regulating the expression of the oncogenic fusion protein associated with the development of Ewing sarcoma resulting from the EWS-ETS gene translocation.[27][28] In addition, the synthetic retinoid derivative fenretinide (4-hydroxy(phenyl)retinamide) has been reported to induce high levels of cell death in Ewing sarcoma cell lines in vitro and to delay growth of xenografts in in vivo mouse models.[29][30] In most pediatric cancers including sarcoma, proton beam radiation (also known as proton therapy) delivers an equally effective dose to the tumor with less damage to the surrounding normal tissue compared to photon radiation.[31] ## Prognosis[edit] Staging attempts to distinguish people with localized from those with metastatic disease.[32] Most often, metastases locate to the lungs, bone and/or bone marrow. Less common sites include the central nervous system and lymph nodes.[citation needed] Five-year survival for localized disease is greater than 70% after therapy.[33] Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%.[34] However, some sources state it is 25–30%.[35] Retrospective research showed that two chemokine receptors, CXCR4 and CXCR7, can be used as molecular prognosis factors. People who express low levels of both chemokine receptors have the highest odds of long-term survival with >90% survival at five years post-diagnosis versus <30% survival at five years for patients with very high expression levels of both receptors.[36] A recent study also suggested a role for SOX2 as an independent prognostic biomarker that can be used to identify patients at high risk for tumor relapse.[37] ## Epidemiology[edit] Ewing sarcomas represent 16% of primary bone sarcomas.[8] In the United States, they are most common in the second decade of life,[8] with a rate of 0.3 cases per million in children under 3 years of age, and as high as 4.6 cases per million in adolescents aged 15–19 years. Internationally, the annual incidence rate averages less than 2 cases per million children.[38] In the United Kingdom, an average of six children per year are diagnosed, mainly males in early stages of puberty. Due to the prevalence of diagnosis during teenage years, a link may exist between the onset of puberty and the early stages of this disease, although no research confirms this hypothesis.[citation needed] A grouping of three unrelated teenagers in Wake Forest, North Carolina, have been diagnosed with Ewing sarcoma. All three children were diagnosed in 2011 and all attended the same temporary classroom together while the school underwent renovation. A fourth teenager living nearby was diagnosed in 2009. The odds of this grouping are considered significant.[39] Ewing sarcoma occurs about 10- to 20-fold more commonly in people of European descent compared to people of African descent.[40] Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses.[41] ## References[edit] 1. ^ a b c d e f g h i j "Ewing Sarcoma Treatment". National Cancer Institute. 25 January 2019. Retrieved 3 February 2019. 2. ^ a b c d e f g h i j "Ewing Sarcoma". NORD (National Organization for Rare Disorders). 2013. Retrieved 4 February 2019. 3. ^ a b c d e f g h i j "Ewing Sarcoma Treatment". National Cancer Institute. 31 January 2019. Retrieved 4 February 2019. 4. ^ "Ewing's sarcoma". Whonamedit. Retrieved 4 February 2019. 5. ^ Ewing J (September 2006). "The Classic: Diffuse endothelioma of bone. Proceedings of the New York Pathological Society. 1921;12:17". Clinical Orthopaedics and Related Research. 450: 25–7. doi:10.1097/01.blo.0000229311.36007.c7. PMID 16951641. 6. ^ "Tumours of the Vagina; Chapter Six" (PDF). International Agency for Research on Cancer, World Health Organization. pp. 291–311. Archived from the original (PDF) on 2015-09-08. Retrieved 2018-03-14. 7. ^ "Vulva and Vagina tumors: an overview". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Archived from the original on 2018-02-22. Retrieved 2018-03-14. 8. ^ a b c d e Goldman L, Cecil RL, Schafer AI (2012). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 1326. ISBN 978-1-4377-2788-3. OCLC 909785616. 9. ^ "Symptoms of Ewing's Sarcoma". Bone Cancer Research Trust. October 2010. Archived from the original on 2013-01-30. Retrieved 2012-11-05. 10. ^ Postel-Vinay S, Véron AS, Tirode F, Pierron G, Reynaud S, Kovar H, et al. (February 2012). "Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma". Nature Genetics. 44 (3): 323–7. doi:10.1038/ng.1085. PMID 22327514. S2CID 205343425. 11. ^ Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, et al. (September 2015). "Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite". Nature Genetics. 47 (9): 1073–8. doi:10.1038/ng.3363. PMC 4591073. PMID 26214589. 12. ^ Gomez NC, Davis IJ (September 2015). "Linking germline and somatic variation in Ewing sarcoma". Nature Genetics. 47 (9): 964–5. doi:10.1038/ng.3387. PMID 26313223. S2CID 5454861. 13. ^ Owen LA, Kowalewski AA, Lessnick SL (April 2008). "EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewing sarcoma". PLOS ONE. 3 (4): e1965. Bibcode:2008PLoSO...3.1965O. doi:10.1371/journal.pone.0001965. PMC 2291578. PMID 18414662. 14. ^ Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT (February 1994). "A second Ewing sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG". Nature Genetics. 6 (2): 146–51. doi:10.1038/ng0294-146. PMID 8162068. S2CID 19747268. 15. ^ Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN (March 1995). "A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1". Oncogene. 10 (6): 1229–34. PMID 7700648. 16. ^ Bernstein M, Kovar H, Paulussen M, Randall RL, Schuck A, Teot LA, Juergens H (May 2006). "Ewing's sarcoma family of tumors: current management". The Oncologist. 11 (5): 503–19. doi:10.1634/theoncologist.11-5-503. PMID 16720851. 17. ^ McCuiston A, Bishop JA (March 2018). "Usefulness of NKX2.2 Immunohistochemistry for Distinguishing Ewing Sarcoma from Other Sinonasal Small Round Blue Cell Tumors". Head and Neck Pathology. 12 (1): 89–94. doi:10.1007/s12105-017-0830-1. PMC 5873485. PMID 28616785. 18. ^ "Soft tissue tumors: Ewing's tumors/Primitive neurectodermal tumors (PNET)". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Archived from the original on 29 October 2012. Retrieved 5 November 2012. 19. ^ Turc-Carel C, Aurias A, Mugneret F, Lizard S, Sidaner I, Volk C, Thiery JP, Olschwang S, Philip I, Berger MP (June 1988). "Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12)". Cancer Genetics and Cytogenetics. 32 (2): 229–38. doi:10.1016/0165-4608(88)90285-3. PMID 3163261. 20. ^ Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G (September 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature. 359 (6391): 162–5. Bibcode:1992Natur.359..162D. doi:10.1038/359162a0. PMID 1522903. S2CID 4331584. 21. ^ Grünewald TG, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E, Kovar H, et al. (July 2018). "Ewing sarcoma". Nature Reviews. Disease Primers. 4 (1): 5. doi:10.1038/s41572-018-0003-x. PMID 29977059. S2CID 49571421. 22. ^ Koelsche C, Hartmann W, Schrimpf D, Stichel D, Jabar S, Ranft A, et al. (August 2018). "Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information". Modern Pathology. 31 (8): 1246–1256. doi:10.1038/s41379-018-0045-3. PMID 29572501. 23. ^ Baldauf MC, Gerke JS, Orth MF, Dallmayer M, Baumhoer D, de Alava E, et al. (June 2018). "Are EWSR1-NFATc2-positive sarcomas really Ewing sarcomas?". Modern Pathology. 31 (6): 997–999. doi:10.1038/s41379-018-0009-7. PMID 29895896. 24. ^ Watson S, Perrin V, Guillemot D, Reynaud S, Coindre JM, Karanian M, et al. (May 2018). "Transcriptomic definition of molecular subgroups of small round cell sarcomas". The Journal of Pathology. 245 (1): 29–40. doi:10.1002/path.5053. PMID 29431183. 25. ^ Lahl M, Fisher VL, Laschinger K (February 2008). "Ewing's sarcoma family of tumors: an overview from diagnosis to survivorship". Clinical Journal of Oncology Nursing. 12 (1): 89–97. doi:10.1188/08.CJON.89-97. PMID 18258578. S2CID 10512706. 26. ^ Randall L, Calvert G, Spraker H, Lessnick S (2005). "Ewing's Sarcoma Family of Tumours (ESFT)". Liddy Shriver Sarcoma Initiative. Archived from the original on 2009-02-08. Retrieved 2009-04-15. 27. ^ Asami S, Chin M, Shichino H, Yoshida Y, Nemoto N, Mugishima H, Suzuki T (March 2008). "Treatment of Ewing's sarcoma using an antisense oligodeoxynucleotide to regulate the cell cycle". Biological & Pharmaceutical Bulletin. 31 (3): 391–4. doi:10.1248/bpb.31.391. PMID 18310898. 28. ^ Mateo-Lozano S, Gokhale PC, Soldatenkov VA, Dritschilo A, Tirado OM, Notario V (November 2006). "Combined transcriptional and translational targeting of EWS/FLI-1 in Ewing's sarcoma". Clinical Cancer Research. 12 (22): 6781–90. doi:10.1158/1078-0432.CCR-06-0609. PMID 17121899. S2CID 1404471. 29. ^ Myatt SS, Redfern CP, Burchill SA (April 2005). "p38MAPK-Dependent sensitivity of Ewing's sarcoma family of tumors to fenretinide-induced cell death". Clinical Cancer Research. 11 (8): 3136–48. doi:10.1158/1078-0432.CCR-04-2050. PMID 15837770. 30. ^ Myatt SS, Burchill SA (February 2008). "The sensitivity of the Ewing's sarcoma family of tumours to fenretinide-induced cell death is increased by EWS-Fli1-dependent modulation of p38(MAPK) activity". Oncogene. 27 (7): 985–96. doi:10.1038/sj.onc.1210705. PMID 17700534. 31. ^ Ladra MM, Yock TI (January 2014). "Proton radiotherapy for pediatric sarcoma". Cancers. 6 (1): 112–27. doi:10.3390/cancers6010112. PMC 3980591. PMID 24424260. 32. ^ McTiernan AM, Cassoni AM, Driver D, Michelagnoli MP, Kilby AM, Whelan JS (2006). "Improving Outcomes After Relapse in Ewing's Sarcoma: Analysis of 114 Patients From a Single Institution". Sarcoma. 2006: 1–8. doi:10.1155/SRCM/2006/83548. PMC 1698143. PMID 17496997. 33. ^ "How Is the Ewing Family of Tumors Staged?". American Cancer Society. 19 June 2006. Archived from the original on 2008-04-22. 34. ^ Iwamoto Y (February 2007). "Diagnosis and treatment of Ewing's sarcoma". Japanese Journal of Clinical Oncology. 37 (2): 79–89. doi:10.1093/jjco/hyl142. PMID 17272319. 35. ^ Thacker MM, Temple HT, Scully SP (April 2005). "Current treatment for Ewing's sarcoma". Expert Review of Anticancer Therapy. 5 (2): 319–31. doi:10.1586/14737140.5.2.319. PMID 15877528. S2CID 26773908. 36. ^ Bennani-Baiti IM, Cooper A, Lawlor ER, Kauer M, Ban J, Aryee DN, Kovar H (July 2010). "Intercohort gene expression co-analysis reveals chemokine receptors as prognostic indicators in Ewing's sarcoma". Clinical Cancer Research. 16 (14): 3769–78. doi:10.1158/1078-0432.CCR-10-0558. PMC 2905506. PMID 20525755. 37. ^ Sannino G, Marchetto A, Ranft A, Jabar S, Zacherl C, Alba-Rubio R, Stein S, Wehweck FS, Kiran MM, Hoelting TL, Musa J (2018-12-17). "SOX2 expression identifies Ewing sarcoma patients with high risk for tumor relapse and poor survival". bioRxiv: 498253. doi:10.1101/498253. 38. ^ Ewing Sarcoma Imaging at eMedicine 39. ^ "Three Wake students battle rare cancer: Cluster or coincidence?". WRAL.com. 29 April 2013. Archived from the original on 2013-05-01. Retrieved 2013-04-30. 40. ^ Worch J, Cyrus J, Goldsby R, Matthay KK, Neuhaus J, DuBois SG (March 2011). "Racial differences in the incidence of mesenchymal tumors associated with EWSR1 translocation". Cancer Epidemiology, Biomarkers & Prevention. 20 (3): 449–53. doi:10.1158/1055-9965.EPI-10-1170. PMC 3051020. PMID 21212061. 41. ^ Twardziok M, Kleinsimon S, Rolff J, Jäger S, Eggert A, Seifert G, Delebinski CI (2016). "Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma". PLOS ONE. 11 (9): e0159749. Bibcode:2016PLoSO..1159749T. doi:10.1371/journal.pone.0159749. PMC 5010293. PMID 27589063. ## Further reading[edit] * van der Woude HJ, Smithuis R. "Bone Tumors - Differential diagnosis". Radiology department of the Onze Lieve Vrouwe Gasthuis, Amsterdam and the Rijnland hospital. Leiderdorp, the Netherlands. * "Ewing family of tumors". NCI Dictionary of Cancer Terms. 2011-02-02. ## External links[edit] Classification D * ICD-10: C41.9 * ICD-9-CM: 170.9 * ICD-O: M9260/3 * OMIM: 612219 * MeSH: D012512 * DiseasesDB: 4604 External resources * MedlinePlus: 001302 * eMedicine: ped/2589 * NCI: Ewing's sarcoma * v * t * e Tumours of bone and cartilage Diaphysis * Multiple myeloma * Epithelia * Adamantinoma * Primitive neuroectodermal tumor * Ewing family * Ewing's sarcoma Metaphysis Osteoblast * Osteoid osteoma * Osteoblastoma * Osteoma/osteosarcoma Chondroblast * Chondroma/ecchondroma/enchondroma * Enchondromatosis * Extraskeletal chondroma * Chondrosarcoma * Mesenchymal chondrosarcoma * Myxoid chondrosarcoma * Osteochondroma * Osteochondromatosis * Chondromyxoid fibroma Fibrous * Ossifying fibroma * Fibrosarcoma Epiphysis Chondroblast * Chondroblastoma Myeloid * Giant-cell tumor of bone Other Notochord * Chordoma * 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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Ewing's sarcoma	c0553580	8,467	wikipedia	https://en.wikipedia.org/wiki/Ewing%27s_sarcoma	2021-01-18T18:56:49	{"gard": ["6390"], "mesh": ["D012512"], "umls": ["C1334408", "C0553580", "C0863029", "C0684337", "C0796547", "C0877849"], "icd-9": ["170.9"], "icd-10": ["C41.9"], "orphanet": ["319"], "wikidata": ["Q1138580"]}
Opsoclonus-myoclonus syndrome (OMS) is a rare disorder that affects the nervous system. Symptoms include rapid, multi-directional eye movements (opsoclonus), quick, involuntary muscle jerks (myoclonus), uncoordinated movement (ataxia), irritability, and sleep disturbance. The onset of OMS is usually abrupt and often severe. The disease may become chronic. OMS typically occurs in association with tumors (neuroblastomas), or following a viral or bacterial infection. Treatment may include corticosteroids or ACTH (adrenocorticotropic hormone). When there is a tumor present, treatment may include chemotherapy, surgery, and/or radiation. In some cases, when the underlying cause of OMS is treated, symptoms improve. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Opsoclonus-myoclonus syndrome	c0393626	8,468	gard	https://rarediseases.info.nih.gov/diseases/10009/opsoclonus-myoclonus-syndrome	2021-01-18T17:58:35	{"mesh": ["D053578"], "orphanet": ["1183"], "synonyms": ["Opsoclonus myoclonus syndrome", "OMS", "Kinsbourne syndrome", "Ataxo-opso-myoclonus syndrome", "OMA syndrome", "Opsoclonus-myoclonus-ataxia syndrome", "Dancing eye-dancing feet syndrome", "Dancing eye syndrome", "POMA syndrome", "Paraneoplastic opsoclonus-myoclonus", "Paraneoplastic opsoclonus-myoclonus-ataxia syndrome"]}
Invasive urethelia carcinoma Immunoperoxidase staining of ZIP8 in high grade urothelial carcinoma.A &B. Noninvasive urothelial carcinoma showing weak staining of ZIP8 (+). Asterisks () indicate stromal tissue which is negative for ZIP8. C. Noninvasive urothelial carcinoma with focal moderate staining of ZIP8 (+). Asterisks () indicate stromal tissue which is negative for ZIP8. D. Invasive urothelial carcinoma with negative staining of ZIP8 (−). Few smooth muscle fibers between the invasive tumor nests are weakly positive for ZIP8 (). E. Invasive urothelial carcinoma with focal weak staining of ZIP8 (+). Asterisks () indicate stromal tissue which is negative for ZIP8. F. Invasive urothelial carcinoma with weak staining of ZIP8 (+). A few spindled shaped stromal cells are also weakly positive for ZIP8 (). G. Anaplastic urothelial carcinoma showing moderate staining for ZIP8 (+). Asterisks () indicate stromal tissue which is negative for ZIP8. H. Invasive urothelial carcinoma with moderate to strong staining of ZIP8 (). A few spindled shaped stromal cells are weakly positive for ZIP8 (). I. Poorly differentiated urothelial carcinoma with strong staining for ZIP8 (+). Asterisks () indicate stromal tissue which is negative for ZIP8. SpecialtyOncology Invasive urothelial carcinoma is a type of transitional cell carcinoma. It is a type of cancer that develops in the urinary system: the kidney, urinary bladder, and accessory organs. Transitional cell carcinoma is the most common type of bladder cancer and cancer of the ureter, urethra, renal pelvis, the ureters, the bladder, and parts of the urethra and urachus.[1][2] It originates from tissue lining the inner surface of these hollow organs - transitional epithelium.[3][4] The invading tumors can extend from the kidney collecting system to the bladder.[5] Carcinoma (from the Greek karkinos, or "crab", and -oma, "growth") is a type of cancer.[6] A carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during embryogenesis. ## Contents 1 Symptoms * 2 Prognosis and treatment * 3 See also * 4 References * 4.1 Bibliography * 5 External links ## Symptoms[edit] Symptoms vary between individuals and can be dependent upon the stage of growth of the carcinoma. Presence of the carcinoma can lead to be asymptomatic blood in the urine (hematuria), Hematuria can be visible or detected microscopically. Visible hematuria is when urine appears red or brown and can be seen with the naked eye. Other symptoms are not specific. Other inflammatory conditions that affect the bladder and kidney can create similar symptoms. Early detection facilitates curing the disease. Other symptoms can involve: * pain or burning on urination * the sensation of not being able to completely empty the bladder * the sensation of needing to urinate more often or more frequently than normal These symptoms are general and also indicate less serious problems.[7] ## Prognosis and treatment[edit] Prognosis is highly variable and dependent upon a multitude of factors. Reoccurrence does occur.[8] Treatment is determined on a case-by-case basis.[9][10] ## See also[edit] Transitional epithelium ## References[edit] 1. ^ Andersson, 2011: p. 134 2. ^ Amornpan, Ajjimaporn; Botsford, Tom; Garrett, Scott H; Sens, Mary Ann; Zhou, Xu Dong; Dunlevy, Jane R; Sens, Donald A; Somji, Seema (2012-07-04). "ZIP8 expression in human proximal tubule cells, human urothelial cells transformed by Cd+2 and As+3 and in specimens of normal human urothelium and urothelial cancer". Cancer Cell Int. 12 (16): 16. doi:10.1186/1475-2867-12-16. PMC 3390278. PMID 22550998. 3. ^ "transitional cell carcinoma" at Dorland's Medical Dictionary 4. ^ "Definition of Carcinoma". Archived from the original on 2012-10-10. Retrieved 2017-06-12. 5. ^ Selvaraj V, Govindarajan P, Deepak M, Sivaraj M. "The creeping tumor:" An unusual presentation of upper urinary tract malignancy. Indian J Urol 2014;30:454-5. 6. ^ Lemoine, Nigel Kirkham, Nicholas R. (2001). Progress in pathology. London: Greenwich Medical Media. p. 52. ISBN 9781841100500. 7. ^ "Bladder Cancer: SYMPTOMS OF BLADDER CANCER". Johns Hopkins University. Retrieved 2015-03-04. 8. ^ May M, Brookman-Amissah S, Roigas J, et al. (March 2009). "Prognostic Accuracy of Individual Uropathologists in Noninvasive Urinary Bladder Carcinoma: A Multicentre Study Comparing the 1973 and 2004 World Health Organisation Classifications". Eur. Urol. 57 (5): 850–8. doi:10.1016/j.eururo.2009.03.052. PMID 19346063. 9. ^ Babjuk, M.; Oosterlinck, W.; Sylveste, R.; Kaasinen, E.; Böhle, A.; Palou-Redorta, J.; Rouprêt, M. (July–August 2012). "EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update". Actas Urológicas Españolas (English Edition). 36 (7): 389–402. doi:10.1016/j.acuroe.2011.12.007. PMID 22386115. 10. ^ "Bladder cancer treatment; invasive cancer". Retrieved 2015-03-04. ### Bibliography[edit] * Andersson, Karl-Erik (2011). Urinary Tract. Springer. ISBN 978-3-642-16498-9. ## External links[edit] Classification D * Urothelium at the US National Library of Medicine Medical Subject Headings (MeSH) * v * t * e Epithelial tissue Cells * Squamous * Cuboidal * Columnar Types * Simple squamous epithelium * Endothelium * Mesothelium * Simple cuboidal epithelium * Simple columnar epithelium * Pseudostratified columnar epithelium * Respiratory epithelium * Stratified squamous epithelium * Stratified cuboidal epithelium * Stratified columnar epithelium * Transitional epithelium * Urothelium Glands Types Mechanism * Merocrine * Eccrine * Apocrine * Holocrine * Sebaceous * Meibomian Shape * Tubular gland * Alveolar gland Secretion * Serous glands * Mucous glands Components * Myoepithelial cell * Serous demilune * Ducts * Intralobular * Striated * Intercalated * Acinus/Lobe * v * t * e Overview of tumors, cancer and oncology Conditions Benign tumors * Hyperplasia * Cyst * Pseudocyst * Hamartoma Malignant progression * Dysplasia * Carcinoma in situ * Cancer * Metastasis * Primary tumor * Sentinel lymph node Topography * Head and neck (oral, nasopharyngeal) * Digestive system * Respiratory system * Bone * Skin * Blood * Urogenital * Nervous system * Endocrine system Histology * Carcinoma * Sarcoma * Blastoma * Papilloma * Adenoma Other * Precancerous condition * Paraneoplastic syndrome Staging/grading * TNM * Ann Arbor * Prostate cancer staging * Gleason grading system * Dukes classification Carcinogenesis * Cancer cell * Carcinogen * Tumor suppressor genes/oncogenes * Clonally transmissible cancer * Oncovirus * Carcinogenic bacteria Misc. * Research * Index of oncology articles * History * Cancer pain * Cancer and nausea [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Invasive urothelial carcinoma	c1334281	8,469	wikipedia	https://en.wikipedia.org/wiki/Invasive_urothelial_carcinoma	2021-01-18T18:36:35	{"umls": ["C1334281"], "wikidata": ["Q25051685"]}
Tardive Dysmentia is a rarely used term introduced in a 1983 paper to describe "changes in affect, activation level, and interpersonal interaction",[1] and hypothesized to be caused by long-term exposure to neuroleptic drugs in the same way as the much better known syndrome of tardive dyskinesia. Several papers in the following years discussed the validity of the concept, and this small literature was reviewed in a 1993 publication by M. S. Myslobodsky,[2] who drew attention to the "possibility that the syndrome of dysmentia is composed of occasional excessive emotional reactivity, enhanced responsiveness to environmental stimuli, and indifference to or reduced awareness of the patient's abnormal involuntary movements",[2] but concluded that the pathophysiology is uncertain.[2] Since then, the term has fallen into disuse, receiving at most only passing mentions in the literature.[citation needed] ## References[edit] 1. ^ Wilson, I. C; Garbutt, J. C; Lanier, C. F; Moylan, J; Nelson, W; Prange, A. J (1983). "Is There a Tardive Dysmentia?". Schizophrenia Bulletin. 9 (2): 187–92. doi:10.1093/schbul/9.2.187. PMID 6135252. 2. ^ a b c Myslobodsky, M.S (1993). "Central Determinants of Attention and Mood Disorder in Tardive Dyskinesia ('Tardive Dysmentia')". Brain and Cognition. 23 (1): 88–101. doi:10.1006/brcg.1993.1047. PMID 8217124. ## Further reading[edit] * Lavania, Sagar; Praharaj, Samir Kumar; Bains, Hariender Singh; Kumar, Sudhir; Rathore, Dinesh Malkan Singh; Mohanty, Sandhya; Nayak, Madhu (2013). "Does Tardive Dysmentia Really Exist?". The Journal of Neuropsychiatry and Clinical Neurosciences. 25 (1): 58–62. doi:10.1176/appi.neuropsych.12020024. PMID 23487194. * Emsley, R; Niehaus, D.J.H; Oosthuizen, P.P; Koen, L; Chiliza, B; Fincham, D (2011). "Subjective awareness of tardive dyskinesia and insight in schizophrenia". European Psychiatry. 26 (5): 293–6. doi:10.1016/j.eurpsy.2009.12.006. PMID 20615668. * Breggin, Peter R (2017). "Neuroleptic (Antipsychotic) Drugs: An Epidemic of Tardive Dyskinesia and Related Brain Injuries Afflicting Tens of Millions". In Davies, James (ed.). The Sedated Society. pp. 123–61. doi:10.1007/978-3-319-44911-1_6. ISBN 978-3-319-44910-4. This neuroscience 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	Tardive dysmentia	None	8,470	wikipedia	https://en.wikipedia.org/wiki/Tardive_dysmentia	2021-01-18T18:32:50	{"wikidata": ["Q7685722"]}
Usher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). However, many people with retinitis pigmentosa retain some central vision throughout their lives. Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by the severity of hearing loss, the presence or absence of balance problems, and the age at which signs and symptoms appear. The types are further divided into subtypes based on their genetic cause. Most individuals with Usher syndrome type I are born with severe to profound hearing loss. Progressive vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also causes abnormalities of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation in space. As a result of the vestibular abnormalities, children with the condition have trouble with balance. They begin sitting independently and walking later than usual, and they may have difficulty riding a bicycle and playing certain sports. Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects the ability to hear high-frequency sounds. For example, it is difficult for affected individuals to hear high, soft speech sounds, such as those of the letters d and t. The degree of hearing loss varies within and among families with this condition, and it may become more severe over time. Unlike the other forms of Usher syndrome, type II is not associated with vestibular abnormalities that cause difficulties with balance. People with Usher syndrome type III experience hearing loss and vision loss beginning somewhat later in life. Unlike the other forms of Usher syndrome, type III is usually associated with normal hearing at birth. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. Some people with Usher syndrome type III develop vestibular abnormalities that cause problems with balance. ## Frequency Usher syndrome affects around 4 to 17 in 100,000 people. Types I and II are the most common forms of Usher syndrome in most countries. Certain genetic mutations resulting in type 1 Usher syndrome are more common among people of Ashkenazi (eastern and central European) Jewish or French Acadian heritage than in the general population. Type III represents only about 2 percent of all Usher syndrome cases overall. However, type III occurs more frequently in the Finnish population, where it accounts for about 40 percent of cases, and among people of Ashkenazi Jewish heritage. ## Causes Usher syndrome can be caused by mutations in several different genes. Mutations in at least six genes can cause Usher syndrome type I. The most common of these are MYO7A gene mutations, followed by mutations in the CDH23 gene. Usher syndrome type II can result from mutations in three genes; USH2A gene mutations account for most cases of type II. Usher syndrome type III is most often caused by mutations in the CLRN1 gene. The genes associated with Usher syndrome provide instructions for making proteins involved in normal hearing, balance, and vision. In the inner ear, these proteins are involved in the development and function of specialized cells called hair cells, which help to transmit sound and signals from the inner ear to the brain. In the retina, the proteins contribute to the maintenance of light-sensing cells called rod photoreceptors (which provide vision in low light) and cone photoreceptors (which provide color vision and vision in bright light). For some of the proteins related to Usher syndrome, their exact role in hearing, balance, and vision is unknown. Most of the gene mutations responsible for Usher syndrome lead to a loss of hair cells in the inner ear and a gradual loss of rods and cones in the retina. Degeneration of these sensory cells causes the hearing loss, balance problems, and vision loss that occur with Usher syndrome. In some people with Usher syndrome, the genetic cause of the condition has not been identified. Researchers suspect that several additional genes are probably associated with this disorder. ### Learn more about the genes associated with Usher syndrome * CDH23 * CLRN1 * MYO7A * USH2A Additional Information from NCBI Gene: * ADGRV1 * CIB2 * HARS1 * PCDH15 * USH1C * USH1G * WHRN ## Inheritance Pattern All of the types of Usher syndrome are inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have a mutation. The parents of an individual with Usher syndrome each carry one copy of the mutated gene, but they do not have any 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	Usher syndrome	c1848638	8,471	medlineplus	https://medlineplus.gov/genetics/condition/usher-syndrome/	2021-01-27T08:25:28	{"gard": ["7843"], "mesh": ["C564755"], "omim": ["276900", "276904", "601067", "602097", "602083", "606943", "612632", "276901", "605472", "611383", "276902", "614504", "614869", "614990"], "synonyms": []}
Anxiety disorder causing inability to speak under certain circumstances Selective mutism SpecialtyPsychiatry Selective mutism (SM) is an anxiety disorder in which a person normally cannot speak in specific situations, specific places, or to specific people if triggered. Selective mutism usually co-exists with social anxiety disorder.[1] People with selective mutism stay silent even when the consequences of their silence include shame, social ostracism, or punishment.[2] ## Contents * 1 Signs and symptoms * 1.1 Other symptoms * 2 Causes * 3 Treatment * 3.1 Self-modeling * 3.2 Mystery motivators * 3.3 Stimulus fading * 3.4 Desensitization * 3.5 Shaping * 3.6 Spacing * 3.7 Drug treatments * 4 History * 5 See also * 5.1 Related disorders * 6 Notes * 7 References * 8 External links ## Signs and symptoms[edit] This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2010) (Learn how and when to remove this template message) Children and adults with selective mutism are fully capable of speech and understanding language but are physically unable to speak in certain situations, though speech is expected of them.[3] The behaviour may be perceived as shyness or rudeness by others. A child with selective mutism may be completely silent at school for years but speak quite freely or even excessively at home. There is a hierarchical variation among people with this disorder: some people participate fully in activities and appear social but do not speak, others will speak only to peers but not to adults, others will speak to adults when asked questions requiring short answers but never to peers, and still others speak to no one and participate in few, if any, activities presented to them. In a severe form known as "progressive mutism", the disorder progresses until the person with this condition no longer speaks to anyone in any situation, even close family members. Selective mutism is by definition characterized by the following:[4] * Consistent failure to speak in specific social situations (in which there is an expectation for speaking, e.g., at school) despite speaking in other situations. * The disturbance interferes with educational or occupational achievement or with social communication. * The duration of the disturbance is at least 1 month (not limited to the first month of school). * The failure to speak is not due to a lack of knowledge of the spoken language required in the social situation. * The disturbance is not better accounted for by a communication disorder (e.g., childhood-onset fluency disorder) and does not occur exclusively in people with autism spectrum disorders or psychotic disorders such as schizophrenia. Selective mutism is strongly associated with other anxiety disorders, particularly social anxiety disorder. In fact, the majority of children diagnosed with selective mutism also have social anxiety disorder (100% of participants in two studies and 97% in another).[5][6][7] Some researchers therefore speculate that selective mutism may be an avoidance strategy used by a subgroup of children with social anxiety disorder to reduce their distress in social situations.[8][9] Particularly in young children, SM can sometimes be confused with an autism spectrum disorder, especially if the child acts particularly withdrawn around their diagnostician, which can lead to incorrect diagnosis and treatment. Although autistic people may also be selectively mute, they often display other behaviors—hand flapping, repetitive behaviors, social isolation even among family members (not always answering to name, for example)—that set them apart from a child with selective mutism. Some autistic people may be selectively mute due to anxiety in social situations that they do not fully understand. If mutism is entirely due to autism spectrum disorder, it cannot be diagnosed as selective mutism as stated in the last item on the list above. The former name elective mutism indicates a widespread misconception among psychologists that selective mute people choose to be silent in certain situations, while the truth is that they often wish to speak but are unable to do so. To reflect the involuntary nature of this disorder, the name was changed to selective mutism in 1994. The incidence of selective mutism is not certain. Due to the poor understanding of this condition by the general public, many cases are likely undiagnosed. Based on the number of reported cases, the figure is commonly estimated to be 1 in 1000, 0.1%.[10] However, a 2002 study in The Journal of the American Academy of Child and Adolescent Psychiatry estimated the incidence to be 0.71%.[11] ### Other symptoms[edit] Besides lack of speech, other common behaviors and characteristics displayed by selectively mute people, according to Dr. Elisa Shipon-Blum's findings, include:[12][13] * Shyness, social anxiety, fear of social embarrassment or social isolation and withdrawal * Difficulty maintaining eye contact * Blank expression and reluctance to smile or incessant smiling * Difficulty expressing feelings, even to family members * Tendency to worry more than most people of the same age * Sensitivity to noise and crowds ## Causes[edit] Selective mutism (SM) is an umbrella term for the condition of otherwise well-developed children who cannot speak or communicate under certain settings. The exact causes that affect each child may be different and yet unknown. There have been attempts to categorize, but there are no definitive answers yet due to the under-diagnosis and small/biased sample sizes. Many people are not diagnosed until late in childhood only because they do not speak at school and therefore fail to accomplish assignments requiring public speaking. Their involuntary silence makes the condition harder to understand or test. Parents often are unaware of the condition since the children may be functioning well at home. Teachers and pediatricians also sometimes mistake it for severe shyness or common stage fright. Most children with selective mutism are hypothesized to have an inherited predisposition to anxiety. They often have inhibited temperaments, which is hypothesized to be the result of over-excitability of the area of the brain called the amygdala.[14] This area receives indications of possible threats and sets off the fight-or-flight response. Behavioral inhibitions, or inhibited temperaments, encompass feelings of emotional distress and social withdrawals. In a 2016 study,[15] the relationship between behavioral inhibition and selective mutism was investigated. Children between the ages of three and 19 with lifetime selective mutism, social phobia, internalizing behavior, and healthy controls were assessed using the parent-rated Retrospective Infant Behavioral Inhibition (RIBI) questionnaire, consisting of 20 questions that addressed shyness and fear, as well as other subscales. The results indicated behavioral inhibition does indeed predispose selective mutism. Corresponding with the researchers’ hypothesis, children diagnosed with long-term selective mutism had a higher behavioral inhibition score as an infant. This is indicative of the positive correlation between behavioral inhibition and selective mutism. Given the very high overlap between social anxiety disorder and selective mutism (as high as 100% in some studies[5][6][7]), it is possible that social anxiety disorder causes selective mutism. Some children with selective mutism may have trouble processing sensory information. This could cause anxiety and a sense of being overwhelmed in unfamiliar situations, which may cause the child to "shut down" and not be able to speak (something that some autistic people also experience). Many children with selective mutism have some auditory processing difficulties. About 20–30% of children with SM have speech or language disorders that add stress to situations in which the child is expected to speak.[16] Despite the change of name from "elective" to "selective", a common misconception remains that a selectively mute child is defiant or stubborn. In fact, children with SM have a lower rate of oppositional behavior than their peers in a school setting.[17] Some previous studies on the subject of selective mutism have been dismissed as containing serious flaws in their design. According to a more recent systematic study it is believed that children who have selective mutism are not more likely than other children to have a history of early trauma or stressful life events.[18] Another recent study by Dummit et al., in 1997 did not find any evidence of trauma in their sample of children. Recent evidence has shown that trauma does not explain why most children with selective mutism develop the condition.[19] Many children who have selective mutism almost always speak confidently in some situations. Children who have experienced trauma however are known to suddenly stop speaking. ## Treatment[edit] Contrary to popular belief, people with selective mutism do not necessarily improve with age.[20] Effective treatment is necessary for a child to develop properly. Without treatment, selective mutism can contribute to chronic depression, further anxiety, and other social and emotional problems.[21][22] Consequently, treatment at an early age is important. If not addressed, selective mutism tends to be self-reinforcing. Others may eventually expect an afflicted child to not speak and therefore stop attempting to initiate verbal contact. Alternatively, they may pressure the child to talk, increasing their anxiety levels in situations where speech is expected. Due to these problems, a change of environment may be a viable consideration. However, changing school is worth considering only if the alternative environment is highly supportive, otherwise a whole new environment could also be a social shock for the individual or deprive them of any friends or support they have currently. Regardless of the cause, increasing awareness and ensuring an accommodating, supportive environment are the first steps towards effective treatment. Most often afflicted children do not have to change schools or classes and have no difficulty keeping up except on the communication and social front. Treatment in teenage or adult years can be more difficult because the afflicted individual has become accustomed to being mute. The exact treatment depends on the person's age, any comorbid mental illnesses, and a number of other factors. For instance, stimulus fading is typically used with younger children because older children and teenagers recognize the situation as an attempt to make them speak, and older people with this condition and people with depression are more likely to need medication.[23] Like other disabilities, adequate accommodations are needed for the afflicted to succeed at school, work, and in the home. Under the U.S. federal law and the Individuals with Disabilities Education Act (IDEA), those with the disorder qualify for services based upon the fact that they have an impairment that hinders their ability to speak, thus disrupting their lives. This assistance is typically documented in the form of an Individual Educational Plan (IEP). Post-secondary accommodations are also available for people with disabilities. Under another law, Section 504 of the Rehabilitation Act of 1973, public school districts are required to provide a free, appropriate public education to every "qualified handicapped person" residing within their jurisdiction. If the child is found to have impairments that substantially limit a major life activity (in this case, learning), the education agency has to decide what related aids or services are required to provide equal access to the learning environment. ### Self-modeling[edit] An afflicted child is brought into the classroom or the environment where the child will not speak and is videotaped. First, the teacher or another adult prompts the child with questions that likely will not be answered. A parent, or someone the child feels comfortable speaking to, then replaces the prompter and asks the child the same questions, this time eliciting a verbal response. The two videos of the conversations are then edited together to show the child directly answering the questions posed by the teacher or other adult. This video is then shown to the child over a series of several weeks, and every time the child sees themself verbally answering the teacher/other adult, the tape is stopped and the child is given positive reinforcement. Such videos can also be shown to afflicted children's classmates to set an expectation in their peers that they can speak. The classmates thereby learn the sound of the child's voice and, albeit through editing, have the opportunity to see the child conversing with the teacher.[24][25] ### Mystery motivators[edit] Mystery motivation is often paired with self-modeling. An envelope is placed in the child's classroom in a visible place. On the envelope, the child's name is written along with a question mark. Inside is an item that the child's parent has determined to be desirable to the child. The child is told that when they ask for the envelope loudly enough for the teacher and others in the classroom to hear, the child will receive the mystery motivator. The class is also told of the expectation that the child ask for the envelope loudly enough that the class can hear.[24][25][26] ### Stimulus fading[edit] Afflicted subjects can be brought into a controlled environment with someone with whom they are at ease and can communicate. Gradually, another person is introduced into the situation. One example of stimulus fading is the sliding-in technique,[20] where a new person is slowly brought into the talking group. This can take a long time for the first one or two faded-in people but may become faster as the patient gets more comfortable with the technique. As an example, a child may be playing a board game with a family member in a classroom at school. Gradually, the teacher is brought in to play as well. When the child adjusts to the teacher's presence, then a peer is brought in to be a part of the game. Each person is only brought in if the child continues to engage verbally and positively.[24][25][26] ### Desensitization[edit] The subject communicates indirectly with a person to whom he or she is afraid to speak through such means as email, instant messaging (text, audio or video), online chat, voice or video recordings, and speaking or whispering to an intermediary in the presence of the target person. This can make the subject more comfortable with the idea of communicating with this person. ### Shaping[edit] The subject is slowly encouraged to speak. The subject is reinforced first for interacting nonverbally, then for saying certain sounds (such as the sound that each letter of the alphabet makes) rather than words, then for whispering, and finally saying a word or more.[27] ### Spacing[edit] Spacing is important to integrate, especially with self-modeling. Repeated and spaced out use of interventions is shown to be the most helpful long-term for learning. Viewing videotapes of self-modeling should be shown over a spaced out period of time of approximately 6 weeks.[24][25][26] ### Drug treatments[edit] Some practitioners believe there would be evidence indicating anxiolytics to be helpful in treating children and adults with selective mutism,[28] to decrease anxiety levels and thereby speed the process of therapy. Use of medication may end after nine to twelve months, once the person has learned skills to cope with anxiety and has become more comfortable in social situations.[29] Medication is more often used for older children, teenagers, and adults whose anxiety has led to depression and other problems. Medication, when used, should never be considered the entire treatment for a person with selective mutism. However, the reason why medication needs to be considered as a treatment at all is because selective mutism is still prevalent, despite psychosocial efforts. But while on medication, the person should still be in therapy to help them learn how to handle anxiety and prepare them for life without medication, as medication is typically a short-term solution.[30] Since selective mutism is categorized as an anxiety disorder, using similar medication to treat either makes sense. Antidepressants have been used in addition to self-modeling and mystery motivation to aid in the learning process.[further explanation needed][24][25] Furthermore, SSRIs in particular have been used to treat selective mutism. In a systematic review, ten studies were looked at which involved SSRI medications, and all reported medication was well tolerated.[31] In one of them, Black and Uhde (1994) conducted a double-blind, placebo-controlled study investigating the effects of fluoxetine. By parent report, fluoxetine-treated children showed significantly greater improvement than placebo-treated children. In another, Dummit III et al. (1996) administered fluoxetine to 21 children for nine weeks and found that 76% of the children had reduced or no symptoms by the end of the experiment.[32] This indicates that fluoxetine is an SSRI that is indeed helpful in treating selective mutism. ## History[edit] In 1877, German physician Adolph Kussmaul described children who were able to speak normally but often refused to as having a disorder he named aphasia voluntaria.[33] Although this is now an obsolete term, it was part of an early effort to describe the concept now called selective mutism. In 1980, a study by Torey Hayden identified what she called four "subtypes" of elective mutism (as it was called then), although this set of subtypes is not in current diagnostic use.[34] These subtypes are no longer recognized, though "speech phobia" is sometimes used to describe a selectively mute person who appears not to have any symptoms of social anxiety. The Diagnostic and Statistical Manual of Mental Disorders (DSM), first published in 1952, first included elective mutism in its third edition, published in 1980. Selective mutism was described as "a continuous refusal to speak in almost all social situations" despite normal ability to speak. While "excessive shyness" and other anxiety-related traits were listed as associated features, predisposing factors included "maternal overprotection", mental retardation, and trauma. Elective mutism in the third edition revised (DSM III-R) is described similarly to the third edition except for specifying that the disorder is not related to social phobia. In 1994, Sue Newman, co-founder of the Selective Mutism Foundation, requested that the fourth edition of the DSM reflect the name change from elective mutism to selective mutism and describe the disorder as a failure to speak. The relation to anxiety disorders was emphasized, particularly in the revised version (DSM IV-TR). As part of the reorganization of the DSM categories, the DSM-5 moved selective mutism from the section "Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence" to the section for anxiety disorders.[35] ## See also[edit] * June and Jennifer Gibbons, the Silent Twins ### Related disorders[edit] * Auditory processing disorders * Autism spectrum disorders * Sensory processing disorders * Social anxiety disorder ## Notes[edit] 1. ^ Viana, A. G.; Beidel, D. C.; Rabian, B. (2009). "Selective mutism: A review and integration of the last 15 years". Clinical Psychology Review. 29 (1): 57–67. doi:10.1016/j.cpr.2008.09.009. PMID 18986742. 2. ^ Brown, Harriet (12 April 2005). "The Child Who Would Not Speak a Word". The New York Times. 3. ^ Adelman, L. (2007). Don't Call me Shy. LangMarc Publishing. ISBN 978-1880292327. 4. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. p. 195. ISBN 978-0-89042-555-8. 5. ^ a b Dummit, E. S.; Klein, R. G.; Tancer, N. K.; Asche, B.; Martin, J.; Fairbanks, J. A. (1997). "Systematic Assessment of 50 Children with Selective Mutism". Journal of the American Academy of Child & Adolescent Psychiatry. 36 (5): 653–660. doi:10.1097/00004583-199705000-00016. PMID 9136500. 6. ^ a b Vecchio, J. L.; Kearney, C. A. (2005). "Selective Mutism in Children: Comparison to Youths with and Without Anxiety Disorders". Journal of Psychopathology and Behavioral Assessment. 27: 31–37. doi:10.1007/s10862-005-3263-1. 7. ^ a b Black, B.; Uhde, T. W. (1995). "Psychiatric Characteristics of Children with Selective Mutism: A Pilot Study". Journal of the American Academy of Child & Adolescent Psychiatry. 34 (7): 847–856. doi:10.1097/00004583-199507000-00007. PMID 7649954. 8. ^ Yeganeh, R.; Beidel, D. C.; Turner, S. M. (2006). "Selective mutism: More than social anxiety?". Depression and Anxiety. 23 (3): 117–123. doi:10.1002/da.20139. PMID 16421889. 9. ^ Sharp, W. G.; Sherman, C.; Gross, A. M. (2007). "Selective mutism and anxiety: A review of the current conceptualization of the disorder" (PDF). Journal of Anxiety Disorders. 21 (4): 568–579. doi:10.1016/j.janxdis.2006.07.002. PMID 16949249. 10. ^ Chvira, Denise A.; Shipon-Blum, Elisa; Hitchcock, Carla; Cohan, Sharon; Stein, Murray B. (2007). "Selective Mutism and Social Anxiety Disorder: All in the Family?". Journal of the American Academy of Child & Adolescent Psychiatry. 46 (11): 1464–472. doi:10.1097/chi.0b013e318149366a. PMID 18049296. 11. ^ Bergman, RL; Piacentini, J; McCracken, JT (2002). "Prevalence and description of selective mutism in a school-based sample". J Am Acad Child Adolesc Psychiatry. 41 (8): 938–46. doi:10.1097/00004583-200208000-00012. PMID 12162629. 12. ^ "Selective Mutism Symptoms". Theselectivemutism.info. Archived from the original on 2008-08-21. Retrieved 2013-02-21. 13. ^ Online Parent Support (2005-05-26). "Selective Mutism". Myoutofcontrolteen.com. Archived from the original on 2013-01-17. Retrieved 2013-02-21. 14. ^ "SMart Center: What is Selective Mutism?". Archived from the original on 4 May 2009. Retrieved 25 November 2017. 15. ^ Gensthaler, Angelika; Khalaf, Sally; Ligges, Marc; Kaess, Michael; Freitag, Christine M.; Schwenck, Chrstina (October 2016). "Selective mutism and temperament: the silence and behavioral inhibition to the unfamiliar". European Child & Adolescent Psychiatry. 25 (10): 1113–20. doi:10.1007/s00787-016-0835-4. PMID 26970743. 16. ^ "Cohan, Sharon L. Refining the Classification of Children with Selective Mutism: A Latent Profile Analysis" (PDF). Archived from the original (PDF) on 7 October 2011. Retrieved 25 November 2017. 17. ^ Sharp, William G. Selective Mutism and Anxiety: A Review of the Current Conceptualization of the Disorder 18. ^ Steinhausen and Juzi, 1996. 19. ^ Cunningham, Mcholm, Vanier, 2005. 20. ^ a b Johnson, Maggie; Alison Wintgens (2001-06-21). The Selective Mutism Resource Manual. Speechmark Publishing Ltd. ISBN 978-0-86388-280-7. 21. ^ Selective Mutism Group: Ask the Doc archives: When do I need to seek professional help for my child? and What about adults? What are the long-term effects of SM? 22. ^ Emma Ketteley (2008-04-08). "Virginia Tech University mass killer Cho Seung Hui diagnosed with Selective Mutism". BBC This World. 23. ^ Ricki Blau (2005-09-20). "The Older Child or Teen with Selective Mutism" (PDF). Selective Mutism Group. 24. ^ a b c d e Kehle, Thomas J.; Madaus, Melissa R.; Baratta, Victoria S.; Bray, Melissa A. (1998). "Augmented Self-Modeling as a Treatment for Children with Selective Mutism". Journal of School Psychology. 36 (3): 247–260. doi:10.1016/S0022-4405(98)00013-2. 25. ^ a b c d e Shriver, Mark D.; Segool, Natasha; Gortmaker, Valerie (2011). "Behavior Observations for Linking Assessment to Treatment for Selective Mutism". Education and Treatment of Children. 34 (3): 389–411. doi:10.1353/etc.2011.0023. 26. ^ a b c Anstendig, Karin (1998). "Selective Mutism: A Review of the Treatment Literature by Modality from 1980–1996". Psychotherapy. 35 (3): 381–391. doi:10.1037/h0087851. 27. ^ "Nothing found for Library Sm%20General%20Information What%20Is%20Selective%20Mutism Pdf" (PDF). www.selectivemutism.org. Retrieved 25 November 2017. 28. ^ "Treatment Of Selective Mutism". 29. ^ "Nothing found for Find Help Ask The Doc Archives Index_Html Question4 Meds". 30. ^ "Nothing found for Find Help Ask The Doc Archives Index_Html Question27 Meds". 31. ^ Manassis, Katharina; Oerbeck, Beate; Overgaard, Kristen Romvig (June 2016). "The use of medication in selective mutism: A systematic review". European Child & Adolescent Psychiatry. 25 (6): 571–8. doi:10.1007/s00787-015-0794-1. PMID 26560144. 32. ^ DUMMIT III, E STEVEN; KLEIN, RACHEL G.; ASCHE, BARBARA; MARTIN, JACQUELINE; TANCER, NANCY K. (May 1996). "Fluoxetine Treatment of Children with Selective Mutism: An Open Trial". Journal of the American Academy of Child & Adolescent Psychiatry. 35 (5): 615–621. doi:10.1097/00004583-199605000-00016. ISSN 0890-8567. 33. ^ Tots, Bright. "Selective mutism what is selective mutism childhood disorder". 34. ^ Torey Hayden. Classification of Elective Mutism 35. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 189. ISBN 978-0-89042-555-8. ## References[edit] * McHolm, Angela E., Cunningham, Charles E.,& Vanier, Melanie A. (2005). "Helping Your Child With Selective Mutism". New Harbinger Publications, Inc. * Dummit; et al. (1997). "Systematic assessment of fifty children with Selective Mutism". Journal of the American Academy of Child and Adolescent Psychiatry. 36 (5): 653–660. doi:10.1097/00004583-199705000-00016. PMID 9136500. * Steinhausen, H. Juzi, C. (1996) "Elective Mutism: An analysis of 100 Cases". Journal of the American Academy of child and Adolescent Psychiatry. 35. pp. 606–614. * Johnson, Maggie and Wintgens, Alison, (2016). "The Selective Mutism Resource Manual: 2nd Edition (A Speechmark Practical Sourcebook)". ## External links[edit] Classification D * ICD-10: F94.0 * ICD-9-CM: 309.83 313.23 * MeSH: D009155 * SNOMED CT: 71959007 External resources * eMedicine: ped/2660 * v * t * e Emotional and behavioral disorders Emotional/behavioral * ADHD * Conduct disorder * Oppositional defiant disorder * Emotional/behavioral disorder (EBD) * Separation anxiety * Social functioning * Selective mutism * RAD * DAD * Tic disorders * Tourette syndrome * Speech disorders * Stuttering * Cluttering * Stereotypic movement disorder * Elimination disorders * Enuresis * Encopresis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Selective mutism	c0236818	8,472	wikipedia	https://en.wikipedia.org/wiki/Selective_mutism	2021-01-18T19:08:22	{"mesh": ["D009155"], "umls": ["C0236818"], "icd-9": ["309.83", "313.23"], "icd-10": ["F94.0"], "wikidata": ["Q377493"]}
Moore et al. (1976) studied the family of an obese but otherwise healthy 12-year-old boy with respiratory failure and normal lung function. The respiratory failure seemed related to deficient ventilatory responses to hypoxia and hypercapnia. The latter in turn seemed to be familial because both parents and all 4 sibs showed reduced responsiveness to reduced oxygen and carbon dioxide excess. The magnitude of ventilatory responses to hypoxia and hypercapnia varies widely in the 'normal' population. Enga tribesmen of New Guinea (Beral and Read, 1971) and long-distance runners (Byrne-Quinn et al., 1971) show decreased responsiveness. Saunders et al. (1976) found a correlation between the hypercapnic ventilatory responses of championship swimmers and those of their sibs. Collins et al. (1978) studied ventilatory response to isocapnic hypoxia and hyperoxic hypercapnia in 12 pairs of identical twins and 12 pairs of nonidentical twins. A significant correlation could be found for response to isocapnic hypoxia in MZ twins only, but not for response to hypercapnia. Resp \- Normal lung function \- Deficient ventilatory responses to hypoxia and hypercapnia \- Respiratory failure 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	RESPIRATORY UNDERRESPONSIVENESS TO HYPOXIA AND HYPERCAPNIA	c1849430	8,473	omim	https://www.omim.org/entry/267480	2019-09-22T16:22:45	{"mesh": ["C564848"], "omim": ["267480"]}
Galactose-1-phosphate uridylyltransferase deficiency Other namesGalactosemia type 1, Classic galactosemia or GALT deficiency Galactose SpecialtyEndocrinology Galactose-1-phosphate uridylyltransferase deficiency (classic galactosemia), is the most common type of galactosemia, an inborn error of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridylyltransferase.[1] It is an autosomal recessive metabolic disorder that can cause liver disease and death if untreated. Treatment of galactosemia is most successful if initiated early and includes dietary restriction of lactose intake. Because early intervention is key, galactosemia is included in newborn screening programs in many areas. On initial screening, which often involves measuring the concentration of galactose in blood, classic galactosemia may be indistinguishable from other inborn errors of galactose metabolism, including galactokinase deficiency and galactose epimerase deficiency. Further analysis of metabolites and enzyme activities are needed to identify the specific metabolic error. ## Contents * 1 Symptoms * 2 Cause * 3 Genetics * 4 Diagnosis * 5 Treatment * 6 Animal models * 7 References * 8 External links ## Symptoms[edit] In undiagnosed and untreated children, the accumulation of precursor metabolites due to the deficient activity of galactose 1-phosphate uridylyltransferase (GALT) can lead to feeding problems, failure to thrive, liver damage, bleeding, and infections. The first presenting symptom in an infant is often prolonged jaundice. Without intervention in the form of galactose restriction, infants can develop hyperammonemia and sepsis, possibly leading to shock. The accumulation of galactitol and subsequent osmotic swelling can lead to cataracts which are similar to those seen in galactokinase deficiency.[2] Long-term consequences of continued galactose intake can include developmental delay, developmental verbal dyspraxia, and motor abnormalities. Galactosemic females frequently suffer from ovarian failure, regardless of treatment in the form of galactose restriction.[2] ## Cause[edit] Lactose is a disaccharide consisting of glucose and galactose. After the ingestion of lactose, most commonly from breast milk for an infant or cow milk and any milk from an animal, the enzyme lactase hydrolyzes the sugar into its monosaccharide constituents, glucose and galactose. In the first step of galactose metabolism, galactose is converted to galactose-1-phosphate (Gal-1-P) by the enzyme galactokinase. Gal-1-P is converted to uridine diphosphate galactose (UDP-galactose) by the enzyme galactose-1-phosphate uridylyltransferase, with UDP-glucose acting as the UDP donor. UDP-galactose can then be converted to lactose, by the enzyme lactose synthase or to UDP-glucose by UDP-galactose epimerase (GALE).[3] Normal metabolic pathway for galactose in humans. In classic galactosemia, galactose-1-phosphate uridylyltransferase activity is reduced or absent; leading to an accumulation of the precursors, galactose, galactitol, and Gal-1-P.[3] The elevation of precursors can be used to differentiate GALT deficiency from galactokinase deficiency, as Gal-1-P is typically not elevated in galactokinase deficiency. If the activity of the enzyme galactose 1-phosphate uridyltransferase is decreased, there is a buildup of the precursors in the pathway, mainly galactose 1-phosphate and galactose. ## Genetics[edit] Classic galactosemia has an autosomal recessive pattern of inheritance. All forms of galactosemia are inherited in an autosomal recessive manner, meaning individuals affected with classic galactosemia must have inherited a mutated copy of the GALT gene from both parents. Each child from two carrier parents would have a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting normal versions of the gene from each parent. There are several variants in the GALT gene, which have different levels of residual enzyme activity. A patient homozygous for the one of the severe mutations in the GALT gene (commonly referred to as G/G) will typically have less than 5% of the enzyme activity expected in an unaffected patient.[2] Duarte galactosemia is caused by mutations that produce an unstable form of the GALT enzyme, with reduced promoter expression. Patients who are homozygous for Duarte mutations (D/D) will have reduced levels of enzyme activity compared to normal controls, but can often maintain a normal diet. Compound heterozygotes (D/G) will often be detected by newborn screening and treatment is based on the extent of residual enzyme activity.[2] ## Diagnosis[edit] In most regions, galactosemia is diagnosed as a result of newborn screening, most commonly by determining the concentration of galactose in a dried blood spot. Some regions will perform a second-tier test of GALT enzyme activity on samples with elevated galactose, while others perform both GALT and galactose measurements. While awaiting confirmatory testing for classic galactosemia, the infant is typically fed a soy-based formula, as human and cow milk contains galactose as a component of lactose.[4] Confirmatory testing would include measurement of enzyme activity in red blood cells, determination of Gal-1-P levels in the blood, and mutation testing. The differential diagnosis for elevated galactose concentrations in blood on a newborn screening result can include other disorders of galactose metabolism, including galactokinase deficiency and galactose epimerase deficiency. Enzyme assays are commonly done using fluorometric detection or older radioactively labeled substrates. ## Treatment[edit] There is no cure for GALT deficiency, in the most severely affected patients, treatment involves a galactose free diet for life. Early identification and implementation of a modified diet greatly improves the outcome for patients. The extent of residual GALT enzyme activity determines the degree of dietary restriction. Patients with higher levels of residual enzyme activity can typically tolerate higher levels of galactose in their diets. As patients get older, dietary restriction is often relaxed.[2] With the increased identification of patients and their improving outcomes, the management of patients with galactosemia in adulthood is still being understood. After diagnosis, patients are often supplemented with calcium and vitamin D3. Long-term manifestations of the disease including ovarian failure in females, ataxia, and growth delays are not fully understood.[2] Routine monitoring of patients with GALT deficiency includes determining metabolite levels (galactose 1-phosphate in red blood cells and galactitol in urine) to measure the effectiveness of and adherence to dietary therapy, ophthalmologic examination for the detection of cataracts and assessment of speech, with the possibility of speech therapy if developmental verbal dyspraxia is evident.[2] ## Animal models[edit] Gal-1-P is assumed as to be a toxic agent, since the inhibition of the Galactokinase prevents toxicity in disease's models,[5][6] although this is controversial for Drosophila models.[7] Phosphate depletion as a consequence of Gal-1-P is also proposed as a mechanism of toxicity in yeast models.[8] ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): Galactosemia - 230400 2. ^ a b c d e f g Elsas LJ (1993). "Classic Galactosemia and Clinical Variant Galactosemia". Galactosemia. University of Washington, Seattle. PMID 20301691. NBK1518. In Pagon RA, Bird TD, Dolan CR, et al., eds. (1993). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. 3. ^ a b Salway JG (2013). "Chart 47.2 Galactose and galactitol metabolism". Metabolism at a Glance (3rd ed.). John Wiley & Sons. p. 102. ISBN 978-1-118-68207-4. 4. ^ "Newborn Screening ACT Sheet [Absent/Reduced Galactose-1-Phosphate Uridyltransferase (GALT)] Classical Galactosemia" (PDF). American College of Medical Genetics. Retrieved 2011-11-05. 5. ^ De-Souza EA, Pimentel FS, Machado CM, Martins LS, da-Silva WS, Montero-Lomelí M, Masuda CA (January 2014). "The unfolded protein response has a protective role in yeast models of classic galactosemia". Disease Models & Mechanisms. 7 (1): 55–61. doi:10.1242/dmm.012641. PMC 3882048. PMID 24077966. 6. ^ Mumma JO, Chhay JS, Ross KL, Eaton JS, Newell-Litwa KA, Fridovich-Keil JL (February 2008). "Distinct roles of galactose-1P in galactose-mediated growth arrest of yeast deficient in galactose-1P uridylyltransferase (GALT) and UDP-galactose 4'-epimerase (GALE)". Molecular Genetics and Metabolism. 93 (2): 160–71. doi:10.1016/j.ymgme.2007.09.012. PMC 2253667. PMID 17981065. 7. ^ Daenzer JM, Jumbo-Lucioni PP, Hopson ML, Garza KR, Ryan EL, Fridovich-Keil JL (November 2016). "Acute and long-term outcomes in a Drosophila melanogaster model of classic galactosemia occur independently of galactose-1-phosphate accumulation". Disease Models & Mechanisms. 9 (11): 1375–1382. doi:10.1242/dmm.022988. PMC 5117221. PMID 27562100. 8. ^ Machado CM, De-Souza EA, De-Queiroz AL, Pimentel FS, Silva GF, Gomes FM, Montero-Lomelí M, Masuda CA (June 2017). "The galactose-induced decrease in phosphate levels leads to toxicity in yeast models of galactosemia". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863 (6): 1403–1409. doi:10.1016/j.bbadis.2017.02.014. PMID 28213126. ## External links[edit] Classification D * ICD-10: E74.2 * ICD-9-CM: 271.1 * OMIM: 230400 * MeSH: D005693 * DiseasesDB: 5056 External resources * eMedicine: ped/818 * GeneReviews: Galactosemia * v * t * e Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders Including glycogen storage diseases (GSD) Sucrose, transport (extracellular) Disaccharide catabolism * Congenital alactasia * Sucrose intolerance Monosaccharide transport * Glucose-galactose malabsorption * Inborn errors of renal tubular transport (Renal glycosuria) * Fructose malabsorption Hexose → glucose Monosaccharide catabolism Fructose: * Essential fructosuria * Fructose intolerance Galactose / galactosemia: * GALK deficiency * GALT deficiency/GALE deficiency Glucose ⇄ glycogen Glycogenesis * GSD type 0 (glycogen synthase deficiency) * GSD type IV (Andersen's disease, branching enzyme deficiency) * Adult polyglucosan body disease (APBD) Glycogenolysis Extralysosomal: * GSD type III (Cori's disease, debranching enzyme deficiency) * GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency) * GSD type V (McArdle's disease, myophosphorylase deficiency) * GSD type IX (phosphorylase kinase deficiency) Lysosomal (LSD): * GSD type II (Pompe's disease, glucosidase deficiency) Glucose ⇄ CAC Glycolysis * MODY 2/HHF3 * GSD type VII (Tarui's disease, phosphofructokinase deficiency) * Triosephosphate isomerase deficiency * Pyruvate kinase deficiency Gluconeogenesis * PCD * Fructose bisphosphatase deficiency * GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency) Pentose phosphate pathway * Glucose-6-phosphate dehydrogenase deficiency * Transaldolase deficiency * 6-phosphogluconate dehydrogenase deficiency Other * Hyperoxaluria * Primary hyperoxaluria * Pentosuria * Aldolase A 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	Galactose-1-phosphate uridylyltransferase deficiency	c0268151	8,474	wikipedia	https://en.wikipedia.org/wiki/Galactose-1-phosphate_uridylyltransferase_deficiency	2021-01-18T19:00:55	{"gard": ["13639"], "mesh": ["D005693"], "umls": ["C0268151"], "icd-9": ["271.1"], "icd-10": ["E74.2"], "orphanet": ["79239"], "wikidata": ["Q5517832"]}
Immunodeficiency due to a classical component pathway complement deficiency is a primary immunodeficiency due to a deficiency in either complement components C1q, C1r, C1s, C2 or C4 characterized by increased susceptibility to bacterial infections, particularly with encapsulated bacteria, and increased risk for autoimmune disease. Most commonly, these include systemic lupus erythematosus (SLE), SLE-like disease, Henoch-Schonlein purpura, polymyositis and arthralgia. Disease severity is variable and dependent on the complement affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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 due to a classical component pathway complement deficiency	c3150274	8,475	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169147	2021-01-23T18:03:27	{"omim": ["216950", "217000", "613652", "613783", "614379", "614380"], "icd-10": ["D84.1"], "synonyms": ["Immunodeficiency due to C1, C4, or C2 component complement deficiency", "Immunodeficiency due to an early component of complement deficiency"]}
Charcot-Marie-Tooth disease type 4B1 (CMT4B1) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by an early childhood-onset of severe, demyelinating sensorimotor neuropathy, various degrees of complex myelin outfoldings seen on peripheral nerve biopsy, very slow, and often undetectable, nerve conduction velocities, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and frequent pes cavus). Other reported features include facial weakness, vocal cord paresis, respiratory difficulties, and skeletal deformities (e.g. chest deformities, claw hands, pes equinovarus). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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 4B1	c1832399	8,476	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99955	2021-01-23T18:07:37	{"gard": ["1253"], "mesh": ["C535420"], "omim": ["601382"], "umls": ["C1832399"], "icd-10": ["G60.0"], "synonyms": ["CMT4B1"]}
Vulvar childhood pemphigoid SpecialtyDermatology Vulvar childhood pemphigoid is a cutaneous condition, a childhood form of bullous pemphigoid, peculiar variant with involvement of the genital area and perineum.[1] ## See also[edit] * Vesicular pemphigoid * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 434. 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	Vulvar childhood pemphigoid	None	8,477	wikipedia	https://en.wikipedia.org/wiki/Vulvar_childhood_pemphigoid	2021-01-18T18:38:36	{"wikidata": ["Q7943630"]}
## Summary ### Clinical characteristics. STAT3 hyper IgE syndrome (STAT3-HIES) is a primary immune deficiency syndrome characterized by elevated serum IgE, eczema, and recurrent skin and respiratory tract infections, together with several nonimmune features. This disorder typically manifests in the newborn period with a rash (often diagnosed as eosinophilic pustulosis) that subsequently evolves into an eczematoid dermatitis. Recurrent staphylococcal skin boils and bacterial pneumonias usually manifest in the first years of life. Pneumatoceles and bronchiectasis often result from aberrant healing of pneumonias. Mucocutaneous candidiasis is common. Nonimmune features may include retained primary teeth, scoliosis, bone fractures following minimal trauma, joint hyperextensibility, and characteristic facial appearance, which typically emerges in adolescence. Vascular abnormalities have been described and include middle-sized artery tortuosity and aneurysms, with infrequent clinical sequelae of myocardial infarction and subarachnoid hemorrhage. Gastrointestinal (GI) manifestations include gastroesophageal reflux disease, esophageal dysmotility, and spontaneous intestinal perforations (some of which are associated with diverticuli). Fungal infections of the GI tract (typically histoplasmosis, Cryptococcus, and Coccidioides) also occur infrequently. Survival is typically into adulthood, with most individuals now living into or past the sixth decade. Most deaths are associated with gram-negative (Pseudomonas) or filamentous fungal pneumonias resulting in hemoptysis. Lymphomas occur at an increased frequency. ### Diagnosis/testing. The diagnosis of STAT3-HIES is established in a proband with typical clinical findings and a heterozygous dominant-negative pathogenic variant in STAT3 identified by molecular genetic testing. ### Management. Treatment of manifestations: The mainstay of treatment is prevention of staphylococcal abscesses and pneumonias with anti-staphylococcal prophylactic antibiotics as well as early aggressive treatment of infections. Use of antibiotics and antifungal agents depends on the nature of the infection and the extent of involvement. Antiseptic therapies for the skin such as dilute bleach baths and chlorhexidine are beneficial. Medications such as histamine-1 antagonists to control pruritus are helpful for more significant eczema. There is no known treatment or prevention for the nonimmunologic characteristics, although optimization of calcium and vitamin D intake may be considered to improve bone health. The role of hematopoietic cell transplantation (HSCT) in STAT3-HIES is emerging; while successful transplant recipients have improved infection phenotype, the effect of HSCT on the nonimmunologic aspects of the disease remains unclear. Surveillance: Periodic chest imaging and high clinical suspicion assist in early detection of lung infections. Culture of skin lesions and sputum samples helps direct therapy. Routine screening of adolescents for early signs of scoliosis is recommended. Dental monitoring is necessary to ensure timely removal of primary teeth to allow eruption of secondary teeth. Evaluation for coronary artery and cerebral aneurysms every three years in adulthood is recommended as well as monitoring for lymphadenopathy due to increased incidence of lymphoma. ### Genetic counseling. STAT3-HIES is inherited in an autosomal dominant manner. The majority of affected individuals have the disorder as the result of a de novo pathogenic variant. Each child of an individual with STAT3-HIES has a 50% chance of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible once the STAT3 pathogenic variant in the family has been identified. ## Diagnosis ### Suggestive Findings STAT3 hyper IgE syndrome (STAT3-HIES) should be suspected in individuals with the following findings: * Newborn rash and typically eczematous rash at least through childhood * Recurrent skin boils (often "cold," manifesting little inflammatory reaction) * Cyst-forming pneumonias * Mucocutaneous candidiasis * Nonimmune features such as three or more retained primary teeth, scoliosis, bone fractures following minimal trauma, hyperextensibility of joints, characteristic facial appearance, increased nasal width, high palate * Laboratory test results showing: * Elevations of serum concentration of immunoglobulin E (IgE) to levels above 2000 IU/mL (normal <100 IU/mL in adults); * Eosinophilia (>700/μL); * Diminished circulating memory T and B cells and near absence of IL-17-producing Th17 cells. Note: Not all features need to be present to suspect STAT3-HIES, and because features accrue over time, the clinical diagnosis can be uncertain in young children. Moreover, early institution of effective prophylactic antibiotics can attenuate or prevent many of the infectious complications that would otherwise facilitate suspicion of the diagnosis. A clinical scoring system was devised by the NIH group who recognized STAT3-HIES (then known as autosomal dominant HIES) to be a multisystem disorder [Grimbacher et al 1999b]. Woellner et al [2010] have developed guidelines that include the NIH clinical feature scoring system as well as determination of IL-17-producing T cells. However, molecular genetic testing for STAT3 pathogenic variants, readily available on a clinical basis, is the only reliable diagnostic approach. Prior to the genetic diagnosis, a HIES scoring system was developed to assist in the diagnosis [Grimbacher et al 1999b]. The scoring system components included both immunologic/infectious manifestations and skeletal / connective tissue abnormalities. The scoring system may still be helpful in identifying individuals in whom to perform genetic testing, or for considering the diagnosis if resources do not allow for genetic testing. ### Establishing the Diagnosis The diagnosis of STAT3 hyper IgE syndrome (STAT3-HIES) is established in a proband with typical clinical findings and a heterozygous dominant-negative pathogenic variant in STAT3 identified by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, 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 STAT3-HIES is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with atypical clinical findings in whom the diagnosis of STAT3-HIES has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of STAT3-HIES, molecular genetic testing approaches can include single-gene testing (especially if there is a positive family history) or, more typically, the use of a multigene panel: * Single-gene testing. Sequence analysis of STAT3 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. Since STAT3-HIES occurs through a dominant-negative mechanism (see Molecular Genetics), the detection of a large intragenic deletion or duplication is unexpected; however, one in-frame deletion of exons 22 and 23 has been reported [Schimke et al 2010]. Therefore, while it is unlikely to identify a disease-causing variant, testing for intragenic deletions or duplication may be considered. * A multigene panel that includes STAT3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the diagnosis of STAT3-HIES is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible. 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 STAT3 Hyper IgE Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method STAT3Sequence analysis 3>99% 4 Gene-targeted deletion/duplication analysis 51 reported 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Data derived from 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. 6\. An in-frame deletion of exons 22 and 23 has been reported [Schimke et al 2010]. 7\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description STAT3 hyper IgE syndrome (STAT3-HIES) is a primary immune deficiency syndrome characterized by elevated serum IgE, eczema, and recurrent skin and respiratory tract infections, together with several connective tissue and skeletal abnormalities. #### Presentation Individuals with STAT3-HIES typically manifest in the newborn period with a rash, often diagnosed as eosinophilic pustulosis. The rash evolves into an eczematoid dermatitis that is often driven by staphylococcal infection [Chamlin et al 2002, Eberting et al 2004]. #### Immunologic Characteristics Recurrent skin and sinopulmonary infections are noted in early childhood. * Recurrent staphylococcal boils usually manifest in the first few years of life, and may be "cold," lacking the cardinal features of inflammation, warmth, redness, and pain. * Recurrent pneumonias begin as well in the first few years, with the most common bacterial isolates being Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Abnormal healing of these pneumonias frequently leads to pneumatoceles and bronchiectasis. * Staphylococcal infections outside of the skin and lung, such as osteomyelitis or liver abscess, occur but much less frequently. * Mucocutaneous candidiasis affecting the oropharynx, vagina, fingernails, and toenails is common. * Opportunistic infections including Pneumocystis jiroveci pneumonia, disseminated histoplasmosis and Cryptococcus, and secondary infection of the pneumatoceles with molds such as Aspergillus fumigatus or Scedosporium species may occur. Histoplasmosis most frequently disseminates to the intestinal tract and can mimic inflammatory bowel disease. Coccidioides and Cryptococcus have caused meningitis [Odio et al 2015]. * Decreased central memory T-cells may lead to increased incidence of varicella zoster virus (VZV) reactivation and modestly increased levels of circulating Epstein-Barr virus [Siegel et al 2011]. #### Nonimmunologic Characteristics Individuals with STAT3-HIES may have several additional nonimmunologic findings. Facial. A characteristic facial appearance including facial asymmetry, deeply set eyes, a broad nose, and prominent skin pores typically emerges by adolescence [Borges et al 1998, Grimbacher et al 1999a]. Oral findings include a high arched palate and oral mucosal variants including prominent palatine ridges [Domingo et al 2008]. Failure of primary teeth exfoliation is common; secondary tooth development is normal if the primary teeth are removed. Skeletal abnormalities include osteoporosis, minimal trauma fractures, scoliosis, joint hyperextensibility, and craniosynostosis. * Osteoporosis and minimal trauma fractures start in early childhood. * Scoliosis typically develops through childhood and adolescence, and may require surgical correction. * Joint hyperextensibility is common, and adults may have degenerative joint disease. * Varying degrees of craniosynostosis can be seen, although surgical correction is rarely required. Skull radiographs often have a "beaten copper" appearance. Mild craniosynostosis is frequently noted in skull imaging. Brain imaging reveals Chiari 1 malformations in approximately 20% of individuals and focal hyperintensities prominent on T2-weighted images in approximately 70% of individuals. * The focal hyperintensities are usually localized to the white matter and tend to increase in number with age. * Both the Chiari 1 malformations and the hyperintensities are usually asymptomatic [Freeman et al 2007a]. Vascular abnormalities including tortuosity of middle-sized arteries and aneurysms have been described [Ling et al 2007, Freeman et al 2011, Chandesris et al 2012]. The coronary arteries have been the most completely studied. * The combination of tortuosity and dilation is found in approximately 50% of affected individuals; either abnormality is present in approximately 70%. * Clinical sequelae have been rare but include myocardial infarction. Cerebral artery aneurysm has also been described and is infrequently associated with subarachnoid hemorrhage. Gastrointestinal issues vary [Arora et al 2017]: * Symptoms of esophageal dysmotility are present in more than 50% of individuals and manifest as gastrointestinal reflux and dysphagia. * Upper endoscopy frequently shows eosinophilic esophagitis. * Diverticula can occur at a relatively young age and may be associated with bowel perforation [Stover et al 2010]. * Spontaneous intestinal perforations have also been described. * Significant gastrointestinal bleeds can occur from aneurysms and Dieulafoy lesions (abnormally large artery in the lining of the gastrointestinal system). #### Major Causes of Morbidity and Mortality Survival is typically into adulthood, but a shortened life span was typical in the past. Most individuals are now living into or past the sixth decade. * Most deaths of individuals with STAT3-HIES are associated with gram-negative (Pseudomonas) or filamentous fungal pneumonias (most commonly Aspergillus) infecting damaged lung parenchyma (i.e., preexisting pneumatoceles, bronchiectasis) [Freeman et al 2007b]. Fungi may invade the pulmonary vasculature leading to massive hemoptysis, or may disseminate to multiple organs. * Myocardial infarction may be related to coronary artery aneurysms and subarachnoid hemorrhage may be related to intracranial aneurysms [Fathi et al 2011]. * Lymphomas occur at an increased frequency; treatment with standard chemotherapy has been successful. ### Genotype-Phenotype Correlations No genotype-phenotype correlations for STAT3 missense pathogenic variants have been identified. ### Penetrance Intrafamilial variability is minimal and penetrance appears to be complete. ### Nomenclature Dominant-negative pathogenic variants in STAT3 were identified as the cause of autosomal dominant hyper IgE syndrome (AD-HIES) and "Job syndrome" in 2007. Since this time, other clinically overlapping dominant genetic disorders have been characterized and the term AD-HIES is no longer specific to the dominant-negative STAT3 phenotype. Multiple terms are currently used to refer to the dominant-negative STAT3 phenotype: STAT3-HIES (used in this GeneReview), STAT3-mutated HIES, dominant-negative STAT3, LOF STAT3, and STAT3 LOF. ### Prevalence The prevalence of STAT3-HIES is unknown. The condition is rare, likely around 1:1,000,000 population. Enrichment in a specific ethnic or racial group has not been reported. ## Differential Diagnosis ### Table 2. Disorders with Elevated Serum Concentration of IgE to Consider in the Differential Diagnosis of STAT3 Hyper IgE Syndrome View in own window Gene(s)DisorderMOIAdditional Clinical Features of Differential Disorder Overlapping w/STAT3-HIESDistinguishing from STAT3-HIES CARD14 1 FLG 2Atopic dermatitis 3AD AR 4Recurrent staphylococcal skin infections * Absence (typically) of other features of AD-HIES * Individuals w/severe atopic dermatitis often have more (& more severe) allergies (e.g., environmental, food that may lead to anaphylaxis) than those w/AD-HIES. CARD11Immunodeficiency 11B w/atopic dermatitis 5 (OMIM 617638)ADEarly-onset eczema (frequently)↑ viral skin infections; variable hypogammaglobulinemia DCLRE1C RAG1 RAG2Omenn syndrome 6 (OMIM 603554)ARPresents in newborn period w/rash & typically ↑ serum IgE * Affected infants are usually sicker than those w/HIES. * Lymphadenopathy, hepatosplenomegaly, opportunistic infections DOCK8DOCK8 deficiency (DOCK8 AR HIES 7; OMIM 243700)AR * Eczema * Recurrent skin & lung infections 8 * ↑ occurrence of viral skin infections (e.g., Molluscum contagiosum, warts); ↑ malignancies (lymphoma, squamous cell CA); ↑ vasculitis * Absence of nonimmunologic findings of STAT3-HIES (e.g., retention of primary teeth) 8 IL6STIL6ST deficiency 9 (OMIM 618523)AR * Recurrent skin & lung infections * Craniosynostosis & scoliosis Limited cases but potentially more serious infections PGM3PGM3 deficiency 10 (OMIM 615816)ARRecurrent skin & sinopulmonary infections; bone defects incl scoliosis * Developmental delays (common) * Cytopenias w/lymphopenia & neutropenia SPINK5Netherton syndrome (OMIM 256500)ARRash * Rash typically more ichthyotic in appearance w/assoc trichorrhexis invaginata (bamboo hair) * Enteropathy w/failure to thrive frequently present WASWiskott-Aldrich syndrome (see WAS Disorders)XLEczema & recurrent infections * Thrombocytopenia w/small platelets; high incidence of autoimmune disease & lymphoma in later childhood & adulthood; typically more opportunistic infections than in HIES * Typically seen in males (isolated cases of affected females w/skewed X-inactivation resulting in disease phenotype reported) ZNF341ZNF341 deficiency 11 (OMIM 618282)AREczema & recurrent infectionsFewer nonimmunologic manifestations; stronger inflammatory responses w/infection AD = autosomal dominant; AR = autosomal recessive; HIES = hyper IgE syndrome; MOI = mode of inheritance; XL = X-linked 1\. Peled et al [2019] 2\. OMIM 605803 3\. Atopic dermatitis has many causes (many of which are unknown); FLG\- and CARD14-related atopic dermatitis represent selected examples of heritable atopic dermatitis. 4\. Atopic dermatitis caused by FLG pathogenic variants can be inherited in an autosomal dominant or autosomal recessive manner; atopic dermatitis caused by CARD14 pathogenic variants is inherited in an autosomal dominant manner. 5\. Dorjbal et al [2019] 6\. Omenn syndrome is a form of SCID (severe combined immunodeficiency) that can result from pathogenic variants in RAG1, RAG2, DCLRE1C (previously known as Artemis), IL2RG, and additional combined immunodeficiency genes that allow residual functional activity. 7\. Most individuals initially described as having autosomal recessive hyper IgE were found to have biallelic pathogenic variants in DOCK8. DOCK8 deficiency is a combined immunodeficiency characterized by eczema, allergies, sinopulmonary infections, and viral skin infections including herpes simplex virus, varicella-zoster virus, Molluscum contagiosum, and human papillomavirus [Zhang et al 2009, Engelhardt et al 2009]. Affected individuals are at increased risk for malignancy; squamous cell carcinomas and lymphoma have been reported. DOCK8 deficiency is frequently associated with lymphopenia which often progresses with age, and serum IgM levels may be low or undetectable. Eosinophilia and IgE are both variable, but can be extremely elevated. 8\. Renner et al [2004] 9\. Schwerd et al [2017] 10\. Stray-Pedersen et al [2014], Zhang et al [2014] 11\. Béziat et al [2018] Note: A single report of human TYK2 deficiency described moderately high serum concentration of IgE in conjunction with disseminated bacillus Calmette-Guérin infection and susceptibility to viral and other infections [Minegishi et al 2006]. However, subsequent reports of TYK2 deficiency have not been associated with the AR-HIES phenotype [Kilic et al 2012, Kreins et al 2015]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with STAT3 hyper IgE syndrome (STAT3-HIES), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with STAT3 Hyper IgE Syndrome View in own window System/ConcernEvaluationComment SkinDermatologic examinationNewborn rash & eczema during childhood; often improves w/age PulmonaryChest imagingDetection of bronchiectasis & pneumatoceles SkeletalEvaluation for scoliosis & osteoporosis * Scoliosis typically progresses through adolescence. * Osteoporosis can be present in children & adults; DEXA screening recommended. DentalDental examination for possible retention of primary teeth VascularScreening for coronary artery & cerebral artery aneurysms * Aneurysms much more common in adults than in children * Screening by brain MRA & heart CTA or coronary artery MRA every 3 yrs recommended for adolescents & adults OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations Currently, there is no complete cure or targeted treatment for STAT3-HIES. The mainstay of therapy is prevention of staphylococcal abscesses and pneumonias with prophylactic anti-staphylococcal antibiotics as well as early aggressive treatment of infections. It is important to institute antibiotic therapy at the earliest sign of infection. Many affected individuals progress from minor to major infection rapidly, and systemic signs of infection may be minimal. There is no known treatment or prevention for the nonimmunologic characteristics. The role of hematopoietic cell transplantation (HSCT) in STAT3-HIES is emerging. It is clear that successful transplant recipients have improved infection phenotype. The effect of HSCT on the nonimmunologic aspects of the disease remains unclear [Goussetis et al 2010, Patel et al 2015, Yanagimachi et al 2016]. ### Table 4. Treatment of Manifestations in Individuals with STAT3 Hyper IgE Syndrome View in own window Manifestation/ ConcernTreatmentConsiderations/Other Eczema & recurrent boilsTopical antiseptics, e.g., dilute bleach baths 1 & chlorhexidine; frequent swimming in a chlorinated poolAdequate skin lubrication is needed after bleach. Anti-staphylococcal prophylaxis, e.g., w/2x/day TMP/SMX Histamine-1 antagonists (e.g., hydroxyzine) to control pruritusHelpful for more significant eczema Recurrent pneumoniasAntibiotic prophylaxis, typically w/2x/day TMP/SMXTargeting Staphylococcus aureus & other pyogenic bacteria to prevent the pneumonias & their complications In Coccidioides endemic regions use of prophylactic antifungals (e.g., fluconazole) can be considered.To prevent disseminated severe infection * If structural damage to the lungs (e.g., bronchiectasis &/or pneumatoceles) has occurred, the breadth of antimicrobial coverage may need to be extended, incl antifungals, as these structural abnormalities become secondarily infected w/gram-negative bacteria (e.g., Pseudomonas) or fungi (e.g., Aspergillus). * In the setting of bronchiectasis, consideration of azithromycin to prevent exacerbations if no mycobacterial infection present Sputum samples for bacteria, fungi, & mycobacteria (typically nontuberculous) should be obtained for microbiology during lung infections to help guide antimicrobial choice. Intravenous or subcutaneous IgG replacement can be considered.Has been used w/anecdotal improvement for some individuals, esp those who fail to make protective levels of specific antibodies following vaccination challenge; prospective, randomized controlled studies of immunoglobulin supplementation have not been performed. Airway clearance w/bronchiectasisAirway clearance techniques incl airway clearance devices, hypertonic saline nebulizers. Chronic mucocutaneous candidiasisAntifungal prophylaxisConsider fluconazole prophylaxis if living in a Coccidioides endemic region. Osteoporosis & Minimal trauma fracturesOptimize calcium & vitamin D intakeThe role of bisphosphonates for those w/this disorder w/osteoporosis is unclear; some improvement seen in bone density but unclear improvement in fractures [Sowerwine et al 2014]. Arterial aneurysmsOptimal blood pressure management Antiplatelet or anticoagulation therapies may be considered for individuals w/significant coronary artery aneurysms to prevent myocardial infarction related to clotting within the aneurysm.This must be weighed against risk of hemoptysis, a complication of fungal or bacterial lung disease in individuals w/STAT3-HIES. TMP/SMX = trimethoprim/sulfamethoxazole 1\. 1/2 - 1 cup bleach per bathtub of water for 15 minutes 3 times weekly ### Surveillance ### Table 5. Recommended Surveillance for Individuals with STAT3 Hyper IgE Syndrome View in own window System/ConcernEvaluationFrequency SkinDermatology exam & culture of skin lesionsAs needed PulmonaryHigh index of suspicion for infectionLifelong Periodic chest imagingWith ↑ pulmonary symptoms Sputum samplesWith ↑ pulmonary symptoms SkeletalScoliosis evaluationThrough adolescence DentalMonitor for emergence of secondary teeth & possible need for removal of primary teethEvery 6-12 mos during childhood Vascular * Brain MRA for cerebral aneurysm * CTA or MRA for coronary artery aneurysm Every 3 yrs in adults OtherMonitor for lymphadenopathy, or masses due to ↑ incidence of lymphomaAnnually ### Evaluation of Relatives at Risk Molecular genetic testing of at-risk relatives of a proband with a known STAT3 pathogenic variant allows for early diagnosis and prompt initiation of treatment and preventive measures. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Cessation of prophylactic antimicrobials is often advised during pregnancy. This may increase the risk of infection and should be taken into consideration. There have been pregnancies without complication, but also instances in which lung disease has worsened after pregnancy, potentially from limited antimicrobial use, delayed radiographic diagnosis, and impaired pulmonary clearance. Risks associated with pregnancy should be discussed with affected females who have pulmonary compromise, severe scoliosis, or other complications of STAT3-HIES. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. ### Other Parents have reported that due to the severe eczema of their child, there have been occasions when the health care providers have alerted Child Protective Services reporting that the child is not being kept clean. While skin hygiene is very important, in spite of the best efforts of caregivers, sometimes the skin flares are severe. Questions about parental neglect/abuse have also arisen when a toddler or young child appears with evidence of repeated fractures. Health care providers who are attuned to these possibilities can serve as important advocates for the parents and family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	STAT3 Hyper IgE Syndrome	c3887645	8,478	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK25507/	2021-01-18T20:58:23	{"mesh": ["D007589"], "synonyms": ["Job Syndrome", "STAT3-Deficient Hyper-IgE Syndrome", "STAT3 Deficiency", "STAT3-HIES", "STAT3 Loss-of-Function Hyper-IgE Syndrome (STAT3 LOF HIES)"]}
See also: Caffeine-induced sleep disorder, caffeine dependence, and caffeinism Caffeine-induced anxiety disorder is a subclass of the DSM-5 diagnosis of substance/medication-induced anxiety disorder.[1] Consumption of caffeine has long been linked to anxiety.[2] The effects of caffeine and the symptoms of anxiety both increase activity within the sympathetic nervous system. Caffeine has been linked to the aggravation and maintenance of anxiety disorders, and the initiation of panic or anxiety attacks in those who are already predisposed to such phenomena.[3] Caffeine usage surpassing 200 mg has been shown to increase the likelihood for anxiety and panic attacks in a population. Excessive amounts of caffeine can result in symptoms from general anxiety to obsessive-compulsive and phobic symptoms. ## Contents * 1 DSM-5 classification * 1.1 Diagnostic criteria * 1.2 Diagnostic features * 1.3 Prevalence * 2 Caffeine * 3 Mechanism of caffeine action * 3.1 Mobilization of intracellular calcium * 3.2 Inhibition of phosphodiesterases * 3.3 Antagonism of adenosine receptors * 3.4 Other actions of caffeine * 4 Genetics and variability of caffeine consumption * 5 Behavioral effects * 6 Susceptible populations * 7 Long-term health effects * 8 Treatment * 9 References ## DSM-5 classification[edit] ### Diagnostic criteria[edit] Caffeine-induced anxiety disorder is a subclass of the DSM-5 diagnosis of substance/medication-induced anxiety disorder. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, or DSM-5, is the current authority for psychiatric diagnosis in the United States. Substance/medication-induced anxiety disorder falls under the category of anxiety disorders in the DSM-5, and not the category of substance-related and addictive disorders, even though the symptoms are due to the effects of a substance.[4] Diagnosis according to the DSM-5 is dependent on various criteria. Patients must present symptoms of either panic attacks or anxiety. There must also be evidence that the panic or anxiety symptoms are a direct result of the use of the intoxicating substance. In caffeine-induced anxiety disorder, such symptoms would be due to the consumption of caffeine. The DSM-5 makes the distinction that the substance must be physiologically capable of leading to the anxiety and panic symptoms. This establishes the relationship between the abused chemical agent and the observed clinical effects. Caffeine has been proven to act as an antagonist on adenosine receptors, which acts as a stimulant and therefore fulfills this criteria. Symptoms must also not have a more likely clinical cause, such as another type of anxiety disorder, come before the ingestion of the intoxicating substance, or last for an extended amount of time after stopping the use of the substance. Diagnosis also requires that the panic attacks or anxiety due to the use of the intoxicating substance cause a certain amount of disturbance in the patient or lead to deficiency of varying types of daily performance.[4] ### Diagnostic features[edit] In addition to the criteria above, it is important to recognize that the diagnostic criteria for substance/medication-induced anxiety disorder are not met if the symptoms of panic come before the intoxication by the substance. In caffeine-induced anxiety disorder, a diagnosis will not be made if symptoms of anxiety or panic precede the ingestion of caffeine. Also, if symptoms persist for more than one month after substance intoxication, the diagnosis cannot be made. Persistence and continuation of symptoms beyond the initial consumption of caffeine suggest an alternate diagnosis that would better explain the long-lasting symptoms. Anxiety symptoms caused by caffeine are often mistaken for serious mental disorders including bipolar disorder and schizophrenia, leaving patients medicated for the wrong issue.[5] A caffeine-induced anxiety disorder diagnosis should be made, rather than a substance abuse or intoxication diagnosis, when symptoms of panic attacks or anxiety predominate.[6] ### Prevalence[edit] Although exact rates of prevalence are not available, general population data shows a 0.002% prevalence over a year-long period and higher prevalence within clinical populations.[6] ## Caffeine[edit] Caffeine structure Caffeine is a methylxanthine, and is hydrophobic.[7] The structure of caffeine allows the molecule to pass freely through biological membranes including the blood-brain barrier. Absorption in the gastrointestinal tract reaches near completion at about 99% after only 45 minutes. Half-life of caffeine for most adults is between 2.5 and 4.5 hours when consumption is limited to less than 10 mg/kg. However, during neonatal development, half-life for the fetus is significantly longer and decreases exponentially after birth to reach a normal rate at about 6 months.[7] Cytochrome P-450, a hemeprotein, acts in liver microsomes to metabolize caffeine into dimethylxanthines, monomethylxanthines, dimethyl uric acids, monomethyl uric acids, trimethylallantoin, dimethylallantoin, and derivatives of uracil. Most caffeine is metabolized by 3-methyl demethylation, forming the metabolite of paraxanthine. Many metabolites, in addition to caffeine, act within the body and are partly responsible for the physiological response to caffeine.[7] ## Mechanism of caffeine action[edit] Caffeine acts in multiple ways within the brain and the rest of the body. However, due to the concentration of caffeine required, antagonism of adenosine receptors is the primary mode of action.[8] The following mechanisms are ways in which caffeine may act within the body, but depending on necessary caffeine concentration and other factors may not be responsible for the clinical effects of the substance. ### Mobilization of intracellular calcium[edit] At very high concentrations of about 1–2 mM, caffeine lowers the excitability threshold in muscle cells, leading to prolonged contraction. The introduction of such high doses of caffeine allows calcium to enter the muscle cell through the plasma membrane and sarcoplasmic reticulum more readily. Influx of calcium through the membranes in muscle cells requires at least 250 μM of caffeine. Normally, other toxic effects of caffeine begin to occur in concentrations over 200 μM, however average consumption averages lead to concentrations less than 100 μM. This means that calcium influx and mobilization are most likely not the cause of caffeine's effect on the central nervous system, and are therefore not the cause of caffeine-induced anxiety disorder.[8] ### Inhibition of phosphodiesterases[edit] Methylxanthines such as caffeine inhibit the action of cyclic nucleotide phosphodiesterase, which normally acts to break down cAMP. Cyclic adenosine monophosphate, or cAMP, is a second messenger important in many cellular processes and is a critical factor in signal transduction. The inhibition of the phosphodiesterase would lead to a buildup of cAMP, increasing the activity of the second messenger throughout the cell. Though this mechanism is possible, it only occurs after levels of caffeine have reached a toxic level, and therefore it is unlikely to explain the mechanism of caffeine in the brain.[8] ### Antagonism of adenosine receptors[edit] There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these receptors is adenosine, which is a purine nucleoside that is important for processes such as energy transfer in the form of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) and signal transduction in the form of cyclic adenosine monophosphate (cAMP). A2B and A3 receptors require concentrations of caffeine that do not occur at normal physiological levels or with normal levels of caffeine consumption in order to be antagonized, and will therefore not be considered as a possible mechanism for caffeine-induced anxiety.[7] Caffeine acts as an antagonist of adenosine A1 and A2A receptors. Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors oppose each other but are both inhibited by caffeine due to its function as an antagonist.[7] A2A receptors are coupled to Gs proteins which activate adenylate cyclase and some voltage gated Ca2+ channels. A2A receptors are located in dopamine rich brain regions. A2A receptor mRNA was found in the same neurons as the dopamine receptor D2 within the dorsal striatum, nucleus accumbens and tuberculum olfactorium. A2A receptors are not found in neurons that express the dopamine receptor D1 receptors and Substance P. Within the striatum, part of the basal ganglia, activation of A2A receptors by adenosine increases GABA release, an inhibitory neurotransmitter. When caffeine binds to the receptor, less inhibitory neurotransmitter is released, supporting caffeine's role as a central nervous system stimulant.[7] A1 receptors are paired with the G-proteins of Gi-1, Gi-2, Gi-3, Go1, and Go2. The g-proteins of A1 receptors continue to inhibit adenylate cyclase, some voltage gated Ca2+ channels, and activate some K+ channels, and phospholipase C and D. A1 receptors are primarily located in the hippocampus, cerebral and cerebellar cortex, and particular thalamic nuclei. Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease the rate of firing since Ca2+ is necessary for neurotransmitter release. Caffeine's antagonistic action on the A1 receptor thus decreases the action of adenosine, allowing increased Ca2+ entry through N-type channels and higher rates of neurotransmitter release.[7] ### Other actions of caffeine[edit] Though antagonism of adenosine receptors is the primary mechanism of caffeine, Introduction of the methylxanthine into the body also increases the rate of release and recycling of some monoamine neurotransmitters such as noradrenaline and dopamine. Caffeine also has an excitatory effect on mesocortical cholinergic neurons by acting as an antagonist on adenosine receptors that normally inhibit the neuron.[7] ## Genetics and variability of caffeine consumption[edit] While many factors contribute to individual differences in a person's response to caffeine, such as environmental and demographic factors (i.e. age, drug use, circadian factors, etc.), genetics play an important role in individual variability. This inconsistency in responses to caffeine can take place either at the metabolic or at the drug-receptor level.[6] The effects of genetic factors can occur either directly by changing acute or chronic reactions to the drug or indirectly by altering other psychological or physiological processes.[6] Some of these processes include wakefulness, stimulation, and mood and cognition enhancement. Low doses can result in psychological effects of "mild euphoria, alertness, and enhanced cognitive performance";[6] higher doses produce physiological side effects of nausea, anxiety, trembling, and jitteriness. There are individuals who are prone to caffeine's anxiogenic effects whilst others are susceptible to its caffeine-induced sleep disturbances and insomnia. Studies with twins have shown that genetics influence individual differences in response to caffeine. Homozygous twins have been found to react in more consistent ways to the caffeine than heterozygous twins.[8] ## Behavioral effects[edit] Caffeine's widespread appeal is due primarily to its mild psychostimulant properties, which increase alertness and cognitive arousal and diminish fatigue.[9] Caffeine also produces a wide range of other symptoms, including upregulation of the cardiovascular system, increased global cognitive processing, and improved physical functioning. Cardiovascular effects can range from increased heart rate and reactivity to severe cardiac arrhythmia.[9] The cognitive effects of caffeine include increased performance in memory, attention, and text reading.[10] The physical effects of caffeine include lowered sensations of pain, less perceived effort, and increased muscle strength and endurance. However, at doses above ~400 mg, both cognitive and physical performance begins to worsen and symptoms of anxiety increase.[11] These anxiety symptoms include persisting insomnia, nervousness, and mood fluctuations.[9] When undergoing stress, the body activates a system-wide response mechanism known as the HPA axis. This stress signal begins at the level of the hypothalamus in the brain and undergoes subsequent amplifications throughout the body. This system elevates levels of stress hormones in the blood, which results in the body shutting down secondary bodily processes and increasing alertness to better prepare for response to the perceived threat.[12] Studies show that activation of this pathway is correlated with anxiety-like behaviors, including panic, post-traumatic stress, and generalized anxiety disorders,[13][14] as well as depression.[15] Rodent studies show that caffeine consumption in adolescence results in dysregulation of HPA axis function as well as central nervous system response, which impairs the body's response to stressful stimuli.[16] In cases of prolonged consumption of excess amounts of caffeine, studies show that individuals exhibit a reduced response to HPA axis activation by the hormone ACTH and a generalized increase in basal levels of stress hormone corticosterone. Researchers concluded that the sensitivity of adrenal glands to ACTH is diminished by caffeine consumption. People diagnosed with panic disorder show less HPA activity following stressful stimuli than their healthy control counterparts.[16] ## Susceptible populations[edit] Caffeine has varying effects on anxiety across given populations. The populations most susceptible to caffeine-induced anxiety disorder include those already diagnosed with an anxiety disorder and adolescents. Adolescents, particularly, are at increased risk for developing anxiety disorders and anxiety-related symptoms. While few human studies have been done to investigate this connection, many rodent studies show a correlation between caffeine consumption in adolescence and increased anxiety.[16][17][18][19] These studies showed that in adolescent rodents exposed to caffeine functioning of serotonin systems was affected, leading to increased anxiety;[18] anxiety-related behaviors were higher than in adult rats exposed to the same amount of caffeine;[19] and reward seeking behaviors as well as mood fluctuations were increased as the rodents matured.[17] ## Long-term health effects[edit] To date, there is no evidence to show a connection between caffeine consumption and long-term effects on anxiety. This may be a result of a lack of research investigating this, and not a lack of evidence produced from such studies. However, there is a significant amount of research regarding the long-term health effects of caffeine in general. When consumed in moderation, caffeine can have many beneficial effects. However, over the course of several years, chronic caffeine consumption can produce various long-term health deficits in individuals. Among these, rodent studies have suggested caffeine intake may permanently alter the brain's excitability.[20] As previously stated, long-term effects are most often seen in adolescents who regularly consume excess amounts of caffeine. This can affect their neuroendocrine functions and increase the risk of anxiety-disorder development. ## Treatment[edit] For individuals prescribed anti-anxiety medications such as alprazolam (Xanax), caffeine can introduce further problems by increasing rates of cytotoxicity and cell death by necrosis. This leads to these medications being essentially ruled out as viable treatments for caffeine-induced anxiety.[21] Due to caffeine's negative interaction with anti-anxiety medications such as benzodiazepines, treatments for caffeine-induced anxiety disorder tend to focus on abstinence from or a reduction of caffeine intake and behavioral therapy. Some doctors may recommend a continuance of caffeine consumption but with the provision that the patient actively takes note of physiological changes that happen after caffeine intake. The goal of this approach is to help patients better understand the effects of caffeine on the body and to distinguish threatening symptoms from normal reactions.[22] ## References[edit] 1. ^ Addicott, MA (2014). "Caffeine Use Disorder: A Review of the Evidence and Future Implications". Current Addiction Reports. 1 (3): 186–192. doi:10.1007/s40429-014-0024-9. PMC 4115451. PMID 25089257. 2. ^ Hughes, R.N. (June 1996). "Drugs Which Induce Anxiety: Caffeine" (PDF). 25. New Zealand Journal of Psychology. Archived from the original (PDF) on 2020-01-30. Cite journal requires `\|journal=` (help) 3. ^ Winston, Anthony P.; Hardwick, Elizabeth; Jaberi, Neema (October 2005). "Neuropsychiatric effects of caffeine". Advances in Psychiatric Treatment. 11 (6): 432–439. doi:10.1192/apt.11.6.432. ISSN 2056-4678. 4. ^ a b American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5). American Psychiatric Publishing. pp. 226–230. ISBN 978-0-89042-555-8. 5. ^ Torres, Francis M. (April 2009). "Caffeine - Induced Psychiatric Disorders" (PDF). Journal of Continuing Education Topics & Issues. Retrieved 22 February 2016. 6. ^ a b c d e Yang, Amy; Palmer, Abraham A.; de Wit, Harriet (June 9, 2010). "Genetics of caffeine consumption and responses to caffeine". Psychopharmacology. 211 (3): 245–257. doi:10.1007/s00213-010-1900-1. PMC 4242593. PMID 20532872. 7. ^ a b c d e f g h Fredholm, B. B.; Bättig, K.; Holmén, J.; Nehlig, A.; Zvartau, E. E. (1999-03-01). "Actions of caffeine in the brain with special reference to factors that contribute to its widespread use". Pharmacological Reviews. 51 (1): 83–133. ISSN 0031-6997. PMID 10049999. 8. ^ a b c d Nehlig, Astrid; Daval, Jean-Luc; Debry, Gérard (June 2, 1992). "Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic, and psychostimulant effects". Brain Research Reviews. 17 (2): 139–170. doi:10.1016/0165-0173(92)90012-B. PMID 1356551. 9. ^ a b c "Psychiatric emergencies (part II): psychiatric disorders coexisting with organic diseases". European Review (in Italian). 2013-02-15. Retrieved 2016-04-01. 10. ^ Franceschini, Sandro; Lulli, Matteo; Bertoni, Sara; Gori, Simone; Angrilli, Alessandro; Mancarella, Martina; Puccio, Giovanna; Facoetti, Andrea (2020). "Caffeine improves text reading and global perception". Journal of Psychopharmacology. 34 (3): 315–325. doi:10.1177/0269881119878178. hdl:10446/153264. ISSN 0269-8811. PMID 31578918. 11. ^ McLellan, Tom M.; Caldwell, John A.; Lieberman, Harris R. (2016). "A review of caffeine's effects on cognitive, physical and occupational performance". Neuroscience & Biobehavioral Reviews. 71: 294–312. doi:10.1016/j.neubiorev.2016.09.001. PMID 27612937. 12. ^ Smith, Sean M.; Vale, Wylie W. (2006). "The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress". Dialogues in Clinical Neuroscience. 8 (4): 383–395. ISSN 1294-8322. PMC 3181830. PMID 17290797. 13. ^ Trapp, Georgina S.A.; Allen, Karina; O'Sullivan, Therese A.; Robinson, Monique; Jacoby, Peter; Oddy, Wendy H. (2014). "ENERGY DRINK CONSUMPTION IS ASSOCIATED WITH ANXIETY IN AUSTRALIAN YOUNG ADULT MALES: Research Article: Energy-Drink Consumption and Mental Health". Depression and Anxiety. 31 (5): 420–428. doi:10.1002/da.22175. PMID 24019267. 14. ^ Ruxton, C. H. S. (2014). "The suitability of caffeinated drinks for children: a systematic review of randomised controlled trials, observational studies and expert panel guidelines". Journal of Human Nutrition and Dietetics. 27 (4): 342–357. doi:10.1111/jhn.12172. PMID 25099503. 15. ^ McEwen, Bruce S. (2005). "Glucocorticoids, depression, and mood disorders: structural remodeling in the brain". Metabolism. 54 (5): 20–23. doi:10.1016/j.metabol.2005.01.008. PMID 15877308. 16. ^ a b c O’Neill, Casey E.; Newsom, Ryan J.; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C.; Spencer, Robert L.; Campeau, Serge; Bachtell, Ryan K. (2016-05-01). "Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling". Psychoneuroendocrinology. 67: 40–50. doi:10.1016/j.psyneuen.2016.01.030. PMC 4808446. PMID 26874560. 17. ^ a b Hinton, David J.; Andres-Beck, Lindsey G.; Nett, Kelle E.; Oliveros, Alfredo; Choi, Sun; Veldic, Marin; Choi, Doo-Sup (2019). "Chronic caffeine exposure in adolescence promotes diurnal, biphasic mood-cycling and enhanced motivation for reward in adult mice". Behavioural Brain Research. 370: 111943. doi:10.1016/j.bbr.2019.111943. PMC 6662205. PMID 31095992. 18. ^ a b Arnold, M.R.; Williams, P.H.; McArthur, J.A.; Archuleta, A.R.; O'Neill, C.E.; Hassell, J.E.; Smith, D.G.; Bachtell, R.K.; Lowry, C.A. (2019). "Effects of chronic caffeine exposure during adolescence and subsequent acute caffeine challenge during adulthood on rat brain serotonergic systems". Neuropharmacology. 148: 257–271. doi:10.1016/j.neuropharm.2018.12.019. PMC 6438184. PMID 30579884. 19. ^ a b Ardais, A.P.; Borges, M.F.; Rocha, A.S.; Sallaberry, C.; Cunha, R.A.; Porciúncula, L.O. (2014). "Caffeine triggers behavioral and neurochemical alterations in adolescent rats". Neuroscience. 270: 27–39. doi:10.1016/j.neuroscience.2014.04.003. PMID 24726984. 20. ^ Tchekalarova, Jana D.; Kubová, Hana; Mareš, Pavel (2014). "Early caffeine exposure: Transient and long-term consequences on brain excitability". Brain Research Bulletin. 104: 27–35. doi:10.1016/j.brainresbull.2014.04.001. PMID 24727007. 21. ^ Saha, Biswarup; Mukherjee, Ananda; Samanta, Saheli; Saha, Piyali; Ghosh, Anup Kumar; Santra, Chitta Ranjan; Karmakar, Parimal (2009-09-01). "Caffeine augments Alprazolam induced cytotoxicity in human cell lines". Toxicology in Vitro. 23 (6): 1100–1109. doi:10.1016/j.tiv.2009.05.018. PMID 19490937. 22. ^ "Information on caffeine induced anxiety on MedicineNet.com". MedicineNet. Retrieved 2016-03-31. * v * t * e Psychoactive substance-related disorder General * SID * Substance intoxication / Drug overdose * Substance-induced psychosis * Withdrawal: * Craving * Neonatal withdrawal * Post-acute-withdrawal syndrome (PAWS) * SUD * Substance abuse / Substance-related disorders * Physical dependence / Psychological dependence / Substance dependence Combined substance use * SUD * Polysubstance dependence * SID * Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases * Alcoholic cardiomyopathy * Alcohol flush reaction (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	Caffeine-induced anxiety disorder	c0236712	8,479	wikipedia	https://en.wikipedia.org/wiki/Caffeine-induced_anxiety_disorder	2021-01-18T18:29:14	{"wikidata": ["Q19596215"]}
A number sign (#) is used with this entry because factor X deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding coagulation factor X (F10; 613872) on chromosome 13q34. Description Factor X deficiency is a rare autosomal recessive bleeding disorder showing variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. The disorder can be caused either by reduced levels of the factor X protein or by synthesis of a dysfunctional factor X protein (summary by Millar et al., 2000). Clinical Features Girolami et al. (1970) described a congenital haemorrhagic condition due to the presence of an abnormal factor X in a large kindred from Friuli, a remote valley in northeastern Italy. Girolami et al. (1971) reported another family from Friuli with a bleeding disorder due to an abnormal factor X. The proposita was a 43-year-old woman with a history of bleeding since early childhood. She had had epistaxis, menorrhagia, bleeding after tooth extractions, gum bleeding, postpartum hemorrhage, posttraumatic hemarthroses, and hematuria. Laboratory studies showed prolonged prothrombin time (PT), prolonged partial thromboplastin time (PTT), and correction with Russell viper venom. Factor X activity was significantly decreased (6 to 9% of normal), but antigen levels were normal; however, an abnormal factor X protein was identified immunologically, indicating a qualitative deficiency. The patient's 2 children and mother had 38 to 48% activity levels, consistent with the heterozygous state. Sumer et al. (1986) reported a Saudi Arabian infant with severe factor X deficiency who had had 2 intracranial hemorrhages. De Stefano et al. (1988) reported a 13-year-old girl, born of consanguineous parents, with defective factor X. Laboratory studies showed normal factor X antigen levels, but the protein was severely impaired in activation via the intrinsic pathway (3% of normal) and partially defective in activation via the extrinsic pathway (30-50% of normal). The variant protein, termed factor X Roma, was activated by Russell viper venom. The parents of the proposita showed factor X functional levels compatible with heterozygosity for the abnormality. Millar et al. (2000) determined that the Roma variant results from a T318M substitution (613872.0015) in the F10 gene. Peyvandi et al. (1998) studied 32 Iranian patients with congenital factor X deficiency. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal hemorrhages (e.g., hematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous hematomas and hemarthroses led to severe arthropathy in 5 patients. Bleeding from the umbilical stump was an unexpected finding in 9 patients. The study demonstrated that the bleeding tendency of factor X deficiency can be severe and correlates with factor levels. ### Acquired Factor X Deficiency Furie et al. (1977) presented evidence that the acquired deficiency of factor X associated with systemic amyloidosis is caused by binding of the factor X protein to amyloid. Ashrani et al. (2003) described factor X deficiency associated with lupus anticoagulant and a bleeding diathesis. They reported 2 patients in whom severe bleeding developed after a respiratory infection. Both the factor X deficiency and lupus anticoagulant were transient. Deficiency of factor X may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications. Other Features Endo (1981) observed spontaneously developing hematomyelia with incomplete transverse paralysis in a 17-year-old patient with factor X deficiency. Pregnancy in women with congenital deficiencies of coagulation factors such as factor X is often associated with adverse fetal outcomes. Recurrent spontaneous abortions, placental abruptions, and premature births are reported. Kumar and Mehta (1994) reviewed the outcome of 4 pregnancies in a patient with factor X deficiency. The first 2 pregnancies resulted in the birth of premature babies at 21 and 25 weeks of gestation, both of whom died in the neonatal period. The patient had been treated with fresh frozen plasma for acute bleeding episodes during these pregnancies. In addition, during the second conception she was given factor IX complex prophylactically during the latter half of her pregnancy. During her next 2 pregnancies, she was treated early in pregnancy with prophylactic replacement of factor X. She delivered healthy babies at 34 and 32 weeks of gestation and both babies thrived. Inheritance Factor X deficiency is usually inherited in an autosomal recessive pattern (Cooper et al., 1997). However, Millar et al. (2000) reported a family manifesting an autosomal dominant pattern of inheritance for factor X deficiency. There were 3 clinically affected members who were heterozygous for a splice site mutation that was predicted to lead to the production of a truncated protein product (613872.0012). Millar et al. (2000) presented a model that accounted for the dominant-negative effect of this lesion. Cytogenetics Stoll and Roth (1980) described a girl with a duplication-deficiency syndrome involving chromosomes 4 and 13. The mother had a balanced translocation t(4;13)(q26;q34). The child had partial trisomy of 4q and partial monosomy of 13q. Factor X level was half normal. Pfeiffer et al. (1982) presented evidence suggesting that factors VII (F7; 613878) and X may be encoded by genes on chromosome 13q34. They found deficiency of the 2 factors in 2 cases with 46,XY,t(13;Y)(q11;q34) including probable deletion of a terminal segment of 13q. A prolonged prothrombin time was found before surgery in the first case, leading to studies of coagulation; neither patient had clinical abnormality of coagulation. In 1 case, factor VII was measured as 42%, 40%, and 45% and factor X as 59%, 44%, and 60% of normal, in 2 different laboratories; in the second case, factor VII was 55% and 54% of normal and factor X was 25% and 62%. These values were normal in all 4 parents. Scambler and Williamson (1985) studied a female monosomic for 13q34 and deficient in clotting factors VII and X, as well as her brother, who was trisomic for 13q34 and had elevated levels of these factors. These persons suffered the effects of segregation from a reciprocal translocation in the mother involving the tip of chromosome 13 (13q34) and 6q24-6q26. DNA dosage studies with a cloned human factor X gene showed that the low levels of factor X expression were due to absence of one copy of the factor X structural gene. Molecular Genetics In a patient with a bleeding disorder due to factor X deficiency, Reddy et al. (1989) identified compound heterozygosity for 2 mutations in the F10 gene (613872.0001 and 613872.0002). The patient had prolonged bleeding after surgery, and laboratory studies showed that factor X activity and antigen were 14% and 36% of normal, respectively. This was the first characterization of factor X deficiency at the molecular level. Bernardi et al. (1989) found that a patient with factor X deficiency was a genetic compound for 2 mutations affecting the F10 gene: the maternal allele contained a partially deleted gene missing the 3-prime portion coding for the catalytic domain of the factor; the defect on the paternal F10 allele was not determined. James et al. (1991) demonstrated that factor X Friuli is caused by a homozygous mutation in the F10 gene (P343S; 613872.0004). Wieland et al. (1991) identified an instance of germline mosaicism for deletion of exons 7 and 8 of factor X. One offspring had this deletion and a different deletion inherited from the mother, i.e., she was a compound heterozygote. Millar et al. (2000) sequenced the F10 genes of 14 unrelated individuals with factor X deficiency, including 12 familial and 2 sporadic cases, and found a total of 13 novel mutations (see, e.g., 613872.0012-612872.0014). Missense mutations were studied by means of molecular modeling, whereas single basepair substitutions in splice sites and the 5-prime flanking region were examined by in vitro splicing assay and luciferase reporter gene assay, respectively. The deletion allele of a novel 6-nucleotide insertion/deletion polymorphism in the F10 gene promoter region was shown by reporter gene assay to reduce promoter activity by approximately 20%. Variation in the antigen level of heterozygous relatives of probands was found to be significantly higher between families than within families, consistent with the view that the nature of the F10 lesion(s) segregating in a given family is a prime determinant of the laboratory phenotype. Millar et al. (2000) commented that the complete absence of nonsense mutations in the F10 mutational spectrum is highly unusual. The ratio of nonsense to missense mutations is normally approximately 1 in 4. The observed lack of nonsense mutations was statistically significant. Assuming that the relative rate of single basepair substitutions in the F10 gene is similar to the overall mutational spectrum of human genes, this discrepancy would be explicable only in terms of a reduced relative likelihoods of clinical observation (RCOL; Krawczak et al., 1998) of nonsense versus missense mutations as compared with other genes. The reasons for this reduction were not clear. Peyvandi et al. (2002) analyzed the phenotype and genotype of 15 Iranian patients with factor X deficiency from 13 unrelated families with a high frequency of consanguinity. Nine different homozygous candidate mutations were identified, of which 8 were novel. Population Genetics Factor X deficiency has an estimated prevalence of 1 in 500,000 individuals (summary by Millar et al., 2000). History Giangrande (2003) gave an account, with photograph, of Miss Audrey Prower, who was 22 years old when she was admitted to University College Hospital of London in 1956 for investigation of a bleeding tendency prior to a dental extraction (Telfer et al., 1956; Denson, 1957). She had had significant bleeding after 2 previous dental extractions and after tonsillectomy. A brother had died of postoperative bleeding after tonsillectomy when he was 5 years old. Lewis et al. (1953) described a North Carolina patient seemingly similar to Audrey Prower. Hougie et al. (1957) tracked the patient down and confirmed that the defect was the same. As recounted by Giangrande (2003), Rufus Stuart was a 36-year-old farmer and lay-Baptist preacher, a member of a large and interrelated kindred living in the Blue Ridge Mountains of the northwestern corner of North Carolina and neighboring Virginia. He was born of an aunt-nephew mating. His principal problems had been recurrent epistaxis and significant bruising as well as hemarthrosis. Graham et al. (1957) provided a pedigree and showed that the inheritance pattern of the bleeding disorder was clearly autosomal recessive. Giangrande (2003) provided a photograph of Rufus Stuart with 3 of his physicians, Drs. Hougie, Barrow, and Graham. INHERITANCE \- Autosomal recessive HEAD & NECK Nose \- Epistaxis Mouth \- Bleeding gums GENITOURINARY Internal Genitalia (Female) \- Menorrhagia SKELETAL \- Hemarthrosis MUSCLE, SOFT TISSUES \- Intramuscular hematomas \- Umbilical cord bleeding NEUROLOGIC Central Nervous System \- Intracranial hemorrhage HEMATOLOGY \- Bleeding diathesis LABORATORY ABNORMALITIES \- Factor X deficiency \- Prolonged prothrombin and partial thromboplastin times \- Russell's viper venom assay may be prolonged or normal, depending on the genetic defect MISCELLANEOUS \- Variable severity \- Intermediate levels of factor X in mildly symptomatic heterozygotes \- Incidence of 1 in 500,000 live births MOLECULAR BASIS \- Caused by mutation in the coagulation factor X gene (F10, 613872.0001 ). ▲ 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	FACTOR X DEFICIENCY	c0015519	8,480	omim	https://www.omim.org/entry/227600	2019-09-22T16:27:57	{"mesh": ["D005171"], "omim": ["227600"], "orphanet": ["328"], "synonyms": ["Alternative titles", "F10 DEFICIENCY", "STUART-PROWER FACTOR DEFICIENCY"]}
Termination of a pregnancy in the United States Abortion is legal throughout the United States and its territories, although restrictions and accessibility vary from state to state. Abortion is a controversial and divisive issue in the society, culture and politics of the U.S., and various anti-abortion laws have been in force in each state since at least 1900. The Democratic Party has generally defended access to abortion, whereas the Republican Party has generally sought to restrict abortion access or criminalize abortion.[1] Before the Supreme Court of the United States decisions of Roe v. Wade and Doe v. Bolton decriminalized abortion nationwide in 1973, abortion was already legal in several states, but the decision in the former case imposed a uniform framework for state legislation on the subject. It established a minimal period during which abortion is legal (with more or fewer restrictions throughout the pregnancy). That basic framework, modified in Planned Parenthood v. Casey (1992), remains nominally in place, although the effective availability of abortion varies significantly from state to state, as many counties have no abortion providers.[2] Planned Parenthood v. Casey held that a law cannot place legal restrictions imposing an undue burden for "the purpose or effect of placing a substantial obstacle in the path of a woman seeking an abortion of a nonviable fetus."[3] The abortion rate has continuously fallen from a peak in 1980 of 30 per 1,000 women of childbearing age (15–44), to 12 per 1,000 by 2016.[4][5] In 2016, 66% of abortions were performed at 8 weeks or less gestation, and 91% of abortions were performed at 13 weeks or less gestation.[4][5] The main actors in the abortion debate are often framed as pro-choice, believing that a woman is entitled to choose whether to continue her pregnancy, versus pro-life, believing that the fetus has a sacred right to live, though most Americans are found to agree with some positions of each side.[6] A 2018 Gallup survey found the percentages of "pro-choice" or "pro-life" respondents were equal (at 48%), but more considered abortion morally wrong (48%) than morally acceptable (43%). The poll results also indicated that Americans harbor diverse and shifting opinions on the legal right to abortion. The survey found that 29% of respondents believed that abortion should be legal in all circumstances, 50% that it should be legal under some circumstances, and 20% that it should be illegal in all circumstances.[7] As of 2007[update], polling results found that 34% of Americans were satisfied with abortion laws.[8] ## Contents * 1 Terminology * 2 History * 2.1 Rise of anti-abortion legislation * 2.2 Sherri Finkbine * 2.3 Pre-Roe precedents * 2.4 Roe v. Wade * 2.4.1 Doe v. Bolton * 2.5 Later judicial decisions * 3 Current legal status * 3.1 Federal legislation * 3.2 State-by-state legal status * 3.3 In response to the coronavirus pandemic * 4 Qualifying requirements for abortion providers * 5 Statistics * 5.1 Number of abortions * 5.2 Medical abortions * 5.3 Abortion and religion * 5.4 Abortions and ethnicity * 5.5 Reasons for abortions * 5.6 When women have abortions (by gestational age) * 5.7 Safety of abortions * 6 Public opinion * 6.1 By gender and age * 6.2 By educational level * 6.3 By gender, party, and region * 6.4 By trimester of pregnancy * 6.5 By circumstance or reasons * 6.6 Additional polls * 6.7 "Partial birth abortion" * 7 Abortion financing * 7.1 Medicaid * 7.2 Private insurance * 7.3 Mexico City policy * 8 Positions of U.S. political parties * 9 Effects of legalization * 10 Unintended live birth * 11 See also * 12 References * 13 Further reading * 14 External links ## Terminology[edit] Main article: Abortion The abortion debate most commonly relates to the "induced abortion" of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[9] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[10] In medical parlance, "abortion" can refer to either miscarriage or abortion until the fetus is viable. After viability, doctors call an abortion a "termination of pregnancy". ## History[edit] ### Rise of anti-abortion legislation[edit] Abortion laws in the U.S. before Roe Illegal (30) Legal in case of rape (1) Legal in case of danger to woman's health (2) Legal in case of danger to woman's health, rape or incest, or likely damaged fetus (13) Legal on request (4) [11] When the United States first became independent, most states applied English common law to abortion. This meant it was not permitted after quickening, or the start of fetal movements, usually felt 15–20 weeks after conception.[12] Abortion has existed in America since European colonization. The earliest settlers would often encourage abortions before the "quickening" stage in the pregnancy. There were many reasons given for this, including not having resources to bear children. It was not until the late 1800s[clarification needed] when states began to make abortions illegal. One reason given for the legislation was that abortions had been performed with dangerous methods and were often surgical. Because of this, many states decided to forbid abortions. As technology advanced and abortion methods improved, abortions still remained illegal. Women would resort to illegal unsafe methods, also known as "back alley" abortions. Abortions became illegal by statute in Britain in 1803 with Lord Ellenborough's Act. Various anti-abortion statutes that codified or expanded common law began to appear in the United States in the 1820s. In 1821, a Connecticut law targeted apothecaries who sold "poisons" to women for purposes of inducing an abortion, and New York made post-quickening abortions a felony and pre-quickening abortions a misdemeanor in 1829.[13] Other legal scholars have pointed out that some of the early laws punished not only the doctor or abortionist, but also the woman who hired them.[14] A number of other factors likely played a role in the rise of anti-abortion laws. Physicians, who were the leading advocates of abortion criminalization laws, appear to have been motivated at least in part by advances in medical knowledge. Science had discovered that conception inaugurated a more or less continuous process of development, which would produce a new human being if uninterrupted. Quickening was found to be neither more nor less crucial in the process of gestation than any other step. Many physicians concluded that if society considered it unjustifiable to terminate pregnancy after the fetus had quickened, and if quickening was a relatively unimportant step in the gestation process, then it was just as wrong to terminate a pregnancy before quickening as after quickening.[15] Ideologically, the Hippocratic Oath and the medical mentality of that age to defend the value of human life as an absolute played a significant role in molding opinions about abortion.[15] Doctors were also influenced by practical reasons to advocate anti-abortion laws. For one, abortion providers tended to be untrained and not members of medical societies. In an age where the leading doctors in the nation were attempting to standardize the medical profession, these "irregulars" were considered a nuisance to public health.[16] The more formalized medical profession disliked the "irregulars" because they were competition, often at a cheaper cost. Despite campaigns to end the practice of abortion, abortifacient advertising was highly effective. Contemporary estimates of mid-19th century abortion rates suggest between 20% and 25% of all pregnancies in the United States during that era ended in abortion.[17] This era saw a marked shift in those who were obtaining abortions. Before the start of the 19th century, most abortions were sought by unmarried women who had become pregnant out of wedlock. Out of 54 abortion cases published in American medical journals between 1839 and 1880, over half were sought by married women, and well over 60% of the married women already had at least one child.[18] The sense that married women were now frequently obtaining abortions worried many conservative physicians, who were almost exclusively men. In the post-Civil War era, much of the blame was placed on the burgeoning women's rights movement. Though the medical profession expressed hostility toward feminism, many feminists of the era were also opposed to abortion.[19][20] In The Revolution, operated by Elizabeth Cady Stanton and Susan B. Anthony, an anonymous contributor signing "A" wrote in 1869 about the subject, arguing that instead of merely attempting to pass a law against abortion, the root cause must also be addressed. Simply passing an anti-abortion law would, the writer stated, "be only mowing off the top of the noxious weed, while the root remains. [...] No matter what the motive, love of ease, or a desire to save from suffering the unborn innocent, the woman is awfully guilty who commits the deed. It will burden her conscience in life, it will burden her soul in death; But oh! thrice guilty is he who drove her to the desperation which impelled her to the crime."[20][21][22][23] To many feminists of this era, abortion was regarded as an undesirable necessity forced upon women by thoughtless men.[24] Even the "free love" wing of the feminist movement refused to advocate for abortion and treated the practice as an example of the hideous extremes to which modern marriage was driving women.[25] Marital rape and the seduction of unmarried women were societal ills which feminists believed caused the need to abort, as men did not respect women's right to abstinence.[25] However, physicians remained the loudest voice in the anti-abortion debate, and they carried their agenda to state legislatures around the country, advocating not only anti-abortion laws, but also laws against birth control. This movement presaged the modern debate over women's body rights.[26] A campaign was launched against the movement and the use and availability of contraceptives. Criminalization of abortion accelerated from the late 1860s, through the efforts of concerned legislators, doctors, and the American Medical Association.[27] In 1873, Anthony Comstock created the New York Society for the Suppression of Vice, an institution dedicated to supervising the morality of the public. Later that year, Comstock successfully influenced the United States Congress to pass the Comstock Law, which made it illegal to deliver through the U.S. mail any "obscene, lewd, or lascivious" material. It also prohibited producing or publishing information pertaining to the procurement of abortion or the prevention of conception or venereal disease, even to medical students.[28] The production, publication, importation, and distribution of such materials was suppressed under the Comstock Law as being obscene, and similar prohibitions were passed by 24 of the 37 states.[29] In 1900, abortion was a felony in every state. Some states included provisions allowing for abortion in limited circumstances, generally to protect the woman's life or to terminate pregnancies arising from rape or incest.[30] Abortions continued to occur, however, and became increasingly available. The American Birth Control League was founded by Margaret Sanger in 1921; it would become Planned Parenthood Federation of America in 1942.[31][32] By the 1930s, licensed physicians performed an estimated 800,000 abortions a year.[33] ### Sherri Finkbine[edit] One notable case dealt with a woman named Sherri Finkbine. Born in the area of Phoenix, Arizona, Sherri had 4 healthy children. However, during her pregnancy with her 5th child, she had found that the child might have severe deformities.[34] Finkbine had been taking sleeping pills that contained a drug called Thalidomide which was also very popular in several countries.[35] She had later learned that the drug was causing fetal deformities and she wanted to warn the general public. Finkbine strongly wanted an abortion, however the abortion laws of Arizona limited her decision. In Arizona, an abortion could only occur if the mother's life was in danger. She met with a reporter from The Arizona Republic and told her story. While Sherri Finkbine wanted to be kept anonymous, the reporter disregarded this idea. On August 18, 1962, Finkbine traveled to Sweden where she was able to obtain a legal abortion. It was also confirmed that the child would have been very much deformed.[36] Sherri Finkbine's story marks a turning point for women as well as the history of abortion laws occurring in the United States. Sherri Finkbine, unlike many other women, was able to afford going overseas to have the abortion. However, many women seeking abortions may not be able to afford travel. In such cases, women may turn to illegal forms of abortion. [37] ### Pre-Roe precedents[edit] In 1964, Gerri Santoro of Connecticut died trying to obtain an illegal abortion, and her photo became the symbol of an abortion-rights movement. Some women's rights activist groups developed their own skills to provide abortions to women who could not obtain them elsewhere. As an example, in Chicago, a group known as "Jane" operated a floating abortion clinic throughout much of the 1960s. Women seeking the procedure would call a designated number and be given instructions on how to find "Jane".[38] In 1965, the U.S. Supreme Court case Griswold v. Connecticut struck down one of the remaining contraception Comstock laws in Connecticut and Massachusetts.[39] However, Griswold only applied to marital relationships. Eisenstadt v. Baird (1972) extended its holding to unmarried persons as well.[40] Following the Griswold case, the American College of Obstetricians and Gynecologists (ACOG) issued a medical bulletin accepting a recommendation from six years earlier that clarified that "conception is the implantation of a fertilized ovum";[41] and consequently birth control methods that prevented implantation became classified as contraceptives, not abortifacients. In 1967, Colorado became the first state to decriminalize abortion in cases of rape, incest, or in which pregnancy would lead to permanent physical disability of the woman. Similar laws were passed in California, Oregon, and North Carolina. In 1970, Hawaii became the first state to legalize abortions on the request of the woman,[42] and New York repealed its 1830 law and allowed abortions up to the 24th week of pregnancy. Similar laws were soon passed in Alaska and Washington. In 1970, Washington held a referendum on legalizing early pregnancy abortions, becoming the first state to legalize abortion through a vote of the people.[43] A law in Washington, D.C., which allowed abortion to protect the life or health of the woman, was challenged in the Supreme Court in 1971 in United States v. Vuitch. The court upheld the law, deeming that "health" meant "psychological and physical well-being", essentially allowing abortion in Washington, D. C. By the end of 1972, 13 states had a law similar to that of Colorado, while Mississippi allowed abortion in cases of rape or incest only and Alabama and Massachusetts allowed abortions only in cases where the woman's physical health was endangered. In order to obtain abortions during this period, women would often travel from a state where abortion was illegal to one where it was legal. The legal position prior to Roe v. Wade was that abortion was illegal in 30 states and legal under certain circumstances in 20 states.[44] In the late 1960s, a number of organizations were formed to mobilize opinion both against and for the legalization of abortion. In 1966, the National Conference of Catholic Bishops assigned Monsignor James T. McHugh to document efforts to reform abortion laws, and anti-abortion groups began forming in various states in 1967. In 1968, McHugh led an advisory group which became the National Right to Life Committee.[45][46] The forerunner of the NARAL Pro-Choice America was formed in 1969 to oppose restrictions on abortion and expand access to abortion.[47] Following Roe v. Wade, in late 1973, NARAL became the National Abortion Rights Action League. ### Roe v. Wade[edit] Main article: Roe v. Wade The United States Supreme Court membership in 1973. Prior to Roe v. Wade, 30 states prohibited abortion without exception, 16 states banned abortion except in certain special circumstances (e.g., rape, incest, health threat to mother), 3 states allowed residents to obtain abortions, and New York allowed abortions generally.[48] Early that year, on January 22, 1973, the Supreme Court in Roe v. Wade invalidated all of these laws, and set guidelines for the availability of abortion. Roe established that the right of privacy of a woman to obtain an abortion "must be considered against important state interests in regulation".[49] Roe established a "trimester" (i.e., 12 week) threshold of state interest in the life of the fetus corresponding to its increasing "viability" (likelihood of survival outside the uterus) over the course of a pregnancy, such that states were prohibited from banning abortion early in pregnancy but allowed to impose increasing restrictions or outright bans later in pregnancy. In deciding Roe v. Wade, the Supreme Court ruled that a Texas statute forbidding abortion except when necessary to save the life of the mother was unconstitutional. The Court arrived at its decision by concluding that the issue of abortion and abortion rights falls under the right to privacy (in the sense of the right of a person not to be encroached by the state). In its opinion, it listed several landmark cases where the court had previously found a right to privacy implied by the Constitution. The Court did not recognize a right to abortion in all cases: > State regulation protective of fetal life after viability thus has both logical and biological justifications. If the State is interested in protecting fetal life after viability, it may go so far as to proscribe abortion during that period, except when it is necessary to preserve the life or health of the mother.[50] The Court held that a right to privacy existed and included the right to have an abortion. The court found that a mother had a right to abortion until viability, a point to be determined by the abortion doctor. After viability a woman can obtain an abortion for health reasons, which the Court defined broadly to include psychological well-being. A central issue in the Roe case (and in the wider abortion debate in general) is whether human life or personhood begins at conception, birth, or at some point in between. The Court declined to make an attempt at resolving this issue, noting: "We need not resolve the difficult question of when life begins. When those trained in the respective disciplines of medicine, philosophy, and theology are unable to arrive at any consensus, the judiciary, at this point in the development of man's knowledge, is not in a position to speculate as to the answer." Instead, it chose to point out that historically, under English and American common law and statutes, "the unborn have never been recognized ... as persons in the whole sense", and thus, the fetuses are not legally entitled to the protection afforded by the right to life specifically enumerated in the Fourteenth Amendment. So, rather than asserting that human life begins at any specific point, the court simply declared that the State has a "compelling interest" in protecting "potential life" at the point of viability. #### Doe v. Bolton[edit] Main article: Doe v. Bolton Under Roe v. Wade, state governments may not prohibit late terminations of pregnancy when "necessary to preserve the life or health of the mother", even if it would cause the demise of a viable fetus.[51] This rule was clarified by the 1973 judicial decision Doe v. Bolton, which specifies "that the medical judgment may be exercised in the light of all factors — physical, emotional, psychological, familial, and the woman's age — relevant to the well-being of the patient".[52][53][54] It is by this provision for the mother's mental health that women in the US legally choose abortion after viability when screenings reveal abnormalities that do not cause a baby to die shortly after birth.[55][56][57][58] ### Later judicial decisions[edit] In the 1992 case of Planned Parenthood v. Casey, the Court abandoned Roe's strict trimester framework but maintained its central holding that women have a right to choose to have an abortion before viability.[59] Roe had held that statutes regulating abortion must be subject to "strict scrutiny" — the traditional Supreme Court test for impositions upon fundamental Constitutional rights. Casey instead adopted the lower, undue burden standard for evaluating state abortion restrictions,[60] but re-emphasized the right to abortion as grounded in the general sense of liberty and privacy protected under the constitution: "Constitutional protection of the woman's decision to terminate her pregnancy derives from the Due Process Clause of the Fourteenth Amendment. It declares that no State shall 'deprive any person of life, liberty, or property, without due process of law.' The controlling word in the cases before us is 'liberty'."[61] The Supreme Court continues to grapple with cases on the subject. On April 18, 2007, it issued a ruling in the case of Gonzales v. Carhart, involving a federal law entitled the Partial-Birth Abortion Ban Act of 2003 which President George W. Bush had signed into law. The law banned intact dilation and extraction, which opponents of abortion rights referred to as "partial-birth abortion", and stipulated that anyone breaking the law would get a prison sentence up to 2.5 years. The United States Supreme Court upheld the 2003 ban by a narrow majority of 5-4, marking the first time the Court has allowed a ban on any type of abortion since 1973. The opinion, which came from justice Anthony Kennedy, was joined by Justices Antonin Scalia, Clarence Thomas, and the two recent appointees, Samuel Alito and Chief Justice John Roberts. In the case of Whole Woman's Health v. Hellerstedt, the Supreme Court in a 5-3 decision on June 27, 2016 swept away forms of state restrictions on the way abortion clinics can function. The Texas legislature enacted in 2013 restrictions on the delivery of abortions services that created an undue burden for women seeking an abortion by requiring abortion doctors to have difficult-to-obtain "admitting privileges" at a local hospital and by requiring clinics to have costly hospital-grade facilities. The Court struck down these two provisions "facially" from the law at issue—that is, the very words of the provisions were invalid, no matter how they might be applied in any practical situation. According to the Supreme Court, the task of judging whether a law puts an unconstitutional burden on a woman's right to abortion belongs with the courts, and not the legislatures.[62] The Supreme Court ruled similarly in June Medical Services, LLC v. Russo on June 29, 2020, in a 5–4 decision that a Louisiana state law, modeled after the Texas law at the center of Whole Woman's Health, was unconstitutional.[63] Like Texas' law, the Louisiana law required certain measures for abortion clinics that, if having gone into effect, would have closed five of the six clinics in the state. The case in Louisiana was put on hold pending the result of Whole Woman's Health, and was retried based on the Supreme Court's decision. While the District Court ruled the law unconstitutional, the Fifth Circuit found that unlike the Texas law, the burden of the Louisiana law passed the tests outlined in Whole Woman's Health, and thus the law was constitutional. The Supreme Court issued an order to suspend enforcement of the law pending further review, and agreed to hear the case in full in October 2019. It was the first abortion-related case to be heard by President Donald Trump's appointees to the Court, Neil Gorsuch and Brett Kavanaugh.[64] The Supreme Court found the Louisiana law unconstitutional for the same reasons as the Texas one, reversing the Fifth Circuit. The judgement was supported by Chief Justice John Roberts who had dissented on Whole Woman's Health but joined in judgement as to upheld the court's respect for the past judgement in that case.[63] ## Current legal status[edit] ### Federal legislation[edit] Since 1995, led by congressional Republicans, the U.S. House of Representatives and U.S. Senate have moved several times to pass measures banning the procedure of intact dilation and extraction, commonly known as partial birth abortion. Such measures passed twice by wide margins, but President Bill Clinton vetoed those bills in April 1996 and October 1997 on the grounds that they did not include health exceptions. Congressional supporters of the bill argue that a health exception would render the bill unenforceable, since the Doe v. Bolton decision defined "health" in vague terms, justifying any motive for obtaining an abortion. Congress was unsuccessful with subsequent attempts to override the vetoes. The Born-Alive Infants Protection Act of 2002 ("BAIPA") was enacted August 5, 2002 by an Act of Congress and signed into law by George W. Bush. It asserts the human rights of infants born after a failed attempt to induce abortion. A "born-alive infant" is specified as a "person, human being, child, individual". "Born alive" is defined as the complete expulsion of an infant at any stage of development that has a heartbeat, pulsation of the umbilical cord, breath, or voluntary muscle movement, no matter if the umbilical cord has been cut or if the expulsion of the infant was natural, induced labor, cesarean section, or induced abortion. On October 2, 2003, with a vote of 281-142, the House approved the Partial-Birth Abortion Ban Act to ban partial-birth abortion, with an exemption in cases of fatal threats to the woman. Through this legislation, a doctor could face up to two years in prison and civil lawsuits for performing such a procedure. A woman undergoing the procedure could not be prosecuted under the measure. On October 21, 2003, the United States Senate passed the bill by a vote of 64-34, with a number of Democrats joining in support. The bill was signed by President George W. Bush on November 5, 2003, but a federal judge blocked its enforcement in several states just a few hours after it became public law. The Supreme Court upheld the nationwide ban on the procedure in the case Gonzales v. Carhart on April 18, 2007, signaling a substantial change in the Court's approach to abortion law.[65] The 5-4 ruling said the Partial Birth Abortion Ban Act does not conflict with previous decisions regarding abortion. The current judicial interpretation of the U.S. Constitution regarding abortion, following the Supreme Court of the United States's 1973 landmark decision in Roe v. Wade, and subsequent companion decisions, is that abortion is legal but may be restricted by the states to varying degrees. States have passed laws to restrict late-term abortions, require parental notification for minors, and mandate the disclosure of abortion risk information to patients prior to the procedure.[66] The official report of the U.S. Senate Judiciary Committee, issued in 1983 after extensive hearings on the Human Life Amendment (proposed by Senators Orrin Hatch and Thomas Eagleton), stated that > Thus, the [Judiciary] Committee observes that no significant legal barriers of any kind whatsoever exist today in the United States for a mother to obtain an abortion for any reason during any stage of her pregnancy.[67] One aspect of the legal abortion regime now in place has been determining when the fetus is "viable" outside the womb as a measure of when the "life" of the fetus is its own (and therefore subject to being protected by the state). In the majority opinion delivered by the court in Roe v. Wade, viability was defined as "potentially able to live outside the mother's womb, albeit with artificial aid. Viability is usually placed at about seven months (28 weeks) but may occur earlier, even at 24 weeks". When the court ruled in 1973, the then-current medical technology suggested that viability could occur as early as 24 weeks. Advances over the past three decades allow survival of some babies born at 22 weeks.[68] As of 2006[update], the youngest child to survive a premature birth in the United States was a girl born at Kapiolani Medical Center in Honolulu, Hawaii at 21 weeks and 3 days gestation.[69] Because of the split between federal and state law, legal access to abortion continues to vary by state. Geographic availability varies dramatically, with 87 percent of U.S. counties having no abortion provider.[70] Moreover, due to the Hyde Amendment, many state health programs do not cover abortions; currently 17 states (including California, Illinois and New York) offer or require such coverage.[71] The legality of abortion is frequently a major issue in nomination battles for the U.S. Supreme Court. Nominees typically remain silent on the issue during their hearings, as the issue may come before them as judges. The Unborn Victims of Violence Act, commonly known as "Laci and Conner's Law" was passed by Congress and signed into law by President Bush on April 1, 2004, allowing two charges to be filed against someone who kills a pregnant mother (one for the mother and one for the fetus). It specifically bans charges against the mother and/or doctor relating to abortion procedures. Nevertheless, it has generated much controversy among pro-abortion rights advocates who view it as a potential step in the direction of banning abortion. The Pain-Capable Unborn Child Protection Act is a United States Congress bill to ban late-term abortions nationwide after 20 weeks post-fertilization on the basis that the fetus is capable of feeling pain during an abortion at and after that point of pregnancy. The bill was first introduced in Congress in 2013. It successfully passed the House of Representatives in 2013, 2015, and 2017, but has yet to pass the Senate. Opponents of the bill reject the claims made by the bill's supporters regarding fetal development, and argue that such a restriction would endanger women's health. This map demonstrates an increase in abortion restrictions and a simultaneous decrease in abortion access in the US in 2013. An index of abortion access was created using the supply of abortion providers, TRAP laws, gestational restrictions, and parental notification laws to measure abortion access in the US.[citation needed] ### State-by-state legal status[edit] Main articles: Abortion in the United States by state and Types of abortion restrictions in the United States Abortion is legal in all U.S. states, and every state has at least one abortion clinic.[72][73] Abortion is a controversial political issue, and regular attempts to restrict it occur in most states. Two such cases, originating in Texas and Louisiana, led to the Supreme Court cases of Whole Woman's Health v. Hellerstedt (2016) and June Medical Services, LLC v. Russo (2020) in which several Texas and Louisiana restrictions were struck down.[74][75] The issue of minors and abortion is regulated at the state level, and 37 states require some parental involvement, either in the form of parental consent or in the form of parental notification. In certain situations, the parental restrictions can be overridden by a court.[76] Mandatory waiting periods, mandatory ultrasounds and scripted counseling are common abortion regulations. Abortion laws are generally stricter in a conservative Southern states than they are in other parts of the country. In 2019, New York passed the Reproductive Health Act (RHA), which repealed a pre-Roe provision that banned third-trimester abortions except in cases where the continuation of the pregnancy endangered a pregnant woman's life.[77][78] Abortion in the Northern Mariana Islands, a United States Commonwealth territory, is illegal. Alabama House Republicans passed a law on April 30, 2019 that will criminalize abortion if it goes into effect.[79] Dubbed the "Human Life Protection Act", it offers only two exceptions: serious health risk to the mother or a lethal fetal anomaly.[80] It will also make the procedure a Class A felony.[81] Twenty-five male Alabama senators voted to pass the law on May 13.[82] The next day, Alabama governor Kay Ivey signed the bill into law, primarily as a symbolic gesture in hopes of challenging Roe v. Wade in the Supreme Court.[83][84] Since Alabama introduced the first modern anti-abortion legislation in April 2019, five other states have also adopted abortion laws including Mississippi, Kentucky, Ohio, Georgia and most recently Louisiana on May 30, 2019.[85] In May 2019, the US Supreme Court upheld an Indiana state law that requires fetuses which were aborted be buried or cremated.[86] In a December 2019 case, the court declined to review a lower court decision which upheld a Kentucky law requiring doctors to perform ultrasounds and show fetal images to patients before abortions.[87] On June 29, 2020, previous Supreme Court rulings banning abortion restrictions appeared to be upheld when the U.S Supreme Court struck down the Louisiana anti-abortion law[88] Following the ruling, the legality of laws restricting abortion in states such as Ohio was then called into question.[89] It was also noted that Supreme Court Chief Justice John Roberts, who agreed that the Louisiana anti-abortion law was unconstitutional, had previously voted uphold a similar law in Texas which was struck down by the U.S. Supreme Court in 2016.[90] ### In response to the coronavirus pandemic[edit] Main article: Impact of the COVID-19 pandemic on abortion in the United States Amid the COVID-19 pandemic, anti-abortion government officials in several American states enacted or attempted to enact restrictions on abortion, characterizing it as a non-essential procedure that can be suspended during the medical emergency.[91] The orders have led to several legal challenges and criticism by human rights groups and several national medical organizations, including the American Medical Association.[92] Legal challenges on behalf of abortion providers, many of which are represented by the American Civil Liberties Union and Planned Parenthood, have successfully stopped most of the orders on a temporary basis.[91] One challenge was made against the FDA's rule on the distribution of mifepristone (RU-486), one of the two-part drug regiment to induce abortions. Since 2000, it is only available through health providers under the FDA's ruling. Due to the COVID-19 pandemic, access to mifepristone was a concern, and the American College of Obstetricians and Gynecologists along with other groups sued to have the rule relaxed to allow women to be able to access mifepristone at home through mail-order or retail pharmacies. While the Fourth Circuit issued a preliminary injunction against the FDA's ruling that would have allowed wider distribution, the Supreme Court ordered in a 6-3 decision in January 2021 to put a stay on the injunction, maintaining the FDA's rule.[93] ## Qualifying requirements for abortion providers[edit] Map showing which states require parental involvement (minors). Parental notification or consent not required One parent must be informed beforehand Both parents must be informed beforehand One parent must consent beforehand Both parents must consent beforehand One parent must consent and be informed beforehand Parental notification law currently enjoined Parental consent law currently enjoined Mandatory waiting period laws in the U.S. No mandatory waiting period Waiting period of less than 24 hours Waiting period of 24 hours or more Waiting period law currently enjoined Abortion counseling laws in the U.S. No mandatory counselling Counselling in person, by phone, mail, and/or other Counselling in person only Counselling law enjoined [needs update] Mandatory ultrasound laws in the U.S. Mandatory. Must display image. Mandatory. Must offer to display image. Mandatory. Law unenforceable. Not mandatory. If ultrasound is performed, must offer to display image. Not mandatory. Must offer ultrasound. Not mandatory. Qualifying requirements for performing abortions vary from state to state,[94] and are currently being changed in several states by lawmakers who anticipate the possibility that Roe v. Wade may soon be overturned.[95] Currently, New York,[96] Illinois,[97] and Maine[98] allow non-physician health professionals, such as physicians' assistants, nurse practitioners, and certified nurse midwives, acting within their scope of practice, to perform abortion procedures; their laws do not explicitly specify which types of abortions these non-physicians may do. California, Oregon, Montana, Vermont, and New Hampshire allow qualified non-physician health professionals to do first-trimester aspiration abortions and to prescribe drugs for medical abortions. Washington State, New Mexico, Alaska, Maryland, Massachusetts, Connecticut, and New Jersey allow qualified non-physicians to prescribe drugs for medical abortions only.[99] In all other states, only licensed physicians may perform abortions.[100] In 2016, the FDA issued new guidelines recommending that qualified non-physician health-care professionals be allowed to prescribe mifepristone in all states; however, these guidelines are not binding, and states are free to determine their own policies regarding mifepristone.[101] ## Statistics[edit] Main article: Abortion statistics in the United States Because reporting of abortions is not mandatory, statistics are of varying reliability. Both the Centers For Disease Control (CDC)[102] and the Guttmacher Institute[103][104] regularly compile these statistics. [105] [103][104] ### Number of abortions[edit] The annual number of legal induced abortions in the US doubled between 1973 and 1979, and peaked in 1990. There was a slow but steady decline throughout the 1990s. Overall, the number of annual abortions decreased by 6% between 2000 and 2009, with temporary spikes in 2002 and 2006.[106] By 2011, abortion rate in the nation dropped to its lowest point since the Supreme Court legalized the procedure. According to a study performed by Guttmacher Institute, long-acting contraceptive methods had a significant impact in reducing unwanted pregnancies. There were fewer than 17 abortions for every 1,000 women of child-bearing age. That was a 13%-decrease from 2008's numbers and slightly higher than the rate in 1973, when the Supreme Court's Roe v. Wade decision legalized abortion. The study indicated a long-term decline in the abortion rate.[107][108][109][110] In 2016, the CDC reported 623,471 abortions, a 2% decrease from 636,902 in 2015.[111] ### Medical abortions[edit] A Guttmacher Institute survey of abortion providers estimated that early medical abortions accounted for 17% of all non-hospital abortions and slightly over one-quarter of abortions before 9 weeks gestation in the United States in 2008.[112] Medical abortions voluntarily reported to the CDC by 34 reporting areas (excluding Alabama, California, Connecticut, Delaware, Florida, Hawaii, Illinois, Louisiana, Maryland, Massachusetts, Nebraska, Nevada, New Hampshire, Pennsylvania, Tennessee, Vermont, Wisconsin, and Wyoming) and published in its annual abortion surveillance reports have increased every year since the September 28, 2000 FDA approval of mifepristone (RU-486): 1.0% in 2000, 2.9% in 2001, 5.2% in 2002, 7.9% in 2003, 9.3% in 2004, 9.9% in 2005, 10.6% in 2006, 13.1% in 2007, 15.8% in 2008, 17.1% in 2009 (25.2% of those at less than 9 weeks gestation).[113] Medical abortions accounted for 32% of first-trimester abortions at Planned Parenthood clinics in 2008.[114] ### Abortion and religion[edit] A majority of abortions are obtained by religiously identified women. According to the Guttmacher Institute, "more than 7 in 10 U.S. women obtaining an abortion report a religious affiliation (37% protestant, 28% Catholic, and 7% other), and 25% attend religious services at least once a month. The abortion rate for protestant women is 15 per 1,000 women, while Catholic women have a slightly higher rate, 20 per 1,000."[115] ### Abortions and ethnicity[edit] Abortion rates tend to be higher among minority women in the U.S. In 2000–2001, due to lower access to health care and contraception, the rates among black and Hispanic women were 49 per 1,000 and 33 per 1,000, respectively, vs. 13 per 1,000 among non-Hispanic white women. Note that this figure includes all women of reproductive age, including women that are not pregnant. In other words, these abortion rates reflect the rate at which U.S. women of reproductive age have an abortion each year.[116] In 2004, the rates of abortion by ethnicity in the U.S. were 50 abortions per 1,000 black women, 28 abortions per 1,000 Hispanic women, and 11 abortions per 1,000 white women.[117][118] ### Reasons for abortions[edit] A 1998 study revealed that in 1987 to 1988, women reported the following as their primary reasons for choosing an abortion:[119][120] Percentage of women Primary reason for choosing an abortion 25.5% Want to postpone childbearing 21.3% Cannot afford a baby 14.1% Has relationship problem or partner does not want pregnancy 12.2% Too young; parent(s) or other(s) object to pregnancy 10.8% Having a child will disrupt education or employment 7.9% Want no (more) children 3.3% Risk to fetal health 2.8% Risk to maternal health 2.1% Other The source of this information takes findings into account from 27 nations including the United States, and therefore, these findings may not be typical for any one nation. According to a 1987 study that included specific data about late abortions (i. e., abortions "at 16 or more weeks' gestation"),[121] women reported that various reasons contributed to their having a late abortion: Percentage of women Reasons contributing to a late abortion 71% Woman did not recognize she was pregnant or misjudged gestation 48% Woman had found it hard to make arrangements for an earlier abortion 33% Woman was afraid to tell her partner or parents 24% Woman took time to decide to have an abortion 8% Woman waited for her relationship to change 8% Someone had earlier pressured woman not to have abortion 6% Something changed some time after woman became pregnant 6% Woman did not know timing is important 5% Woman did not know she could get an abortion 2% A fetal problem was diagnosed late in pregnancy 11% Other. In 2000, cases of rape or incest accounted for 1% of abortions.[122] A 2004 study by the Guttmacher Institute reported that women listed the following amongst their reasons for choosing to have an abortion:[120] Percentage of women Reason for choosing to have an abortion 74% Having a baby would dramatically change my life 73% Cannot afford a baby now 48% Do not want to be a single mother or having relationship problems 38% Have completed my childbearing 32% Not ready for another child 25% Do not want people to know I had sex or got pregnant 22% Do not feel mature enough to raise another child 14% Husband or partner wants me to have an abortion 13% Possible problems affecting the health of the fetus 12% Concerns about my health 6% Parents want me to have an abortion 1% Was a victim of rape less than .5% Became pregnant as a result of incest A 2008 National Survey of Family Growth (NSFG) shows that rates of unintended pregnancy are highest among Blacks, Hispanics, and women with lower socio-economic status.[123] * 70% of all pregnancies among Black women were unintended * 57% of all pregnancies among Hispanic women were unintended * 42% of all pregnancies among White women were unintended ### When women have abortions (by gestational age)[edit] According to the Centers for Disease Control, in 2011, most (64.5%) abortions were performed by ≤8 weeks' gestation, and nearly all (91.4%) were performed by ≤13 weeks' gestation. Few abortions (7.3%) were performed between 14 and 20 weeks' gestation or at ≥21 weeks' gestation (1.4%). From 2002 to 2011, the percentage of all abortions performed at ≤8 weeks' gestation increased 6%. [124] Abortion in the United States by gestational age, 2016. (Data source: Centers for Disease Control and Prevention) ### Safety of abortions[edit] See also: Abortion § Safety In the US, the risk of death from carrying a child to term is approximately 14 times greater than the risk of death from a legal abortion.[125] The risk of abortion-related mortality increases with gestational age, but remains lower than that of childbirth through at least 21 weeks' gestation.[126][127][128] ## Public opinion[edit] See also: Societal attitudes towards abortion, United States abortion-rights movement, and United States anti-abortion movement Trend percent of Americans self-identifying as either "pro-life" or "pro-choice" Americans have been equally divided on the issue; a May 2018 Gallup poll indicated that 48% of Americans described themselves as "pro-choice" and 48% described themselves as "pro-life".[citation needed] A July 2018 poll indicated that 64% of Americans did not want the Supreme Court to overturn Roe vs. Wade, while 28% did.[129] The same poll found that support for abortion being generally legal was 60% during the first trimester, dropping to 28% in the second trimester, and 13% in the third trimester.[130] Support for the legalization of abortion has been consistently higher among more educated adults than less educated,[131] and in 2019, 70% of college graduates support abortion being legal in all or most cases, compared to 60% of those with some college, and 54% of those with a high school degree or less.[132] In January 2013, a majority of Americans believed abortion should be legal in all or most cases, according to a poll by NBC News and The Wall Street Journal.[133] Approximately 70% of respondents in the same poll opposed Roe v. Wade being overturned.[133] A poll by the Pew Research Center yielded similar results.[134] Moreover, 48% of Republicans opposed overturning Roe, compared to 46% who supported overturning it.[134] Gallup declared in May 2010 that more Americans identifying as "pro-life" is "the new normal", while also noting that there had been no increase in opposition to abortion. It suggested that political polarization may have prompted more Republicans to call themselves "pro-life".[135] The terms "pro-choice" and "pro-life" do not always reflect a political view or fall along a binary; in one Public Religion Research Institute poll, seven in ten Americans described themselves as "pro-choice" while almost two-thirds described themselves as "pro-life". The same poll found that 56% of Americans were in favor of legal access to abortion in all or some cases.[136] Date of poll "Pro-life" "Pro-choice" Mixed / neither Don't know what terms mean No opinion 2016, May 4–8 46% 47% 3% 3% 2% 2015, May 6–10 44% 50% 3% 2% 1% 2014, May 8–11 46% 47% 3% 3% \- 2013, May 2–7 48% 45% 3% 3% 2% 2012, May 3–6 50% 41% 4% 3% 3% 2011, May 5–8 45% 49% 3% 2% 2% 2010, March 26–28 46% 45% 4% 2% 3% 2009, November 20–22 45% 48% 2% 2% 3% 2009, May 7–10 51% 42% - 0 7% 2008, September 5–7 43% 51% 2% 1% 3% ### By gender and age[edit] Pew Research Center polling shows little change in views from 2008 to 2012; modest differences based on gender or age.[137] (The original article's table also shows by party affiliation, religion, and education level.) 2011–2012 2009–2010 2007–2008 Legal Illegal Don't Know Legal Illegal Don't Know Legal Illegal Don't Know Total 53% 41% 6% 48% 44% 8% 54% 40% 6% Men 51% 43% 6% 46% 46% 9% 52% 42% 6% Women 55% 40% 5% 50% 43% 7% 55% 39% 5% 18-29 53% 44% 3% 50% 45% 5% 52% 45% 3% 30-49 54% 42% 4% 49% 43% 7% 58% 38% 5% 50-64 55% 38% 7% 49% 42% 9% 56% 38% 6% 65+ 48% 43% 9% 39% 49% 12% 45% 44% 11% ### By educational level[edit] Support for the legalization of abortion is significantly higher among more educated adults than less educated, and has been consistently so for decades.[131] In 2019, 70% of college graduates support abortion being legal in all or most cases, as well as 60% of those with some college education, compared to 54% of those with a high school degree or less.[132] 2019 Educational attainment Legal in all or most cases Illegal in all or most cases College grad or more 70% 30% Some college 60% 39% High school or less 54% 44% ### By gender, party, and region[edit] A January 2003 CBS News/The New York Times poll examined whether Americans thought abortion should be legal or not, and found variations in opinion which depended upon party affiliation and the region of the country.[138] The margin of error is +/- 4% for questions answered of the entire sample ("overall" figures) and may be higher for questions asked of subgroups (all other figures).[138] Group Generally available Available, but with stricter limits than now Not permitted Overall 39% 38% 22% Women 37% 37% 24% Men 40% 40% 20% Democrats 43% 35% 21% Republicans 29% 41% 28% Independents 42% 38% 18% Northeasterners 48% 31% 19% Midwesterners 34% 40% 25% Southerners 33% 41% 25% Westerners 43% 40% 16% ### By trimester of pregnancy[edit] A CNN/USA Today/Gallup poll in January 2003 asked about the legality of abortion by trimester, using the question, "Do you think abortion should generally be legal or generally illegal during each of the following stages of pregnancy?"[139] This same question was also asked by Gallup in March 2000 and July 1996.[140][141] Polls indicates general support of legal abortion during the first trimester, although support drops dramatically for abortion during the second and third trimester. Since the 2011 poll, support for legal abortion during the first trimester has declined. 2018 Poll 2012 Poll 2011 Poll 2003 Poll 2000 Poll 1996 Poll Legal Illegal Legal Illegal Legal Illegal Legal Illegal Legal Illegal Legal Illegal First trimester 60% 34% 61% 31% 62% 29% 66% 35% 66% 31% 64% 30% Second trimester 28% 65% 27% 64% 24% 71% 25% 68% 24% 69% 26% 65% Third trimester 13% 81% 14% 80% 10% 86% 10% 84% 8% 86% 13% 82% ### By circumstance or reasons[edit] According to Gallup's long-time polling on abortion, the majority of Americans are neither strictly "pro-life" or "pro-choice"; it depends upon the circumstances of the pregnancy. Gallup polling from 1996 to 2009 consistently reveals that when asked the question, "Do you think abortions should be legal under any circumstances, legal only under certain circumstances, or illegal in all circumstances?", Americans repeatedly answer 'legal only under certain circumstances'. According to the poll, in any given year 48-57% say legal only under certain circumstances (for 2009, 57%), 21-34% say legal under any circumstances (for 2009, 21%), and 13-19% illegal in all circumstances (for 2009, 18%), with 1-7% having no opinion (for 2009, 4%).[140] "Do you think abortions should be legal under any circumstances, legal only under certain circumstances, or illegal in all circumstances?" Legal under any circumstances Legal only under certain circumstances Illegal in all circumstances No opinion 2018 May 1–10 29% 50% 18% 2% 2017 May 3–7 29% 50% 18% 3% 2016 May 4–8 29% 50% 19% 2% 2015 May 6–10 29% 51% 19% 1% 2014 May 8–11 28% 50% 21% 2% 2013 May 2–7 26% 52% 20% 2% 2012 Dec 27-30 28% 52% 18% 3% 2012 May 3–6 25% 52% 20% 3% 2011 Jul 15-17 26% 51% 20% 3% 2011 June 9–12 26% 52% 21% 2% 2011 May 5–8 27% 49% 22% 3% 2009 Jul 17-19 21% 57% 18% 4% 2009 May 7–10 22% 53% 23% 2% 2008 May 8–11 28% 54% 18% 2% 2007 May 10–13 26% 55% 17% 1% 2006 May 8–11 30% 53% 15% 2% According to the aforementioned poll,[140] Americans differ drastically based upon situation of the pregnancy, suggesting they do not support unconditional abortions. Based on two separate polls taken May 19–21, 2003, of 505 and 509 respondents respectively, Americans stated their approval for abortion under these various circumstances: Poll Criteria Total Poll A Poll B When the woman's life is endangered 78% 82% 75% When the pregnancy was caused by rape or incest 65% 72% 59% When the child would be born with a life-threatening illness 54% 60% 48% When the child would be born mentally disabled 44% 50% 38% When the woman does not want the child for any reason 32% 41% 24% Another separate trio of polls taken by Gallup in 2003, 2000, and 1996,[140] revealed public support for abortion as follows for the given criteria: Poll criteria 2003 Poll 2000 Poll 1996 Poll When the woman's life is endangered 85% 84% 88% When the woman's physical health is endangered 77% 81% 82% When the pregnancy was caused by rape or incest 76% 78% 77% When the woman's mental health is endangered 63% 64% 66% When there is evidence that the baby may be physically impaired 56% 53% 53% When there is evidence that the baby may be mentally impaired 55% 53% 54% When the woman or family cannot afford to raise the child 35% 34% 32% Gallup furthermore established public support for many issues supported by the anti-abortion community and opposed by the abortion rights community:[140] Legislation 2003 Poll 2000 Poll 1996 Poll A law requiring doctors to inform patients about alternatives to abortion before performing the procedure 88% 86% 86% A law requiring women seeking abortions to wait 24 hours before having the procedure done 78% 74% 73% Legislation 2005 Poll 2003 Poll 1996 Poll 1992 Poll A law requiring women under 18 to get parental consent for any abortion 69% 73% 74% 70% A law requiring that the husband of a married woman be notified if she decides to have an abortion 64% 72% 70% 73% An October 2007 CBS News poll explored under what circumstances Americans believe abortion should be allowed, asking the question, "What is your personal feeling about abortion?" The results were as follows:[139] Permitted in all cases Permitted, but subject to greater restrictions than it is now Only in cases such as rape, incest, or to save the woman's life Only permitted to save the woman's life Never Unsure 26% 16% 34% 16% 4% 4% ### Additional polls[edit] Results of Gallup opinion poll in USA since 1975 - legal restriction of abortion[142] * A June 2000 Los Angeles Times survey found that, although 57% of polltakers considered abortion to be murder, half of that 57% believed in allowing women access to abortion. The survey also found that, overall, 65% of respondents did not believe abortion should be legal after the first trimester, including 72% of women and 58% of men. Further, the survey found that 85% of Americans polled supported abortion in cases of risk to a woman's physical health, 54% if the woman's mental health was at risk, and 66% if a congenital abnormality was detected in the fetus.[143] * A July 2002 Public Agenda poll found that 44% of men and 42% of women thought that "abortion should be generally available to those who want it", 34% of men and 35% of women thought that "abortion should be available, but under stricter than limits it is now", and 21% of men and 22% of women thought that "abortion should not be permitted".[144] * A January 2003 ABC News/The Washington Post poll also examined attitudes towards abortion by gender. In answer to the question, "On the subject of abortion, do you think abortion should be legal in all cases, legal in most cases, illegal in most cases or illegal in all cases?", 25% of women responded that it should be legal in "all cases", 33% that it should be legal in "most cases", 23% that it should be illegal in "most cases", and 17% that it should be illegal in "all cases". 20% of men thought it should be legal in "all cases", 34% legal in "most cases", 27% illegal in "most cases", and 17% illegal in "all cases".[144] * Most Fox News viewers favor both parental notification as well as parental consent, when a minor seeks an abortion. A Fox News poll in 2005 found that 78% of people favor a notification requirement, and 72% favor a consent requirement.[145] * An April 2006 Harris poll on Roe v. Wade, asked, "In 1973, the U.S. Supreme Court decided that states' laws which made it illegal for a woman to have an abortion up to three months of pregnancy were unconstitutional, and that the decision on whether a woman should have an abortion up to three months of pregnancy should be left to the woman and her doctor to decide. In general, do you favor or oppose this part of the U.S. Supreme Court decision making abortions up to three months of pregnancy legal?", to which 49% of respondents indicated favor while 47% indicated opposition. The Harris organization has concluded from this poll that, "49 percent now support Roe vs. Wade".[146] * Two polls were released in May 2007 asking Americans "With respect to the abortion issue, would you consider yourself to be pro-choice or pro-life?" May 4–6, a CNN poll found 45% said "pro-choice" and 50% said pro-life.[147] Within the following week, a Gallup poll found 50% responding "pro-choice" and 44% pro-life.[148] * In 2011, a poll conducted by the Public Religion Research Institute found that 43% of respondents identified themselves as both "pro-life" and "pro-choice".[149] ### "Partial birth abortion"[edit] See also: Partial-Birth Abortion Ban Act "Partial-Birth abortion" is nomenclature for a procedure called intact dilation and extraction generally used by those who oppose the procedure. A Rasmussen Reports poll four days after the Supreme Court's opinion in Gonzales v. Carhart found that 40% of respondents "knew the ruling allowed states to place some restrictions on specific abortion procedures." Of those who knew of the decision, 56% agreed with the decision and 32% were opposed.[150] An ABC poll from 2003 found that 62% of respondents thought partial-birth abortion should be illegal; a similar number of respondents wanted an exception "if it would prevent a serious threat to the woman's health". Gallup has repeatedly queried the American public on this issue, as seen on its Abortion page:[140] Legislation 2003 2000 2000 2000 1999 1998 1997 1996 A law which would make it illegal to perform a specific abortion procedure conducted in the last six months (or second and/or third trimester) of pregnancy known by some opponents as a partial birth abortion, except in cases necessary to save the life of the mother 70% 63% 66% 64% 61% 61% 55% 57% ## Abortion financing[edit] State Medicaid coverage of medically necessary abortion services. Navy blue: Medicaid covers medically necessary abortion for low-income women through legislation Royal blue: Medicaid covers medically necessary abortions for low-income women under court order Gray: Medicaid denies abortion coverage for low-income women except for cases of rape, incest, or life endangerment. The abortion debate has also been extended to the question of who pays the medical costs of the procedure, with some states using the mechanism as a way of reducing the number of abortions. The cost of an abortion varies depending on factors such as location, facility, timing, and type of procedure. In 2005, a non-hospital abortion at 10 weeks' gestation ranged from $90 to $1,800 (average: $430), whereas an abortion at 20 weeks' gestation ranged from $350 to $4,520 (average: $1,260). Costs are higher for a medical abortion than a first-trimester surgical abortion. ### Medicaid[edit] The Hyde Amendment is a federal legislative provision barring the use of federal Medicaid funds to pay for abortions except for rape and incest.[151] The provision, in various forms, was in response to Roe v. Wade, and has been routinely attached to annual appropriations bills since 1976, and represented the first major legislative success by the pro-life movement. The law requires that states cover abortions under Medicaid in the event of rape, incest, and life endangerment. Based on the federal law: * 32 states and D. C. fund abortions through Medicaid only in the cases of rape, incest, or life endangerment. SD covers abortions only in the cases of life endangerment, which does not comply with federal requirements under the Hyde Amendment. IN, UT, and WI have expanded coverage to women whose physical health is jeopardized, and IA, MS, UT, and VA also include fetal abnormality cases. * 17 states (AK, AZ, CA, CT, HI, IL, MD, MA, MN, MT, NJ, NM, NY, OR, VT, WA, WV) use their own funds to cover all or most "medically necessary" abortions sought by low-income women under Medicaid, 12 of which are required by State court orders to do so.[152] ### Private insurance[edit] * 5 states (ID, KY, MO, ND, OK) restrict insurance coverage of abortion services in private plans: OK limits coverage to life endangerment, rape or incest circumstances; and the other four states limit coverage to cases of life endangerment. * 11 states (CO, KY, MA, MS, NE, ND, OH, PA, RI, SC, VA) restrict abortion coverage in insurance plans for public employees, with CO and KY restricting insurance coverage of abortion under any circumstances. * U.S. laws also ban federal funding of abortions for federal employees and their dependents, Native Americans covered by the Indian Health Service, military personnel and their dependents, and women with disabilities covered by Medicare.[153] ### Mexico City policy[edit] Under this policy, US federal funding to NGOs that provide abortion is not permitted. ## Positions of U.S. political parties[edit] Though members of both major political parties come down on either side of the issue, the Republican Party is often seen as being anti-abortion, since the official party platform opposes abortion and considers unborn fetuses to have an inherent right to life. Republicans for Choice represents the minority of that party. In 2006, pollsters found that 9% of Republicans favor the availability of abortion in most circumstances.[154] Of Republican National Convention delegates in 2004, 13% believed that abortion should be generally available, and 38% believed that it should not be permitted. The same poll showed that 17% of all Republican voters believed that abortion should be generally available to those who want it, while 38% believed that it should not be permitted.[155] The Democratic Party platform considers abortion to be a woman's right. Democrats for Life of America represents the minority of that party. In 2006, pollsters found that 74% of Democrats favor the availability of abortion in most circumstances.[154] Of Democratic National Convention delegates in 2004, 75% believed that abortion should be generally available, and 2% believed that abortion should not be permitted. The same poll showed that 49% of all Democratic voters believed that abortion should be generally available to those who want it, while 13% believed that it should not be permitted.[156] The Green Party of the United States supports legal abortion as a woman's right. The Libertarian Party platform (2012) states that "government should be kept out of the matter, leaving the question to each person for their conscientious consideration".[157] Abortion is a contentious issue among Libertarians, and the Maryland-based organization Libertarians for Life opposes the legality of abortion in most circumstances. The issue of abortion has become deeply politicized: in 2002, 84% of state Democratic platforms supported the right to having an abortion while 88% of state Republican platforms opposed it. This divergence also led to Christian Right organizations like Christian Voice, Christian Coalition and Moral Majority having an increasingly strong role in the Republican Party. This opposition has been extended under the Foreign Assistance Act: in 1973 Jesse Helms introduced an amendment banning the use of aid money to promote abortion overseas, and in 1984 the Mexico City Policy prohibited financial support to any overseas organization that performed or promoted abortions. The "Mexico City Policy" was revoked by President Bill Clinton and subsequently reinstated by President George W. Bush. President Barack Obama overruled this policy by Executive Order on January 23, 2009,[citation needed] and it was reinstated on January 23, 2017, by President Donald Trump. ## Effects of legalization[edit] The 2013 winter issue of Ms. magazine was about abortion rights The risk of death due to legal abortion has fallen considerably since legalization in 1973, due to increased physician skills, improved medical technology, and earlier termination of pregnancy.[158] From 1940 through 1970, deaths of pregnant women during abortion fell from nearly 1,500 to a little over 100.[158] According to the Centers for Disease Control, the number of women who died in 1972 from illegal abortion was thirty-nine.[159] The Roe effect is a hypothesis which suggests that since supporters of abortion rights cause the erosion of their own political base by having fewer children, the practice of abortion will eventually lead to the restriction or illegalization of abortion. The legalized abortion and crime effect is another controversial theory that posits legal abortion reduces crime, because unwanted children are more likely to become criminals. Since Roe v. Wade, there have been numerous attempts to reverse the decision. In the 2011 election season, Mississippi placed an amendment on the ballot that redefine how the state viewed abortion. The personhood amendment defined personhood as "every human being from the moment of fertilization, cloning or the functional equivalent thereof". If passed, it would have been illegal to get an abortion in the state.[160] On July 11, 2012, a Mississippi federal judge ordered an extension of his temporary order to allow the state's only abortion clinic to stay open. The order will stay in place until U.S. District Judge Daniel Porter Jordan III can review newly drafted rules on how the Mississippi Department of Health will administer a new abortion law. The law in question came into effect on July 1, 2012.[161] According to a 2019 study, if Roe v. Wade is reversed and abortion bans are implemented in trigger law states and states considered highly likely to ban abortion, "increases in travel distance are estimated to prevent 93,546 to 143,561 women from accessing abortion care."[162] ## Unintended live birth[edit] Although it is uncommon, women sometimes give birth in spite of an attempted abortion.[163][164][165][166][167][168][169] Reporting of livebirth after attempted abortion may not be consistent from state to state, but 38 were recorded in one study in upstate New York in the two-and-a-half years before Roe v. Wade.[170] Under the Born-Alive Infants Protection Act of 2002, medical staff must report live birth if they observe any breathing, heartbeat, umbilical cord pulsation, or confirmed voluntary muscle movement, regardless of whether the born-alive is non-viable ex utero in the long term because of birth defects, and regardless of gestational age, including gestational ages which are too early for long-term viability ex utero.[171][172][173][174][175] ## See also[edit] * United States portal * Abortion and religion * Abortion by country * Anti-abortion violence in the United States * Catholic Church and abortion in the United States * Feminism in the United States * Reproductive rights * Types of abortion restrictions in the United States * War on Women Notable cases * Becky Bell, an American teenage girl who died as a result of an unsafe abortion in 1988. * Gianna Jessen, an American woman who was born alive after an attempted saline abortion. * Sherri Finkbine, an actress who had difficulty seeking an abortion for her Thalidomide deformed baby. * Gerardo Flores, convicted in 2005 on two counts of capital murder for giving his girlfriend, who was carrying twins, an at-home abortion. * Rosie Jimenez, an American woman who died the first recorded death due to an illegal abortion after federal Medicaid funds for abortions were removed by the Hyde Amendment. * Gerri Santoro, an American woman who died because of an illegal abortion in 1964. ## References[edit] 1. ^ Wilson, Joshua C. 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Vox. 96. ^ Burke, Michael (January 22, 2019). "New York passes bill expanding abortion access". TheHill. 97. ^ Caroline Kelly. "Illinois governor signs sweeping abortion protection bill into law". CNN. 98. ^ "Maine expands list of abortion providers". Associated Press. June 10, 2019. Archived from the original on June 11, 2019. Retrieved September 19, 2019. "Maine is making it easier to get an abortion with the governor’s signing of a bill Monday to allow medical professionals who are not doctors to perform the procedure. The bill, which Democratic Gov. Janet Mills introduced herself, will go into effect 90 days after the Legislature adjourns, which is expected in mid-June. Maine is now set to allow nurse practitioners, physician assistants and certified nurse-midwives to provide abortion medication and perform in-clinic abortions, which typically involve suction. ... Maine will be the second state after California with a law allowing non-doctors to perform in-clinic abortions, according to Maine’s Office of Policy and Legal Analysis." 99. ^ "Study: Abortions Are Safe When Performed By Nurse Practitioners, Physician Assistants, Certified Nurse Midwives". Retrieved January 25, 2017. 100. ^ Technically, Colorado, Kansas, and West Virginia do not have laws forbidding non-physicians from doing abortions, but liability issues effectively prevent non-physicians from doing them in these states. 101. ^ "FDA relaxes guidelines for abortion pill - The Portland Press Herald". March 30, 2016. Retrieved January 25, 2017. 102. ^ "CDCs Abortion Surveillance System FAQs". Center for Disease Control and Prevention. November 21, 2012. Retrieved August 8, 2013. 103. ^ a b Jones, Rachel K.; Kooistra, Kathryn (March 2011). "Abortion Incidence and Access to Services in the United States, 2008" (PDF). Perspectives on Sexual and Reproductive Health. 43 (1): 41–50. doi:10.1363/4304111. PMID 21388504. Retrieved December 8, 2017. 104. ^ a b Jones, Rachel K.; Witwer, Elizabeth; Jerman, Jenna (September 2019). "Abortion Incidence and Service Availability in the United States, 2017". doi:10.1363/2019.30760. Retrieved December 12, 2020. Cite journal requires `\|journal=` (help) 105. ^ Jones, Laurie (2003). "Abortion Surveillance --- United States, 2000". Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C. : 2002). Center for Disease Control. 52 (12): 1–32. PMID 14647014. Retrieved October 2, 2013. 106. ^ D. Elam-Evans, Ph.D., Laurie (2003). "Abortion Surveillance --- United States, 2000". Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C. : 2002). Center for Disease Control. 52 (12): 1–32. PMID 14647014. Retrieved October 2, 2013. 107. ^ Somashekhar, Sandhya (February 2, 2014). "Study: Abortion rate at lowest point since 1973". Washington Post. Retrieved February 3, 2014. 108. ^ Moon, Angela (February 2, 2014). "U.S. abortion rate hits lowest level since 1973: study". Reuters. Retrieved February 3, 2014. 109. ^ Bassett, Laura (February 2, 2014). "U.S. Abortion Rate Hits Lowest Point Since 1973". Huffington Post. Retrieved February 3, 2014. 110. ^ Jayson, Sharon (February 2, 2014). "Abortion rate at lowest level since 1973". USA Today. Retrieved February 3, 2014. 111. ^ Jatlaoui, TC; Eckhaus, L; Mandel, MG; Nguyen, A; Oduyebo, T; Petersen, Emily; Whiteman, MK (November 29, 2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68 (11): 1–41. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738. PMID 31774741. 112. ^ Jones, Rachel K.; Kooistra, Kathryn (March 2011). "Abortion incidence and access to services in the United States, 2008" (PDF). Perspectives on Sexual and Reproductive Health. 43 (1): 41–50. doi:10.1363/4304111. PMID 21388504. 94% of non-hospital medical abortions used mifepristone and misoprostol—6% used methotrexate and misoprostol—in the United States in 2008. 113. ^ Pazol, Karen; Creanga, Andreea A.; Zane, Suzanne B.; Burley, Kim D.; Jamieson, Denise J; Division of Reproductive Health (November 23, 2012). "Abortion surveillance - United States, 2009" (PDF). MMWR Surveillance Summaries. 61 (8): 1–44. PMID 23169413. 114. ^ Fjerstad, Mary; Trussell, James; Sivin, Irving; Lichtenberg, E. Steve; Cullins, Vanessa (July 9, 2009). "Rates of serious infection after changes in regimens for medical abortion". New England Journal of Medicine. 361 (2): 145–151. doi:10.1056/NEJMoa0809146. PMC 3568698. PMID 19587339. 115. ^ Jones, Rachel K (June 2011). "Changes in Abortion Rates Between 2000 and 2008 and Lifetime Incidence of Abortion". Obstetrics & Gynecology. 117 (6): 1358–1366. doi:10.1097/AOG.0b013e31821c405e. PMID 21606746. S2CID 21593113. 116. ^ Guttmacher.org"Get "In the Know": Questions About Pregnancy, Contraception and Abortion". Archived from the original on March 11, 2008. Retrieved April 26, 2007.CS1 maint: bot: original URL status unknown (link) 117. ^ Abortion Rate Falls, But Not Equally for All Women, Time magazine, September 23, 2008 118. ^ Abortion and Women of Color: The Bigger Picture, Guttmacher Policy Review, Volume 11, Issue 3 119. ^ Bankole, Akinrinola; Singh, Susheela; Haas, Taylor (1998). "Reasons Why Women Have Induced Abortions: Evidence from 27 Countries". International Family Planning Perspectives. 24 (3): 117–27, 152. doi:10.2307/3038208. JSTOR 3038208. 120. ^ a b Finer, Lawrence B.; Frohwirth, Lori F.; Dauphinee, Lindsay A.; Singh, Susheela; Moore, Ann M. (September 2005). "Reasons U.S. Women Have Abortions: Quantitative and Qualitative Perspectives" (PDF). Perspectives on Sexual and Reproductive Health. 37 (3): 110–8. doi:10.1111/j.1931-2393.2005.tb00045.x. JSTOR 3650599. PMID 16150658. 121. ^ Torres, Aida; Forrest, Jacqueline Darroch (Jul–Aug 1988). "Why Do Women Have Abortions?". Family Planning Perspectives. 20 (4): 169–76. doi:10.2307/2135792. JSTOR 2135792. PMID 3243347. S2CID 25224865. "Some 42 facilities were originally invited to participate in the study; these include six at which a relatively large number of late abortions (those at 16 or more weeks' gestation) were performed." 122. ^ "Induced Abortion Facts in Brief" (2002) (13,000 out of 1.31 million abortions in 2000 were on account of rape or incest). Retrieved via InfoPlease January 7, 2007. Adapted from "Alan Guttmacher Institute, Induced Abortion, Facts in Brief, 2002". Facts in Brief Archived October 13, 2007, at the Wayback Machine from Guttmacher Institute does not include the 13 000 statistic though, nor does the 2003 version. 123. ^ Dehlendorf, Christine; Lisa Harris (October 1, 2013). "Disparities in Abortion Rates: A Public Health Approach". American Journal of Public Health. 103 (10): 1772–1779. doi:10.2105/ajph.2013.301339. PMC 3780732. PMID 23948010. 124. ^ "Abortion Surveillance — United States, 2011". Retrieved January 25, 2017. 125. ^ Raymond, E. G.; Grimes, D. A. (2012). "The Comparative Safety of Legal Induced Abortion and Childbirth in the United States". Obstetrics & Gynecology. 119 (2, Part 1): 215–219. doi:10.1097/AOG.0b013e31823fe923. PMID 22270271. S2CID 25534071. " > ...The pregnancy-associated mortality rate among women who delivered live neonates was 8.8 deaths per 100,000 live births. The mortality rate related to induced abortion was 0.6 deaths per 100,000 abortions...The risk of death associated with childbirth is approximately 14 times higher than that with abortion. " 126. ^ Bartlett LA; Berg CJ; Shulman HB; et al. (April 2004). "Risk factors for legal induced abortion-related mortality in the United States". Obstetrics & Gynecology. 103 (4): 729–37. doi:10.1097/01.AOG.0000116260.81570.60. PMID 15051566. S2CID 42597014. 127. ^ Trupin, Suzanne (May 27, 2010). "Elective Abortion". eMedicine. Archived from the original on December 14, 2004. Retrieved June 1, 2010. "At every gestational age, elective abortion is safer for the mother than carrying a pregnancy to term." 128. ^ Pittman, Genevra (January 23, 2012). "Abortion safer than giving birth: study". Reuters. Archived from the original on February 6, 2012. Retrieved February 4, 2012. 129. ^ "Gallup: Abortion". Gallup poll. June 22, 2007. 130. ^ "Trimesters Still Key to U.S. Abortion Views". June 13, 2018. 131. ^ a b Saad, Lydia (April 28, 2010). "Education Trumps Gender in Predicting Support for Abortion - College-educated adults -- and especially college-educated women -- most supportive". Gallop. Archived from the original on September 16, 2017. Retrieved January 5, 2020. "Educational achievement is much more important than gender in determining support for broadly legal abortion, with college-educated adults -- and especially college-educated women -- the most supportive. This has been the case since the 1970s. Gallup's long-term abortion question -- instituted two years after the 1973 Roe v. Wade ruling gave sweeping constitutional protection to abortion -- asks Americans to say whether they believe abortion should be "legal under any circumstances," "legal only under certain circumstances," or "illegal in all circumstances."" 132. ^ a b "Public Opinion on Abortion - Views on abortion, 1995-2019". Pew Research Center. August 29, 2019. Archived from the original on September 19, 2019. Retrieved January 5, 2020. "Seven-in-ten college graduates (70%) say abortion should be legal in all or most cases, as do 60% of those with some college education. A slim majority of those with a high school degree or less education share this opinion: 54% say abortion should be legal in all or most cases, while 44% say it should be illegal in all or most cases." 133. ^ a b Murray, Mark (January 21, 2013). "NBC/WSJ poll: Majority, for first time, want abortion to be legal". NBC News. Retrieved August 8, 2013. 134. ^ a b "Roe v. Wade at 40: Most Oppose Overturning Abortion Decision". January 16, 2013. 135. ^ Saad, Lydia (May 14, 2010). "The New Normal on Abortion: Americans More "Pro-Life"". Gallup. Retrieved August 8, 2013. 136. ^ "Committed to Availability, Conflicted about Morality: What the Millennial Generation Tells Us about the Future of the Abortion Debate and the Culture Wars". Public Religion Research Institute. June 9, 2011. 137. ^ "Abortion views table 2008–2012". Pew Research Center for the People & the Press. April 25, 2012. Retrieved August 8, 2013. 138. ^ a b "Poll: Strong Support For Abortion Rights" (January 22, 2003). CBS News. Retrieved January 11, 2007. 139. ^ a b The Polling Report. (2008). Retrieved September 10, 2008. 140. ^ a b c d e f "Abortion". Gallup Poll. Gallup.com. June 22, 2007. p. 2. Archived from the original on May 13, 2010. Retrieved May 13, 2010. 141. ^ See Saad, "Americans Walk the Middle Road on Abortion", The Gallup Poll Monthly (April 2000); "Gallup Poll Topics". Archived from the original on June 3, 2008. Retrieved August 25, 2016. from Florida Right to Life. Retrieved January 12, 2007. 142. ^ "Abortion". Gallup.com. June 22, 2007. Retrieved August 8, 2013. 143. ^ Rubin, Allisa J. (June 18, 2000). "Americans Narrowing Support for Abortion." Los Angeles Times. Retrieved January 11, 2007. 144. ^ a b Public Agenda Online. (2006). Men and women hold similar views on the legality of abortion 145. ^ FOX News/Opinion Dynamics Poll. April 25–26, 2005: "Do you think a female under age 18 should be required by state law to notify at least one parent or guardian before having an abortion?" 78% yes, 17% no. "Do you think a female under age 18 should be required by state law to get permission or consent from at least one parent or guardian before having an abortion?" 72% yes, 22% no. 146. ^ Harris Interactive, (May 4, 2006). "Support for Roe vs. Wade Declines to Lowest Level Ever." Retrieved 2007-01-04. Pro-life activists have disputed whether the Harris poll question is a valid measure of public opinion about Roe's overall decision, because the question focuses only on the first three months of pregnancy. See Franz, Wanda. "The Continuing Confusion About Roe v. Wade" Archived May 12, 2008, at the Wayback Machine, NRL News (June 2007). Also see Adamek, Raymond. "Abortion Polls", Public Opinion Quarterly, Vol. 42, No. 3 (Autumn, 1978), pp. 411–413. 147. ^ CNN Opinion Research Poll, (May 9, 2007). Retrieved 2007-05-27. 148. ^ "Abortion" The Gallup Poll (May 21, 2007) Retrieved May 28, 2007. 149. ^ "Moving Beyond "Pro-Choice" and "Pro-Life" - PRRI". Retrieved January 25, 2017. 150. ^ Most Who Know of Decision Agree With Supreme Court on Partial Birth Abortion Archived 2007-04-27 at the Wayback Machine Rasmussen Reports. April 22, 2007. Retrieved on April 26, 2007 151. ^ "The Hyde Amendment" (PDF). National Committee for a Human Life Amendment. April 2008. Archived from the original (PDF) on November 16, 2009. Retrieved January 23, 2009. text and history 152. ^ Francis Roberta W. "Frequently Asked Questions". Equal Rights Amendment. Alice Paul Institute. Archived from the original on April 17, 2009. Retrieved September 13, 2009. 153. ^ "Women's Health Policy Facts" (PDF). The Henry J. Kaiser Family Foundation. 2008. Archived from the original (PDF) on February 25, 2009. Retrieved January 2, 2009. 154. ^ a b Archived June 3, 2008, at the Wayback Machine (archived from the original on June 3, 2008) 155. ^ "The New York Times/CBS News Poll 2004 Republican National Delegate Survey (Q29)" (PDF). The New York Times. 156. ^ "The New York Times/CBS News Poll 2004 Democratic National Delegate Survey (Q29)" (PDF). The New York Times. 157. ^ National Platform of the Libertarian Party, 1.4 Abortion, adopted in Convention, May 2012. 158. ^ a b Coble, Yank D. (1992). "Induced Termination of Pregnancy Before and After Roe v Wade: Trends in the Mortality and Morbidity of Women". JAMA: The Journal of the American Medical Association. 268 (22): 3231. doi:10.1001/jama.1992.03490220075032. 159. ^ Strauss, Lilo T.; Herndon, Joy; Chang, Jeani; Parker, Wilda Y.; Bowens, Sonya V.; Zane, Suzanne B.; Berg, Cynthia J.; Berg, CJ (2004). "Abortion surveillance--United States, 2001". Morbidity and Mortality Weekly Report. 53 (9): 1–32. PMID 15562258. 160. ^ "Mississippi 'Personhood' Amendment Vote Fails". Huffington Post. November 8, 2011. 161. ^ Phillips, Rich. "Judge lets Mississippi's only abortion clinic stay open -- for now". CNN. 162. ^ Myers, Caitlin; Jones, Rachel; Upadhyay, Ushma (July 31, 2019). "Predicted changes in abortion access and incidence in a post-Roe world". Contraception. 100 (5): 367–373. doi:10.1016/j.contraception.2019.07.139. ISSN 0010-7824. PMID 31376381. 163. ^ "Termination of Pregnancy for Fetal Abnormality" (PDF). Royal College of Obstetricians and Gynaecologists: 30. May 2010. Retrieved October 26, 2015. " Live birth following medical termination of pregnancy before 21+6 weeks of gestation is very uncommon. Nevertheless, women and their partners should be counselled about this unlikely possibility and staff should be trained to deal with this eventuality. Instances of recorded live birth and survival increase as gestation at birth extends from 22 weeks. In accordance with prior RCOG guidance, feticide should be routinely offered from 21+6 weeks of gestation.Where the fetal abnormality is not compatible with survival, termination of pregnancy without prior feticide may be preferred by some women. In such cases, delivery management should be discussed and planned with the parents and all health professionals involved and a written care plan agreed before termination takes place. Where the fetal abnormality is not lethal and termination of pregnancy is being undertaken after 22 weeks of gestation, failure to perform feticide could result in live birth and survival, an outcome that contradicts the intention of the abortion. In such situations, the child should receive the neonatal support and intensive care that is in the child's best interest and its condition managed within published guidance for neonatal practice." 164. ^ Hollander, D. (May 2004). "For Second-Trimester Abortion, Women Given Misoprostol Vaginally Report the Greatest Satisfaction". Perspectives on Sexual and Reproductive Health. 36 (3): 133. doi:10.1111/j.1931-2393.2004.tb00203.x. Retrieved October 26, 2015. "...Additionally, a significantly higher proportion of women in the vaginal misoprostol group, and a marginally higher proportion of those in the oral misoprostol group, than of those in the intra-amniotic prostaglandin group had a live birth (20%, 15% and 5%, respectively)...." 165. ^ Hopper, Tristin (February 1, 2013). "Birth of a legal quandry[sic]: Live-birth abortions a perilous grey zone in Canada's criminal code". National Post. Retrieved October 26, 2015. 166. ^ Vellacott, Maurice (January 23, 2013). "Letter to RCMP Commissioner Rob Paulson" (PDF). www.straight.com. Archived from the original (Letter) on May 2, 2013. Retrieved October 26, 2015. Alt URL 167. ^ The Associated Press (February 7, 2009). "Doctor loses license over live-birth abortion". New York Daily News. Retrieved October 26, 2015. 168. ^ Jeffries, Liz (August 2, 1981). "Abortion". The Philadelphia Inquirer. Archived from the original (PDF) on September 9, 1981. Retrieved October 26, 2015. 169. ^ Wyldes (May 2007). "Termination of pregnancy for fetal anomaly: a population-based study 1995 to 2004". BJOG: An International Journal of Obstetrics & Gynaecology. 114 (5): 639–642. doi:10.1111/j.1471-0528.2007.01279.x. PMID 17355269. S2CID 9966493. 170. ^ Stroh, G. (September 1, 1976). "Reported live births following induced abortion: two and one-half years' experience in Upstate New York". American Journal of Obstetrics and Gynecology. 126 (1): 83–90. doi:10.1016/0002-9378(76)90469-5. PMID 961751. 171. ^ "House Report 107-186 - BORN-ALIVE INFANTS PROTECTION ACT OF 2001". Retrieved January 25, 2017. 172. ^ Pear, Robert (April 23, 2005). "New Attention for 2002 Law on Survivors of Abortion". The New York Times. Retrieved October 26, 2015. 173. ^ Diedrich, J.; Drey, E. (January 2010). "Clinical Guidelines: Induction of fetal demise before abortion" (PDF). Contraception. 81 (6): 462–73. doi:10.1016/j.contraception.2010.01.018. PMID 20472112. Retrieved October 26, 2015. 174. ^ Jansen, Robert (1990). "Unfinished Feticide". Journal of Medical Ethics. 16 (2): 61–65. doi:10.1136/jme.16.2.61. PMC 1375929. PMID 2195170. 175. ^ Sfakianaki, Anna K. (February 1, 2014). "Potassium Chloride-Induced Fetal Demise: A Retrospective Cohort Study of Efficacy and Safety". Journal of Ultrasound in Medicine. 33 (2): 337–341. doi:10.7863/ultra.33.2.337. PMID 24449738. S2CID 6060208. Archived from the original on October 28, 2015. Retrieved October 26, 2015. ## Further reading[edit] * Reagan, Leslie J. (1997). When Abortion Was a Crime: Women, Medicine, and Law in the United States, 1867–1973. Berkeley, Calif.: University of California Press. ISBN 0-520-08848-4. * Rowland, Debran (2004). The Boundaries of Her Body: The Troubling History of Women's Rights in America. Naperville, Ill.: Sphinx Publishing. ISBN 1-57248-368-7. * Shimabukuro, Jon O. (December 7, 2018). "Abortion: Judicial History and Legislative Response" (PDF). Washington, DC: Congressional Research Service. * Weingarten, Karen (2014). Abortion in the American Imagination: Before Life and Choice, 1880–1940. New Brunswick, NJ: Rutgers University Press. ISBN 978-0-8135-6530-9. ## External links[edit] * Abortion pill access * * Full Text of Roe v. 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stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Abortion in the United States	None	8,481	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_the_United_States	2021-01-18T18:32:38	{"wikidata": ["Q283681"]}
Brain abscess Brain abscess in a person with a CSF shunt.[1] SpecialtyNeurology Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone, epidural abscess) or remote (lung, heart, kidney etc.) infectious sources, within the brain tissue. The infection may also be introduced through a skull fracture following a head trauma or surgical procedures. Brain abscess is usually associated with congenital heart disease in young children. It may occur at any age but is most frequent in the third decade of life. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 2.1 Bacterial * 2.2 Other organisms * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 References * 7 External links ## Signs and symptoms[edit] Fever, headache, and neurological problems, while classic, only occur in 20% of people with brain abscess.[2] The famous triad of fever, headache and focal neurologic findings are highly suggestive of brain abscess. These symptoms are caused by a combination of increased intracranial pressure due to a space-occupying lesion (headache, vomiting, confusion, coma), infection (fever, fatigue etc.) and focal neurologic brain tissue damage (hemiparesis, aphasia etc.). The most frequent presenting symptoms are headache, drowsiness, confusion, seizures, hemiparesis or speech difficulties together with fever with a rapidly progressive course. Headache is characteristically worse at night and in the morning, as the intracranial pressure naturally increases when in the supine position. This elevation similarly stimulates the medullary vomiting center and area postrema, leading to morning vomiting. Other symptoms and findings depend largely on the specific location of the abscess in the brain. An abscess in the cerebellum, for instance, may cause additional complaints as a result of brain stem compression and hydrocephalus. Neurological examination may reveal a stiff neck in occasional cases (erroneously suggesting meningitis). ## Pathophysiology[edit] ### Bacterial[edit] Brain abscess after metastasis treatment. Anaerobic and microaerophilic cocci and gram-negative and gram-positive anaerobic bacilli are the predominate bacterial isolates. Many brain abscesses are polymicrobical. The predominant organisms include: Staphylococcus aureus, aerobic and anaerobic streptococci (especially Streptococcus intermedius), Bacteroides, Prevotella, and Fusobacterium species, Enterobacteriaceae, Pseudomonas species, and other anaerobes.[3] Less common organisms include: Haemophillus influenzae, Streptococcus pneumoniae and Neisseria meningitidis.[4] Bacterial abscesses rarely (if ever) arise de novo within the brain, although establishing a cause can be difficult in many cases. There is almost always a primary lesion elsewhere in the body that must be sought assiduously, because failure to treat the primary lesion will result in relapse. In cases of trauma, for example in compound skull fractures where fragments of bone are pushed into the substance of the brain, the cause of the abscess is obvious. Similarly, bullets and other foreign bodies may become sources of infection if left in place. The location of the primary lesion may be suggested by the location of the abscess: infections of the middle ear result in lesions in the middle and posterior cranial fossae;[5] congenital heart disease with right-to-left shunts often result in abscesses in the distribution of the middle cerebral artery;[6][7] and infection of the frontal and ethmoid sinuses usually results in collection in the subdural sinuses. ### Other organisms[edit] Fungi and parasites may also cause the disease. Fungi and parasites are especially associated with immunocompromised patients. Other causes include: Nocardia asteroides, Mycobacterium, Fungi (e.g. Aspergillus, Candida, Cryptococcus, Mucorales, Coccidioides, Histoplasma capsulatum, Blastomyces dermatitidis, Bipolaris, Exophiala dermatitidis, Curvularia pallescens, Ochroconis gallopava, Ramichloridium mackenziei, Pseudallescheria boydii), Protozoa (e.g. Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, Schistosoma, Paragonimus), and Helminths (e.g. Taenia solium). Organisms that are most frequently associated with brain abscess in patients with AIDS are poliovirus, Toxoplasma gondii, and Cryptococcus neoformans, though in infection with the latter organism, symptoms of meningitis generally predominate. These organisms are associated with certain predisposing conditions: * Sinus and dental infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. Prevotella, Porphyromonas, Bacteroides), Fusobacterium, S. aureus, and Enterobacteriaceae * Penetrating trauma—S. aureus, aerobic streptococci, Enterobacteriaceae, and Clostridium spp. * Pulmonary infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. Prevotella, Porphyromonas, Bacteroides), Fusobacterium, Actinomyces, and Nocardia * Congenital heart disease—Aerobic and microaerophilic streptococci, and S. aureus * HIV infection—T. gondii, Mycobacterium, Nocardia, Cryptococcus, and Listeria monocytogenes * Transplantation—Aspergillus, Candida, Cryptococcus, Mucorales, Nocardia, and T. gondii * Neutropenia—Aerobic gram-negative bacilli, Aspergillus, Candida, and Mucorales ## Diagnosis[edit] MRI (T1 with contrast) showing the ring-enhancing lesion. From a rare case report of an abscess formed as a complication of the CSF shunt. Jamjoom et al., 2009.[1] The diagnosis is established by a computed tomography (CT) (with contrast) examination. At the initial phase of the inflammation (which is referred to as cerebritis), the immature lesion does not have a capsule and it may be difficult to distinguish it from other space-occupying lesions or infarcts of the brain. Within 4–5 days the inflammation and the concomitant dead brain tissue are surrounded with a capsule, which gives the lesion the famous ring-enhancing lesion appearance on CT examination with contrast (since intravenously applied contrast material can not pass through the capsule, it is collected around the lesion and looks as a ring surrounding the relatively dark lesion). Lumbar puncture procedure, which is performed in many infectious disorders of the central nervous system is contraindicated in this condition (as it is in all space-occupying lesions of the brain) because removing a certain portion of the cerebrospinal fluid may alter the concrete intracranial pressure balances and causes the brain tissue to move across structures within the skull (brain herniation). Ring enhancement may also be observed in cerebral hemorrhages (bleeding) and some brain tumors. However, in the presence of the rapidly progressive course with fever, focal neurologic findings (hemiparesis, aphasia etc.) and signs of increased intracranial pressure, the most likely diagnosis should be the brain abscess. ## Treatment[edit] The treatment includes lowering the increased intracranial pressure and starting intravenous antibiotics (and meanwhile identifying the causative organism mainly by blood culture studies). Hyperbaric oxygen therapy (HBO2 or HBOT) is indicated as a primary and adjunct treatment which provides four primary functions. Firstly, HBOT reduces intracranial pressure.[8] Secondly, high partial pressures of oxygen act as a bactericide and thus inhibits the anaerobic and functionally anaerobic flora common in brain abscess. Third, HBOT optimizes the immune function thus enhancing the host defense mechanisms and fourth, HBOT has been found to be of benefit when brain abscess is concomitant with cranial osteomyleitis. Secondary functions of HBOT include increased stem cell production and up-regulation of VEGF which aid in the healing and recovery process.[9] Surgical drainage of the abscess remains part of the standard management of bacterial brain abscesses. The location and treatment of the primary lesion also crucial, as is the removal of any foreign material (bone, dirt, bullets, and so forth). There are few exceptions to this rule: Haemophilus influenzae meningitis is often associated with subdural effusions that are mistaken for subdural empyemas. These effusions resolve with antibiotics and require no surgical treatment. Tuberculosis can produce brain abscesses that look identical to conventional bacterial abscesses on CT imaging. Surgical drainage or aspiration is often necessary to identify Mycobacterium tuberculosis, but once the diagnosis is made no further surgical intervention is necessary. CT guided stereotactic aspiration is also indicated in the treatment of brain abscess. The use of pre-operative imaging, intervention with post-operative clinical and biochemical monitoring used to manage brain abscesses today dates back to the Pennybacker system pioneered by Somerset, Kentucky-born neurosurgeon Joseph Buford Pennybacker, director of the neurosurgery department of the Radcliffe Infirmary, Oxford from 1952 to 1971. [10] ## Prognosis[edit] While death occurs in about 10% of cases, people do well about 70% of the time.[2] This is a large improvement from the 1960s due to improved ability to image the head, more effective neurosurgery and more effective antibiotics.[2] ## References[edit] 1. ^ a b Jamjoom AA, Waliuddin AR, Jamjoom AB (2009). "Brain abscess formation as a CSF shunt complication: a case report". Cases J. 2 (1): 110. doi:10.1186/1757-1626-2-110. PMC 2639569. PMID 19183497. 2. ^ a b c Brouwer, MC; Coutinho, JM; van de Beek, D (Mar 4, 2014). "Clinical characteristics and outcome of brain abscess: systematic review and meta-analysis". Neurology. 82 (9): 806–13. doi:10.1212/WNL.0000000000000172. PMID 24477107. 3. ^ Brook I (September 2009). "Microbiology and antimicrobial treatment of orbital and intracranial complications of sinusitis in children and their management". Int. J. Pediatr. Otorhinolaryngol. 73 (9): 1183–6. doi:10.1016/j.ijporl.2009.01.020. PMID 19249108. 4. ^ Brook I (July 1995). "Brain abscess in children: microbiology and management". J. Child Neurol. 10 (4): 283–8. doi:10.1177/088307389501000405. PMID 7594262. 5. ^ Macewan W (1893). Pyogenic Infective Diseases of the Brain and Spinal Cord. Glasgow: James Maclehose and Sons. 6. ^ Ingraham FD, Matson DD (1954). Neurosurgery of Infancy andChildhood. Springfield, Ill: Charles C Thomas. p. 377. 7. ^ Raimondi AJ, Matsumoto S, Miller RA (1965). "Brain abscess in children with congenital heart disease". J Neurosurg. 23 (6): 588–95. doi:10.3171/jns.1965.23.6.0588. PMID 5861142. S2CID 22383252. 8. ^ "Home - Undersea & Hyperbaric Medical Society". 9. ^ Thom, Stephen R.; Bhopale, Veena M.; Velazquez, Omaida C.; Goldstein, Lee J.; Thom, Lynne H.; Buerk, Donald G. (1 April 2006). "Stem cell mobilization by hyperbaric oxygen". Am. J. Physiol. Heart Circ. Physiol. 290 (4): H1378–1386. doi:10.1152/ajpheart.00888.2005. PMID 16299259. S2CID 29013782. 10. ^ Visagan R, Ellis H (2017). "Joseph Buford Pennybacker, C.B.E., M.D., F.R.C.S. (1907-1983): Continuing Sir Hugh Cairns' Oxford Legacy and Pioneer of the Modern Management of Cerebral Abscesses". World Neurosurg. 104: 339–345. doi:10.1016/j.wneu.2017.01.113. PMID 28185969. ## External links[edit] Classification D * ICD-10: G06.0, G07 * ICD-9-CM: 324.0 * MeSH: D001922 * DiseasesDB: 6880 External resources * MedlinePlus: 000783 * Brain abscess at eMedicine * MR Diagnosis[permanent dead link] MedPix Imaging Brain Abscess * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Brain abscess	c0006105	8,482	wikipedia	https://en.wikipedia.org/wiki/Brain_abscess	2021-01-18T18:44:19	{"mesh": ["D001922"], "umls": ["C0006105"], "icd-9": ["324.0"], "wikidata": ["Q141440"]}
A number sign (#) is used with this entry because of evidence that distal arthrogryposis type 3 (DA3) is caused by heterozygous mutation in the PIEZO2 gene (613629) on chromosome 18p11. Description DA3, or Gordon syndrome, is distinguished from other distal arthrogryposes by short stature and cleft palate (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA3 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 5 (DA5; 108145) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of ocular abnormalities and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120). Clinical Features Gordon et al. (1969) described 6 affected persons (3 males, 3 females) in 3 generations. All 3 anomalies were present in 2 persons, whereas the other 4 persons had 1 or 2 of the 3 anomalies. Among the 6 affected, clubfoot occurred in 5, camptodactyly in 4, and cleft palate in 3. A useful list of camptodactyly syndromes was provided. Higgins et al. (1972) studied a father and 2 children with the same syndrome. The oldest affected son had several holes in the palate, camptodactyly, and minor foot deformity, while the youngest child had a bifid uvula, camptodactyly, and foot anomaly, but no cleft palate; the father had camptodactyly and foot anomaly without cleft palate. The syndrome was validated by the report of a 5-generation kindred by Halal and Fraser (1979). Penetrance was reduced more in females than in males, and cleft palate was the least frequently manifested trait. Say et al. (1980) described a sporadic case. Robinow and Johnson (1981) reported affected mother and daughter. Hall et al. (1982) referred to Gordon syndrome as 'distal arthrogryposis, type IIA'; they suggested that the first report was that of Moldenhauer (1964) and that the same disorder may have been present in the case of Krieger and Espiritu (1972). Moldenhauer (1964) described 4 females of 3 generations of a family with a condition he called Nielson syndrome. The features were short stature, ptosis, cleft palate, camptodactyly, pterygium colli, and vertebral anomalies. Fertility was normal. Ioan et al. (1993) reported a kindred with affected members in 5 generations. They pointed to reduced penetrance and carrier females as a cardinal feature of the Gordon syndrome. Schrander-Stumpel et al. (1993) described an isolated case of arthrogryposis, ophthalmoplegia, and retinopathy in a Dutch family. The patient had rigid fingers and bilateral clubfeet at birth. Deep-set eyes, a triangular face, and prominent ears were evident from an early age. At age 17, he had limited horizontal and vertical eye movements, a rigid back, stiff walk, anteverted hunched shoulders, and pectus excavatum. The fingers were long, phalangeal creases were totally absent, and flexion was limited to about 30 degrees. Abnormal pigmentation was present in both retinal maculas. Becker and Splitt (2001) reported a mother and 2 affected children with distal arthrogryposis and cleft palate and suggested a clinical overlap between Gordon syndrome and Aase-Smith syndrome (147800). None of the affected family members had Dandy-Walker malformation, but Becker and Splitt (2001) suggested that it may be a variable feature of Gordon syndrome. Alisch et al. (2017) reported a father and 2 sons who exhibited multiple contractures that involved the metacarpophalangeal and interphalangeal joints as well as the elbow, shoulder, knee, and ankle joints, who also had clubfeet, short stature, bifid uvula or cleft palate, and a distinct facial phenotype including ptosis. In addition, mild intellectual disability and delay in psychomotor development were present. In the younger son, arthrogryposis multiplex was evident on prenatal ultrasound at 13 weeks' gestation, which revealed flexed wrists and elbows as well as bilateral clubfeet. Li et al. (2018) reported 4 affected members of a 3-generation Chinese family segregating distal arthrogryposis. The proband (II5) was a 37-year-old man with congenital bilateral and symmetric contractures of fingers 2 through 5. The other 3 affected members had mild contractures restricted to the distal phalanges. All had short stature and clubfeet. None had cleft palate or ocular/facial abnormalities. Li et al. (2018) clinically diagnosed the phenotype in this family as DA1 (see 108120). Molecular Genetics McMillin et al. (2014) studied 12 families with DA3 that were negative for mutation in genes associated with distal arthrogryposis or other congenital contracture disorders, including TPM2 (190990), TNNT3 (600692), TNNI2 (191043), MYH3 (160720), and CHRNG (100730). Exome sequencing in 5 families revealed heterozygosity for a recurrent missense mutation in the PIEZO2 gene (R2686H; 613629.0003) in 4 of them, including the family originally reported by Becker and Splitt (2001). The fifth proband was heterozygous for an 8-bp deletion in PIEZO2 (613629.0005). Using molecular inversion probes for targeted sequencing in an additional 7 DA families revealed another 5 families that were heterozygous for the recurrent R2686H mutation. In addition, 2 probands who had been diagnosed with DA5, 1 of whom was the Dutch patient described by Schrander-Stumpel et al. (1993), were heterozygous for R2686H. Neither proband had cleft palate or bifid uvula; however, given the reduced penetrance of cleft palate in DA3, McMillin et al. (2014) suggested that the correct diagnosis in the 2 cases was DA3 rather than DA5. Noting that 3 syndromes with overlapping features, DA3, DA5, and MWKS, are all caused by heterozygous mutation in the PIEZO2 gene, McMillin et al. (2014) proposed that they share a common developmental mechanism and may represent variable expressivity of the same condition. In a father and 2 sons with DA3, Alisch et al. (2017) sequenced the PIEZO2 gene and identified heterozygosity for the recurrent R2686H mutation. The authors noted that affected individuals in this family exhibited mild intellectual disability and psychomotor delay, suggesting phenotypic overlap between DA3 and MWKS. In affected members of a Chinese family segregating distal arthrogryposis type 3, Li et al. (2018) identified heterozygosity for a missense mutation in the PIEZO2 gene (R2718Q; 613629.0017). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in several public variant databases. Nomenclature Hall et al. (1982) referred to Gordon syndrome as distal arthrogryposis type IIA (DAIIA); Bamshad et al. (1996) presented a revised and extended classification of the distal arthrogryposes, and referred to DAIIA as DA3. DAIIA is distinct from DA2A (193700), which is also known as Freeman-Sheldon syndrome. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Micrognathia \- Facial asymmetry (mild) Eyes \- Ptosis \- Epicanthal folds \- Ophthalmoplegia (in some patients) Mouth \- Cleft palate \- Submucous cleft \- Bifid uvula \- High-arched palate Neck \- Short neck \- Mild neck webbing CHEST External Features \- Sloping shoulders \- Pectus excavatum GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKELETAL Spine \- Lumbar lordosis \- Kyphoscoliosis \- Thoracolumbar scoliosis Pelvis \- Congenital hip dislocation \- Limited hip abduction Limbs \- Knee flexion contractures Hands \- Short fingers \- Camptodactyly of proximal interphalangeal joint \- Ulnar deviation \- Cutaneous syndactyly \- Single transverse palmar creases \- Absence of interphalangeal creases Feet \- Talipes equinovarus \- Camptodactyly \- Overlapping toes SKIN, NAILS, & HAIR Skin \- Single transverse palmar creases \- Absence of interphalangeal creases MUSCLE, SOFT TISSUES \- Decreased muscle mass (especially of limbs) NEUROLOGIC Central Nervous System \- Chiari I malformation of the cerebellum (in some patients) \- Intellectual disability, mild (in some patients) \- Psychomotor delay, mild (in some patients) MOLECULAR BASIS \- Caused by mutation in the PIEZO-type mechanosensitive ion channel component 2 gene (PIEZO2, 613629.0001 ) ▲ 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	ARTHROGRYPOSIS, DISTAL, TYPE 3	c0220666	8,483	omim	https://www.omim.org/entry/114300	2019-09-22T16:43:51	{"doid": ["0050646"], "mesh": ["C537288"], "omim": ["114300"], "orphanet": ["376"], "synonyms": ["Alternative titles", "GORDON SYNDROME", "ARTHROGRYPOSIS MULTIPLEX CONGENITA, DISTAL, TYPE IIA", "CAMPTODACTYLY, CLEFT PALATE, AND CLUBFOOT"]}
A number sign (#) is used with this entry because mutations in several genes have been demonstrated to lead to renal cell carcinoma, either familial or sporadic. Description The Heidelberg histologic classification of renal cell tumors subdivides renal cell tumors into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most common documented genetic abnormalities (Kovacs et al., 1997). Malignant tumors are subclassified into common or conventional renal cell carcinoma (clear cell); papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and unclassified renal cell carcinoma. The common or conventional type accounts for about 75% of renal cell neoplasms and is characterized genetically by a highly specific deletion of chromosome 3p. Papillary renal cell carcinoma (see 605074) accounts for about 10% of renal cell tumors. Chromophobe renal cell carcinoma accounts for approximately 5% of renal cell neoplasms. Genetically, chromophobe RCC is characterized by a combination of loss of heterozygosity of chromosomes 1, 2, 6, 10, 13, 17, and 21 and hypodiploid DNA content. Collecting duct carcinoma accounts for about 1% of renal cell carcinoma. Renal cell carcinoma occurs nearly twice as often in men as in women; incidence in the United States is equivalent among whites and blacks. Cigarette smoking doubles the likelihood of renal cell carcinoma and contributes to as many as one-third of cases. Obesity is also a risk factor, particularly in women. Other risk factors include hypertension, unopposed estrogen therapy, and occupational exposure to petroleum products, heavy metals, or asbestos (summary by Motzer et al., 1996). ### Genetic Heterogeneity of Renal Cell Carcinoma Germline mutation resulting in nonpapillary renal cell carcinoma of the clear cell and chromophobe type occurs in the HNF1A gene (142410) and the HNF1B gene (189907). Somatic mutations in renal cell carcinomas occur in the VHL gene (608537), the TRC8 gene (603046), the OGG1 gene (601982), the ARMET gene (601916), the FLCN gene (607273), and the BAP1 gene (603089). See also RCCX1 (300854) for a discussion of renal cell carcinoma associated with translocations of chromosome Xp11.2 involving the TFE3 gene (314310). For a discussion of papillary renal cell carcinoma, see RCCP1 (605074). ### Occurrence of Renal Cell Carcinoma in Other Disorders Von Hippel-Lindau syndrome (193300) is a familial multicancer syndrome in which there is a susceptibility to a variety of neoplasms, including renal cell carcinoma of clear cell histology and renal cysts. A syndrome of predisposition to uterine leiomyomas and papillary renal cell carcinoma has been reported (605839). Medullary carcinoma of the kidney is believed to arise from the collecting ducts of the renal medulla and is associated with sickle cell trait (603903) (Kovacs et al., 1997). Renal cell carcinoma occurs in patients with the Birt-Hogg-Dube syndrome (135150). Bertolotto et al. (2011) identified a missense mutation in the MITF (156845) gene that increases the risk of renal cell carcinoma with or without malignant melanoma (CMM8; 614456). Clinical Features Familial renal cell carcinoma (RCC) is relatively rare. Reports (e.g., Franksson et al., 1972; Goldman et al., 1979) suggest an early average age at diagnosis and frequent bilateral or multiple primary tumors in familial cases. Rusche (1953) observed hypernephroma in 2 brothers. Both had distant metastasis as the first manifestation and both were in their early thirties at the time of diagnosis. Brinton (1960) described a family in which 2 brothers and a sister had hypernephroma. The father had died of kidney tumor and the mother of cancer, site unstated. One of the patients had polycythemia, a known accompaniment of hypernephroma on occasion. It should be noted that hypernephroma and cerebellar hemangioblastoma, which histologically resembles hypernephroma, are features of von Hippel-Lindau disease. Polycythemia also occurs with cerebellar hemangioblastoma. Jakesz and Wuketich (1978) reported an instructive family in which 3 brothers had bilateral renal cell carcinoma. The index case also had cerebellar hemangioblastoma. The authors suggested that von Hippel-Lindau disease was the fundamental problem. Braun et al. (1975) studied 3 families, each with multiple cases of renal cell carcinoma. There appeared to be an association with HLA W17 tissue type. Li et al. (1982) reviewed 9 families in which 2 or more members had renal carcinoma. Multiple generations were affected in 5, sibs in 4. The median age at diagnosis was a decade earlier than usual, and individual patients had bilateral or multifocal lesions; these are features of hereditary forms of diverse cancers. No patient had von Hippel-Lindau disease and none had 3;8 translocation. Levinson et al. (1990) reported that, since 1961, 28 families with multiple cases of renal cell carcinoma had been reported, with an abnormality in the constitutional karyotype having been found in only 1 family. They identified 5 more families in which a total of 12 relatives had renal cell carcinoma; peripheral blood karyotypes from 7 patients and 5 unaffected relatives showed no significant abnormalities. They suggested that members of families with multiple cases of renal cell carcinoma be screened with renal ultrasound initially at age 30, with repeat examinations every 2 or 3 years. The recommendations are similar to those for von Hippel-Lindau disease. Woodward et al. (2000) reported a clinical and molecular study of familial renal cell carcinoma in 9 kindreds with 2 or more cases of renal cell carcinoma in first-degree relatives. Familial RCC was characterized by an earlier age at onset (mean 47.1 years, 52% of cases less than 50 years of age) as compared to sporadic cases. Mutation analysis of the VHL (608537), MET (164860), and CUL2 (603135) genes revealed no germline mutations. Woodward et al. (2000) concluded that the VHL, MET, and CUL2 genes do not have a major role in familial renal cell carcinoma. Cytogenetics ### Translocations and Deletions Involving Chromosome 3p Cohen et al. (1979) described a family in which members with an inherited chromosomal translocation, t(3;8)(p21;q24), were predisposed to renal cancer. In 1 patient, cancer developed in residual renal tissue after partial nephrectomy. One patient had polycythemia. In the family reported by Cohen et al. (1979), Wang and Perkins (1984) used high resolution prometaphase G-banding analysis to demonstrate that the breakpoints occurred at the subbands 3p14.2 (not 3p21) and 8q24.1. Because of the findings of the role of the MYC gene (190080), located at 8q24, in Burkitt lymphoma with reciprocal translocation between 8q24 and 14q32, the possibility exists that a similar mechanism is involved in the translocation between 8q24 and 3p21 in the family reported by Cohen et al. (1979). All 10 members of the family that developed renal cancer carried the translocation, whereas no member with a normal karyotype had renal cancer. Another oncogene, RAF1 (164760), has been assigned to chromosome 3 (3p25), but its possible role in RCC (or in small cell cancer of the lung, 182280, which also is related to chromosome 3p) is unknown. Harris et al. (1986) sorted the chromosome from a cell line established from a subject with the t(3;8)(p14.2;q24.1) translocation. They found that the RAF1 gene was translocated to the derivative chromosome 8 and, conversely, that the MYC gene was translocated to the derivative chromosome 3. By in situ hybridization with an RAF1 probe, Teyssier et al. (1986) showed that in 2 renal cancers with 3p deletion, the oncogene had shifted from 3p25 to 3p14. By the use of cosmid cloning, Harris et al. (1986) showed that there was no rearrangement 31 kb 5-prime or 19 kb 3-prime to the translocated MYC gene. Gemmill et al. (1989) found that a 1.5-Mb segment surrounding MYC did not include the translocation breakpoint in familial RCC with t(3;8); thus, again, MYC seems not to be implicated in the development of RCC. Li et al. (1993) followed up on the family reported by Cohen et al. (1979). Renal carcinoma had recurred in all 5 patients carrying the 3;8 translocation at 1 to 16 years after resection. Two translocation carriers with renal carcinoma also had thyroid cancer. Cancer was the cause of death in 3 patients; 2 were in a second remission. The tumors from 3 family members consistently showed loss of the entire derivative chromosome 8, which bore the segment 3pter-p14. In contrast, no genetic change was detected in the derivative chromosome 3 or in normal chromosomes 3 and 8. One interpretation from these findings is that the breakpoints in chromosomes 3 and 8 per se had no relevance to the renal carcinoma. Instead, the renal carcinoma was related to the tendency toward loss of the terminal part of 3p containing the von Hippel-Lindau gene (VHL) in the tumors of the affected patients. Ohta et al. (1996) pointed out that a 200- to 300-kb region of 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines. By exon amplification from cosmids covering this deleted region, they identified the human gene called FHIT (601153) for 'fragile histidine triad gene.' The gene encodes a protein with 69% similarity to an enzyme of Schizosaccharomyces pombe, diadenosine 5-prime,5-triple prime-P(1),P(4)-tetraphosphate, asymmetric hydrolase. They found that the FHIT locus is composed of 10 exons distributed over at least 50 kb, with three 5-prime untranslated exons centromeric to the RCC-associated 3p14.2 breakpoint, the remaining exons telomeric to this translocation breakpoint, and exon 5 within the homozygously deleted fragile region. Aberrant transcripts of the FHIT locus were found in approximately 50% of esophageal, stomach, and colon carcinomas. The first 3 exons of the gene mapped centromeric to the t(3;8) break and between the break and the 5-prime end of the PTPRG gene (176886). Pathak and Goodacre (1986) found reciprocal translocations involving 3p14-p13 and chromosomes 6, 8, 11 and 16. Yoshida et al. (1986) found rearrangement of chromosome 3 in 8 of 12 nonfamilial renal cell carcinomas. Using RFLPs, Zbar et al. (1987) examined tumors from 18 patients with nonhereditary renal cell carcinomas and found loss of alleles at loci on the short arm of chromosome 3 in all 11 of the patients who could be evaluated. Szucs et al. (1987) described deletion of 3p as the only chromosome loss in a nonfamilial renal cell carcinoma. The deletion was thought to be at 3p11. The tumor also contained t(Y;3). Carroll et al. (1987) found clonal abnormalities affecting the short arm of chromosome 3 in the 3p21-p12 region in 5 of 6 clear cell renal carcinomas. In the remaining case, of 15 karyotyped metaphases suitable for interpretation, 1 showed a deletion in 3p. In tumor cells from a patient with renal cell carcinoma and von Hippel-Lindau disease, King et al. (1987) found a deletion in proximal 3p, thus providing support for the idea that genetic material in this area is critical to the development of RCC. In 22 of 25 primary renal cell carcinomas, Kovacs et al. (1987) found an aberration of chromosome 3, deletion of 3p, or translocation of chromosome segments to the deleted chromosome 3. The breakpoints in rearrangements of chromosome 3 clustered in the region of 3p13-p11.2. In 8 of the 25 RCCs, the rearrangement of chromosome 3 was the only karyotype change. Kovacs and Hoene (1988) studied a patient with renal cancer and a constitutional reciprocal translocation t(3;12)(q13.2;q24.1). They found that tumor cells were characterized by loss of the derivative chromosome 3, supporting the hypothesis that loss of a specific 3p segment is associated with the development of renal cancer. Kovacs et al. (1988) examined renal cell carcinoma and normal kidney tissues from 34 patients with sporadic, nonhereditary RCC. Of the 21 cytogenetically examined tumors, 18 had a detectable anomaly of 3p distal to band 3p11.2-p13, combined with the nonreciprocal translocation of a segment from another chromosome or monosomy 3. RFLP analysis showed loss of heterozygosity (LOH). The authors suggested that RCC may arise from the deletion of a 'recessive cancer gene.' Van der Hout et al. (1988) compared chromosome 3 markers in normal and tumorous nephrectomy specimens from 7 RCC patients. Three patients were not informative because of homozygosity at all loci studied. One patient showing heterozygosity at 3q in normal tissue had a tumor that remained heterozygous. In 3 patients the tumor showed LOH for a short arm marker at 3p21; in 1 of them, heterozygosity for a second short arm marker was also lost. A second of these 3 patients retained heterozygosity for the second short arm marker, as well as for a long arm marker, suggesting a chromosomal breakpoint between the loci for the 2 short arm markers. In a study of the karyotype of 75 sporadic, nonpapillary renal cell carcinomas, Kovacs and Frisch (1989) found aberration of chromosome 3 in 71 cases; see 144700. The rearrangement of chromosome 3p was the only change in 13 tumors. Abnormalities of chromosome 5 resulting in trisomy for the 5q22-qter region were found in 36 cases, whereas the loss of the 14q22-qter segment was observed in 34 tumors. By studying LOH in 41 matched tumor/normal kidney tissue pairs, van der Hout et al. (1991) limited the commonly deleted part of 3p to the region between THRB (190160) in 3p24.3 and D3S2 in 3p21. The regions on 3p thought to be involved in the von Hippel-Lindau syndrome and in hereditary renal cell carcinoma are both outside this smallest region of overlapping deletions. Unlike some other tumor types, RCC does not show multiple allelic losses on a number of chromosomes; LOH is restricted mainly to chromosome 3. Erlandsson et al. (1988) compared the age distribution of 51 hereditary and 56 sporadic cases of RCC sampled from the literature. The age-incidence curve of the hereditary RCC was compatible with a single event, whereas the sporadic tumors arose as predicted from a 2-hit curve. Thus, in analogy with Knudson's original prediction for retinoblastoma and Wilms tumor, RCC appears to arise by the loss of a recessive cancer gene, probably located in band 3p14.2. Anglard et al. (1992) found LOH on 3p in 25 cell lines derived from 28 informative nonpapillary forms of RCC. Deletion-mapping analysis showed retention of the distal locus D3S18 in one of the RCC lines, further localizing the putative tumor suppressor gene. Ogawa et al. (1992) found an inverse relationship between allelic losses at chromosome 17p in renal cell carcinoma and allelic losses at 3p: none of the 5 informative RCCs with allelic losses at 17p showed allelic losses at 3p. Conversely, 17 of 25 informative RCCs with retention of 17p alleles lost alleles at 3p. They demonstrated that allelic losses at 17p were infrequent in the clear cell type of RCC, whereas allelic losses at 17p were significantly more frequent in the granular cell type of RCC. Ogawa et al. (1991) had previously reported that allelic losses at 3p were specific to the clear cell type of RCC. Rodriguez-Perales et al. (2004) characterized a 5-kb microdeletion at the chromosome 3 breakpoint in a family with a translocation t(3;8)(p14.2;q24.2) that segregated with conventional RCC. In this gene-poor region, only LRIG1 (608868), which was located more than 200 kb away from the breakpoint, showed expression in any of the tested tissues, including normal adult and fetal kidney, sporadic kidney tumors, and tumor samples from the proband's family. The authors proposed that a 3-step model of tumor development (translocation, loss of the 3p chromosome, and mutation in a tumor suppressor gene located within that region) could be the biological mechanism that takes place in this familial form of conventional RCC. In a retrospective analysis of 123 patients from 55 families with von Hippel Lindau syndrome (193300), including 13 with complete germline deletion of the VHL gene (608537) and 42 with partial gene deletions, Maranchie et al. (2004) observed a paradoxically lower prevalence of renal cell carcinoma in those with complete gene deletions. RCC occurred more frequently in patients with partial germline VHL deletions relative to complete deletions (48.9% vs 22.6%, p = 0.007). Deletion mapping demonstrated that development of RCC had an even greater correlation with retention of HSPC300 (C3ORF10; 611183), located within the 30-kb region of 3p immediately telomeric to the VHL gene (52.3% vs 18.9%, p less than 0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Cascon et al. (2007) found that 6 of 8 patients with VHL without RCC had large germline deletion of the VHL gene including deletion of HSPC300. In contrast, 9 of the 10 with RCC had retention of the HSPC300 gene. Analysis of 9 sporadic RCC tumors showed that all retained an HSPC300 allele. Studies in RCC tumor cell lines showed that genetic depletion of HSPC300 resulted in cytoskeleton abnormalities and defects in cytokinesis, indicating an alteration in actin kinetics and suggesting that tumor cell proliferation was compromised in the absence of HSPC300. Cascon et al. (2007) concluded that loss of the HSPC300 gene confers protection against renal clear cell carcinoma. In a brother and sister diagnosed with bilateral clear cell RCC in their forties, Poland et al. (2007) detected a constitutional balanced translocation t(3;8)(p14;q24.1). This was the same translocation reported in the family studied by Cohen et al. (1979) and Gemmill et al. (1998). Poland et al. (2007) reported that, as in the case of the previously reported family, the translocation disrupted the FHIT gene on chromosome 3p14 and the TRC8 gene (603046) on chromosome 8q24.1. FISH analysis demonstrated that the TRC8 signal was absent in a set of diploid and pseudotetraploid cells from the tumor. Additionally, a heterozygous frameshift mutation in the VHL gene was found in the tumor. Poland et al. (2007) concluded that inactivation of TRC8 may cooperate with VHL mutations during the development and progression of clear cell RCCs. ### Translocation t(2;3) Koolen et al. (1998) identified a familial case of renal cell carcinoma. Four patients over 3 generations developed nonpapillary RCCs, and 1 patient was diagnosed with squamous bladder carcinoma. Cytogenetic analysis showed that all these patients and several unaffected members carried a balanced t(2;3)(q35;q21) translocation. To elucidate the role of this novel chromosome 3 translocation in RCC development, Bodmer et al. (1998) performed allele segregation, loss of heterozygosity, and mutation analyses of various normal tissues and primary tumor samples. They demonstrated loss of the translocation-derivative chromosome 3 in 5 independent renal cell tumors of the clear-cell type, obtained from 3 members of the family carrying the constitutional translocation. In addition, analysis of the VHL gene revealed distinct insertion, deletion, and substitution mutations in 4 of the 5 tumors tested. On the basis of these findings, Bodmer et al. (1998) concluded that, in this familial case, an alternative route for RCC development was implied. In contrast to the first hit in the generally accepted 2-hit tumor-suppressor model proposed by Knudson, the familial translocation in this case may act as a primary oncogenic event, leading to nondisjunctional loss of the derivative chromosome 3 harboring the VHL tumor-suppressor gene. Mutations in the VHL gene on the other chromosome would result in subsequent tumor formation. The risk of developing renal cell carcinoma may be correlated directly with the extent of somatic (kidney) mosaicism resulting from the loss of the der(3) chromosome. Podolski et al. (2001) analyzed a balanced constitutional chromosome translocation, t(2;3)(q33;q21), associated with multifocal clear cell renal carcinoma in a Polish family. The site of the break was similar to that in the family reported by Bodmer et al. (1998) and Koolen et al. (1998). Physical mapping showed that the 3q break was in 3q13 in the Polish family, possibly near the border with 3q21. Physical mapping illustrated that the 2q break was closely telomeric to the 2q31 FRA2G site, consistent with the G-band assignment. Druck et al. (2001) identified a novel gene, DIRC1 (606423), at the chromosome 2q33 breakpoint of the RCC-related translocation t(2;3)(q33;q21) reported by Podolski et al. (2001). Bodmer et al. (2002) identified the DIRC2 gene (602773) at the chromosome 3q21 breakpoint of the familial RCC-associated t(2;3)(q35;q21) translocation. The breakpoint was within intron 7 of the DIRC2 gene. Since they detected normal DIRC2 transcripts in t(2;3)-positive tumor cells and in several sporadic cases of RCC, they concluded that the observed gene disruption may result in haploinsufficiency and, through this mechanism, the onset of tumor growth. Van Erp et al. (2003) initiated a survey of all known Dutch families known to segregate the chromosome 3 translocations for the occurrence of renal cell carcinomas, and also for the establishment of refined risk estimates. Four novel tumors had been detected: 3 in a t(2;3)(q35;q21) family; 2 of the tumors (bilateral RCC) being in a 30-year-old translocation carrier (Bodmer et al., 2002); and 1 in a 67-year-old member of the t(3;6)(q12;q15) family (Eleveld et al., 2001). Van Erp et al. (2003) provided a table of the general features of the 7 RCC families with constitutional chromosome 3 translocations, and a diagram of chromosome 3 showing the location of the breakpoints in 93 Dutch families with chromosome 3 translocations and in somatic chromosome 3 translocations found in 157 sporadic RCCs. Bodmer et al. (2003) identified the DIRC3 gene (608262) at the chromosome 2q35 breakpoint in the family with RCC and the t(2;3)(q35;q21) translocation. They determined that the translocation resulted in the formation of a DIRC3-HSPBAP1 (608263) fusion transcript. The breakpoints in both genes were intronic, and the fusion created a transcript where the first 2 exons of DIRC3 replaced exon 1 of HSPBAP1. The putative truncated HSPBAP1 protein retained its JmjC and Hsp27 (602195)-interacting domains, which are associated with chromatin remodeling and stress response, respectively. To determine if phenotypic differences in the family carrying the RCC-associated t(2;3)(q35;q21) translocation were due to minor differences in the chromosomal breakpoints, Bodmer et al. (2003) examined the breakpoints in 9 different translocation carriers in the family, including 2 who had developed renal cancer, 1 who had developed bladder cancer, and 6 who had not developed cancer. In all translocation carriers, the chromosome 3 breakpoint coincided with a 3.4 kb-deletion, and the chromosome 2 breakpoint coincided with a 34-bp deletion; no differences could be detected in any of these breakpoint fragments. ### Other Cytogenetic Abnormalities Pathak et al. (1982) reported an acquired balanced 3;11 translocation in tumor cells from a patient with a normal constitutional karyotype and a history of renal cell carcinoma in the paternal grandfather and a paternal uncle. Miles et al. (1988) found trisomy or tetrasomy of chromosome 7 as the most frequent abnormality in nonfamilial renal cell carcinoma, being present in tumors from 15 of 19 patients with cytogenetically abnormal neoplasms. An abnormal chromosome 3 was found in 10 of the cases: 2 were trisomic for chromosome 3; 2 were monosomic; 3 were hyperdiploid; and 3 had interstitial deletions with breakpoints clustered from p11 to p25. Kovacs and Brusa (1988) could find no correlation between breakpoints on 3p or 5q and fragile sites on those chromosome arms. In a study of the karyotype of 75 sporadic, nonpapillary renal cell carcinomas, Kovacs and Frisch (1989) abnormalities of chromosome 5 resulting in trisomy for the 5q22-qter region were found in 36 cases, whereas the loss of the 14q22-qter segment was observed in 34 tumors. Kuiper et al. (2003) collected 3 cases of RCC from patients 14 to 42 years of age, wherein a somatic t(6;11)(p21;q13) translocation was the sole cytogenetic abnormality in the tumor cells. Molecular analysis revealed fusion of the TFEB gene (600744) on chromosome 6 to the Alpha gene (MALAT1; 607924) on chromosome 11. The Alpha/TFEB fusion gene linked all coding exons of the TFEB gene to 5-prime upstream regulatory sequences of the Alpha gene. Alpha/TFEB mRNA levels were significantly upregulated in primary tumor cells as compared with wildtype TFEB mRNA levels in normal kidney samples, resulting in a dramatic upregulation of TFEB protein levels. The TFEB protein encoded by the Alpha/TFEB fusion gene was efficiently targeted to the nucleus. Kuiper et al. (2003) speculated that this resulted in severely unbalanced nuclear ratios of MITF (156845)/TFE subfamily members and that this imbalance may lead to changes in the expression of downstream target genes, ultimately resulting in the development of RCC. Mapping ### Nonpapillary Renal Carcinoma 1 Locus Evidence for a tumor suppressor gene in the 3p region proximal to the fragile histidine triad gene (FHIT; 601153) was shown by the functional studies of Sanchez et al. (1994), who transferred an intact human chromosome 3 and subsequently a centric fragment of 3p (encompassing the 3p14-q11 region) into a nonpapillary renal cell carcinoma (RCC) cell line. In all experiments, the 3p centric fragment mediated a dramatic tumor suppression and rapid induction of tumor cell death after subcutaneous injection of microcell hybrids in athymic nude mice. Physical mapping of suppressed and unsuppressed fragment-containing microcell hybrids, performed by Lott et al. (1998), limited the region containing the tumor suppressor locus, designated NRC1 ('nonpapillary renal carcinoma-1'), to within 3p12 and distinct from the gene (VHL; 608537) mutant in von Hippel-Lindau syndrome (193300). Lovell et al. (1999) reported the suppression of tumorigenicity of RCC cells in vivo after the transfer of the defined centric 3p fragment by microcell-mediated transfer into different histologic types of RCC. The results documented the functional involvement of NRC1 not only in different cell types of RCC (i.e., clear cell, mixed granular cell/clear cell, and sarcomatoid types) but also in papillary RCC, a less frequent histologic type of RCC for which 3p loss of heterozygosity (LOH) and genetic aberrations have only rarely been observed. They also reported that the tumor suppression observed in functional genetic screens was independent of the microenvironment of the tumor, further supporting the role of NRC1 as a more general mediator of in vivo growth control. This report demonstrated the first functional evidence for a VHL-independent pathway to tumorigenesis in the kidney via the genetic locus NRC1. Teh et al. (1997) described 2 kindreds, 1 Australian and 1 French, with 9 cases of non-von Hippel Lindau nonpapillary clear cell renal cancer. Mutation analysis of the VHL gene and linkage analysis of flanking markers excluded VHL and the 3p14.2 region as the site of mutation. Molecular Genetics Shimizu et al. (1990) introduced a single chromosome containing the short arm of chromosome 3 into a human renal cell carcinoma cell line via microcell fusion. They observed suppression of tumorigenicity in nude mice or modulation of tumor-growth rate in vitro. Gnarra et al. (1994) demonstrated that the VHL gene on chromosome 3p26-p25 was mutated in the tumors of individuals with familial renal carcinoma reported by Cohen et al. (1979); furthermore, a renal tumor from one of the affected individuals carrying the constitutional translocation t(3;8)(p14;q24) had loss of the VHL gene on the other chromosome. Thus the findings adhere to the Knudson 2-hit hypothesis as for many other tumors related to tumor suppressor genes. As outlined earlier, the 3;8 chromosomal translocation in the family reported by Cohen et al. (1979) suggested the existence of a locus on 3p underlying clear cell renal carcinoma. The frequent 3p loss of heterozygosity in sporadic RCC further led to the assumption that a critical tumor suppressor gene would be located at 3p14. Identification of the VHL gene at 3p25 provided an alternative explanation for at least some observed 3p loss of heterozygosity. Furthermore, van den Berg and Buys (1997) reported that region 3p21 may be involved in the malignant progression of renal tumors. Within 3p14, Ohta et al. (1996) identified the FHIT gene, which was interrupted in its 5-prime untranslated region by the 3;8 translocation. However, a number of findings suggested that FHIT was an unlikely causative gene in the hereditary t(3;8) family. The fact that FHIT in a case of parathyroid adenoma underwent fusion with the high mobility group protein gene HMGIC (600698), the causative gene in a variety of benign tumors (Geurts et al., 1997) suggested to Gemmill et al. (1998) that FHIT might be a bystander in the fusion with an alternative candidate gene on chromosome 8. By use of 5-prime rapid amplification of cDNA ends (RACE), Gemmill et al. (1998) identified a gene, which they called TRC8 (603046), with characteristics compatible with oncogenic properties. In addition, they identified a TRC8 mutation in a sporadic renal carcinoma. Rebouissou et al. (2005) screened 35 renal neoplasms for HNF1A (142410) and HNF1B (189907) inactivation. Biallelic HNF1B inactivation was detected in 2 of 12 chromophobe renal carcinomas, resulting from a germline mutation (189907.0014 and 189907.0015) and a somatic gene deletion. In these cases, the expression of PKHD1 (606702) and uromodulin (UMOD; 191845), 2 genes regulated by HNF1B, was turned off. In 2 of 13 clear cell renal carcinomas, the authors found monoallelic germline mutations (142410.0001 and 142410.0022) of HNF1A with no associated suppression of target mRNA expression. In normal and tumor renal tissues, there was a network of transcription factors differentially regulated in tumor subtypes. There were 2 related clusters of coregulated genes associating HNF1B, PKHD1, and UMOD in the first group and HNF1A, HNF4A (600281), FABP1 (134650), and UGT2B7 (600068) in the second group. Rebouissou et al. (2005) suggested that germline mutations of HNF1B and HNF1A may predispose to renal tumors. Furthermore, they proposed that HNF1B may function as a tumor suppressor gene in chromophobe renal cell carcinogenesis through control of PKHD1 expression. To determine further the genetics of clear cell renal cell carcinoma, Dalgliesh et al. (2010) sequenced 101 cases through 3,544 protein-coding genes and identified inactivating mutations in 2 genes encoding enzymes involved in histone modification: SETD2 (612778), a histone H3 lysine-36 methyltransferase; and JARID1C (314690), a histone H3 lysine-4 demethylase. They also found mutations in the histone H3 lysine-27 demethylase UTX (300128), in which mutations had been reported previously in other tumor types. Dalgliesh et al. (2010) concluded that their results highlighted the role of mutations in components of the chromatin modification machinery in human cancer. Furthermore, NF2 (607379) mutations were found in non-VHL mutated clear cell renal cell carcinoma, and several other probable cancer genes were identified. Varela et al. (2011) sequenced the protein coding exome in a series of primary clear cell renal cell carcinoma (ccRCC) and reported the identification of mutations in PBRM1 (606083) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. Varela et al. (2011) concluded that their data further elucidated the somatic genetic architecture of ccRCC and emphasized the marked contribution of aberrant chromatin biology. Pena-Llopis et al. (2012) provided evidence that the BAP1 gene (603089) can act as a tumor suppressor gene in clear cell renal cell carcinoma. The authors used whole-genome and exome sequencing of ccRCC tumors as well as analyses of mutant allele ratios of a murine tumorgraft to identify putative 2-hit tumor suppressor genes. BAP1 was found to be somatically mutated in 24 (14%) of 176 tumors, and most mutations were predicted to truncate the protein. In a cell line with a missense BAP1 mutation, expression of wildtype BAP1 repressed cell proliferation without causing apoptosis. In this cell line, the majority of BAP1 cofractionated with and bound to HCFC1. Mutations disrupting the HCFC1 binding motif impaired BAP1-mediated suppression of cell proliferation, but not its deubiquitination of monoubiquitinated histone 2A. BAP1 loss sensitized RCC cells in vitro to genotoxic stress. Although mutations in BAP1 and PBRM1 anticorrelated in renal cell tumors, the few tumors that had combined loss of BAP1 and PBRM1 were associated with rhabdoid features. Moreover, BAP1 loss was associated with high tumor grade. In an integrated molecular study of clear cell renal cell carcinoma involving more than 100 cases, Sato et al. (2013) identified a full spectrum of genetic lesions and analyzed gene expression and DNA methylation signatures to determine their impact on tumor behavior. Defective VHL (608537)-mediated proteolysis was a common feature of clear cell renal cell carcinoma, which was caused not only by VHL inactivation but also by hotspot TCEB1 (600788) mutations, which abolished elongin C-VHL binding, leading to HIF accumulation. Other pathways and components recurrently mutated in clear cell renal cell carcinoma identified included PI3K (see 171834)-AKT (164730)-mTOR (601231) signaling, the KEAP1 (606016)-NRF2 (600492)-CUL3 (603136) apparatus, DNA methylation, p53 (191170)-related pathways, and mRNA processing. Benusiglio et al. (2015) sequenced the PBRM1 gene in 35 unrelated patients with unexplained personal history of clear cell renal cell carcinoma (ccRCC) and at least 1 affected first-degree relative. The authors identified a germline frameshift mutation (606083.0001) in 1 patient. The patient's mother, his sister, and niece also had ccRCC, and the mutation segregated with the disease in the family. Somatic studies supported these findings, as both loss of heterozygosity for the mutation and loss of protein expression in renal tumors was identified. ### Reviews Motzer et al. (1996) reviewed all aspects of renal cell carcinoma in detail, including the molecular genetic abnormalities and the evidence for a locus on 3p distinct from the von Hippel-Lindau gene; the VHL gene is involved in the great majority of cases of renal cell carcinomas of the clear cell type. Bodmer et al. (2002) reviewed the molecular genetics of familial and nonfamilial cases of RCC, including the roles of VHL, MET, and translocations involving chromosomes 1, 3, and X. Genotype/Phenotype Correlations Although deletions on chromosome 3 had been suggested to be specific for the clear cell type, Anglard et al. (1992) could find no correlation between LOH and clear or granular cell types. To explore the role of allelic losses at chromosome 3p25 and genetic alterations of chromosome 8, Yamaguchi et al. (2003) investigated the relationships between genetic alterations in these chromosomal regions and clinicopathologic findings (such as tumor size and grade), by employing FISH. They examined 50 Japanese clear-cell renal cell carcinomas with DNA probes for 3p25.3-p25.1 and probes for various locations on chromosome 8, specifically using a probe for MYC (190080), located at 8q24. Deletion at the 3p region was detected in 38 patients (76%); MYC gain was detected in 20 patients (40%). The deletion at 3p with MYC gain showed a significant correlation with tumor size. Biochemical Features Krambeck et al. (2006) found that 153 (59%) of 259 tissue specimens from patients with renal cell carcinoma expressed the B7H4 molecule (608162), a coregulatory molecule that inhibits T-cell activity. Ninety-four (36%) cancer specimens expressed both B7H4 and B7H1 (605402), a similar molecule. Expression of both molecules was associated with increased tumor aggressiveness and increased risk of death. The findings suggested that expression of these molecules by tumor cells may impair host immunity and facilitate tumor progression. Jiang et al. (2006) found that tumor expression of IMP3 (IGF2BP3; 608259) was greatly was associated with metastasis in clear cell RCC. Among 371 patients with localized clear cell RCC, those with IMP3 tumor expression had a significantly lower 5-year metastasis-free survival than those with IMP3-negative tumors (44% vs 98% for stage I; 41% vs 94% for stage II; and 16% vs 62% for stage III). IMP3 expression was also associated with reduced 5-year overall survival. These findings were replicated by Hoffmann et al. (2008) who studied 716 clear cell RCC specimens and found that 213 (29.8%) of 716 tumors expressed IMP3, which was associated with advanced stage and grade of primary tumors as well as other adverse features, including coagulative tumor necrosis and sarcomatoid differentiation. After multivariate adjustment, positive IMP3 expression was still associated with a 42% increase in the risk of death from RCC. Among those with initially localized disease, positive IMP3 expression was associated with a 4.71-fold increased risk of distant metastases. Jiang et al. (2008) found that 40 (12%) of 334 RCCs, including 254 papillary and 80 chromophobic tumors, expressed IMP3. Positive IMP3 expression was significantly associated with later tumor stage and higher tumor grade. An analysis of patient outcomes showed that 28 of 317 with initially localized disease progressed to metastasis. Fifteen (45.5%) of the 33 patients with IMP3-positive tumors developed metastases compared to only 13 (4.6%) of the 284 patients with IMP3-negative tumors. Statistical analysis showed that those with initially localized IMP3-positive tumors were over 10 times more likely to have metastasis (risk ratio of 11.38; p less than 0.001), and were nearly twice as likely to die compared to patients with localized IMP3-negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared to 98% and 85% for patients with IMP3-negative tumors, respectively. Jiang et al. (2008) concluded that IMP3 expression can be used as a prognostic biomarker for metastasis in all subtypes of renal cell carcinoma. By microarray analysis, Liu et al. (2009) found high expression of the SPOP gene (602650) in up to 99% of human renal cell carcinomas, but not in normal kidney tissue, suggesting that it may be a specific tumor marker for renal cell carcinoma. The Cancer Genome Atlas Research Network (2013) surveyed more than 400 clear cell renal carcinoma tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/AKT pathway (see 164730) was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the histone 3 lysine-36 (H3K36) methyltransferase SETD2 (612778), and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, 606083; ARID1A, 603024; SMARCA4, 603254) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the tricarboxylic acid cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of MIR21 (611020) and GRB10 (601523). The Cancer Genome Atlas Research Network (2013) concluded that remodeling cellular metabolism constitutes a recurrent pattern in clear cell renal cell carcinoma that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. Li et al. (2014) used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that FBP1 (611570) was uniformly depleted in over 600 clear cell renal cell carcinoma (ccRCC) tumors examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. The data further indicated that FBP1 inhibits ccRCC progression through 2 distinct mechanisms: first, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cells of origin, thereby inhibiting a potential Warburg effect; second, in VHL (608537)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis, and the pentose phosphate pathway in a catalytic activity-independent manner by inhibiting nuclear HIF (see 603348) function via direct interaction with the HIF inhibitory domain. Li et al. (2014) concluded that this unique dual function of the FBP1 protein explains its ubiquitous loss in clear cell renal cell carcinoma, distinguishing FBP1 from previously identified tumor suppressors that are not consistently mutated in all tumors. Other Features Linehan et al. (1989) demonstrated that removal of leukocytes from disaggregated renal cell carcinomas improved the detection of allele loss in these carcinomas. The technique should be useful in allele deletion analysis of other solid tumors that are contaminated with host leukocytes. History Fairchild et al. (1979) described a 29-year-old woman who had neuroblastoma during infancy, developed an extraadrenal pheochromocytoma at age 16 years, with subsequent hepatic recurrence, and was found to have multifocal renal cell carcinoma. Renal cell carcinoma and pheochromocytoma are combined in the von Hippel-Lindau syndrome, but there was no evidence in this patient or her family. The association of pheochromocytoma and neuroblastoma had, it seemed, not been previously noted. Schimke et al. (2010) reported 2 sibs of the patient reported by Fairchild et al. (1979) who developed paraspinal paragangliomas in adulthood, and a cousin of these sibs who died of metastatic renal cell carcinoma and had a history of a benign paraaortic PGL. Genetic analysis identified a heterozygous mutation in the SDHB gene (V140F; 185470.0016), consistent with paragangliomas-4 (PGL4; 115310). There were 2 unaffected family members, suggesting decreased penetrance or a 'leaky' mutation. Schimke et al. (2010) noted the importance of family history in elucidating the etiology of this inherited disorder. Animal Model Everitt et al. (1992) described the Eker rat, a rodent model of hereditary cancer in which a single gene mutation predisposes them to bilateral multicentric renal cell carcinoma. The disorder bore similarities to von Hippel-Lindau disease. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At that age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. In this rat model of human renal carcinoma, Walker et al. (1992) identified a germline mutation at a tumor susceptibility locus that caused a 70-fold increase in susceptibility to chemical carcinogenesis. A carcinogen that targeted both renal epithelial and mesenchymal cells caused an increase in tumors of epithelial origin in susceptible animals but no increase in carcinogen-induced mesenchymal tumors. Rats that are heterozygous for the so-called Eker mutation develop spontaneous RCCs between 4 and 12 months of age. When homozygous, the mutation is lethal prenatally at 9 to 10 days of gestation. At the histologic level, renal carcinomas in the Eker rat develop through multiple stages from early preneoplastic lesions (e.g., atypical tubules) to adenomas in virtually all heterozygotes by the age of 1 year. Hino et al. (1993) demonstrated that ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes 2 events (one inherited, one somatic) are necessary to produce tumors, and that the predisposing gene is a tumor suppressor gene. No genetic linkage was found between the Eker mutation and rat DNA sequences homologous to those in human chromosome 3p, the presumed site of the putative tumor suppressor gene responsible for human renal cell carcinoma. Nonrandom loss of rat chromosome 5 in RCC-derived cell lines was sometimes associated with homozygous deletion of the interferon gene loci at rat chromosome bands 5q31-q33. Since this locus is not linked to the predisposing inherited gene in the Eker rat, it probably represented a second tumor suppressor gene involved in tumor progression. Kobayashi et al. (1995) demonstrated that a germline mutation in the tuberous sclerosis-2 gene (191092), caused by the insertion of a DNA fragment approximately 5 kb long, is responsible for aberrant RNA expression from the mutant allele in the Eker rat. Except for the occurrence of renal tumors, the phenotype of tuberous sclerosis in human differs from that of the Eker rat. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	RENAL CELL CARCINOMA, NONPAPILLARY	c0279702	8,484	omim	https://www.omim.org/entry/144700	2019-09-22T16:39:55	{"doid": ["0050387"], "mesh": ["D002292"], "omim": ["144700"], "orphanet": ["422526"], "synonyms": ["Hereditary clear cell renal cell adenocarcinoma", "Alternative titles", "ADENOCARCINOMA OF KIDNEY", "HYPERNEPHROMA"]}
In the family reported by Berlin (1961), 2 males and 2 females were affected out of 12 offspring of a cousin marriage. The condition in some ways resembles Naegeli syndrome (161000), but clearly is distinguished by its mode of inheritance. Growth \- Growth retardation Teeth \- Hypodontia Neuro \- Mental retardation Inheritance \- Autosomal recessive Skin \- Congenital generalized melanoleukoderma \- Hypotrichosis ▲ 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	LEUKOMELANODERMA, INFANTILISM, MENTAL RETARDATION, HYPODONTIA, HYPOTRICHOSIS	c1855504	8,485	omim	https://www.omim.org/entry/246500	2019-09-22T16:25:58	{"mesh": ["C565440"], "omim": ["246500"], "orphanet": ["1816"]}
Not to be confused with anorexia. Anorectal anomalies are congenital malformations of the anus and rectum.[1] One anal anomaly, imperforate anus has an estimated incidence of 1 in 5000 births.[2][3] It affects boys and girls with similar frequency.[4] Examples of anorectal anomalies include:[citation needed] * Anal stenosis * Proctitis * Anal bleeding * Anal fistula ## References[edit] 1. ^ Cho, Sechin; Moore, Shawn P.; Fangman, Tony (2001-05-01). "One Hundred Three Consecutive Patients With Anorectal Malformations and Their Associated Anomalies". Archives of Pediatrics & Adolescent Medicine. 155 (5): 587–91. doi:10.1001/archpedi.155.5.587. ISSN 1072-4710. PMID 11343503. 2. ^ Texas Pediatric Associates. "Imperforate anus." Retrieved 13 July 2005. 3. ^ MedLine Plus. "Imperforate anus." Retrieved 13 July 2005. 4. ^ Adotey JM, Jebbin NJ (2004). "Anorectal disorders requiring surgical treatment in the University of Port Harcourt Teaching Hospital, Port Harcourt". Nigerian Journal of Medicine. 13 (4): 350–4. 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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	Anorectal anomalies	c3495676	8,486	wikipedia	https://en.wikipedia.org/wiki/Anorectal_anomalies	2021-01-18T18:42:38	{"mesh": ["D000071056", "C537771"], "umls": ["C3495676"], "orphanet": ["96346"], "wikidata": ["Q4770166"]}
Toxic megacolon Other namesMegacolon toxicum Micrograph of pseudomembranous colitis, a cause of toxic megacolon. H&E stain. SpecialtyGastroenterology ComplicationsSeptic shock, perforation of the colon Risk factorsChronic bowel disease PrognosisFatal without treatment Toxic megacolon is an acute form of colonic distension.[1] It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock. Toxic megacolon is usually a complication of inflammatory bowel disease, such as ulcerative colitis and, more rarely, Crohn's disease, and of some infections of the colon, including Clostridium difficile infections, which have led to pseudomembranous colitis. Other forms of megacolon exist and can be congenital (present since birth, such as Hirschsprung's disease). It can also be caused by Entamoeba histolytica and Shigella. It may also be caused by the use of loperamide. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Treatment * 4 Prognosis * 5 Complications * 6 References * 7 Further reading * 8 External links ## Signs and symptoms[edit] * Abdominal pain * Abdominal bloating * Abdominal tenderness * Fever * Tachycardia (rapid heart rate) * Dehydration There may be signs of septic shock. A physical examination reveals abdominal tenderness and possible loss of bowel sounds. An abdominal radiography shows colonic dilation. White blood cell count is usually elevated. Severe sepsis may present with hypothermia or leukopenia. ## Pathophysiology[edit] Toxic megacolon in a patient with ulcerative colitis: The patient subsequently underwent a colectomy. A pathological specimen showing toxic megacolon The pathological process involves inflammation and damage to the colonic wall with unknown toxins breaking down the protective mucosal barrier and exposing the muscularis propria.[2] There is relative destruction of the ganglion cells and swelling of the nerve fibers in the myenteric plexus, with concomitant damage to the colonic musculature.[2] This results in almost complete paralysis of the diseased segment of the colon with loss of smooth muscle substance, tone and motility.[2] This can lead to further complications as pressure builds up in the colon due to relative fecal stasis including sepsis, intestinal hemorrhage or free perforation and spontaneous decompression.[2] ## Treatment[edit] The objective of treatment is to decompress the bowel and to prevent swallowed air from further distending the bowel. If decompression is not achieved or the patient does not improve within 24 hours, a colectomy (surgical removal of all or part of the colon) is indicated. When surgery is required the recommended procedure is a subtotal colectomy with end ileostomy.[3] Fluid and electrolyte replacement help to prevent dehydration and shock. Use of corticosteroids may be indicated to suppress the inflammatory reaction in the colon if megacolon has resulted from active inflammatory bowel disease. Antibiotics may be given to prevent sepsis.[4] ## Prognosis[edit] If the condition does not improve, the risk of death is significant. In case of poor response to conservative therapy, a colectomy is usually required.[5] ## Complications[edit] * Perforation of the colon[6] * Sepsis * Shock Emergency action may be required if severe abdominal pain develops, particularly if it is accompanied by fever, rapid heart rate, tenderness when the abdomen is pressed, bloody diarrhea, frequent diarrhea, or painful bowel movements. Colonoscopy is contraindicated, as it may rupture the dilated colon resulting in peritonitis and septic shock. ## References[edit] 1. ^ "Toxic megacolon" at Dorland's Medical Dictionary 2. ^ a b c d Michael B; et al. (1980). "Toxic megacolon complicating Crohn's Colitis". Ann. Surg. 191 (1): 75–80. doi:10.1097/00000658-198001000-00015. PMC 1344622. PMID 7352781. 3. ^ Seltman, AK (December 2012). "Surgical Management of Clostridium difficile Colitis". Clinics in Colon and Rectal Surgery. 25 (4): 204–9. doi:10.1055/s-0032-1329390. PMC 3577611. PMID 24294121. 4. ^ Autenrieth, DM; Baumgart, DC (August 2011). "Toxic megacolon". Inflammatory Bowel Diseases. 18 (3): 584–91. doi:10.1002/ibd.21847. PMID 22009735. 5. ^ Benchimol, EI; Turner, D; Mann, EH; Thomas, KE; et al. (June 2008). "Toxic megacolon in children with inflammatory bowel disease: Clinical and radiographic characteristics". The American Journal of Gastroenterology. 103 (6): 1524–31. PMID 18510624. 6. ^ Panos, MZ; Wood, MJ; Asquith, P (December 1993). "Toxic megacolon: The knee-elbow position relieves bowel distension". Gut. 34 (12): 1726–7. doi:10.1136/gut.34.12.1726. PMC 1374472. PMID 8282262. * This article incorporates text from the United States National Library of Medicine (Toxic megacolon), which is in the public domain. ## Further reading[edit] * Ausch, C; Madoff, RD; Gnant, M; Rosen, HR; Garcia-Aguilar, J; Hölbling, N; Herbst, F; Buxhofer, V; Holzer, B; Rothenberger, DA; Schiessel, R (March 2006). "Aetiology and surgical management of toxic megacolon". Colorectal Disease. 8 (3): 195–201. doi:10.1111/j.1463-1318.2005.00887.x. PMID 16466559. * Toxic Megacolon at eMedicine ## External links[edit] Classification D * ICD-10: K59.3 * ICD-10-CM: K59.31 * ICD-9-CM: 556.9 * MeSH: D008532 * DiseasesDB: 27702 External resources * MedlinePlus: 000248 * eMedicine: med/1418 radio/702 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Toxic megacolon	c0025162	8,487	wikipedia	https://en.wikipedia.org/wiki/Toxic_megacolon	2021-01-18T18:44:21	{"mesh": ["D008532"], "umls": ["C0025162"], "icd-9": ["556.9"], "wikidata": ["Q588321"]}
Not to be confused with Diastasis recti. Umbilical hernia Children with umbilical hernias, Sierra Leone (West Africa), 1967. SpecialtyGeneral surgery An umbilical hernia is a health condition where the abdominal wall behind the navel is damaged. It may cause the navel to bulge outwards—the bulge consisting of abdominal fat from the greater omentum or occasionally parts of the small intestine. The bulge can often be pressed back through the hole in the abdominal wall, and may "pop out" when coughing or otherwise acting to increase intra-abdominal pressure. Treatment is surgical, and surgery may be performed for cosmetic as well as health-related reasons. ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Congenital * 2.2 Acquired * 2.3 Paraumbilical * 3 Diagnosis * 4 Treatment * 4.1 Children * 4.2 Adults * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] A hernia is present at the site of the umbilicus (commonly called a navel or belly button) in newborns; although sometimes quite large, these hernias tend to resolve without any treatment by around the age of 2–3 years.[1] Obstruction and strangulation of the hernia is rare because the underlying defect in the abdominal wall is larger than in an inguinal hernia of the newborn. The size of the base of the herniated tissue is inversely correlated with risk of strangulation (i.e., a narrow base is more likely to strangulate). Babies are prone to this malformation because of the process during fetal development by which the abdominal organs form outside the abdominal cavity, later returning into it through an opening which will become the umbilicus.[2] Hernias may be asymptomatic and present only as a bulge of the umbilicus. Symptoms may develop when the contracting abdominal wall causes pressure on the hernia contents. This results in abdominal pain or discomfort. These symptoms may be worsened by the patient lifting or straining. ## Causes[edit] In more severe cases of umbilical hernias, the small intestine can poke out through the opening. This can very rarely cause ischemia and necrosis of the intestine and is potentially life-threatening. The bulge is often caused by fat or parts of the greater omentum. The causes of umbilical hernia are congenital and acquired malformation, but an apparent third cause is really a cause of a different type, a paraumbilical hernia. ### Congenital[edit] Congenital umbilical hernia is a congenital malformation of the navel (umbilicus). Among adults, it is three times more common in women than in men; among children, the ratio is roughly equal.[3] It is also found to be more common in children of African descent.[4][5][6] ### Acquired[edit] An acquired umbilical hernia directly results from increased intra-abdominal pressure caused by obesity, heavy lifting, a long history of coughing, or multiple pregnancies.[7][8] Another type of acquired umbilical hernias are incisional hernias, which are hernia developing in a scar following abdominal surgery, e.g. after insertion of laparoscopy trocars through the umbilicus. ### Paraumbilical[edit] Importantly, an umbilical hernia must be distinguished from a paraumbilical hernia, which occurs in adults and involves a defect in the midline near to the umbilicus, and from omphalocele.[citation needed] ## Diagnosis[edit] Navels with the umbilical tip protruding past the umbilical skin ("outies") are often mistaken for umbilical hernias, which are a completely different shape. Treatment for cosmetic purposes is not necessary, unless there are health concerns such as pain, discomfort or incarceration of the hernia content.[clarification needed] Incarceration refers to the inability to reduce the hernia back into the abdominal cavity. Prolonged incarceration can lead to tissue ischemia (strangulation) and shock when untreated. Umbilical hernias are common. With a study involving Africans, 92% of children had protrusions, 49% of adults, and 90% of pregnant women. However, a much smaller number actually suffered from hernias: only 23% of children, 8% of adults, and 15% of pregnant women.[4] When the orifice is small (< 1 or 2 cm), 90% close within 3 years (some sources state 85% of all umbilical hernias, regardless of size),[citation needed] and if these hernias are asymptomatic, reducible, and don't enlarge, no surgery is needed (and in other cases it must be considered).[citation needed] * Play media Ultrasound showing an incarcerated umbilical hernia[9] * Play media Ultrasound showing an incarcerated umbilical hernia[9] * Ultrasound showing an incarcerated umbilical hernia[9] ## Treatment[edit] ### Children[edit] In some communities mothers routinely push the small bulge back in and tape a coin over the palpable hernia hole until closure occurs. This practice is not medically recommended as there is a small risk of trapping a loop of bowel under part of the coin resulting in a small area of ischemic bowel. This "fix" does not help and germs may accumulate under the tape, causing infection. The use of bandages or other articles to continuously reduce the hernia is not evidence-based. An umbilical hernia can be fixed in two different ways. The surgeon can opt to stitch the walls of the abdomen or he/she can place mesh over the opening and stitch it to the abdominal walls. The latter is of a stronger hold and is commonly used for larger defects in the abdominal wall. Most surgeons will not repair the hernia until 5–6 years after the baby is born. Most umbilical hernias in infants and children close spontaneously and rarely have complications of gastrointestinal-content incarcerations.[10] How far the projection of the swelling extends from the surface of the abdomen (the belly) varies from child to child. In some, it may be just a small protrusion; in others it may be a large rounded swelling that bulges out when the baby cries. It may hardly be visible when the child is quiet and or sleeping. Normally, the abdominal muscles converge and fuse at the umbilicus during the formation stage, however, in some cases, there remains a gap where the muscles do not close and through this gap the inner intestines come up and bulge under the skin, giving rise to an umbilical hernia. The bulge and its contents can easily be pushed back and reduced into the abdominal cavity.[citation needed] Recently, a novel technique of treatment of umbilical hernia in infants was published by Dr. Ganesh Kumar K Ammannaya. Named as Ammannaya’s Technique [11][unreliable medical source?], after the innovating surgeon, this new technique facilitates speedy resolution of hernia without the need for surgery in a matter of 6-8 weeks at the cost of 2 USD and without any adverse effects. In contrast to an inguinal hernia, the complication incidence is very low, and in addition, the gap in the muscles usually closes with time and the hernia disappears on its own. The treatment of this condition is essentially conservative: observation allowing the child to grow up and see if it disappears. Operation and closure of the defect is required only if the hernia persists after the age of 3 years or if the child has an episode of complication during the period of observation like irreducibility, intestinal obstruction, abdominal distension with vomiting, or red shiny painful skin over the swelling. Surgery is always done under anesthesia. The defect in the muscles is defined and the edges of the muscles are brought together with sutures to close the defect. In general, the child needs to stay in the hospital for 1 day[12] and the healing is complete within 8 days.[citation needed] At times, there may be a fleshy red swelling seen in the hollow of the umbilicus that persists after the cord has fallen off. It may bleed on touch, or may stain the clothes that come in contact with it. This needs to be shown to a pediatric surgeon. This is most likely to be an umbilical polyp and the therapy is to tie it at the base with a stitch so that it falls off and there is no bleeding. Alternatively, it may be an umbilical granuloma that responds well to local application of dry salt or silver nitrate but may take a few weeks to heal and dry.[13] ### Adults[edit] Many hernias never cause any problems, and do not require any treatment at all. However, because the risk of complications with age are higher and the hernia is unlikely to resolve without treatment, surgery is usually recommended.[2] Usually hernia has content of bowel, abdominal fat or omentum, tissue that normally would reside inside the abdominal cavity if it wasn't for the hernia. In some cases, the content gets trapped in the hernia sac, outside the abdominal wall. The blood flow to this trapped tissue may be compromised, or the content even strangulated in some cases. Depending on the severity and duration of blood flow compromise, it can cause some pain and discomfort. Usually the situation resolves itself, when the protrusion of content is returned to the abdominal cavity. Sometimes this needs to be done by a doctor at the ICU.[14] If the hernia content get trapped combined with severe pain, inability to perform bowel movement or pass gas, swelling, fever, nausea and/or discoloration over the area, it could be signs of a prolonged compromise in blood flow of the hernia content. If so, emergency surgery is often required, since prolonged compromise in blood flow otherwise threatens organ integrity.[14] Hernias that are symptomatic and disturb daily activity, or hernias that have had episodes of threatening incarceration, preventive surgical treatment can be considered. The surgery is performed under anaesthesia, while the surgeon identifies the edges of the defect and bring them together permanently using either suture or mesh.[15] Small umbilical hernias are often successfully repaired with suture, while larger hernias may require a suitable mesh,[16] although some surgeons advocate mesh treatment for most hernias. The most common complications for both techniques are superficial wound infections, recurrence of the hernia[17] and some people experience pain from the surgical site.[18] ## See also[edit] * Fetal development * Umbilicoplasty * Paraumbilical hernia * Omphalocoele ## References[edit] 1. ^ Lissauer T, Clayden G (2007). Illustrated Textbook of Paediatrics (3rd ed.). Edinburgh: Mosby Elsevier. ISBN 978-0-7234-3397-2. 2. ^ a b "Umbilical hernia repair". NHS choices. UK.GOV. 2017-10-23. Retrieved March 3, 2018. 3. ^ Abdominal Hernias at eMedicine 4. ^ a b Meier DE, OlaOlorun DA, Omodele RA, Nkor SK, Tarpley JL (May 2001). "Incidence of umbilical hernia in African children: redefinition of "normal" and reevaluation of indications for repair". World Journal of Surgery. 25 (5): 645–8. doi:10.1007/s002680020072. PMID 11369993. 5. ^ Arca MJ (November 2016). "APSA - Umbilical Conditions" (Website). APSA - Family and Parent Resources. Oakbrook Terrace, Illinois, USA: American Pediatric Surgical Association. Retrieved November 5, 2017. 6. ^ MedlinePlus Encyclopedia: Umbilical hernia repair 7. ^ Mayo Clinic staff. "Umbilical hernia: Causes - MayoClinic.com". Retrieved 2010-03-31. 8. ^ "Hernia: MedlinePlus Medical Encyclopedia". 2014-10-25. Retrieved 2016-07-15. 9. ^ a b c "UOTW #44 - Ultrasound of the Week". Ultrasound of the Week. 18 April 2015. Retrieved 27 May 2017. 10. ^ Papagrigoriadis S, Browse DJ, Howard ER (December 1998). "Incarceration of umbilical hernias in children: a rare but important complication". Pediatric Surgery International. 14 (3): 231–2. doi:10.1007/s003830050497. PMID 9880759. 11. ^ Ammannaya GK, Sripad NS (September 2019). "A Novel Cost-Effective Technique for Speedy Resolution of Infantile Umbilical Hernia: Ammannaya's Technique". Case Reports in Surgery. doi:10.1155/2019/3806358. PMID 31583155. 12. ^ Barreto L, Khan AR, Khanbhai M, Brain JL (July 2013). "Umbilical hernia". BMJ. 347: f4252. doi:10.1136/bmj.f4252. PMID 23873946. 13. ^ "Child with Umbilical Swellings/Hernia". Archived from the original on April 7, 2013. Retrieved 2013-10-10. 14. ^ a b Summers A (March 2014). "Congenital and acquired umbilical hernias: examination and treatment". Emergency Nurse. 21 (10): 26–8. doi:10.7748/en2014.03.21.10.26.e1260. PMID 24597817. 15. ^ Nguyen MT, Berger RL, Hicks SC, Davila JA, Li LT, Kao LS, Liang MK (May 2014). "Comparison of outcomes of synthetic mesh vs suture repair of elective primary ventral herniorrhaphy: a systematic review and meta-analysis". JAMA Surgery. 149 (5): 415–21. doi:10.1001/jamasurg.2013.5014. PMID 24554114. 16. ^ Dalenbäck J, Andersson C, Ribokas D, Rimbäck G (August 2013). "Long-term follow-up after elective adult umbilical hernia repair: low recurrence rates also after non-mesh repairs". Hernia. 17 (4): 493–7. doi:10.1007/s10029-012-0988-0. PMID 22971796. 17. ^ Winsnes A, Haapamäki MM, Gunnarsson U, Strigård K (August 2016). "Surgical outcome of mesh and suture repair in primary umbilical hernia: postoperative complications and recurrence". Hernia. 20 (4): 509–16. doi:10.1007/s10029-016-1466-x. PMID 26879081. 18. ^ Christoffersen MW, Helgstrand F, Rosenberg J, Kehlet H, Strandfelt P, Bisgaard T (April 2015). "Long-term recurrence and chronic pain after repair for small umbilical or epigastric hernias: a regional cohort study". American Journal of Surgery. 209 (4): 725–32. doi:10.1016/j.amjsurg.2014.05.021. PMID 25172168. ## External links[edit] Classification D * ICD-10: K42 * ICD-9-CM: 551-553 * MeSH: D006554 * DiseasesDB: 23647 External resources * MedlinePlus: 000987 Wikimedia Commons has media related to Umbilical hernia. * Overview at Cincinnati Children's Hospital Medical Center * Overview at Penn State * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Umbilical hernia	c0795690	8,488	wikipedia	https://en.wikipedia.org/wiki/Umbilical_hernia	2021-01-18T18:35:32	{"mesh": ["D006554"], "umls": ["C0795690", "C1306503"], "wikidata": ["Q2737426"]}
Sturtevant (1940) described two classes, 'roller' and 'non-roller,' the roller phenotype being dominant. However, Sturtevant (1965) cited Matlock as finding a high frequency of discordance in monozygotic twins, suggesting little genetic basis for the trait. Hsu (1948) described the ability to fold up the tip of the tongue as a recessive. Liu and Hsu (1949) and Lee (1955) demonstrated independence of the two traits. The cloverleaf tongue (ability to fold the tongue in a particular configuration) may be yet another distinct trait (Whitney, 1950), inherited probably as a dominant. Gorlin (1982) observed cloverleaf tongue in a mother and her 2 sons. Cohen (1993) described mother and daughter with the ability to transform the tongue into a cloverleaf shape. Hirschhorn (1970) emphasized that ample time for learning must be allowed in doing family studies of tongue gymnastic ability. Martin (1975) excluded genetic determination by showing that the frequency of concordance is the same in monozygotic and dizygotic twin pairs. In Barcelona, Hernandez (1980) found the ability to roll the tongue in 63.7% of males and 66.84% of females. In males, an association with ability to move the ears (129100) was found. Mouth \- Tongue curling Inheritance \- ? Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	TONGUE CURLING, FOLDING, OR ROLLING	c1861056	8,489	omim	https://www.omim.org/entry/189300	2019-09-22T16:32:29	{"omim": ["189300"]}
Cyst form of Pneumocystis. GMS Stain. Close apposition of cysts may simulate budding. Pneumocystosis is an infection by Pneumocystis jirovecii, that primarily occurs as a pulmonary infection AIDS patients,[1] with extrapulmonary involvement being uncommon but, if occurring in the skin, presenting most often as nodular growths in the auditory canal.[2]:442 ## See also[edit] * Skin lesion * Pneumocystis pneumonia ## References[edit] 1. ^ Dugdale, III, MD, David C. "Pneumocystosis". MedLinePlus. Retrieved 1 April 2014.CS1 maint: multiple names: authors list (link) 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. * 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 This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Pneumocystosis	c1535939	8,490	wikipedia	https://en.wikipedia.org/wiki/Pneumocystosis	2021-01-18T19:07:56	{"gard": ["4386"], "mesh": ["D011020"], "umls": ["C1535939"], "orphanet": ["723"], "wikidata": ["Q7205993"]}
Essential fructosuria is a rare autosomal recessive disorder of fructose metabolism (see this term) caused by a deficiency of fructokinaseenzyme activity. It is characterized by elevated fructosemia and presence of fructosuria following ingestion of fructose and related sugars (sucrose, sorbitol). Essential fructosuria is clinically asymptomatic and harmless. Dietary restriction is not indicated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Essential fructosuria	c0268160	8,491	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2056	2021-01-23T18:33:53	{"mesh": ["C538068"], "omim": ["229800"], "umls": ["C0268160"], "icd-10": ["E74.1"], "synonyms": ["Fructokinase deficiency", "Ketohexokinase deficiency"]}
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by psychomotor and growth delay, severe intellectual disability, microcephaly, and hypoplastic corpus callosum. Additional reported manifestations include increased muscle tonus, seizures, cardiac anomalies, recurrent bronchopneumonia, camptodactyly, preauricular skin tag, and dysmorphic facial features (such as broad forehead, hypertelorism, flat nasal bridge, anteverted nostrils, and prominent ears), 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	Intellectual disability-hypoplastic corpus callosum-preauricular tag syndrome	c4302530	8,492	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1495	2021-01-23T19:03:33	{"gard": ["12487"], "icd-10": ["Q87.8"], "synonyms": ["Da Silva syndrome"]}
Large-cell lymphoma Micrograph of a primary mediastinal large B-cell lymphoma, a type of large-cell lymphoma. H&E stain. SpecialtyOncology The large-cell lymphomas have large cells. One classification system for lymphomas divides the diseases according to the size of the white blood cells that has turned cancerous. A large cell, in this context, has a diameter of 17 to 20 μm.[1] Other groups of lymphomas in this system are the small-cell lymphomas and mixed-cell lymphomas. ## Contents * 1 Types * 1.1 B cell * 1.2 T cell * 2 References * 3 External links ## Types[edit] ### B cell[edit] Diffuse large B-cell lymphoma is the most common of the large-cell lymphomas. MeSH now classifies the phrase "large-cell lymphoma" under "Diffuse large B cell lymphoma".[2] Many other B-cell lymphomas feature large cells: * Angiocentric lymphoma * Burkitt's lymphoma * Follicular large-cell lymphoma * Immunoblastic lymphoma * Intravascular large-cell lymphoma * Primary mediastinal B-cell lymphoma * T-cell–rich B-cell lymphoma * Primary splenic lymphoma (rare) * Primary central nervous system lymphomas, which are often diffuse large-B-cell lymphomas Activated B-Cell Diffuse Large B-Cell Lymphoma, or ABC-DLBCL, is believed to be caused by aberrant activation of a critical intracellular pathway. This intracellular signaling pathway involved in B-cell activation and proliferation stays constantly activated, driving lymphocytes to proliferate continuously. The inhibition of this pathway can be induced by a drug known as NEMO Binding Domain, or NBD, a peptide causing increased cell death of malignant lymphocytes.[citation needed] ### T cell[edit] Less commonly, a large-cell lymphoma may feature T cells. Anaplastic large-cell lymphoma is an example of a large-cell lymphoma that involves T cells. Of the large-cell T-cell lymphomas, it has the best prognosis.[citation needed] ## References[edit] 1. ^ Turgeon, Mary Louise (2005). Clinical hematology: theory and procedures. Hagerstown, MD: Lippincott Williams & Wilkins. pp. 221. ISBN 0-7817-5007-5. 2. ^ Large+cell+lymphoma at the US National Library of Medicine Medical Subject Headings (MeSH) ## External links[edit] Classification D * ICD-9-CM: 200.7 * MeSH: D016403 * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Large-cell lymphoma	c0024302	8,493	wikipedia	https://en.wikipedia.org/wiki/Large-cell_lymphoma	2021-01-18T18:44:21	{"gard": ["8220"], "mesh": ["D008228"], "umls": ["C0024302"], "wikidata": ["Q6488977"]}
HIV/AIDS in Lesotho constitutes a very serious threat to the Basotho people and Lesotho's economic development. Since its initial detection in 1986, HIV/AIDS has spread at alarming rates in Lesotho.[1] In 2000, King Letsie III declared HIV/AIDS a natural disaster.[2] According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) in 2016, Lesotho's adult prevalence rate of 25% is the second highest in the world, following Eswatini.[3] Estimated HIV infection rates in Africa (% of population aged 15–49) show highest prevalence in Eswatini, Lesotho, South Africa, and Botswana in 2011. (World Bank) over 15% 5-15% 2-5% 1-2% 0.5-1% 0.1-0.5% not available HIV has affected the majority of the general population, while disproportionately affecting the rural, working-age population.[3] The spread of HIV in Lesotho is compounded by cultural practices, serodiscordancy, and gender-based violence.[4][5] Lack of developed sexual education programs in schools places the young demographic at increased risk of HIV infection.[6][7] Over the past three decades, the Government of Lesotho, in collaboration with global organizations such as The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), World Health Organization (WHO), and President's Emergency Plan for AIDS Relief (PEPFAR), has dramatically improved HIV testing and treatment coverage through comprehensive program implementation.[8][9][10] However, high levels of poverty, inequality, and stigma towards HIV remain major barriers to HIV prevention in Lesotho.[1][11][12] As such, Lesotho seeks financial aid and guidance in program reform from its neighbor South Africa, which, despite having the highest number of people living with HIV in the world,[13] has dramatically reduced costs of HIV prevention efforts in the past decade.[14] ## Contents * 1 Prevalence * 1.1 By gender * 1.2 By age * 1.3 By occupation * 2 National response * 2.1 1980-2000 * 2.2 2000-2010 * 2.3 2010-present * 3 Risk factors * 3.1 Cultural practices * 3.2 Violence against women * 3.3 Serodiscordant couples * 3.4 Sexual education * 4 Difficulties in treatment * 4.1 Stigma and discrimination * 4.2 Political factionalism * 4.3 Lack of resources * 4.4 Health conditions * 4.4.1 Malnutrition * 4.4.2 Parasitic infections * 4.4.3 Tuberculosis co-infection * 4.5 Adherence to treatment * 5 Economic impact * 5.1 Macroeconomic * 5.2 Microeconomic * 6 See also * 6.1 General * 7 References ## Prevalence[edit] Lesotho's adult prevalence rate of 25% has remained relatively constant since 2005. In 2016, there was an estimated 330,000 people living with HIV as compared to 240,000 people in 2005, and 270,000 people in 2010. Overall, HIV incidence is declining, from 30,000 new infections in 2005 to an estimated 21,000 new infections of HIV in 2016.[3] ### By gender[edit] According to the 2014 Lesotho Demographic and Health Survey (LDHS), prevalence among women has increased from 26% in 2004 to 30% in 2014, whereas male HIV prevalence has stagnated around 19% over the same time period.[15] In 2014, Lesotho's Ministry of Health and Social Welfare (MOHSW) determined the prevalence rate among young women was 10.2%, whereas among young men it was 5.9%.[8] In 2015, pregnant women had a prevalence rate of 25.9%.[8] Men who have sex with men (MSM) had a 32.9% prevalence rate in 2016.[3] Women work in a Chinese-owned textile factory in Lesotho. ### By age[edit] According to the 2003 HIV Sentinel Survey Report, the 25–29 age group was most affected by HIV, with prevalence of 39.1%. For the 15–19 and 20–24 age groups, median prevalence was 14.4% and 30.1%, respectively.[16] In 2014, LDHS found that 13% of young women and 6% of young men ages 15–24 were infected with HIV.[8] In 2003, the Ministry of Health estimated that there were around 100,000 children under the age of 15 in Lesotho's 10 districts who had lost one or both parents to AIDS.[16] ### By occupation[edit] Sex workers and factory workers are disproportionately affected by HIV, with prevalence rates of 79.1% and 42.7% in 2015, respectively.[8] Prison inmates constitute another key affected population, with a prevalence rate of 32.9% in 2015.[8] ## National response[edit] The government of Lesotho has taken concrete actions to address the epidemic since King Letsie III's declaration of HIV/AIDS as a national emergency. Establishment of the National AIDS Prevention and Control Program and the Lesotho AIDS Programme Coordinating Authority (LAPCA) under the Prime Minister’s Office accelerated national and international response to the epidemic.[5] ### 1980-2000[edit] Lesotho's National AIDS Prevention and Control Program was formed in 1987.[5] However, funding and infrastructural limitations prompted the United Nations to intervene in 1992 and assist with release of sentinel surveys to monitor the spread of HIV. As such, data collection remained inconsistent until 2000.[5] It was not until 2004 that LDHS included HIV testing data to assess magnitude and patterns of HIV infection.[5] ### 2000-2010[edit] LAPCA was established in 2001 to coordinate the multisectoral response to HIV/AIDS, but several factors hindered it in fulfilling its strategic role.[17] In October 2003, the government used Turning a Crisis into an Opportunity, a document constructed by a Lesotho-based United Nations interagency group, as an official working model to address the epidemic.[18] In 2005, the government passed a bill establishing the semi-autonomous National AIDS Commission (NAC) and National AIDS Secretariat (NAS) to coordinate and support strategies for the period 2005 to 2008.[2] Community health workers receive training in Lesotho. Lesotho committed itself to the World Health Organization (WHO) goal of having 28,000 people on antiretroviral therapy (ART) by the end of 2005.[19] In May 2004, the first comprehensive HIV/AIDS center to provide ART opened.[16] The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), international private organizations, local and international nongovernmental organizations (NGOs), and community-based organizations (CBOs) provided the mainstay of the response to HIV/AIDS, especially in the area of community mobilization.[16] Most of these operations were small and localized to specific geographical areas in urban centers. The biggest challenge was the establishment of national networks and civil society organizations on HIV/AIDS, most importantly among people living with HIV/AIDS and within the NGO network.[16] In 2005, the apparel and textile industry, Lesotho's biggest private employer, established an innovative sector-wide and comprehensive HIV workplace program through a public private partnership with the government of Lesotho, buyers, employers, and other donors.[20] In May 2009, the Apparel Lesotho Alliance to fight AIDS (ALAFA) provided close to 90% of the 42,000 employees with prevention services, and up to 80% with treatment services.[21] Lesotho has increasingly used community mobilization and education, as well as offering HIV testing and counseling (HTC) upon individual request.[22] The burden of determining how and when people access treatment and counseling services is placed on local communities. Communities are responsible to ensure confidentiality and provide access to post-test services.[22] In 2004, only 2.7% of Basotho adults participated in HTC. However, HTC participation increased to 35% by 2011.[8] ### 2010-present[edit] In 2014, the Ministry of Health initiated a new program involving provider-initiated testing and counseling, where providers traveled to homes providing HTC services instead of through individual request. However, lack of staffing and HIV test kit shortages severely impacted the program's effectiveness.[8] A research study conducted by Labhardt et al. (2014) examined the relative merits of home-based versus mobile clinic HTC services, finding that mobile clinics were more effective at detecting new HIV infections, whereas home clinics were more effective for testing those who were getting tested for the first time.[23] In 2014, 63% of Basotho men and 84% of Basotho women had been tested for HIV at least once in their life, according to LDHS.[8] Other HIV prevention efforts spearheaded by Lesotho's Ministry of Health include preventing mother-to-child transmission (PMTCT) programs, voluntary medical male circumcision (VMMC), and condom distribution.[24] A Basotho woman kisses her son, who was born HIV-free in 2008 due to successful PMTCT treatment at Molikaliko health clinic, Lesotho. In 2011, the Ministry of Health successfully launched the VMMC program. By 2012, 10,400 men had undergone VMMC; by 2014, around 36,200 men had undergone treatment.[8] VMMC is most prevalent and effective among the 15-19 age group.[3] VMMC program expansion is most hindered in rural areas, where traditional initiation rituals promote circumcision of young boys.[17] PMTCT efforts include ART for infected women throughout pregnancy, and HIV medication for babies 4–6 weeks after birth. In some cases, mothers will undergo cesarean deliveries to further prevent MTCT.[25] In 2010, WHO recommended providing ART to all pregnant women regardless of CD4 count or viral load, causing the Ministry of Health to revise its PMTCT program accordingly.[17] As a direct result, the number of infected pregnant women receiving ART increased significantly from 58% in 2009 to 89% in 2012. However, staffing and funding challenges have compromised this program's effectiveness.[8] In 2016, UNAIDS reported only 66% coverage among pregnant women.[3] The Ministry of Health proposed a HIV prevention strategy aimed to eliminate MTCT and reduce sexual transmission of HIV by 50% by 2015. MTCT is considered eliminated when transmission rate drops below 5%, according to UNAIDS.[8] Data from Lesotho's 2015 UNAIDS Report indicates neither target was reached.[8] In 2012, MTCT rates in Lesotho stagnated around 3.5%, but subsequently increased to 5.9% in 2014.[8] In 2015, the National Aids Commission (NAC) of Lesotho reported a distribution of 31 condoms per adult man, exceeding the United Nations Population Fund’s average of 30.[24] Male condom use with sex workers has increased from 64% in 2009 to 90% in 2014.[24] Additionally, in 2016, UNAIDS reported that 76% of adults aged 15-49 with more than one sexual partner in the past year used condoms.[3] In June 2016, the Ministry of Health launched the “Test and Treat” initiative, where every person tested HIV positive is offered ART, regardless of CD4 count. Lesotho is the first country in sub-Saharan Africa to implement this program.[19] ## Risk factors[edit] There are various factors that place Basotho at increased risk for HIV contraction. ### Cultural practices[edit] Bulled (2015) argues that the primary risk factor for heterosexual partnerships is multiple concurrent partnerships (MCP).[5] LDHS data from 2009 indicates that bonyatsi practices, the culturally sanctioned practice of maintaining many sexual partners, continues after marriage, as 9% of women and 24.4% of men ages 30–39 had two or more sexual partners in the past year.[5] Gender differences in self-reporting of MCP is strongly influenced by social norms: men gain social standing by having multiple partners, whereas women are driven by economic need.[5] However, recent research (Tanser et al., 2011; Thorton, 2008) found that the spread of HIV was not compounded by MCP.[5] ### Violence against women[edit] Basotho women protest violence against women at the National University of Lesotho on National Women's Day, 2008. Lesotho's highly patriarchal society strongly influences females’ experiences with gender-based violence, particularly in schools. Basotho communities exhibit dominant perceptions of heteronormal relations, but the social construction of male superiority places females at risk of adverse experiences through these heterosexual relations.[4] Many women and girls are placed at risk for HIV infection through gender-based violence, which commonly comes in the form of marital rape, rape, or domestic abuse. Particularly in rural areas, females are subject to this violence because they often lack social and economic power in sexual decision making.[26] These unequal power dynamics prohibit Basotho women from adopting HIV-preventative behaviors, thereby increasing their vulnerability to HIV.[26] The prevalence of customary law in Lesotho, despite constitutional amendments in 1993 granting civil rights to all individuals, acts as a barrier to women's inheritance, ownership, and equity in marriage and other sexual relationships.[5] Customary law treats women as legal minors who are dependent on men—fathers, brothers, or husbands. As a result of the customary law, Lesotho experiences high rates of violence, inter-generational sex, and payment for sex, all of which increases an individual's risk of HIV infection.[5] Through marriage, a Basotho man becomes sexually entitled to his wife's body through payment of the bride price, making the women property of her husband.[26] In 2006, the government of Lesotho passed a civil law to counteract the gender discrimination engendered by customary law, but it was ineffective.[5] However, women rarely report these acts of violence out of fear, choosing to forget, or economic dependency on men.[26] Basotho women fear bringing shame to their families for accusing their husbands of rape. Often, women are emotionally coerced into sex through a sense of marital obligation.[26] According to LDHS (2014), 33% of Basotho women and 40% of Basotho men affirmed the belief that under certain circumstances, a man is justified in beating his wife.[15] Furthermore, according to survey results from GenderLinks, 62% of Basotho women experienced intimate partner violence, and 37% of Basotho men perpetuated it in 2013.[27] ### Serodiscordant couples[edit] Serodiscordant relationships are a significant source of new HIV infection in Lesotho, according to Makwe and Osato (2013). The unaffected partner of serodiscordant couples is at disproportionately high risk of contracting HIV from their partner, especially when engaging in risky sexual behaviors such as pregnancy attempts.[28] HIV transmission between heterosexual serodiscordant couples, irrespective of the infected partner's gender, was found to be around 20-25% per year in 2007.[28] In 2013, serodiscordance rates in Lesotho were estimated to be around 13%.[28] Separated, divorced, and widowed individuals are also at high risk for HIV contraction. Research conducted by De Walque and Kline (2012) has shown that unusually high HIV rates are found in remarried individuals, because many couples become serodiscordant. In Lesotho, around 32.6% of men and 45.6% of women who remarried were HIV infected between 2003-2006.[29] HIV prevalence rates among remarried women in Lesotho were especially high compared to other African countries.[29] Interventions including consistent condom use, voluntary medical male circumcision (VMMC), and use of ART drugs can keep couples serodiscordant indefinitely. VMMC is widely recommended as a prevention strategy, with research in sub-Saharan Africa finding that female-to-male HIV transmission decreased by 38-66% over two years (Gray et al., 2007; Bailey et al., 2007).[28] ### Sexual education[edit] Uniformed children attend class in Ha Nqabeni primary school, Lesotho. In Lesotho and other sub-Saharan countries, schools are often viewed as the vehicle for HIV education and prevention for the young generation. However, several internal problems greatly affect schools’ ability to change attitudes and sexual behaviors. These include lack of appropriate materials, overcrowded curriculum, lack of effective teacher training, and teachers’ embarrassment to engage students in discussions regarding HIV.[26] According to multiple research studies conducted by Mturi and collaborators (2003; 2005), the most frequently reported reason for contraception non-use is simply lack of knowledge regarding contraception. Young people tend to use friends or the media for information on sexual health and contraception, which can be misleading sources of information.[6] Mturi (2005) found that 90% of young people in Lesotho lacked understanding of the fertile period in females’ monthly cycles.[6] Additionally, in many African societies, including Lesotho, it is considered taboo to discuss issues of sex with children. For this reason, research found that only about 20% of females and 10% of males discuss sex-related issues with their parents.[30] As parents are often embarrassed to discuss such issues with their children, they rely on schools.[6] In Lesotho, around 90% of schools are managed by churches, and thus do not have an established sex education program. Without proper sex education, young people are at risk for HIV contraction.[6] As a result, Lesotho's Ministry of Education proposed the Population and Family Life Education (POP/FLE) initiative to introduce sex education curriculum into schools.[6] ## Difficulties in treatment[edit] There are several obstacles to effective HIV/AIDS treatment in Lesotho. ### Stigma and discrimination[edit] There exists a strong cultural stigma against HIV diagnoses in many countries of Sub-Saharan Africa, including Lesotho, which leads to discrimination against those infected. Discrimination can take the form of gossip, verbal and physical abuse, or social exclusion.[12] Access to treatment, prevention, and support services is greatly hindered by discrimination.[12] In 2014, 4% of HIV-infected Basotho reported denied access to healthcare services in the past year, while 5.5% reported denied access to family planning services in the same time period.[12] Discrimination can negatively impact employment opportunities as well as workers' livelihoods. In 2016, 13.9% of Basotho reported that they would not buy vegetables from a vendor living with HIV, according to UNAIDS.[3] Lesotho is divided into ten districts, each of which are further subdivided into 80 constituencies. Conflicts between constituencies perpetuate political instability. ### Political factionalism[edit] Turkon (2008) suggested that efforts to combat the HIV/AIDS epidemic in Lesotho are undermined by strong partisan divisions in rural communities. UNAIDS has expressed hope that the HIV/AIDS crisis will be the catalyst for Basotho communities to transcend partisan lines and work together as a unit.[11] Political factions in Lesotho arise from vested interest in governmental control.[11] The people of Lesotho place little trust in the Basotho's political elite to uphold communal values or demonstrate hierarchical reciprocity. This is in part due to political instability present in the country. While the government of Lesotho is a constitutional monarchy, with the Prime Minister of Lesotho heading the government, a system of chieftaincy informally governs the rural areas.[31] The chieftaincy operates as an administrative hierarchy, responsible for governing the colonial structure of wards and districts in rural communities. The chieftaincy system as a whole receives support from villagers, while individual chiefs are often heavily criticized for corrupt practices, including dereliction, favoritism, and bribery.[31] Nevertheless, partisan divisions do not only exist between chief and commoner. They often manifest as antagonistic relationships between neighbors in the same village.[11] As a result, community-based approaches to HIV/AIDS treatment are often unsuccessful.[11] ### Lack of resources[edit] Lack of proper resources and lack of access to resources compromises efficacy of HIV treatments. Healthcare centers often lack basic equipment and drug supplies, or are chronically understaffed.[32] Furthermore, travel distance to healthcare centers can be financially and physically burdensome for many, particularly rural patients. Round-trip transportation to the healthcare clinic and cost of treatment, totaling about $10, prevents a problem for many Basotho.[32] Moreover, follow-up visits following initial treatment is cost-prohibitive. In 2014, LDHS found that 38% of rural patients walked for more than two hours to reach their healthcare facility, whereas only 3% of urban patients walked.[15] Those too ill to travel alone require accompaniment, at the risk of worsening existing health conditions.[32] ### Health conditions[edit] Preexisting or concurrent health conditions, both communicable and chronic, can increase an individual's risk of HIV contraction as well as exacerbate the progression of the disease. A young boy preps Mielie pap, the staple food in Lesotho. #### Malnutrition[edit] Malnutrition may be the greatest obstacle to effective HIV treatment. Starvation allows rapid progression of HIV by undermining the body's natural defense mechanisms[32] and promoting viral replication.[33] This can lead to increased toxicity of HIV/AIDS treatment drugs.[32] General maternal malnutrition and vitamin deficiencies can increase risk of MTCT.[33] In 2015, the World Bank estimated that 11% of Lesotho's population was undernourished.[34] #### Parasitic infections[edit] Parasitic infections, commonly in the form of malaria infections, intestinal parasites, or schistosomiasis, compromise the immune system and exacerbate malnutrition. Malaria is estimated to increase HIV viral load by seven to ten times.[33] Consequently, people with malaria are at increased risk of transmitting HIV to partners. There is very little data on malaria prevalence in Lesotho.[15][35] In contrast, prevalence rates of schistosomiasis in Lesotho were estimated to be 8.3% in 2015.[36] Worms that cause schistosomiasis live in streams and lakes, which women often frequent through activities such as bathing, washing clothes, or collecting water.[33] Schistosomiasis promotes HIV transmission through genital lesions and inflammation. It is estimated to triple women's risk of HIV infection.[33] #### Tuberculosis co-infection[edit] Recent increases in the number of tuberculosis (TB) co-infections, particularly multi drug resistant tuberculosis (MDR-TB), in HIV-infected Basotho hinders effective HIV treatment. The risk of contracting TB is much greater for those already infected with HIV.[37] In 2014, 74% of Basotho infected with TB tested positive for HIV.[8] In 2015, it was estimated that there was about 12,000 incident tuberculosis cases among those living with HIV.[3] Lesotho, among several other sub-Saharan countries, struggles to control the TB epidemic. Reasons include competing national health system priorities (such as the HIV/AIDS epidemic), and the toll of TB/HIV co-infection on healthcare workers. Delayed diagnosis, inadequate initial treatment, and prolonged infectiousness of TB further exacerbate the severity of the epidemic.[37] ### Adherence to treatment[edit] Adherence to treatment, most commonly ART, remains a large barrier to effective provision of HIV treatment. In 2016, about 53% of adults living with HIV in Lesotho were receiving ART.[3] Lesotho has seen a decline in access to ART medication between 2010 and 2016, as 66% of pregnant Basotho women living with HIV had access to ART medicines in 2016, as compared to 72% in 2010.[3] Once a patient seeks out initial treatment for HIV, follow-up visits are critical to improve and maintain a patient's clinical, immunological, and virological outcome. Adherence to ART drugs delays onset of drug resistance, treatment failure, and subsequent necessity to use a different drug treatment.[9] Maintaining proper adherence to treatment involves meticulous processes, such as taking the correct amount of medication in the specific, regimented manner mandated by health professionals. Drug treatments must also be stored properly.[9] Costs of medication and continual treatment are prohibitive for many Basotho. Other barriers to adherence include lack of transportation to healthcare facilities, lack of access to medication refills, or inconsistency of caregiver.[9] Cultural attitudes of stigma toward HIV diagnosis in Lesotho often leaves those infected without social support, which can negatively impact adherence.[12] ## Economic impact[edit] HIV/AIDS has had a devastating economic impact in Lesotho at both the macroeconomic level and the microeconomic level. Increased morbidity and mortality rates has reduced living standards and has exacerbated poverty, inequality, and unemployment levels throughout the country.[17] ### Macroeconomic[edit] Basotho workers often cross the borders into South Africa to seek employment opportunities. From 1993 to 1998, HIV/AIDS response cost Lesotho's government an estimated 151.2 million Maloti.[38] In 2016 alone, UNAIDS estimated HIV/AIDS costs to be $124 million[3] (around M1.7 billion[39]). Domestic expenditure was nearly equal to international expenditure.[3] Lesotho's government relies heavily on international sources of funding for HIV response, from organizations such as The Global Fund, PEPFAR, and UN agencies.[10] HIV has decreased growth in many of Lesotho's economic sectors, including the agricultural sector,[1] which holds an estimated 86% of the labor force.[40] Death from AIDS reduces the number of productive workers in the workforce, diminishing worker productivity as younger, less experienced workers replace experienced laborers.[41] Many Basotho migrate to South Africa to work; as they fall ill and return home, money inflows to the country decrease.[41] HIV negatively impacts educational outcomes, mostly in Lesotho's rural populations where prevalence is highest. Children, particularly girls, are less likely to attend school or complete primary school because they are expected to care for sick family members or younger siblings orphaned by AIDS.[7] Falling school retention rates and decreased worker productivity may have a long-term, widespread effect on human capital investment and future economic growth of Lesotho.[42] ### Microeconomic[edit] HIV incurs several costs on caregivers and households. Caregivers, while mostly women, can be children and the elderly as well. Costs of treatment and management of HIV, including the purchase of scarce items such as water, disinfectants, and soaps, consumes about one-third of household incomes.[43] Akintola (2008) found that volunteer caregivers in Lesotho reported giving their own personal items or food to patients due to insufficient income.[43] As such, households where women combine the roles of caregiver, head of household, and breadwinner are common in Lesotho and other sub-Saharan countries.[43] Caregiving can be physically and emotionally distressing to caregivers, as ill patients require continuous, demanding care. Many caregivers, particularly working-age caregivers, lose the opportunity to earn a primary income or engage in other activities due to this demanding role.[43] ## See also[edit] * Lesotho * Politics of Lesotho * LGBT rights in Lesotho * Human trafficking in Lesotho * HIV/AIDS in South Africa ### General[edit] * HIV/AIDS in Africa * UNAIDS * President's Emergency Plan for AIDS Relief ## References[edit] 1. ^ a b c Central Bank of Lesotho, comp. Economic Impact of HIV/AIDS in Lesotho. Report. March 2004. https://www.centralbank.org.ls/images/Publications/Research/Reports/MonthlyEconomicReviews/2004/Economic_Review_Mar_04.pdf. 2. ^ a b National AIDS Commission, Lesotho. COORDINATION FRAMEWORK FOR THE NATIONAL RESPONSE TO HIV AND AIDS. Publication. 2007. Accessed November 25, 2017. http://www.ilo.org/wcmsp5/groups/public/---ed_protect/---protrav/---ilo_aids/documents/legaldocument/wcms_126753.pdf. 3. ^ a b c d e f g h i j k l m UNAIDS. UNAIDS Data 2017, 2017, pp. 32. Joint United Nations Programme on HIV/AIDS. 4. ^ a b Morojele, Pholoho. “Gender Violence: Narratives and Experiences of Girls in Three Rural Primary Schools in Lesotho.” Agenda: Empowering Women for Gender Equity, no. 80, 2009, pp. 80–87. JSTOR, JSTOR, www.jstor.org/stable/27868967. 5. ^ a b c d e f g h i j k l Bulled, Nicola. Prescribing HIV Prevention: Bringing Culture into Global Health Communication. Vol. 1. N.p.: Left Coast Press, 2015. Print. 6. ^ a b c d e f Mturi, Akim J., and Monique M. Hennink. “Perceptions of Sex Education for Young People in Lesotho.” Culture, Health & Sexuality, vol. 7, no. 2, 2005, pp. 129–143. JSTOR, JSTOR, www.jstor.org/stable/4005445. 7. ^ a b Nyabanyaba, Thabiso. “Improving the Quality of Education among Rural Learners through the Use of Open and Flexible Approaches in Lesotho’s Secondary Schools.” Journal of Higher Education in Africa / Revue De L'enseignement Supérieur En Afrique, vol. 13, no. 1-2, 2015, pp. 111–131. JSTOR, JSTOR, www.jstor.org/stable/jhigheducafri.13.1-2.111. 8. ^ a b c d e f g h i j k l m n o Lesotho Ministry of Health and Social Welfare (MOHSW) “Global AIDS Response Country Progress Report: January -December 2014.” 2015, pp. 1-36, UNAIDS. 9. ^ a b c d Ramatlapeng, Mphu. “Working Draft—Lesotho National ART Guidelines.” Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing Infection, 2004, pp. 1-156. Lesotho Ministry of Health and Social Welfare (MOHSW), World Health Organization, https://www.who.int/hiv/pub/guidelines/lesotho_art.pdf. 10. ^ a b Lesotho Country Operational Plan (COP) 2016: Strategic Direction Summary, 2016, pp. 1-69. Lesotho Ministry of Health and Social Welfare (MOHSW), President’s Emergency Plan for Aids Relief (PEPFAR), https://www.pepfar.gov/documents/organization/257640.pdf 11. ^ a b c d e Turkon, David. “Commoners, Kings, and Subaltern: Political Factionalism and Structured Inequality in Lesotho.” Political and Legal Anthropology Review, vol. 31, no. 2, 2008, pp. 203–223. JSTOR, JSTOR, www.jstor.org/stable/24497353. 12. ^ a b c d e “Lesotho 2014.” The People Living with HIV Stigma Index, 2014, pp. 1-42. Lesotho Network of People Living with HIV and AIDS (LENEPWHA). 13. ^ The Joint United Nations Programme on HIV/AIDS (UNAIDS). 2017. Ending AIDS: Progress Towards 90-90-90. Report. Geneva: UNAIDS. 14. ^ Barton-Knott, Sophie. June 2013. Around 10 million people living with HIV now have access to antiretroviral treatment. Press Report. Geneva: The Joint United Nations Programme on HIV/AIDS (UNAIDS). 15. ^ a b c d Ministry of Health [Lesotho] and ICF International. Lesotho Demographic and Health Survey 2014, 2006, pp. 1-538. Maseru, Lesotho: Ministry of Health and ICF International. 16. ^ a b c d e Bowsky, Sara. US Government Rapid Appraisal for HIV/AIDS Program Expansion: Lesotho. Report. 2004. Accessed November 25, 2017. http://pdf.usaid.gov/pdf_docs/Pdacf093.pdf. 17. ^ a b c d Lesotho Ministry of Health and Social Welfare (MOHSW) “Global AIDS Response Country Progress Report: January 2010-December 2011.” 2012, pp. 1-106, UNAIDS, http://www.unaids.org/sites/default/files/country/documents//file,68395,fr..pdf 18. ^ Sprague, Courtenay (2005). "New Strategies in the Battle against HIV/AIDS". African Studies Review. 48 (3): 143. doi:10.1353/arw.2006.0042. JSTOR 20065147. 19. ^ a b "Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV". World Health Organization. September 2015. 20. ^ Overseas Development Institute. Aid for Trade in Lesotho: ComMark’s Lesotho Textile and Apparel Sector Programme. Publication. 2009. Accessed November 25, 2017. https://www.odi.org/sites/odi.org.uk/files/odi-assets/publications-opinion-files/5948.pdf. 21. ^ "Apparel Lesotho Alliance to Fight Aids (ALAFA) Project." DAI: International Development. Accessed November 25, 2017. https://www.dai.com/our-work/projects/lesotho-apparel-lesotho-alliance-fight-aids-alafa-project. 22. ^ a b “HIV Testing, Treatment and Education Campaigns: Lesotho, Botswana and Swaziland.” Reproductive Health Matters, vol. 14, no. 27, 2006, pp. 229–229. JSTOR, JSTOR, www.jstor.org/stable/3775938. 23. ^ Labhardt, N.D. et al. (2014). Home-Based Versus Mobile Clinic HIV Testing and Counseling in Rural Lesotho: A Cluster-Randomized Trial. PLOS Medicine. 24. ^ a b c Prevention Gap Report 2016. Report. UNAIDS, 2017. Accessed November 25, 2017. http://www.unaids.org/sites/default/files/media_asset/2016-prevention-gap-report_en.pdf. 25. ^ "Understanding HIV/AIDS". US Department of Health and Human Services. 2017. 26. ^ a b c d e f Motalingoane-Khau, Mathabo. “'But He Is My Husband! How Can That Be Rape?': Exploring Silences around Date and Marital Rape in Lesotho.” Agenda: Empowering Women for Gender Equity, no. 74, 2007, pp. 58–66. JSTOR, JSTOR, www.jstor.org/stable/27739343. 27. ^ Chipatiso, Linda Musariri, Mercilene Machisa, Violet Nyambo, and Kevin Chiramba.Gender-Based Violence Indicators Study: Lesotho. Gender Links. Gender Links: For Equality and Justice. 2014. Accessed November 25, 2017. http://genderlinks.org.za/wp-content/uploads/imported/articles/attachments/20068_final_gbv_ind_lesotho.pdf. 28. ^ a b c d Makwe, Christian C., and Osato F. Giwa-Osagie. “Sexual and Reproductive Health in HIV Serodiscordant Couples.” African Journal of Reproductive Health / La Revue Africaine De La Santé Reproductive, vol. 17, no. 4, 2013, pp. 99–106. JSTOR, JSTOR, www.jstor.org/stable/24362091. 29. ^ a b De Walque, Damien, and Rachel Kline. “The Association Between Remarriage and HIV Infection in 13 Sub-Saharan African Countries.” Studies in Family Planning, vol. 43, no. 1, 2012, pp. 1–10. JSTOR, JSTOR, www.jstor.org/stable/23409375. 30. ^ Mturi, Akim J. “Parents' Attitudes to Adolescent Sexual Behaviour in Lesotho.” African Journal of Reproductive Health / La Revue Africaine De La Santé Reproductive, vol. 7, no. 2, 2003, pp. 25–33. JSTOR, JSTOR, www.jstor.org/stable/3583210. 31. ^ a b Coplan, David B., and Tim Quinlan. "A Chief by the People: Nation versus State in Lesotho." Africa: Journal of the International African Institute 67, no. 1 (1997): 27-60. http://www.jstor.org/stable/1161269. 32. ^ a b c d e McMurchy, Dale (2005). "OHAfrica: Initial Learnings as the OHAfrica Team Commences Its Work at an HIV Clinic in Lesotho". Healthcare Quarterly. 8 (2): 14–15. doi:10.12927/hcq..17050. 33. ^ a b c d e Stillwaggon, Eileen (2008). "Race, Sex, and the Neglected Risks for Women and Girls in Sub-Saharan Africa". Feminist Economics. 14 (4): 67–86. doi:10.1080/13545700802262923. 34. ^ World Bank Group. "Prevalence of Undernourishment (% of Population)." World Bank. Accessed November 19, 2017. https://data.worldbank.org/indicator/SN.ITK.DEFC.ZS. 35. ^ WHO, and United Nations. "Lesotho: WHO Statistical Profile." World Health Organization. Accessed November 19, 2017. https://www.who.int/gho/countries/lso.pdf. 36. ^ Lai, YS; et al. (2015). "Spatial distribution of Schistosomiasis and Treatment Needs in Sub-Saharan Africa: A Systematic Review and Geostatistical Analysis". The Lancet Infectious Diseases. 15 (8): 927–40. doi:10.1016/S1473-3099(15)00066-3. PMID 26004859. 37. ^ a b Wells, Charles D., et al. “HIV Infection and Multidrug-Resistant Tuberculosis: The Perfect Storm.” The Journal of Infectious Diseases, vol. 196, 2007, pp. s86–s107. JSTOR, JSTOR, www.jstor.org/stable/30086663. 38. ^ McMurchy, Dale (1997). "The economic impact of HIV / AIDS in Lesotho". AIDS Analysis Africa. 7 (4): 11–12. PMID 12157888. 39. ^ "XE Currency Converter: USD to LSL." XE Currency Converter. Accessed November 25, 2017. http://www.xe.com/currencyconverter/convert/?Amount=124%2C000%2C000&From=USD&To=LSL. 40. ^ United States of America. Central Intelligence Agency. Lesotho. Accessed November 25, 2017. CIA World Factbook. 41. ^ a b Sackey, James, and Tejaswi Raparla. "Lesotho: The Development, Impact of HIV/AIDS-Selected Issues and Options." World Bank Report 21103-LSO (2000). 42. ^ Fortson, Jane G. “MORTALITY RISK AND HUMAN CAPITAL INVESTMENT: THE IMPACT OF HIV/AIDS IN SUB-SAHARAN AFRICA.” The Review of Economics and Statistics, vol. 93, no. 1, 2011, pp. 1–15. JSTOR, JSTOR, www.jstor.org/stable/23015916. 43. ^ a b c d Akintola, Olagoke (2008). "Unpaid HIV/AIDS Care in Southern Africa: Forms, Context, and Implications". Feminist Economics. 14 (4): 117–147. doi:10.1080/13545700802263004. * v * t * e HIV/AIDS in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion 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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	HIV/AIDS in Lesotho	None	8,494	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Lesotho	2021-01-18T19:02:58	{"wikidata": ["Q5629857"]}
A number sign (#) is used with this entry because the French Canadian type of Leigh syndrome is caused by homozygous or compound heterozygous mutation in the LRPPRC gene (607544) on chromosome 2p21. Description The French Canadian type of Leigh syndrome is an autosomal recessive severe neurologic disorder with onset in infancy. Features include delayed psychomotor development, mental retardation, mild dysmorphic facial features, hypotonia, ataxia, and the development of lesions in the brainstem and basal ganglia. Affected individuals tend to have episodic metabolic and/or neurologic crises in early childhood, which often lead to early death (summary by Debray et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of Leigh syndrome, see 256000. Clinical Features Two clinical forms of cytochrome c oxidase (COX, complex IV) deficiency (220110) are recognized (DiMauro et al., 1990): a 'muscular' form in which marked weakness predominates, and a 'nonmuscular' form presenting with Leigh disease, a neurodegenerative condition of the brainstem, cerebellum, and basal ganglia, with symmetric, well-demarcated regions of necrosis, gliosis, and vascular proliferation (van Erven et al., 1987). Leigh disease can also result from other inborn errors of energy metabolism, such as pyruvate dehydrogenase deficiency (266150), complex I deficiency (252010), and mutation in a mitochondrial DNA gene for complex V (516060). In the Saguenay-Lac-Saint-Jean (SLSJ) region of Quebec province in Canada, Merante et al. (1993) described a biochemically distinct form of Leigh syndrome with COX deficiency. Thirty-four children were observed to have a similar phenotype consisting of developmental delay, hypotonia, mild facial dysmorphism, chronic well-compensated metabolic acidosis, and high mortality due to episodes of severe acidosis and coma. Enzyme activity was close to normal in kidney and heart, 50% of normal in fibroblasts and skeletal muscle, and nearly absent in brain and liver. The deficiency of enzyme activity appeared to result from a failure to assemble an active enzyme complex. The cDNA sequences of cytochrome oxidase subunits VIa and VIIa were normal. Merante et al. (1993) demonstrated that the underlying defect was deficiency of COX, which was particularly severe in the liver. Morin et al. (1993) described the clinical findings of 15 of the 34 patients referred to by Merante et al. (1993) who had biochemical evidence of COX deficiency. Fifteen patients in whom clinical findings were reported in detail were aged 6 months to 11 years; 11 children died in episodes of fulminant metabolic acidosis. These patients had elevated blood and cerebrospinal fluid lactate levels, decreased blood bicarbonate levels, and normal blood pH. Characteristic changes of Leigh disease were found in the central nervous system and microvesicular steatosis was found in the liver in all affected patients in whom postmortem examination was performed. Merante et al. (1993) found that the severity of the biochemical defect varied greatly in different tissues. The activity of COX in skin fibroblasts, amniocytes, and skeletal muscle was 50% of normal, while in kidney and heart it was close to normal. Brain and liver, on the other hand, had very low activities. The deficiency of activity appeared to result from a failure of assembly of the cytochrome oxidase complex in liver, but levels of mRNA for both mitochondrially encoded and nuclear-encoded subunits in liver and skin fibroblasts were found to be the same as those in controls. The cDNA sequence of the liver-specific cytochrome oxidase subunits VIa and VIIa were determined in samples from patient liver and skin fibroblasts and showed normal coding sequence. Segregation analysis was consistent with autosomal recessive inheritance. Debray et al. (2011) retrospectively reviewed the clinical course of 56 patients with genetically confirmed French Canadian Leigh syndrome. The median age at onset was 5 months, and patients presented with neonatal distress, psychomotor delay, failure to thrive, ataxia, and acute metabolic acidosis. Other features during the neonatal period included hypotonia (58%), transient tachypnea of the newborn (47%), poor sucking (44%), tremor (28%), and hypoglycemia (17%). There were mild craniofacial features such as prominent forehead, midfacial hypoplasia, wide nasal bridge, hypertelorism, hirsutism, and arched eyebrows. All had developmental and language delay. Older ambulatory patients had truncal ataxia with wide-based gait and mild intention tremor. Most (90%) had 1 or more episodes of acute metabolic and/or neurologic decompensation, most of which (82%) resulted in death at a median age of 1.6 years. Metabolic crises were often associated with an infectious illness and were characterized by increased serum lactate, hyperglycemia, hypotonia, coma, liver dysfunction, shock, respiratory distress, and multiorgan failure. Neurologic crises were characterized by hypotonia, ataxia, coma, abnormal breathing patterns, seizures, and stroke-like episodes. There was a higher incidence of these acute episodes in patients with LRPPC mutations compared to patients with Leigh syndrome due to SURF1 (185620) mutations (see 256000). Olahova et al. (2015) reported 10 patients from 7 unrelated families that were not of French Canadian origin who had a severe neurodevelopmental disorder associated with biallelic LRPPRC mutations. Most presented at birth with lactic acidosis, hypotonia, and severely delayed psychomotor development with absent speech, although a few patients had normal early development with episodic decompensation and developmental regression associated with infection. A few patients had mild nonspecific dysmorphic features. Six patients died in infancy or early childhood. Those that survived showed variable neurologic features, including dystonia, ataxia, dysphagia, strabismus, and seizures. Neuroimaging in 2 patients showed features consistent with Leigh syndrome, but lesions were absent in other patients. Three had a striking leukoencephalopathy and 4 had cerebral malformations, such as cerebellar hypoplasia, gyral abnormalities, and hippocampal abnormalities. Other features included hypertrophic cardiomyopathy (in 2 patients), hypospadias (2 patients), anteriorly placed anus (1 patient), polysyndactyly (1 patient), and complex congenital heart disease (1 patient). All patients tested had variably decreased complex IV activity in fibroblasts and/or muscle tissue (range 3 to 70% residual activity). Inheritance The transmission pattern of LSFC in the families reported by Olahova et al. (2015) was consistent with autosomal recessive inheritance. Mapping To identify the gene involved in the Saguenay-Lac-Saint-Jean form of Leigh disease, Lee et al. (1998) performed linkage disequilibrium mapping with a 318-marker genomewide scan using DNA from 14 affected individuals and their parents. One marker on chromosome 2 showed significant linkage disequilibrium. Further testing with additional affected individuals and additional markers spanning approximately 8 to 10 cM and observation of recombination events narrowed the SLSJ cytochrome oxidase deficiency critical region to approximately 1 to 2 cM. Lee et al. (2001) performed a genomewide linkage disequilibrium scan and localized the LSFC gene to 2p16. By identifying a common ancestral haplotype, they limited the critical region to approximately 2 cM between D2S119 and D2S2174. Molecular Genetics Lee et al. (2001) performed mutation screening of the COX7A2L gene (605771), which maps to chromosome 2, in patients with LSFC and in controls and found no functional mutations. In 21 of 22 patients with LSFC, Mootha et al. (2003) identified a homozygous mutation in the LRPPRC gene (607544.0001). The remaining patient was a compound heterozygote; see 607544.0001. In 10 patients from 7 unrelated families with LSFC who were not of French Canadian origin, Olahova et al. (2015) identified 5 different biallelic mutations in the LRPPRC gene (607544.0003-607544.0007). Patients from 4 unrelated families of Indian or Pakistani origin were homozygous for the same mutation (607544.0003). The mutations were found by whole-exome sequencing or candidate gene sequencing and segregated with the disorder in the families. Studies of fibroblast and muscle tissue from 3 patients showed decreased levels of the LRPPRC protein compared to controls, as well as a significant decrease in the basal oxygen consumption rate. There was almost complete loss of complex IV subunits as well as variable loss of other mitochondrial respiratory subunits, particularly complex I, and decreased levels of steady-state mitochondrial mRNA in patient fibroblasts and muscle tissue. Pathogenesis Sasarman et al. (2010) found that mutant LRPPRC was targeted normally to the mitochondrial compartment in immortalized LSFC patient fibroblasts, but that LRPPRC protein content was reduced. In vitro assays revealed that COX activity was reduced in LSFC patient fibroblasts compared with controls. Patient fibroblasts also showed reduced amounts of mitochondrial-encoded COX subunits I (MTCO1; 516030) and II (MTCO2; 516040), with a smaller decrease in the level of nuclear-encoded subunit IV (COX4I1; 123864). LSFC patient fibroblasts showed reduced steady-state levels of mitochondrial mRNAs and had a defect in mitochondrial protein synthesis. Mitochondrial rRNAs and tRNAs were normal in LSFC fibroblasts. Knockdown of LRPPRC in control fibroblasts via siRNA replicated the generalized assembly defect in oxidative phosphorylation complexes. Sasarman et al. (2010) observed that COX mRNAs appeared to be more sensitive than other mRNAs to reduced LRPPRC content in LSFC fibroblasts. Population Genetics In the French Canadian population of the Saguenay-Lac-Saint-Jean region of Quebec province, De Braekeleer (1991) estimated the prevalence at birth of cytochrome c oxidase deficiency to be 1 in 2,473, giving a carrier frequency of 1 in 28. Morin et al. (1993) estimated the incidence of LSFC at 1 in 2,063 live births between 1979 and 1990, giving a carrier rate of 1 in 23 among inhabitants of the SLSJ region. The genealogic reconstruction of 54 obligate carriers identified 26 ancestors common to all of them. Of these, 22 were 17th-century Europeans, suggesting that the COX-deficient gene was introduced into the French Canadian population by early settlers. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Prominent forehead Face \- Midface hypoplasia \- Unexpressive facies Eyes \- Hypertelorism \- Strabismus \- Arched eyebrows Nose \- Anteverted nares \- Wide nasal bridge RESPIRATORY \- Transient tachypnea of the newborn ABDOMEN Liver \- Liver biopsy shows increased lipid droplets (microvesicular steatosis) \- Decreased cytochrome c oxidase activity SKIN, NAILS, & HAIR Hair \- Low frontal hairline \- Arched eyebrows \- Hirsutism MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Developmental delay \- Psychomotor retardation \- Language delay \- Hypotonia \- Ataxia \- Tremor \- Seizures (less common) \- Increased CSF lactate \- Neurologic crises with coma (in some patients) \- Lesions in basal ganglia, brainstem, cerebellum, thalamus, spinal cord \- Lesions characterized by demyelination, necrosis, gliosis, spongiosis, and capillary proliferation METABOLIC FEATURES \- Lactic acidosis \- Hypoglycemia \- Metabolic crises \- Hyperglycemia during crises LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased CSF lactate \- Decreased cytochrome c oxidase activity in skin fibroblasts, liver, and skeletal muscle MISCELLANEOUS \- Onset in infancy \- Death usually occurs by age 2 years \- Death often occurs during metabolic/acidotic crisis \- First described in the geographically isolated Saguenay-Lac-Saint-Jean region of Quebec, Canada \- Incidence of 1 in 2,000 in Saguenay-Lac-Saint-Jean region \- See also Leigh syndrome ( 256000 ) MOLECULAR BASIS \- Caused by mutation in the leucine-rich PPR motif-containing protein gene (LRPPRC, 607544.0001 ) ▲ 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	LEIGH SYNDROME, FRENCH CANADIAN TYPE	c1857355	8,495	omim	https://www.omim.org/entry/220111	2019-09-22T16:29:00	{"doid": ["0111180"], "mesh": ["C537004"], "omim": ["220111"], "orphanet": ["70472"], "synonyms": ["Alternative titles", "CYTOCHROME c OXIDASE DEFICIENCY, FRENCH CANADIAN TYPE", "COX DEFICIENCY, FRENCH CANADIAN TYPE", "COX DEFICIENCY, SAGUENAY-LAC-SAINT-JEAN TYPE", "LEIGH SYNDROME, SAGUENAY-LAC-SAINT-JEAN TYPE"]}
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: "Fleischer's syndrome" – news · newspapers · books · scholar · JSTOR (October 2016) (Learn how and when to remove this template message) Fleischer's syndrome SpecialtyMedical genetics Fleischer's syndrome is an extremely rare congenital anomaly characterized by displacement of the nipples, occasional polymastia, and hypoplasia of both kidneys.[1] ## References[edit] 1. ^ Zink, Christoph (2011). Dictionary of Obstetrics and Gynecology. Berlin, DEU: Walter de Gruyter. p. 97. ISBN 9783110857276. This article about a congenital malformation 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	Fleischer's syndrome	None	8,496	wikipedia	https://en.wikipedia.org/wiki/Fleischer%27s_syndrome	2021-01-18T19:09:25	{"wikidata": ["Q5458521"]}
Trisomy 9p is a rare chromosomal anomaly syndrome, resulting from a partial or complete trisomy of the short arm of chromosome 9, with a wide phenotypic variablility, typically characterized by intellectual disability, craniofacial dysmorphism (e.g. microcephaly, large anterior fontanel, hypertelorism, strabismus, downslanting palpebral fissures, malformed, low-set, protruding ears, bulbous nose, macrostomia, down-turned corners of mouth, micrognathia), digital anomalies (brachydactyly and clinodactyly), and short stature. Less frequently patients present with cardiopathy and renal, skeletal, and central nervous system malformations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Trisomy 9p	c0265428	8,497	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=236	2021-01-23T17:45:42	{"mesh": ["C538026"], "umls": ["C0265428"], "icd-10": ["Q92.2"], "synonyms": ["Duplication 9p", "Duplication of the short arm of chromosome 9", "Trisomy of the short arm of chromosome 9"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-44 (DFNA44) is caused by heterozygous mutation in the CCDC50 gene (611051) on chromosome 3q28. One such family has been reported. Clinical Features Modamio-Hoybjor et al. (2003) reported a 5-generation Spanish family in which 18 members had onset of moderate hearing loss, mainly affecting low-mid frequencies, between 6 and 10 years of age. Deafness later involved all frequencies and progressed to profound hearing loss in the sixth decade. Mapping By linkage analysis, Modamio-Hoybjor et al. (2003) identified a novel DFNA locus on chromosome 3q28-q29 in a Spanish family with postlingual and progressive hearing loss. They narrowed the locus, DNFA44, to a 3-cM interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of 2 genes in this interval, claudin-16 (603959) and fibroblast growth factor-12 (601513), revealed no disease-causing mutations. Molecular Genetics Modamio-Hoybjor et al. (2007) identified the CCDC50 gene within the critical linkage area and considered it a candidate gene for DFNA44 hearing loss, given that it is expressed in cochlea. Sequence analysis of all exons and flanking intronic sequences of CCDC50 in an affected subject revealed a heterozygous mutation in exon 11 (1394_1401dupCACGGCAT; 611051.0001). CCDC50 encodes Ymer, an effector of epidermal growth factor (EGF)-mediated cell signaling that is ubiquitously expressed in different organs and has been suggested to inhibit downregulation of an EGF receptor. Modamio-Hoybjor et al. (2007) suggested that DFNA44 hearing loss may result from a time-dependent disorganization of the microtubule-based cytoskeleton in the pillar cells and stria vascularis of the adult auditory system. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural, postlingual progressive (mainly affecting 125Hz to 2,000 Hz) MISCELLANEOUS \- One Spanish family has been reported (last curated August 2015) MOLECULAR BASIS \- Caused by mutation in the coiled-coil domain-containing protein 50 (CCDC50, 611051.0001 ) ▲ 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	DEAFNESS, AUTOSOMAL DOMINANT 44	c1843895	8,498	omim	https://www.omim.org/entry/607453	2019-09-22T16:09:17	{"doid": ["0110569"], "mesh": ["C564399"], "omim": ["607453"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]}
A rare, genetic, subtype of autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by early childhood-onset of slowly progressive, predominantly distal, lower limb muscle weakness and atrophy, delayed motor development, variable sensory loss, and pes cavus in the presence of normal or near-normal nerve conduction velocities. Additional variable features may include proximal muscle weakness, abnormal gait, arthrogryposis, scoliosis, cognitive impairment, and spasticity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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 Charcot-Marie-Tooth disease type 2O	c3280220	8,499	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284232	2021-01-23T17:26:27	{"gard": ["12434"], "omim": ["614228"], "icd-10": ["G60.0"], "synonyms": ["CMT2O"]}

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