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Tumor budding is loosely defined by the presence of individual cells and small clusters of tumor cells at the invasive front of carcinomas. It has been postulated to represent an epithelial–mesenchymal transition (EMT). Tumor budding is a well-established independent adverse prognostic factor in colorectal carcinoma that may allow for stratification of patients into risk categories more meaningful than those defined by TNM staging, and also potentially guide treatment decisions, especially in T1 and T3 N0 (Stage II, Dukes’ B) colorectal carcinoma. Unfortunately, its universal acceptance as a reportable factor has been held back by a lack of definitional uniformity with respect to both qualitative and quantitative aspects of tumor budding.[1] ## External links[edit] * Pathology Images ## References[edit] 1. ^ Mitrovic, B.; Schaeffer, D. F.; Riddell, R. H.; Kirsch, R. (2012). "Tumor budding in colorectal carcinoma: Time to take notice". Modern Pathology. 25 (10): 1315–25. doi:10.1038/modpathol.2012.94. PMID 22790014. This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Tumor budding	c4049272	5,600	wikipedia	https://en.wikipedia.org/wiki/Tumor_budding	2021-01-18T18:32:11	{"umls": ["C4049272"], "wikidata": ["Q16948689"]}
Perianal hematoma Other namesExternal hemorroidal thrombosis, perianal thrombosis, anal vein thrombosis SpecialtyGeneral surgery Perianal hematoma is a hematoma located in, or on the border of the anus.[1][2] It is sometimes inappropriately referred to as an external hemorrhoid.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Management * 4 References ## Signs and symptoms[edit] A perianal hematoma, identified by the typical blue tinge under the skin (to the left in the above image) The symptoms of a perianal hematoma can present over a short period of time. Pain, varying from mild to severe,[3] will occur as the skin surrounding the rupture expands due to pressure. This pain will usually last even after the blood has clotted, and may continue for two to four days.[citation needed] ## Causes[edit] Perianal hematoma are caused by the rupture of a small vein that drains blood from the anus.[4] This rupture may be the result of forceful or strained bowel movement, anal sex or caused by heavy lifting, coughing or straining. Once the rupture has formed, blood quickly pools within a few hours and, if left untreated, forms a clot.[citation needed] ## Management[edit] Management of thrombosed external hemorrhoids has been poorly studied as of 2018.[5] If diagnosed within the first few hours of presentation, the pooling blood may be evacuated using a syringe. Once the blood has clotted, removal by this method is no longer possible and the clot can be removed via an incision over the lump under local anesthetic. The incision is not stitched but will heal. Care needs to be taken in regard to bleeding from the wound and possible infection with fecal bacteria. If left alone it will usually heal within a few days or weeks.[6] The topical application of a cream containing a heparinoid is often advised to clear the clot.[7] ## References[edit] 1. ^ Australian Doctor Patient information sheet – Author: Professor John Murtagh 2. ^ a b Stein, Ernst (2003). Anorectal and colon diseases : textbook and color atlas of proctology (1st English ed.). Berlin: Springer-Verlag. p. 80. ISBN 9783540430391. 3. ^ Clinical Anatomy by Regions – Richard S. Snell (Google Books) 4. ^ "MerckSource". Archived from the original on 2008-02-02. Retrieved 2008-02-12. 5. ^ Davis, BR; Lee-Kong, SA; Migaly, J; Feingold, DL; Steele, SR (March 2018). "The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Hemorrhoids". Diseases of the Colon and Rectum. 61 (3): 284–292. doi:10.1097/DCR.0000000000001030. PMID 29420423. 6. ^ Perianal hematoma – Medbroadcast Archived 2008-05-07 at the Wayback Machine 7. ^ Superficial thrombophlebitis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Perianal hematoma	c0155784	5,601	wikipedia	https://en.wikipedia.org/wiki/Perianal_hematoma	2021-01-18T19:10:25	{"umls": ["C0155784"], "wikidata": ["Q1324103"]}
Dravet syndrome is the most severe of a group of conditions known as SCN1A-related seizure disorders. Symptoms include seizures which first occur in infancy that are often triggered by high temperatures (febrile seizures). In childhood, many types of seizures may occur and they may increase in frequency. Seizures may be difficult to treat. Other symptoms include loss of motor skills, intellectual disability, speech impairment, and difficulty with movement. Most cases of Dravet syndrome occur when the SCN1A gene is not working correctly. It can be inherited in an autosomal dominant pattern, but most people with Dravet syndrome do not have a family history of the condition. Diagnosis is based on a clinical exam, medical history, and the results of genetic testing. The main goal of treatment is to reduce the number and length of seizures. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Dravet syndrome	c0751122	5,602	gard	https://rarediseases.info.nih.gov/diseases/10430/dravet-syndrome	2021-01-18T18:00:49	{"mesh": ["D004831"], "omim": ["607208"], "umls": ["C0751122"], "orphanet": ["33069"], "synonyms": ["Severe Myoclonic Epilepsy of Infancy", "SMEI", "Myoclonic epilepsy, severe, of infancy", "SME"]}
Compulsive sexual behaviour driven by use of pornography Addiction and dependence glossary[1][2][3][4] * addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences * addictive behavior – a behavior that is both rewarding and reinforcing * addictive drug – a drug that is both rewarding and reinforcing * dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) * drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose * drug withdrawal – symptoms that occur upon cessation of repeated drug use * physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens) * psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia) * reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them * rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach * sensitization – an amplified response to a stimulus resulting from repeated exposure to it * substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress * tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose * v * t * e Pornography addiction is an addiction model of compulsive sexual activity with concurrent use of pornographic material, despite negative consequences to one's physical, mental, social, or financial well-being. Neither the DSM-5 nor the ICD-11 classify pornography as a mental disorder or addiction. Problematic Internet pornography viewing is viewing of Internet pornography that is problematic for an individual due to personal or social reasons, including excessive time spent viewing pornography instead of interacting with others. Individuals may report depression, social isolation, career loss, decreased productivity, or financial consequences as a result of their excessive Internet pornography viewing impeding their social life.[5][6] ## Contents * 1 Symptoms and diagnosis * 1.1 Diagnostic status * 2 Treatment * 2.1 Online pornography * 2.2 Medications * 3 Epidemiology * 4 Society and culture * 4.1 Support groups * 4.2 Political and religious motivation * 4.3 Mainstream media * 5 See also * 6 References * 7 Further reading * 8 External links ## Symptoms and diagnosis[edit] See also: Effects of pornography Universally accepted diagnostic criteria do not exist for pornography addiction or problematic pornography viewing.[5] Pornography addiction is often defined operationally by the frequency of pornography viewing and negative consequences.[7] The only diagnostic criteria for a behavioral addiction in the current Diagnostic and Statistical Manual of Mental Disorders are for pathological gambling, and they are similar to those for substance abuse and dependence, such as preoccupation with the behavior, diminished ability to control the behavior, tolerance, withdrawal, and adverse psychosocial consequences. Diagnostic criteria have been proposed for other behavioral addictions, and these are usually also based on established diagnoses for substance abuse and dependence.[8] A proposed diagnosis for hypersexual disorder includes pornography as a subtype of this disorder. It included such criteria as time consumed by sexual activity interfering with obligations, repetitive engagement in sexual activity in response to stress, repeated failed attempts to reduce these behaviors, and distress or impairment of life functioning.[9] A study on problematic Internet pornography viewing used the criteria of viewing Internet pornography more than three times a week during some weeks, and viewing causing difficulty in general life functioning.[5] According to the American Society of Addiction Medicine, some psychological and behavioral changes characteristic of addiction brain changes include addictive cravings, impulsiveness, weakened executive function, desensitization, and dysphoria.[10] BOLD fMRI results have shown that individuals diagnosed with compulsive sexual behavior (CSB) show enhanced cue reactivity in brain regions associated traditionally with drug-cue reactivity.[11] These regions include the amygdala and the ventral striatum. Men without CSB who had a long history of viewing pornography exhibited a less intense response to pornographic images in the left ventral putamen, possibly suggestive of desensitization.[11] ASAMs position is inconsistent with the American Association of Sex Educators, Counselors, and Therapists, who cite strong evidence against such classification, describing ASAM as not informed by "accurate human sexuality knowledge".[12] ### Diagnostic status[edit] The status of pornography addiction as an addictive disorder, rather than simply a compulsivity, has been hotly contested.[13][unreliable medical source?][14][unreliable medical source?] Furthermore, research suggests that the use of a pornography addiction label may indicate a socially (as opposed to clinically) driven nosology [6] > It is worth considering whether the apparent epidemic of self-diagnosed pornography addicts seeking help today perhaps represents the ready uptake of a relatively new way to describe one’s problematic behaviour, and not the development of a modern disease entity whose description should dictate its treatment.[6] > > — Kris Taylor, Nosology and metaphor: How pornography viewers make sense of pornography addiction In November 2016, the American Association of Sexuality Educators, Counselors and Therapists (AASECT) issued a position statement on sex/porn addiction which states that AASECT "does not find sufficient empirical evidence to support the classification of sex addiction or porn addiction as a mental health disorder, and does not find the sexual addiction training and treatment methods and educational pedagogies to be adequately informed by accurate human sexuality knowledge. Therefore, it is the position of AASECT that linking problems related to sexual urges, thoughts or behaviors to a porn/sexual addiction process cannot be advanced by AASECT as a standard of practice for sexuality education delivery, counseling or therapy." The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes a new section for behavioral addictions, but includes only one disorder: pathological gambling.[15] One other behavioral addiction, internet gaming disorder, appears in the conditions proposed for further study in DSM-5.[15] Psychiatrists cited a lack of research support for refusing to include other behavioral disorders at this time.[15] Porn addiction is not a diagnosis in DSM-5 (or any previous version).[16][17][18] "Viewing pornography online" is mentioned verbatim in the DSM-5,[15] but it is not considered a mental disorder either.[16][17][18] > When the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was being drafted, experts considered a proposed diagnostic addiction called hypersexual disorder, which also included a pornography subtype. But in the end, reviewers determined that there wasn't enough evidence to include hypersexual disorder or its subtypes in the 2013 edition.[16] > > — Kirsten Weir, Is pornography addictive? A number of studies have found neurological markers of addiction in internet porn users,[19][20][21] which is consistent with a large body of research finding similar markers in other kinds of problematic internet users.[20] Yet other studies found that critical biomarkers of addiction were missing,[22] and most addiction biomarkers have never been demonstrated for pornography.[23] The International Classification of Disorders 11 (ICD-11) rejected "pornography addiction". Specifically, the World Health Organization (WHO) wrote: "Based on the limited current data, it would therefore seem premature to include [pornography viewing] in ICD-11."[24] Introductory psychology textbook authors Coon, Mitterer and Martini, passingly mentioning NoFap, speak of pornography as a "supernormal stimulus" but use the model of compulsion rather than addiction.[25] ## Treatment[edit] Cognitive-behavioral therapy has been suggested as a possible effective treatment for pornography addiction based on its success with internet addicts, though no clinical trials have been performed to assess effectiveness among pornography addicts as of 2012.[26] Acceptance and commitment therapy has also been shown to be a potentially effective treatment for problematic internet pornography viewing.[5] ### Online pornography[edit] See also: Internet addiction disorder § Internet addiction and pornography Some clinicians and support organizations recommend voluntary use of Internet content-control software, internet monitoring, or both, to manage online pornography use.[27][28][29] Sex researcher Alvin Cooper and colleagues suggested several reasons for using filters as a therapeutic measure, including curbing accessibility that facilitates problematic behavior and encouraging clients to develop coping and relapse prevention strategies.[27] Cognitive therapist Mary Anne Layden suggested that filters may be useful in maintaining environmental control.[29] Internet behavior researcher David Delmonico stated that, despite their limitations, filters may serve as a "frontline of protection."[28] ### Medications[edit] See also: Behavioral addiction § Treatment Studies of those with non-paraphilic expressions of hypersexuality have hypothesized that various mood disorders, as defined in the DSM, may occur more frequently in sexually compulsive men.[30][31][32] Compulsive sexual behavior has been treated with antidepressants including SSRIs and serotonin-norepinephrine reuptake inhibitors, naltrexone, a medication used to inhibit reward mechanisms in opiate or alcohol addictions, other mood-stabilizers, and anti-androgens. ## Epidemiology[edit] There is only one representative sample (published in 2017) to date concerning distress about sex video use.[33] They found that of 10,131 women surveyed, 0.5% of women agreed with the statement that they were "addicted" to pornography; 1.2% (of 4,218 who viewed) when limited to women who say they viewed sex films. The comparable figure limiting to men who view sex films was 4.4%. This was without any clinical screening that should eliminate primary disorders (e.g., depression) or religious-based concerns, so these should be considered high-end estimates for potential disorders, if any exist. Most studies of rates use a convenience sample. One study of a convenience sample of 9,265 people found that 1% of Internet users have concerns about their Internet use and 17% of users meet criteria for problematic sexual compulsivity, meaning they score above one standard deviation of the mean on the Kalichman Sexual Compulsivity Scale.[34][full citation needed] A survey of 84 college-age males found that 20–60% of a sample of college-age males who use pornography found it to be problematic.[35] Research on internet addiction disorder indicates rates may range from 1.5 to 8.2% in Europeans and Americans.[36] ## Society and culture[edit] ### Support groups[edit] Twelve-step programs such as Sex Addicts Anonymous (SAA), Sexaholics Anonymous (SA), Sex and Love Addicts Anonymous (SLAA), Sexual Recovery Anonymous (SRA) and Sexual Compulsives Anonymous (SCA) are fellowships of men and women who share their experience, strength and hope with each other so they may overcome their common problem and help others recover from addiction or dependency, by using the 12 steps of AA and other recovery tools. NoFap is an online community founded in 2011.[37] It serves as a support group for those who wish to avoid the use of pornography, masturbation, and/or sexual intercourse.[38][39] Recent peer-reviewed data highlighted considerable misogyny and poor understanding of sexual relationships in this online community.[40] There is also a PornFree reddit group which focuses on giving up porn rather than masturbation.[41][42] Additionally, Fight the New Drug, a Salt Lake City based non-profit, is a non-religious and non-legislative organization, which seeks to inform and educate individuals regarding pornography usage with science and personal stories. It is aimed at the youth demographic to raise awareness of potential problems with pornography Celebrate Recovery (CR) is a Christian inter-denominational 12 step program with about 35,000 available groups and is open to any person who is struggling with life's bad habits, hurts, and hang-ups. CR was started in 1991 at Saddleback Church in CA, and the CR program is based on the 8 Beatitudes from Christ's sermon on the Mountain, and Twelve-step programs from Alcoholics Anonymous. ### Political and religious motivation[edit] See also: Anti-pornography feminism According to professor E.T.M. Laan, a sexologist working for the Academic Medical Center, it is usually the American religious right which claims the existence of pornography addiction and such claims are rare among sexologists.[43] A meta-analysis showed a correlation between a person being religious and perceiving themself as having a pornography addiction, possibly due to people using pornography despite their religion prohibiting it.[44][45] ### Mainstream media[edit] In 2013, American actor Joseph Gordon-Levitt wrote, directed, and starred in the comedy-drama film Don Jon, in which the protagonist is addicted to pornography.[46] In an interview to promote the film, Gordon-Levitt discussed what he referred to as the "fundamental difference between a human being and an image on a screen".[47] In his 2014 autobiography, American actor Terry Crews talked about his long-standing pornography addiction, which he said had seriously affected his marriage and life and which he was only able to overcome after entering rehab in 2009.[48] He now takes an active role in speaking out about pornography addiction and its impact.[49][50][51] In 2015, English comedian Russell Brand appeared in videos by American anti-pornography group Fight the New Drug, in which he discussed pornography and its harmful effects.[52] Later that year, American actress Rashida Jones produced the documentary Hot Girls Wanted, which gave an in-depth look into the exploitation of women in the pornography industry.[53] In 2016, American comedian Chris Rock and his wife Malaak Compton divorced after 20 years of marriage,[54] which Rock attributed to his infidelity and pornography addiction.[55] He later discussed the details of his pornography addiction in his 2018 stand-up comedy special Tamborine.[56] French actress Juliette Binoche, English actor Hugh Grant, American actor Josh Radnor, and English actress Emma Thompson have also spoken out against pornography.[57][58] ## See also[edit] * Accountability software * Anti-pornography movement * Content-control software * National Center on Sexual Exploitation * Rational Recovery * Sexaholics Anonymous * Sex Addicts Anonymous * Sexual ethics * Sexual addiction * Psychology portal ## References[edit] 1. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN 9780071481274. 2. ^ Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. "Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict." 3. ^ "Glossary of Terms". Mount Sinai School of Medicine. Department of Neuroscience. Retrieved 9 February 2015. 4. ^ Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". New England Journal of Medicine. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMC 6135257. PMID 26816013. "Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe. Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder." 5. ^ a b c d Twohig, M. P.; Crosby, J. M. (2010). "Acceptance and Commitment Therapy as a Treatment for Problematic Internet Pornography Viewing". Behavior Therapy. 41 (3): 285–295. doi:10.1016/j.beth.2009.06.002. PMID 20569778. 6. ^ a b c Taylor, Kris (May 7, 2019). "Nosology and metaphor: How pornography viewers make sense of pornography addiction". Sexualities. 23 (4): 609–629. doi:10.1177/1363460719842136. S2CID 164221337. 7. ^ Duffy, A; Dawson, DL; das Nair, R (May 2016). "Pornography Addiction in Adults: A Systematic Review of Definitions and Reported Impact" (PDF). The Journal of Sexual Medicine. 13 (5): 760–77. doi:10.1016/j.jsxm.2016.03.002. PMID 27114191. 8. ^ Grant, J. E.; Potenza, M. N.; Weinstein, A.; Gorelick, D. A. (2010). "Introduction to Behavioral Addictions". The American Journal of Drug and Alcohol Abuse. 36 (5): 233–241. doi:10.3109/00952990.2010.491884. PMC 3164585. PMID 20560821. 9. ^ Kafka, M. P. (2009). "Hypersexual Disorder: A Proposed Diagnosis for DSM-V" (PDF). Archives of Sexual Behavior. 39 (2): 377–400. doi:10.1007/s10508-009-9574-7. PMID 19937105. S2CID 2190694. 10. ^ "ASAM Definition of Addiction". 19 April 2011. Retrieved 7 November 2016. 11. ^ a b Kraus, Shane W.; Voon, Valerie; Potenza, Marc N. (December 2016). "Should compulsive sexual behavior be considered an addiction?". Addiction (Abingdon, England). 111 (12): 2097–2106. doi:10.1111/add.13297. ISSN 0965-2140. PMC 4990495. PMID 26893127. 12. ^ "AASECT Position on Sex Addiction". April 2018. Retrieved 25 April 2019. 13. ^ Steele, V.; Prause, N.; Staley, C.; Fong, G. W. (2013). "Sexual Desire, not Hypersexuality, is Related to Neurophysiological Responses Elicited by Sexual Images". Socioaffective Neuroscience of Psychology. 3: 20770. doi:10.3402/snp.v3i0.20770. PMC 3960022. PMID 24693355. 14. ^ Hilton, Donald L. (21 February 2014). "'High desire', or 'merely' an addiction? A response to Steele et al". Socioaffective Neuroscience & Psychology. 4 (1): 23833. doi:10.3402/snp.v4.23833. PMC 3975913. PMID 24707350. 15. ^ a b c d American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 481, 797–798. ISBN 978-0-89042-555-8. "In addition to the substance-related disorders, this chapter also includes gambling disorder, reflecting evidence that gambling behaviors activate reward systems similar to those activated by drugs of abuse and produce some behavioral symptoms that appear comparable to those produced by the substance use disorders. Other excessive behavioral patterns, such as Internet gaming, have also been described, but the research on these and other behavioral syndromes is less clear. Thus, groups of repetitive behaviors, which some term behavioral addictions, with such subcategories as "sex addiction," "exercise addiction," or "shopping addiction," are not included because at this time there is insufficient peer-reviewed evidence to establish the diagnostic criteria and course descriptions needed to identify these behaviors as mental disorders. ... Excessive use of the Internet not involving playing of online games (e.g., excessive use of social media, such as Facebook; viewing pornography online) is not considered analogous to Internet gaming disorder, and future research on other excessive uses of the Internet would need to follow similar guidelines as suggested herein. Excessive gambling online may qualify for a separate diagnosis of gambling disorder." 16. ^ a b c Weir, Kirsten (April 2014). "Is pornography addictive?". Monitor on Psychology. 45 (4): 46. ISSN 1529-4978. OCLC 612512821. Archived from the original on 2014-04-05. 17. ^ a b Allez, Glyn Hudson, ed. (4 June 2014). "Chapter Ten. The pleasure, the power, and the perils of Internet pornography". Sexual Diversity and Sexual Offending: Research, Assessment, and Clinical Treatment in Psychosexual Therapy. Karnac Books. p. 161. ISBN 978-1-78181-368-3. Retrieved 27 April 2019. 18. ^ a b Since it is neither of two behavioral addictions mentioned above. 19. ^ Kraus, Shane W; Voon, Valerie; Potenza, Marc N (2015-09-22). "Neurobiology of Compulsive Sexual Behavior: Emerging Science". Neuropsychopharmacology. 41 (1): 385–386. doi:10.1038/npp.2015.300. ISSN 0893-133X. PMC 4677151. PMID 26657963. 20. ^ a b Brand, Matthias; Young, Kimberly S.; Laier, Christian; Wölfling, Klaus; Potenza, Marc N. (2016-12-01). "Integrating psychological and neurobiological considerations regarding the development and maintenance of specific Internet-use disorders: An Interaction of Person-Affect-Cognition-Execution (I-PACE) model". Neuroscience & Biobehavioral Reviews. 71: 252–266. doi:10.1016/j.neubiorev.2016.08.033. PMID 27590829. 21. ^ Kühn, S.; Gallinat, J. (2016-01-01). "Neurobiological Basis of Hypersexuality". In Zahr, Natalie M.; Peterson, Eric T. (eds.). Imaging the Addicted Brain. International Review of Neurobiology. Imaging the Addicted Brain. 129. pp. 67–83. doi:10.1016/bs.irn.2016.04.002. ISBN 9780128039144. PMID 27503448. 22. ^ Prause, Nicole; Steele, Vaughn R.; Staley, Cameron; Sabatinelli, Dean; Hajcak, Greg (2015). "Modulation of late positive potentials by sexual images in problem users and controls inconsistent with 'porn addiction'". Biological Psychology. 109: 192–199. doi:10.1016/j.biopsycho.2015.06.005. PMID 26095441. S2CID 1446388. 23. ^ Prause, Nicole; Janssen, Erick; Georgiadis, Janniko; Finn, Peter; Pfaus, James (2017). "Data do not support sex as addictive". The Lancet Psychiatry. 4 (12): 899. doi:10.1016/S2215-0366(17)30441-8. PMID 29179928. 24. ^ Grant, J. (2014). "Impulse control disorders and 'behavioural addictions' in the ICD‐11". World Psychiatry. 13 (2): 125–127. doi:10.1002/wps.20115. PMC 4102276. PMID 24890056. 25. ^ Coon, Dennis; Mitterer, John O.; Martini, Tanya S. (5 December 2016). Psychology: Modules for Active Learning. Cengage Learning. pp. 413–414. ISBN 978-1-337-51708-9. 26. ^ Laier, Christian. Cybersex addiction: Craving and cognitive processes. Diss. Universität Duisburg-Essen, Fakultät für Ingenieurwissenschaften» Ingenieurwissenschaften-Campus Duisburg» Abteilung Informatik und Angewandte Kognitionswissenschaft, 2012. 27. ^ a b Cooper, Alvin; Putnam, Dana E.; Planchon, Lynn A.; Boies, Sylvain C. (1999). "Online sexual compulsivity: Getting tangled in the net". Sexual Addiction & Compulsivity. 6 (2): 79–104. doi:10.1080/10720169908400182. 28. ^ a b Delmonico, David L. (1997). "Cybersex: High tech sex addiction". Sexual Addiction & Compulsivity. 4 (2): 159–167. doi:10.1080/10720169708400139. 29. ^ a b Layden, Mary Anne (September 2005). "Cyber Sex Addiction" (PDF). Advances in Cognitive Therapy: 1–2, 4–5.[permanent dead link] 30. ^ Kafka, M.P., & Hennen, J. (2002). A DSM IV axis I comorbidity study of males (n¼120) with paraphilias and paraphilia-related disorders. Sexual Abuse: A Journal of Research and Treatment. 14. 349–366. 31. ^ Kafka, M.P., & Prentky, R.A. (1994). Preliminary observations of DSM III-R axis I comorbidity in men with paraphilias and paraphilia-related disorders. Journal of Clinical Psychiatry. 55. 481–487. 32. ^ Kafka, M.P., & Prentky, R.A. (1998). Attention deficit hyperactivity disorder in males with paraphilias and paraphilia-related disorders: a comorbidity study. Journal of Clinical Psychiatry. 1998; 59:388–396. 33. ^ Rissel, C; Richters, J.; de Visser, R.; McKee, A.; Yeung, A. (2017). "A profile of pornography users in australia: Findings from the second australian study of health and relationships". The Journal of Sex Research. 54 (2): 227–240. doi:10.1080/00224499.2016.1191597. hdl:10453/48993. PMID 27419739. S2CID 11724798. 34. ^ Cooper A.; Delmonico D. L.; Burg R. (2000). "Cybersex user, abusers, and compulsives". Sexual Addiction and Compulsivity. 7 (1–2): 5–29. doi:10.1080/10720160008400205. S2CID 144124065. 35. ^ Twohig, M. P.; Crosby, J. M.; Cox, J. M. (2009). "Viewing Internet Pornography: For Whom is it Problematic, How, and Why?". Sexual Addiction & Compulsivity. 16 (4): 253–266. doi:10.1080/10720160903300788. S2CID 144495292. 36. ^ Weinstein, A.; Lejoyeux, M. (2010). "Internet Addiction or Excessive Internet Use". The American Journal of Drug and Alcohol Abuse. 36 (5): 277–283. CiteSeerX 10.1.1.1025.8525. doi:10.3109/00952990.2010.491880. PMID 20545603. S2CID 17713327. 37. ^ "NoFap " About". NoFap LLC. Retrieved 22 May 2015. "NoFap was originally founded by Alexander Rhodes on June 20, 2011 as a forum on the social media platform 'Reddit' and has since grown to become much more". 38. ^ Cowell, Tom (17 September 2013). "No fapping, please, it's making us ill". The Telegraph. London, England: Telegraph Media Group. Retrieved 22 May 2015. 39. ^ McMahon, Tamsin (20 January 2014). "Will quitting porn improve your life?: A growing 'NoFap' movement of young men are saying no to porn and masturbation". Maclean's. Toronto, Canada: Rogers Media. Retrieved 22 May 2015. 40. ^ Taylor, K.; Jackson, S. (2018). "'I want that power back': Discourses of masculinity within an online pornography abstinence forum". Sexualities. 21 (4): 621–639. doi:10.1177/1363460717740248. S2CID 149306706. 41. ^ Hosie, Rachel (3 May 2017). "Inside the community of men who have given up porn". The Independent. Retrieved 2 July 2018. 42. ^ "Man deletes 18 terabyte porn collection to try and end his addiction". The Independent. 2017-08-15. Retrieved 2020-01-31. 43. ^ Casper van der Veen (17 August 2016). "'Erectieproblemen bij jongeren door porno op internet' - NRC". Retrieved 20 September 2016. 44. ^ "Science Stopped Believing in Porn Addiction, You Should Too". Psychology Today. Retrieved 2018-11-26. 45. ^ Grubbs, Joshua B.; Perry, Samuel L.; Wilt, Joshua A.; Reid, Rory C. (2018-08-03). "Pornography Problems Due to Moral Incongruence: An Integrative Model with a Systematic Review and Meta-Analysis". Archives of Sexual Behavior. 48 (2): 397–415. doi:10.1007/s10508-018-1248-x. ISSN 0004-0002. PMID 30076491. S2CID 51911309. 46. ^ "Don Jon". 47. ^ Minow, Nell. "Joseph Gordon-Levitt discusses "Don Jon" - Interviews". Roger Ebert. Retrieved 31 December 2019. 48. ^ "No One Wants To Be With The Marlboro Man: Terry Crews On 'Manhood'". NPR.org. May 17, 2014. 49. ^ "Terry Crews' New Book Details Struggle With Porn Addiction - Black America Web". Black America Web. May 27, 2014. Archived from the original on May 28, 2014. 50. ^ ABC News (2016-02-25). "Terry Crews Says Porn Addiction Nearly Ruined His Life". ABC News. 51. ^ Brandon Griggs, CNN (February 24, 2016). "Terry Crews: Porn addiction 'messed up my life'". CNN. 52. ^ https://www.youtube.com/watch?v=5kvzamjQW9M 53. ^ "Hot Girls Wanted". 54. ^ Corriston, Michele (December 28, 2014). "Chris Rock & Wife Malaak Compton-Rock Split". People. Retrieved December 28, 2014. 55. ^ Bitette, Nicole (August 23, 2016). "Chris Rock, Malaak Compton finalize divorce after 20 years of marriage". New York Daily News. Retrieved November 13, 2016. 56. ^ Sharf, Zach (February 14, 2018). "Chris Rock Gets Brutally Honest About Porn Addiction and Cheating on His Wife: 'I Wasn't a Good Husband'". Indiewire.com. Retrieved February 14, 2018. 57. ^ "7 Hollywood Stars Who Are Speaking Out Against Porn". 2017-08-10. 58. ^ "5 Celebrities Who Hate Porn". 2015-03-19. ## Further reading[edit] * Klein, M. (2017). His Porn, Her Pain: Confronting America’s Porn Panic With Honest Talk About Sex (ISBN 1440842868) Praeger * Cooper, Al (2002). Sex and the Internet: A Guidebook for Clinicians (ISBN 1-58391-355-6) Routledge * P. Williamson, S. Kisser (1989). Answers In the Heart: Daily Meditations for Men and Women Recovering from Sex Addiction (ISBN 978-0-89486-568-8) Hazelden * Patrick Carnes (2001). Out of the Shadows: Understanding Sexual Addiction (ISBN 978-1-56838-621-8) Hazelden * Sex Addicts Anonymous (ISBN 0-9768313-1-7) * Rosenberg, Matthew (1999). “Understanding, Assessing, and Treating Sexual Offenders: Tools for the Therapist, downloadable version on stopoffending.com * "Science of Arousal and Relationships". ## External links[edit] * Pornography addiction at Curlie * v * t * e Reinforcement disorders: Addiction and Dependence Addiction Drug * Alcohol * Amphetamine * Cocaine * Methamphetamine * Methylphenidate * Nicotine * Opioid Behavioral * Financial * Gambling * Shopping * Palatable food * Sex-related * Intercourse * Pornography * Internet-related * Internet addiction disorder * Internet sex addiction * Video game addiction * Digital media addictions Cellular mechanisms * Transcriptional * ΔFosB * c-Fos * Cdk5 * CREB * GluR2 * NF-κB * Epigenetic * G9a * G9a-like protein * HDAC1 * HDAC2 * HDAC3 * HDAC4 * HDAC5 * HDAC9 * HDAC10 * SIRT1 * SIRT2 * ... Dependence Concepts * Physical dependence * Psychological dependence * Withdrawal Disorders * Drugs * Alcoholism * Amphetamine * Barbiturate * Benzodiazepine * Caffeine * Cannabis * Cocaine * Nicotine * Opioid * Non-drug stimuli * Tanning dependence Treatment and management Detoxification * Alcohol detoxification * Drug detoxification Behavioral therapies * Cognitive behavioral therapy * Relapse prevention * Contingency management * Community reinforcement approach and family training * Motivational enhancement therapy * Motivational interviewing * Motivational therapy * Physical exercise Treatment programs * Drug rehab * Residential treatment center * Heroin-assisted treatment * Intensive outpatient program * Methadone maintenance * Smoking cessation * Nicotine replacement therapy * Tobacco cessation clinics in India * Twelve-step program Support groups * Addiction recovery groups * List of twelve-step groups Harm reduction * Category:Harm reduction * Drug checking * Reagent testing * Low-threshold treatment programs * Managed alcohol program * Moderation Management * Needle exchange program * Responsible drug use * Stimulant maintenance * Supervised injection site * Tobacco harm reduction See also * Addiction medicine * Allen Carr * Category:Addiction * Discrimination against drug addicts * Dopamine dysregulation syndrome * Cognitive control * Inhibitory control * Motivational salience * Incentive salience * Sober companion * Category * v * t * e Pornography Pornography Types * Amateur * Cartoon * Hentai * Tijuana bible * Child * Erotica * Simulated * Deepfake * Feminist * Hardcore * Internet * Mobile * Phone * Revenge * Sexting * Softcore Genres * Alt * Bisexual * Bondage * Casting couch * Celebrity * Sex tape * Clothed female, naked male * Clothed male, naked female * Convent * Ethnic * Gang bang * Gay * Gonzo * Incest * Lesbian * MILF * Mormon * Queer * Rape * Reality * Tentacle * Transgender * Women's Related * History * Film actor Organizations * Adult Film Association of America * Critics Adult Film Association * Fans of X-Rated Entertainment * Free Speech Coalition * X-Rated Critics Organization * List of pornography companies * List of pornographic film studios Opposition to pornography Movements * Anti-pornography movement in the United Kingdom * Anti-pornography movement in the United States * Antipornography Civil Rights Ordinance Organizations * Churchmen's Committee for Decent Publications * Feminists Fighting Pornography * Fight the New Drug * The Marriage Vow * No More Page 3 * Stop Bild Sexism * Stop Child Trafficking Now * Stop Porn Culture * Women Against Pornography * Women Against Violence in Pornography and Media * XXXchurch.com Overuse * NoFap * Content-control software * Accountability software * Parental controls * Employee monitoring software Views * Feminist * Religious * Sex-positive feminist Media * Audio * Film * Parody * Cartoon * Magazines * List * Video games * Eroge * Newspaper features * Page 3 Possible effects * Addiction * Internet sex addiction * Pornography addiction * Sex addiction * Objectification of women / sexism * STDs People * Performers by decade * British performers * Gay male performers * Pornographic actors who appeared in mainstream films * Mainstream actors who have appeared in pornographic films * Film directors Events * Adultcon * AVN Adult Entertainment Expo * Barcelona International Erotic Film Festival * Brussels International Festival of Eroticism * Exotic Erotic Ball * Exxxotica Expo * HUMP * Porn Sunday Miscellaneous * Adult movie theater * Blue Movie * Golden Age * Not safe for work * Pornographication * Pornotopia * R18 certificate * Rule 34 * Sex shop * Sexualization * X rating See also * Erotica * Art * Comics * Film * Literature * Photography * Sexual activity * Ribaldry * Right to sexuality * Sex-positive movement * Sexual repression * Sexual revolution * Category * Erotica and pornography portal * Human sexuality 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	Pornography addiction	None	5,603	wikipedia	https://en.wikipedia.org/wiki/Pornography_addiction	2021-01-18T18:29:57	{"wikidata": ["Q1319971"]}
Krabbe disease is a lysosomal disorder that affects the white matter of the central and peripheral nervous systems. It includes infantile, late-infantile/juvenile and adult forms. ## Epidemiology It has an estimated prevalence of 1/100,000 in the Northern European population (higher in certain populations) and a worldwide incidence of 1/100,000-1/250,000 live births. The infantile form is the most common form and accounts for 85-90% of cases in the Northern European population. ## Clinical description The infantile form has an onset at 2-6 months of age and is divided into 3 stages. In the first stage, symptoms include irritability, stiffness, poor head control, feeding difficulties, intermittent thumb clasp, episodes of increased temperature, and developmental delay. In the second stage, hypertonic episodes occur with opisthotonus, myoclonic seizures, developmental regression, fisting and vision deficits. In the third stage, hypotonia, blindness and deafness occur. Patients progress into a vegetative state and die before the age of 2-3 years, generally due to respiratory infections. In the late infantile/juvenile (1-8 years) and adult (>8 years) forms, the presenting symptoms vary greatly and progression is variable (generally slower in older patients). Patients with late infantile /juvenile onset most resemble infantile patients, while the first signs in adult forms are often weakness, gait disturbances (spastic paraparesis or ataxia), burning paresthesias, hemiplegia, and/or vision loss, with or without peripheral neuropathy. Cognitive regression is variable and often absent in adult forms. ## Etiology The disease is due to mutations in the GALC gene (14q31) encoding the lysosomal enzyme galactocerebrosidase, that catabolizes the hydrolysis of galactose from galactocerebroside and galactosylsphingosine (psychosine). The accumulation of cytotoxic psychosine leads to apoptosis of oligodendrocytes and demyelination of the CNS and PNS. Rarely, infantile Krabbe disease is caused by a mutation in the prosaposin (PSAP) gene (10q21-q22), encoding sphingolipid activator protein saposin-A, necessary for GALC activity. ## Diagnostic methods Diagnosis is suspected by the clinical picture, slow nerve conduction velocity, abnormal electroencephalogram, and brain MRI revealing white matter abnormalities (demyelination, gliosis, late-stage cerebral atrophy, cerebral calcifications). It is established from enzymatic assays in leukocytes or in cultured fibroblasts that reveal, in almost all cases, the GALC deficiency. Histologically, characteristic globoid cells (often multinucleated cells derived from macrophages that contain non-hydrolyzed galactocerebroside) are present in the white matter. Mutation analysis confirms the diagnosis. ## Differential diagnosis Differential diagnosis includes metachromatic leukodystrophy, GM1 gangliosidosis, GM2 gangliosidosis, Canavan disease, encephalopathy due to prosaposin deficiency, X-linked adrenoleukodystrophy, Pelizaeus-Merzbacher disease and Alexander disease (see these terms). ## Antenatal diagnosis Antenatal diagnosis (enzymatic assay or mutation analysis) is possible for at-risk families. If the disease-causing mutations in the family are known, pre-implantation genetic diagnosis is possible. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child. ## Management and treatment Treatment is limited to hematopoietic stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients and has been shown to slow the progression of the disease. Other treatment options (i.e. chaperone therapy, enzyme replacement therapy, gene therapy) are currently under investigation in animal models. ## Prognosis Neurodegeneration and early death (< 2-3 years) occurs in most infantile cases. In late infantile/juvenile patients, the disease is generally fatal 2-7 years after the symptoms begin. Adult-onset patients can survive many years after symptoms present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Krabbe disease	c0023521	5,604	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=487	2021-01-23T19:04:24	{"gard": ["6844"], "mesh": ["D007965"], "omim": ["245200", "611722"], "umls": ["C0023521"], "icd-10": ["E75.2"], "synonyms": ["GALC deficiency", "Galactocerebrosidase deficiency", "Galactosylceramidase deficiency", "Globoid cell leukodystrophy"]}
A number sign (#) is used with this entry because of evidence that vesicoureteral reflux-3 (VUR3) is caused by heterozygous mutation in the SOX17 gene (610928) on chromosome 8q11. For a general phenotypic description and a discussion of genetic heterogeneity of vesicoureteral reflux, see 193000. Clinical Features Gimelli et al. (2010) reported 2 unrelated families with vesicoureteral reflux associated in some cases with renal scarring and/or congenital anomalies of the kidney and urinary tract (CAKUT). In the first family, the young female proband had congenital defects of the urinary tract, chronic constipation, and mild mental retardation, and she was conceived by in vitro fertilization. At 34 weeks' gestation, she had polyhydramnios and severe bilateral hydronephrosis necessitating cesarean section. Early in life, her right kidney showed a duplicated pyeloureteral collecting system about 7 cm in diameter, and bilateral VUR (grade III). Ureteroplasty was performed to correct these urinary defects. Other features of the patient included mild axial hypotonia, delayed psychomotor development with a defect in expressive language, a large patent ductus arteriosus, and thinning of the corpus callosum. The patient's mother showed grade IV VUR associated with megaureter, recurrent urinary infections, chronic constipation, and coloboma of the iris in her left eye. Cytogenetic analysis of the girl showed a de novo pseudodicentric duplication of chromosome 8q11-q12 of maternal origin. In the second family, a young male proband had left hydronephrosis due to stenosis of the pyeloureteral joint and grade III VUR; his mother also had grade III VUR. Four additional unrelated patients with sporadic occurrence of vesicoureteral reflux were also reported. Molecular Genetics By candidate gene sequencing of a duplicated region of chromosome 8q11-q12 in a female patient with VUR, Gimelli et al. (2010) identified a heterozygous mutation in the SOX17 gene (Y259N; 610928.0001). The same heterozygous mutation was found in her affected mother, in an affected mother and son from an unrelated family, and in 2 of 178 patients with sporadic occurrence of VUR. Two additional patients with sporadic VUR were found to carry 2 different heterozygous mutations in the SOX17 gene (610928.0002 and 610928.0003, respectively). Gimelli et al. (2010) postulated that altered levels of WNT (see 164820) signaling during development caused the observed congenital urinary defects, although a role for alterations in other genes regulated by SOX17 could not be excluded. INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Hydronephrosis \- Renal scarring \- Duplication of the renal pelvis (1 patient) Ureters \- Megaureter \- Ureteral dilatation Bladder \- Vesicoureteral reflux PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Onset in utero or in infancy MOLECULAR BASIS \- Caused by mutation in the SRY-box 17 gene (SOX17, 610928.0001 ) ▲ 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	VESICOURETERAL REFLUX 3	c3150927	5,605	omim	https://www.omim.org/entry/613674	2019-09-22T15:57:58	{"doid": ["9620"], "omim": ["613674"], "orphanet": ["289365"], "synonyms": ["Familial VUR"]}
A number sign (#) is used with this entry because the Lom type of hereditary motor and sensory neuropathy, also called Charcot-Marie-Tooth disease type 4D, is caused by homozygous mutation in the N-myc downstream-regulated gene-1 (NDRG1; 605262) on chromosome 8q24. Description Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive disorder of the peripheral nervous system characterized by early-onset distal muscle weakness and atrophy, foot deformities, and sensory loss affecting all modalities. Affected individuals develop deafness by the third decade of life (summary by Okamoto et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive Charcot-Marie-Tooth disease, see CMT4A (214400). Clinical Features Kalaydjieva et al. (1996) described an autosomal recessive peripheral neuropathy with deafness and unusual neuropathologic features, initially identified in 14 affected individuals from the Gypsy community of Lom, a small town on the Danube River in the northwest of Bulgaria (see HISTORY). They proposed to refer to the disorder as 'hereditary motor and sensory neuropathy-Lom' (HMSNL). Kalaydjieva et al. (1996) stated that HMSNL is characterized by distal muscle wasting and atrophy, foot and hand deformities, tendon areflexia, and sensory loss. Onset is in the first decade and most patients become severely disabled in the fifth decade. Deafness is an invariant feature of the phenotype and usually develops in the third decade. Conduction velocities in the median, ulnar, tibial, and peroneal nerves are severely reduced in the youngest patients and unattainable after age 15 years. Decreased conduction velocity and compound action muscle potential amplitude are also found proximally, in the axillary and facial nerves. Brainstem auditory evoked potentials are markedly abnormal, with prolonged interpeak latencies consistent with demyelination. Neuropathologic investigations showed that myelinated fibers were severely reduced in number and those that remained were a very small size. The parents of affected individuals were asymptomatic and electrophysiologic investigations failed to detect any abnormality. Kalaydjieva et al. (1998) reviewed all aspects of the Lom type of HMSN. It begins consistently in the first decade of life with gait disorder followed by upper limb weakness in the second decade and, in most subjects, by deafness which is most often first noticed in the third decade. Sensory loss affecting all modalities is present, both this and the motor involvement predominating distally in the limbs. Skeletal deformity, particularly foot deformity, is frequent. Severely reduced motor nerve conduction velocity indicates a demyelinating basis, which is confirmed by nerve biopsy. The 3 younger patients biopsied showed a hypertrophic 'onion bulb' neuropathy. The hypertrophic changes were not evident in the oldest individual biopsied, and it is likely that they had regressed secondarily to axon loss. In the 8 cases in which brainstem auditory evoked potentials could be recorded, the results suggested demyelination in the eighth cranial nerve and also abnormal conduction in the central auditory pathways in the brainstem. Merlini et al. (1998) described the same disorder in 4 sibs of an Italian family of Gypsy ethnic origin. The parents were clinically normal and apparently nonconsanguineous. Four of 5 children presented foot deformities and hand weakness in the first decade of life. All 4 children began walking late. The 3 oldest children, aged 15, 13, and 11 years, showed distal wasting and weakness in all 4 limbs, which was most marked in the oldest sib. They also showed talipes cavus equinovarus. Tendon reflexes were absent in the legs of all 4 sibs. Mild distal sensory loss was also present. No autonomic nervous system dysfunctions were observed. The 13-year-old patient presented a pure sensorineural hearing loss, while the other 3 sibs showed a mixed pattern, with loss of the stapedial reflex. The affected children were homozygous for the same haplotype, which was identical to the common HMSNL haplotype found in Bulgarian Gypsy patients for 6 markers. One of these markers displayed a rare allele that had also been found in a subset of affected families in Bulgaria. Navarro and Teijeira (2003) noted that HMSNL is phenotypically similar to the Russe form of hereditary motor and sensory neuropathy (605285), which is also common in the Gypsy population. Okamoto et al. (2014) reported 3 sibs, born of consanguineous Turkish parents, with CMT4D. The patients had delayed motor milestones in early childhood, with gait instability due to muscle weakness. The disorder was progressive, and patients developed severe distal and mild proximal muscle weakness. Other features included pes cavus, kyphoscoliosis, hammertoes, and claw hands. Sensation was severely diminished distally, and electrophysiologic studies showed loss of sensory nerve action potentials as well as loss of compound action muscle potentials. The patients developed sensorineural deafness in the first decade. Two affected individuals had signs of glaucoma, but this feature may have been unrelated to the CMT phenotype. ### Pathologic Findings King et al. (1999) made ultrastructural observations on sural nerve biopsy specimens from 5 cases of HMSNL. Longitudinal sections showed demyelination/remyelination. Severe progressive axonal loss was conspicuous, but there was no indication of axonal atrophy. Hypertrophic onion bulb changes were present in younger patients which later regressed. The axons were hypomyelinated, and partial ensheathment of axons by Schwann cells was observed. Uncompacted myelin and accumulations of pleomorphic material in the adaxonal Schwann cell cytoplasm were features. An unusual finding was the presence of intraaxonal accumulation of irregularly arranged curvilinear profiles. The amount of endoneurial collagen was markedly increased. Inheritance The transmission pattern of CMT4D in the family reported by Okamoto et al. (2014) was consistent with autosomal recessive inheritance. Mapping To map HMSNL, Kalaydjieva et al. (1996) adopted a 2-stage genome screening strategy. During the first stage, analysis for segment sharing was conducted in a selected small subset of the Lom kindred, connected via 5 different paths with an average of 9.5 meiotic steps. The analysis of approximately 30% of the genome identified 2 shared segments, namely D8S257-D8S200 and D8S198-D8S284, which satisfied all screening criteria. During the second stage, the entire pedigrees were analyzed for linkage to 17 markers on 8q, telomeric to D8S257. Two-point linkage analysis provided strong evidence that HMSNL is located on 8q24-qter, between D8S284 and D8S534. The highest lod score of 7.7 was obtained for D8S378 at theta = 0.0. Multipoint lod scores pointed to the D8S284-D8S537 interval as the most likely location for HMSNL with a maximum lod likelihood difference of 6.6 at D8S378. The transmission disequilibrium test (TDT) revealed existence of strong linkage disequilibrium in the interval D8S557-D8S537 (5.3 cM). Kalaydjieva et al. (1996) stated that no myelin genes are known to be located on 8q24. Evidence of linkage to roughly the same region was reported in a black American family with dominantly inherited Dejerine-Sottas neuropathy (145900) (Ionasescu et al., 1996). Taken together, the findings suggested to Kalaydjieva et al. (1996) that allelic mutations in a previously unknown myelin gene on 8q24 may be responsible for different demyelinating phenotypes with recessive as well as dominant modes of inheritance. Haplotype information appeared to indicate that the HMSNL mutation predated the divergence of Bulgarian Gypsies, implying that it should occur in other Gypsy groups within (and probably also outside) Bulgaria. On the basis of linguistic evidence, the Gypsy exodus from India has been dated to around 1000 AD. A phenotype similar to HMSNL, Charcot-Marie-Tooth disease and deafness (214370), has been described in an Indian family. Molecular Genetics Kalaydjieva et al. (2000) reduced the HMSNL interval to 200 kb and characterized it by means of large-scale genomic sequencing. Sequence analysis of 2 genes located in the critical region identified the founder HMSNL mutation: a premature-termination codon at position 148 of the N-myc downstream-regulated gene-1 (NDRG1; 605262.0001). NDRG1 is ubiquitously expressed and has been proposed to play a role in growth arrest and cell differentiation, possibly as a signaling protein shuttling between the cytoplasm and the nucleus. Kalaydjieva et al. (2000) studied expression in peripheral nerve and detected particularly high levels in Schwann cells. Taken together, these findings pointed to NDRG1 having a role in the peripheral nervous system, possibly in the Schwann cell signaling necessary for axonal survival. In 3 sibs, born of consanguineous Turkish parents, with CMT4D, Okamoto et al. (2014) identified a homozygous 6.25-kb intragenic duplication in the NDRG1 gene (605262.0003). The duplication, which was found by array CGH analysis, segregated with the disorder in the family. RT-PCR studies of patient cells showed that the duplication resulted in a nonsense mutation at codon 223 and decreased levels of NDRG1 mRNA. Breakpoint sequence analysis suggested a replicative mechanism for generating the duplication. History The Gypsies studied by Kalaydjieva et al. (1996) stemmed from a small group of 50 to 100 individuals who moved into Bulgaria from Macedonia and settled in Lom in 1886. Their traditional trade suggested that they belong to the Djambazi, an ethnonym that means 'trading in horses.' The main Djambazi migration to Bulgaria occurred from the west in the 16th century, and the largest number of this group still live in Macedonia and Serbia. The group is highly endogamous; in 1 study of 78 marriages, 70 were contracted within the community, 7 involved an individual from a different area but the same Gypsy group, and 1 (4 generations ago) was reportedly between a Bulgarian man and a Gypsy woman. Consanguineous marriage was not practiced, however, and the closest relationship between the parents in a family with HMSNL was third cousins once removed. In the course of the study, a second cluster comprising 3 families with 6 affected individuals was identified 250 km east of Lom. The affected families belonged to different Gypsy groups and were unaware of any connection to the Lom kindred. Two families were Wallachian Gypsies, a group that has lived for centuries in the Wallachian kingdom to the north of the Danube, in present-day Romania. Wallachian Gypsies speak a Romany dialect that belongs to a stratum different from that of the Djambazi. Their migrations into Bulgaria were dated mainly to the 16th-18th centuries and also to the late 19th-early 20th century. The third kindred from this cluster were Turkish-speaking Muslim Gypsies. Since Gypsies easily adopt the language and the religion of the surrounding populations, the past group identity of this family was difficult to define. Navarro and Teijeira (2003) provided a detailed review of neuromuscular disorders among the Romany Gypsies. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness (often in third decade) SKELETAL Hands \- Hand deformities Feet \- Foot deformities \- Talipes cavus equinovarus NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Gait disorder \- Hyporeflexia \- Areflexia \- Distal sensory loss \- Severely reduced nerve conduction velocities (NCV) (may become unattainable) \- 'Onion bulbs' on nerve biopsy \- Segmental demyelination/remyelination on nerve biopsy \- Axonal loss \- Intraaxonal accumulation of curvilinear profiles \- Abnormal brainstem auditory evoked potentials, suggesting demyelination MISCELLANEOUS \- Onset in first decade \- Usually begins in feet and legs (peroneal distribution) \- Upper limb involvement usually occurs later \- First described in Gypsy group from Bulgaria MOLECULAR BASIS \- Caused by mutation in the N-myc downstream regulated gene-1 (NDRG1, 605262.0001 ) ▲ 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	CHARCOT-MARIE-TOOTH DISEASE, TYPE 4D	c1832334	5,606	omim	https://www.omim.org/entry/601455	2019-09-22T16:14:44	{"doid": ["0110186"], "mesh": ["C535716"], "omim": ["601455"], "orphanet": ["99950"], "synonyms": ["Alternative titles", "NEUROPATHY, HEREDITARY MOTOR AND SENSORY, LOM TYPE", "CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, AUTOSOMAL RECESSIVE, TYPE 4D", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 4D", "HMSN4D"]}
Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade malignant mesenchymal neoplasm of the soft tissues, that differs from other sarcomas by unique histology and characteristic chromosomal translocation. There is an uncertain differentiation (there is no evidence yet showing that EMC exhibits the feature of cartilaginous differentiation) and neuroendocrine differentiation is even possible.[1] ## Contents * 1 Classification * 2 Diagnosis * 3 Cytogenetics * 4 Pathological features * 5 Prognosis * 6 Treatment * 7 References ## Classification[edit] EMC was firstly described in 1953 by Stout et al. when they discussed the different species of extraskeletal chondrosarcoma,[2] but EMC concept was firstly proposed in 1972 by Enzinger et al.[3] Brody thought that this was a unique low-grade malignancy with a low growth rate and both clinically and histopathologically distinct anamnesis beside the typical chondrosarcomas.[4] However, the parental line of EMC cells remains indeterminate. According to the most recent edition of the World Health Organization Classification of Tumors of Soft Tissue and Bone, EMC has been classified as a type of soft tissue tumor with uncertain differentiation.[5] Recent statistics demonstrate that EMC shows a higher incidence of local recurrence, metastasis and patient mortality[6] and therefore are classified as mean-grade malignancies. EMC is rare and accounts for less than 3% of soft tissue tumors. It mainly affects adults with an average age of about 54 years (age range 29 to 73 years) and is more common in males, the ratio of male to female is 2:1.[5] ## Diagnosis[edit] EMCS appears clinically as a slowly developing mass of soft tissue associated with pain and tenderness.[7] Two-thirds of EMC tumors are primarily found in sub-fascia soft tissues of the proximal extremities and limb girdles, especially the thigh and popliteal fossa. The average tumor size is about 9.3 cm (3.3–18 cm).[5] Uncommon locations are the distal extremities, the paraspinal part and the head and neck region. [8] Incidence of the head and neck region is less than 5%.[1] ## Cytogenetics[edit] There is no specific immunoprofile for EMC; less than 20% of cases show immunoreactivity for the S-100 protein.[8] The cytogenetics of this tumor reside in the reciprocal translocations of the 9q22 locus with chromosomes 3q11, 15q21, 17q11, and 22q12. Other cytogenetic events can be observed but are not characteristic. The most common translocation includes the EWSR1 locus at 22q12 and the NR4A3 (also known as TEC and CHN) locus at 9q22. As often can be seen in chimeric transcripts including EWSR1, the transactivation domain of EWSR1 fused to the DNA-binding domain of NR4A3. Several types of fusion products can be observed, depending on which exons are involved. NR4A3 is an orphan nuclear receptor that is able to activate the FOS promoter and plays a role in the regulation of hematopoietic growth and differentiation. In EMC the DNA-binding domain is constant and the transactivation domains of several genes are involved. These genes include TAF2N (17q11) encoding an RNA-binding protein, that presents subunit of RNA polymerase II, TCF12 (15q21) encoding a transcription factor in the basic helix–loop–helix family, and TFG (3q11) which encodes a regulator of the nuclear factor-κB (NF-κB) signaling pathway with homology to FUS and EWSR1 in its N-terminal region. TFG is also observed as a fusion transcript with ALK (2p23) in anaplastic large-cell lymphoma and with NTRK1 (1q21) in some of thyroid papillary carcinomas. Recent evidence demonstrates that tumors with these various translocations have similar profiles of the gene expression.[9] ## Pathological features[edit] EMC shows the smallest morphological variation between the tumors among all myxoid soft tissue neoplasms. The myxoid matrix has a fibrous structure that is different from the grainy appearance of most other myxoid lesions. It is stained with magenta in the air-dried samples. Among all myxoid tumors, EMC has the least vascular structures. Chondroblast-like lacunas may be formed, but no differentiation of hyaline cartilago has been described. Smears contain plump spindle-shaped or oval tumor cells arranged in a lacelike pattern of loosely cohesive cords and nests. The malignant cells are uniform and lack nuclear pleomorphism. The nuclei have round or oval shape and are hyperchromatic with finely stippled chromatin. The nucleolus is small and inconspicuous. Nuclear clefts and grooves are common and the cytoplasm is homogeneous, scanty to moderately abundant, and often appears wispy and tapered, with well-defined borders of cells. ## Prognosis[edit] EMC patients have a long-term clinical course with a survival rate of 5 years in 90% of patients, 10 years at 70% and 15 years at 60%. Local recurrences occur in up to 48% of patients.[10] Metastasis occurs in approximately 50% of cases with the most frequent occurrence in the lungs, which is common site of metastasis in all sarcomas. There have been rare cases of spontaneous regression of pulmonary metastases without any treatment.[11] ## Treatment[edit] As with all these subgroups of sarcomas, standard treatment for primary EMC is complete surgical resection, in high risk cases followed by radiation therapy. Unfortunately, the rates of response to conventional chemotherapeutic and radiation regimens are low.[1] ## References[edit] 1. ^ a b c Stacchiotti, Silvia; Dagrada, Gian Paolo; Morosi, Carlo; Negri, Tiziana; Romanini, Antonella; Pilotti, Silvana; Gronchi, Alessandro; Casali, Paolo G (2012-10-11). "Extraskeletal myxoid chondrosarcoma: tumor response to sunitinib". Clinical Sarcoma Research. 2 (1): 22. doi:10.1186/2045-3329-2-22. ISSN 2045-3329. PMC 3534218. PMID 23058004. 2. ^ Stout, Arthur Purdy; Verner, Edward W. (May 1953). "Chondrosakcoma of the extraskeletal soft tissues". Cancer. 6 (3): 581–590. doi:10.1002/1097-0142(195305)6:3<581::aid-cncr2820060315>3.0.co;2-t. ISSN 0008-543X. 3. ^ Enzinger, Franz M.; Shiraki, Masanori (September 1972). "Extraskeletal myxoid chondrosarcoma". Human Pathology. 3 (3): 421–435. doi:10.1016/s0046-8177(72)80042-x. ISSN 0046-8177. PMID 4261659. 4. ^ M., Brody, R. I. Ueda, T. Hamelin, A. Jhanwar, S. C. Bridge, J. A. Healey, J. H. Huvos, A. G. Gerald, W. L. Ladanyi. Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. OCLC 676931484. 5. ^ a b c Yang, Lei; Qin, Genggeng; Xu, Rong; Wang, Ruoning; Zhang, Ling (2018). "Extraskeletal Myxoid Chondrosarcoma: A Comparative Study of Imaging and Pathology". BioMed Research International. 2018: 9684268. doi:10.1155/2018/9684268. PMC 6011095. PMID 29977924. 6. ^ Jacobi, Adam; Khanna, Neha; Gupta, Sushilkumar Satish (2017-03-01). "Curious case of extraskeletal myxoid chondrosarcoma". Lung India. 34 (2): 170–172. doi:10.4103/0970-2113.201312. ISSN 0970-2113. PMC 5351361. PMID 28360467. 7. ^ Molecular and Cellular Changes in the Cancer Cell. Progress in Molecular Biology and Translational Science. 144. 2016. doi:10.1016/s1877-1173(16)x0008-7. ISBN 9780128093283. ISSN 1877-1173. 8. ^ "Myxoid Chondrosarcoma - an overview \| ScienceDirect Topics". www.sciencedirect.com. Retrieved 2019-02-04. 9. ^ Rubin, Brian P.; Lazar, Alexander J.F.; Oliveira, Andre M. (2009). "Molecular Pathology of Bone and Soft Tissue Tumors". Cell and Tissue Based Molecular Pathology. Elsevier. pp. 325–359. doi:10.1016/b978-044306901-7.50031-6. ISBN 9780443069017. 10. ^ Ogura, Koichi; Fujiwara, Tomohiro; Beppu, Yasuo; Chuman, Hirokazu; Yoshida, Akihiko; Kawano, Hirotaka; Kawai, Akira (2012-06-08). "Extraskeletal myxoid chondrosarcoma: a review of 23 patients treated at a single referral center with long-term follow-up". Archives of Orthopaedic and Trauma Surgery. 132 (10): 1379–1386. doi:10.1007/s00402-012-1557-9. ISSN 0936-8051. PMID 22678528. 11. ^ Young, Philip J; Francis, Jonathan W; Lince, Diane; Coon, Keith; Androphy, Elliot J; Lorson, Christian L (November 2003). "The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein". Molecular Brain Research. 119 (1): 37–49. doi:10.1016/j.molbrainres.2003.08.011. ISSN 0169-328X. PMID 14597228. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Extraskeletal myxoid chondrosarcoma	c1275278	5,607	wikipedia	https://en.wikipedia.org/wiki/Extraskeletal_myxoid_chondrosarcoma	2021-01-18T18:42:59	{"mesh": ["C563195"], "wikidata": ["Q61478087"]}
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type In (CDG In, CDG1N) is caused by homozygous or compound heterozygous mutation in the RFT1 gene (611908) on chromosome 3p21. Description Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). Clinical Features Stibler et al. (1998) identified a patient with an untyped disorder of N-linked glycosylation on the basis of detection of abnormal isoelectric focusing of serum transferrin. The patient, designated KS by Imtiaz et al. (2000), showed symptoms often encountered in CDG, namely, marked developmental delay, hypotonia, seizures, hepatomegaly, and coagulopathy. Vleugels et al. (2009) reported 3 unrelated children with CDG1N. One was of Scottish descent, the second was born of consanguineous Italian parents, and the third was born of consanguineous Algerian parents. All were severely affected and presented in infancy with feeding difficulties and failure to thrive. Dysmorphic features were somewhat variable, but included microcephaly, micrognathia, short neck, adducted thumbs, valgus foot deformities, and inverted nipples. All had severe mental retardation with limited development, hypotonia, seizures, myoclonic jerks, decreased visual acuity, and sensorineural deafness. One patient died at age 8 months. All had normal liver function, but 1 patient had a coagulopathy. Biochemical analysis showed a type 1 pattern of serum sialotransferrins and accumulation of the incomplete oligosaccharide Man(5)GlcNAc(2)-PP-dolichol. Jaeken et al. (2009) reported 2 unrelated children with CDG1N. Common features included feeding problems, failure to thrive, severe developmental delay, epilepsy, hypotonia, and sensorineural deafness. Both children also had deficiencies in coagulation factors. Ondruskova et al. (2012) reported 2 sibs, born of unrelated Czech parents, with CDG1N. The patients were 19 and 21 years old at the time of the report. Both had delayed psychomotor development apparent in infancy, as well as early-onset seizures. As young adults, both had significant cognitive impairment, short stature, mild dysmorphic features, ataxia, axial hypotonia, mild spasticity with hyperreflexia, and a mild coagulopathy without clinical consequences. Only 1 sib had hearing impairment, which was diagnosed at age 13 years. Laboratory studies were consistent with CDG1N. Ondruskova et al. (2012) noted that the phenotype in these sibs was milder than that previously reported in patients with CDG1N. Biochemical Features To determine whether the glycosylation disorder in patient KS (Imtiaz et al., 2000) was related to a defect of lipid-linked oligosaccharide (LLO) assembly, Haeuptle et al. (2008) analyzed the LLO composition of the patient. The profile was marked by an accumulation of the intermediate LLO DolPP-GlcNAc(2)Man(5) and a strong reduction of complete LLO DolPP-GlcNAc(2)Man(9)Glc(3). The biochemical phenotype of DolPP-GlcNAc(2)Man(5) accumulation and severe protein underglycosylation was reminiscent of that seen in yeast depleted for the Rft1 protein. Inheritance The transmission pattern of CDG1N in the families reported by Vleugels et al. (2009) was consistent with autosomal recessive inheritance. Molecular Genetics In a patient with an untyped congenital disorder of glycosylation, Haeuptle et al. (2008) found a homozygous point mutation in the RFT1 gene (R67C; 611908.0001). Despite the low sequence identity (22%) between yeast and human RFT1 protein, Haeuptle et al. (2008) demonstrated both their functional orthology and the pathologic effect of the human R67C mutation by complementation assay in Rft1-deficient yeast cells. The causality of the RFT1 R67C mutation was further established by restoration of normal glycosylation profiles in patient-derived fibroblasts after lentiviral expression of the normal RFT1 cDNA. In 3 unrelated children with CDG1N, Vleugels et al. (2009) identified 3 different homozygous missense mutations in the RFT1 gene (611908.0001-611908.0003). All mutations were located in 1 of the hydrophilic loops predicted to be within the ER lumen. Patient fibroblasts showed accumulation of Man(5)GlcNAc(2)-PP-dolichol and decreased DNase I secretion compared to controls, and these defects were restored by expression of wildtype RFT1. In 2 unrelated children with CDG1N, Jaeken et al. (2009) identified biallelic mutations in the RFT1 gene (611908.0002; 611908.0004-611908.0005). In 2 sibs, born of unrelated Czech parents, with CDG1N, Ondruskova et al. (2012) identified compound heterozygous missense mutations in the RFT1 gene (M408V; 611908.0006 and R442Q; 611908.0007). Functional studies were not performed, but both mutations occurred in the transmembrane domain, unlike previous RFT1 mutations that occurred in the luminal loops. The phenotype in the Czech sibs was somewhat milder compared to other patients, which Ondruskova et al. (2012) postulated may be due to the location of the mutation. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Failure to thrive HEAD & NECK Head \- Microcephaly Face \- Micrognathia Ears \- Sensorineural deafness Eyes \- Decreased visual acuity \- Lack of eye contact Neck \- Short neck RESPIRATORY \- Respiratory insufficiency CHEST Breasts \- Inverted nipples ABDOMEN Liver \- Hepatomegaly (in some patients) Gastrointestinal \- Feeding difficulties SKELETAL Hands \- Adducted thumbs Feet \- Valgus foot deformity MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Mental retardation, severe \- Seizures \- Myoclonus \- Ataxia \- Spasticity \- Hyperreflexia HEMATOLOGY \- Coagulopathy (in some patients) LABORATORY ABNORMALITIES \- Type I pattern of serum sialotransferrins \- Accumulation of the incomplete oligosaccharide Man(5)GlcNAc(2)-PP-dolichol MISCELLANEOUS \- Onset in infancy MOLECULAR BASIS \- Caused by mutation in the RFT1 homolog gene (RFT1, 611908.0001 ) ▲ 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	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE In	c2677590	5,608	omim	https://www.omim.org/entry/612015	2019-09-22T16:02:29	{"doid": ["0080566"], "mesh": ["C567437"], "omim": ["612015"], "orphanet": ["244310"], "synonyms": ["Alternative titles", "CDG In"], "genereviews": ["NBK1332"]}
Baylisascaris roundworms are intestinal parasites found in many different animals. Baylisascaris infection in humans is uncommon but can be severe. While Baylisascaris can infect different types of animals, Baylisascaris procyonis, carried by raccoons, is thought to pose the greatest risk to humans because raccoons often live in close proximity to humans. Humans can acquire the parasite by ingesting the eggs of infected raccoons. Young children are at greatest risk for Baylisascaris infection because they are more likely to put contaminated soil in their mouths. Though rare, human infections can be severe if the parasite invades the eye (ocular larva migrans), organs (visceral larva migrans), or the brain (neural larva migrans). Symptoms of a Baylisascaris infection may include nausea, fatigue, an enlarged liver, loss of coordination, lack of muscle control, blindness, and coma. Baylisascaris infections cannot be spread from one person to another. No drug has been found to be completely effective against Baylisascaris infections in humans though albendazole has been used in some cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Baylisascaris infection	None	5,609	gard	https://rarediseases.info.nih.gov/diseases/12654/baylisascaris-infection	2021-01-18T18:01:51	{"synonyms": []}
Caudal regression syndrome is a disorder that impairs the development of the lower (caudal) half of the body. Affected areas can include the lower back and limbs, the genitourinary tract, and the gastrointestinal tract. In this disorder, the bones of the lower spine (vertebrae) are frequently misshapen or missing, and the corresponding sections of the spinal cord are also irregular or missing. Affected individuals may have incomplete closure of the vertebrae around the spinal cord, a fluid-filled sac on the back covered by skin that may or may not contain part of the spinal cord, or tufts of hair at the base of the spine. People with caudal regression syndrome can also have an abnormal side-to-side curvature of the spine (scoliosis). The spinal abnormalities may affect the size and shape of the chest, leading to breathing problems in some individuals. Individuals with caudal regression syndrome may have small hip bones with a limited range of motion. The buttocks tend to be flat and dimpled. The bones of the legs are typically underdeveloped, most frequently the upper leg bones (femurs). In some individuals, the legs are bent with the knees pointing out to the side and the feet tucked underneath the hips (sometimes called a frog leg-like position). Affected individuals may be born with inward- and upward-turning feet (clubfeet), or the feet may be outward- and upward-turning (calcaneovalgus). Some people experience decreased sensation in their lower limbs. Abnormalities in the genitourinary tract in caudal regression syndrome are extremely varied. Often the kidneys are malformed; defects include a missing kidney (unilateral renal agenesis), kidneys that are fused together (horseshoe kidney), or duplication of the tubes that carry urine from each kidney to the bladder (ureteral duplication). These kidney abnormalities can lead to frequent urinary tract infections and progressive kidney failure. Additionally, affected individuals may have protrusion of the bladder through an opening in the abdominal wall (bladder exstrophy). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. Genital abnormalities in males can include the urethra opening on the underside of the penis (hypospadia) or undescended testes (cryptorchidism). Females may have an abnormal connection between the rectum and vagina (rectovaginal fistula). In severe cases, both males and females have a lack of development of the genitalia (genital agenesis). People with caudal regression syndrome may have abnormal twisting (malrotation) of the large intestine, an obstruction of the anal opening (imperforate anus), soft out-pouchings in the lower abdomen (inguinal hernias), or other malformations of the gastrointestinal tract. Affected individuals are often constipated and may experience loss of control of bladder and bowel function. ## Frequency Caudal regression syndrome is estimated to occur in 1 to 2.5 per 100,000 newborns. This condition is much more common in infants born to mothers with diabetes when it affects an estimated 1 in 350 newborns. ## Causes Caudal regression syndrome is a complex condition that may have different causes in different people. The condition is likely caused by the interaction of multiple genetic and environmental factors. One risk factor for the development of caudal regression syndrome is the presence of diabetes in the mother. It is thought that increased blood sugar levels and other metabolic problems related to diabetes may have a harmful effect on a developing fetus, increasing the likelihood of developing caudal regression syndrome. The risks to the fetus are further increased if the mother's diabetes is poorly managed. Caudal regression syndrome also occurs in infants of non-diabetic mothers, so researchers are trying to identify other factors that contribute to the development of this complex disorder. Some researchers believe that a disruption of fetal development around day 28 of pregnancy causes caudal regression syndrome. The developmental problem is thought to affect the middle layer of embryonic tissue known as the mesoderm. Disruption of normal mesoderm development impairs normal formation of parts of the skeleton, gastrointestinal system, and genitourinary system. Other researchers think that caudal regression syndrome results from the presence of an abnormal artery in the abdomen, which diverts blood flow away from the lower areas of the developing fetus. Decreased blood flow to these areas is thought to interfere with their development and result in the signs and symptoms of caudal regression syndrome. Some scientists believe that the abnormal development of the mesoderm causes the reduction of blood flow, while other scientists believe that the reduction in blood flow causes the abnormal mesoderm development. Many scientists think that the cause of caudal regression syndrome is a combination of abnormal mesoderm development and decreased blood flow to the caudal areas of the fetus. ## Inheritance Pattern Caudal regression syndrome occurs sporadically, which means it occurs in people with no history of the condition in their family. Multiple genetic and environmental factors likely play a part in determining the risk of developing this 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	Caudal regression syndrome	c1838569	5,610	medlineplus	https://medlineplus.gov/genetics/condition/caudal-regression-syndrome/	2021-01-27T08:25:09	{"gard": ["6007"], "mesh": ["C537221"], "omim": ["600145"], "synonyms": []}
A number sign (#) is used with this entry because congenital generalized lipodystrophy type 2 (CGL2) is caused by homozygous or compound heterozygous mutation in the gene encoding seipin (BSCL2; 606158) on chromosome 11q12. Biallelic mutation in the BSCL2 gene can also cause progressive encephalopathy with or without lipodystrophy (PELD; 615924), a severe neurodegenerative disorder. Description Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes (Garg, 2004). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594). Clinical Features Van Maldergem et al. (2002) studied 70 affected individuals from 44 unrelated families with congenital generalized lipodystrophy. Forty-five patients from 24 families had BSCL2 and 21 patients from 17 families had BSCL1 (608594). Two European families had no BSCL2 mutations and did not show linkage to chromosome 9q34, indicating the existence of an additional locus, which the authors termed BSCLX. All subjects of African ancestry (35%) were in the BSCL1 group. Congenital onset of lipoatrophy occurred in 79.5% of patients with BSCL2 compared to 61% of other cases. Onset of diabetes was the same in all patients. All patients had skeletal muscle hypertrophy, and the prevalence of hypertrophic cardiomyopathy was approximately 20% in all groups. Seven of 45 (15%) BSCL2 patients died prematurely (range, 4 months to 35 years of age), compared to no premature deaths in patients with BSCL1. The most significant finding was an increased frequency of mild or moderate intellectual impairment in the BSCL2 group (78%) compared to BSCL1 (10%), yielding an odds ratio of 23.5. There was no correlation between site and type of seipin mutation and intellectual impairment. Van Maldergem et al. (2002) concluded that BSCL1 is a milder disease than BSCL2. Simha and Garg (2003) compared whole-body adipose tissue distribution by magnetic resonance imaging (MRI) in 10 congenital generalized lipodystrophy patients, of whom 7 (6 females, 1 male) had CGL1 (608594) and 3 (2 males, 1 female) had CGL2. Both subtypes had marked lack of metabolically active adipose tissue located at most subcutaneous, intermuscular, bone marrow, intraabdominal, and intrathoracic regions. Paucity of mechanical adipose tissue in the palms, soles, orbits, scalp, and periarticular regions was noted in CGL2, whereas it was well preserved in CGL1 patients. The authors concluded that congenital generalized lipodystrophy patients with BSCL2 mutations have a more severe lack of body fat, which affects both metabolically active and mechanical adipose tissue. Friguls et al. (2009) reported a 4-month-old Chinese boy with a severe form of congenital lipodystrophy caused by a homozygous truncating mutation in the BSCL2 gene (E189X; 606158.0016). He had hirsutism with dry, thick hair, enlarged hands and feet, and lipoatrophy affecting the trunk, limbs, and face. He also had hepatomegaly with steatosis, acute pancreatitis, insulin resistance, and low serum leptin. Cardiac examination revealed hypertension and an apical murmur, and ultrasound showed severe obstructive and asymmetric septal hypertrophic cardiomyopathy. Dietary management resulted in clinical improvement. Friguls et al. (2009) emphasized the early onset of severe cardiac disease in this patient. Haghighi et al. (2016) compared the clinical features of 5 patients with genetically confirmed CGL1 and 5 with CGL2. All patients had generalized lipodystrophy and muscular hypertrophy, and most had hepatomegaly and splenomegaly. Additional features were found in both groups, but tended to be more frequent in patients with CGL2 than in those with CGL1; these features included acromegaloid appearance, large ears, triangular facies, acanthosis nigricans, increased insulin levels, elevated liver enzymes, hernias, and cardiomyopathy. Genital abnormalities and hypertriglyceridemia were found equally in both groups. Two CGL1 patients and 1 CLG2 patient had nephrolithiasis. Only 1 CGL1 patient had bone cysts, and only CGL2 patients had intellectual disability, hypertrichosis, and high-pitched voice. Mapping Using a genomewide scan of 9 BSCL families from 2 geographic clusters in Lebanon and Norway, Magre et al. (2001) identified a disease locus, designated BSCL2, within a 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13 (maximum multipoint lod score of 13.2). Five Lebanese families were homozygous for the same alleles at 9 contiguous markers within an interval spanned by markers D11S4076 to PYGM (608455), probably because of a founder effect. Among families clustered in the southwest region of Norway, Magre et al. (2001) found that affected family members were homozygous for 4 consecutive markers, D11S1765, D11S4076, CA10, and CA9, confirming a founder effect. Analysis of 20 additional BSCL families of various ethnic origins led to the identification of 11 families in which the disease cosegregated with the 11q13 locus; the remaining families provided confirmation of linkage to 9q34. Molecular Genetics In chromosome 11q13-linked families with congenital generalized lipodystrophy type 2, and in 3 isolated patients, Magre et al. (2001) identified mutations in the BSCL2 gene (606158.0001-606158.0012). Affected individuals were either homozygous for a specific mutation or compound heterozygous; all parents of unaffected sibs carried only 1 mutation. Agarwal et al. (2002) pointed out that individuals with congenital generalized lipodystrophy type 2 who carry mutations in the BSCL2 gene tend to have mild mental retardation and cardiomyopathy, features not seen in families with congenital generalized lipodystrophy type 1 who have mutations in the AGPAT2 gene. Based on the high expression of seipin in brain and weak expression in adipocytes, Magre et al. (2001) suggested a primary defect in hypothalamic pituitary axis. Agarwal et al. (2002) suggested that different forms of congenital generalized lipodystrophy may be caused by disruption of different pathways. Fu et al. (2004) screened for mutations in AGPAT2 and BSCL2 in 27 families with congenital generalized lipodystrophy. In 3 sibs with the features of congenital generalized lipodystrophy with cystic angiomatosis of long bones (a phenotype designated Brunzell syndrome) they identified a splice site mutation in AGPAT2 (603100.0002). Eighteen patients from 15 families from the same region of northeastern Brazil were homozygous for a frameshift mutation in BSCL2 (669insA; 606158.0006). Despite having the same mutation, the subjects had widely divergent clinical manifestations. The authors concluded that there did not appear to be any distinguishing clinical characteristics between subjects with congenital generalized lipodystrophy with AGPAT2 or BSCL2 mutations with the exception of mental retardation in carriers of BSCL2. Ebihara et al. (2004) reported 4 Japanese patients with Berardinelli-Seip congenital generalized lipodystrophy. In 3 of them the same homozygous nonsense mutation in the BSCL2 gene was found (606158.0015); analysis of flanking microsatellite markers and single-nucleotide polymorphisms (SNPs) within the gene revealed common ancestry in which the mutation originated. No mutation in either the BSCL2 or the AGPAT2 (603100) gene was found in the fourth patient, whose phenotype was considered atypical of patients with mutation in either gene. The authors stated that this was the first report of gene and phenotype analysis of congenital generalized lipodystrophy in Japanese. Population Genetics Gedde-Dahl et al. (1996) stated that 5 of the 6 families studied by Seip and Trygstad (1996) came from adjacent rural 'municipalities' of southwestern Norway. Six patients from this area were born between 1951 and 1973, and none between 1974 and 1995. The absence of new cases might be explained by a decrease in the intraregion marriage rate and inbreeding. Genealogic investigation showed that the mutation must have occurred at least 400 years ago. The sixth family was clinically different and geographically sporadic from a Finnish-descent rural east Norwegian population. In general, males appeared to be less severely affected than females. INHERITANCE \- Autosomal recessive GROWTH Height \- Increased linear growth HEAD & NECK Face \- Large mandible \- Triangular facies \- Acromegaloid appearance Ears \- Large ears CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy ABDOMEN External Features \- Prominent umbilicus \- Umbilical hernia Liver \- Hepatomegaly \- Hepatic steatosis \- Cirrhosis Pancreas \- Pancreatitis, acute Spleen \- Splenomegaly Gastrointestinal \- Voracious appetite GENITOURINARY \- Genital anomalies External Genitalia (Female) \- Labial hypertrophy \- Clitoromegaly Internal Genitalia (Female) \- Polycystic ovaries \- Decreased fertility in females Kidneys \- Nephrolithiasis SKELETAL \- Advanced bone age \- Lytic cystic lesions in appendicular bones (occurs after puberty) Hands \- Large hands Feet \- Large feet SKIN, NAILS, & HAIR Skin \- Acanthosis nigricans Hair \- Hirsutism MUSCLE, SOFT TISSUES \- Nearly complete absence of metabolically active adipose tissue (subcutaneous, intraabdominal, intrathoracic) \- Nearly complete absence of mechanical adipose tissue (joints, orbits, palms, soles) \- Generalized muscular appearance from birth \- Hernias NEUROLOGIC Central Nervous System \- Mental retardation, mild VOICE \- High-pitched voice ENDOCRINE FEATURES \- Insulin-resistant diabetes mellitus at puberty \- Decreased fertility in females LABORATORY ABNORMALITIES \- Hyperinsulinemia \- Hypertriglyceridemia \- Decreased serum leptin \- Elevated liver enzymes MISCELLANEOUS \- Onset at birth or early infancy MOLECULAR BASIS \- Caused by mutations in the seipin gene (BSCL2, 606158.0001 ). ▲ 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	LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 2	c0221032	5,611	omim	https://www.omim.org/entry/269700	2019-09-22T16:22:26	{"doid": ["0111136"], "mesh": ["D052497"], "omim": ["269700"], "orphanet": ["528"], "synonyms": ["Alternative titles", "BERARDINELLI-SEIP CONGENITAL LIPODYSTROPHY, TYPE 2", "SEIP SYNDROME", "BERARDINELLI SYNDROME", "LIPODYSTROPHY, TOTAL, AND ACROMEGALOID GIGANTISM", "LIPOATROPHIC DIABETES, CONGENITAL", "LIPODYSTROPHY, BERARDINELLI-SEIP CONGENITAL, TYPE 2", "BRUNZELL SYNDROME, BSCL2-RELATED"], "genereviews": ["NBK1212"]}
Abortion in Tennessee is legal. The number of abortion clinics in Tennessee has decreased over the years, with 128 in 1982, 33 in 1992 and seven in 2014. There were 12,373 legal abortions in 2014, and 11,411 in 2015. ## Contents * 1 Terminology * 2 Context * 3 History * 3.1 Legislative history * 3.2 Judicial history * 3.3 Clinic history * 4 Statistics * 5 Criminal prosecutions of abortion * 6 Abortion rights views and activities * 6.1 Protests * 7 Footnotes * 8 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.[1] Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[2][3] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[4][5] 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".[6] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[7] ## Context[edit] See also: Abortion in the United States Free birth control correlates to teenage girls having a 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.[8] 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.[9] According to Megan Donovan, a senior policy manager at the Guttmacher Institute, states have legislation seeking to protect a woman's right to access abortion services have the lowest rates of infant mortality in the United States.[9] ## History[edit] 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 Trump, with 80% of these voters supporting him at the ballot box in 2016. In November 2018, during US House exit polling, 75% of southern white evangelical Christian women indicated they supported Trump and only 20% said they voted for Democratic candidates.[10] ### 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.[11] 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.[11] The state was one of 10 states in 2007 to have a customary informed consent provision for abortions.[12] In 2013, state Targeted Regulation of Abortion Providers (TRAP) had provisions related to admitting privileges and licensing. They required clinics have hospital privileges and transfer agreement with a hospital.[13] The state legislature was one of eight states nationwide that tried, and failed, to pass a fetal heartbeat bill in 2017.[14] They tried again in 2018, where they were one of ten states that tried and failed to pass a fetal heartbeat bill.[14] Two fetal heartbeat bills were filed in the Tennessee General Assembly in 2019. On January 23, 2019, by Rep. James "Micah" Van Huss filed HB 77 in the Tennessee House of Representatives.[15] On February 7, 2019, Sen. Mark Pody filed SB 1236 in the Tennessee Senate.[16] On February 20, 2019, HB 77 was passed out of a Public Health subcommittee and sent to the full committee.[17] On February 26, 2019, the House Public Health Committee voted 15–4 to send HB 77 to the House floor for a full vote.[18][19] On February 7, 2019, HB 77 was passed out of the Tennessee House by a vote of 66–21.[20] As of May 14, 2019, the state prohibited abortions after the fetus was viable, generally some point between week 24 and 28. This period uses a standard defined by the US Supreme Court in 1973 with the Roe v. Wade ruling and was not a result of state based legislation.[14] In 2020 Tennessee banned abortions because of a prenatal diagnosis of Down syndrome or because of the gender or race of the fetus.[21] ### 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.[11] ### Clinic history[edit] Number of abortion clinics in Tennessee by year. See also: Abortion clinic Between 1982 and 1992, the number of abortion clinics in the state declined by 47, going from 128 in 1982 to 33 in 1992.[22] In 2014, there were seven abortion clinics in the state.[23] In 2014, 96% of the counties in the state did not have an abortion clinic. That year, 63% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[24] In 2017, there were four Planned Parenthood clinics in a state with a population of 1,519,130 women aged 15 – 49 of which all offered abortion services.[25] ## Statistics[edit] In the period between 1972 and 1974, there were zero recorded illegal abortion death in the state.[26] In 1990, 554,000 women in the state faced the risk of an unintended pregnancy.[22] In 2010, the state had 0 publicly funded abortions.[27] In 2014, 40% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[28] In 2013, among white women aged 15–19, there were abortions 690, 650 abortions for black women aged 15–19, 50 abortions for Hispanic women aged 15–19, and 20 abortions for women of all other races.[29] In 2017, the state had an infant mortality rate of 7.4 deaths per 1,000 live births.[9] Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[30] 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^^ Tennessee 10,987 8.5 135 12,373 9.5 152 21.3 2014 [31] Tennessee 10,361 8 127 11,411 8.8 140 20.3 2015 [32] Tennessee 10,523 8.1 130 11,235 8.6 139 18.6 2016 [33] ^number of abortions per 1,000 women aged 15-44; ^^number of abortions per 1,000 live births ## Criminal prosecutions of abortion[edit] 31-year-old Anna Yocca was charged with attempted first-degree murder in December 2015. The charge was based on her trying to give herself an illegal abortion using a coat hanger.[34] ## Abortion rights views and activities[edit] Participants in the "March for life" walk along Concord Avenue in Knoxville, Tennessee, United States. The march is held annually to mark the anniversary (January 22) of the U.S. Supreme Court decision, Roe v. Wade. The signs, designed to resemble stop signs, read, "Stop abortion now." Knoxville Women's March 2017 ### Protests[edit] Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[35] ## 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". ## References[edit] 1. ^ Watson, Katie (20 Dec 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 17 May 2019. 2. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1). 3. ^ "The Roberts Court Takes on Abortion". New York Times. November 5, 2006. Retrieved January 18, 2008. 4. ^ Brennan 'Dehumanizing the vulnerable' 2000 5. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review. 6. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on 2011-07-27. Retrieved 2011-11-16. 7. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007. 8. ^ Castillo, Stephanie (2014-10-03). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Retrieved 2019-05-27. 9. ^ a b c "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved May 25, 2019. 10. ^ Brownstein, Ronald (2019-05-23). "White Women Are Helping States Pass Abortion Restrictions". The Atlantic. Retrieved 2019-05-26. 11. ^ a b c Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66: 1774–1831. 12. ^ "STATE POLICY ON INFORMED CONSENT FOR ABORTION" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019. 13. ^ "TRAP Laws Gain Political Traction While Abortion Clinics—and the Women They Serve—Pay the Price". Guttmacher Institute. 2013-06-27. Retrieved 2019-05-27. 14. ^ a b c Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24. 15. ^ "TN HB0077 \| 2019–2020 \| 111th General Assembly". legiscan.com. Legi Scan. Retrieved February 21, 2019. "Summary: As introduced, prohibits abortions from the point a fetal heartbeat is detected" 16. ^ "TN SB1236 \| 2019–2020 \| 111th General Assembly". legiscan.com. Legi Scna. Retrieved February 21, 2019. "Summary: As introduced, prohibits abortions from the point a fetal heartbeat is detected" 17. ^ Wadhwani, Anita (February 20, 2019). "'Heartbeat' abortion ban advances in Tennessee legislature". Tennessean. USA Today Network. Retrieved February 20, 2019. "A bill that would outlaw abortions in Tennessee after a fetal heartbeat can be detected advanced out of a legislative subcommittee on Wednesday. The measure, proposed by state Rep. Micah Van Huss, R-Jonesborough, and state Sen. Mark Pody, R-Lebanon, would make it a crime to perform an abortion in Tennessee once a fetal heartbeat can be detected — which typically occurs in the early weeks of a woman's pregnancy." 18. ^ Kruesi, Kimberlee (February 26, 2019). "Abortion: Tennessee lawmakers advance fetal heartbeat bill". ABC 6. Associated Press. Retrieved February 26, 2019. "Republicans on the House Health Committee voted 15-4 to send the legislation to the House floor for a full vote" 19. ^ Wadhwani, Anita (February 26, 2019). "Bill that bans abortions in Tennessee after fetal heart beat sails through House committee". Tennessean. USA Today Network. Retrieved February 26, 2019. "A House committee voted 15-4 in favor of a bill that would ban most abortions in Tennessee, getting one step closer to a vote by the legislature on one of the most restrictive abortion bans in the nation. The so-called "fetal heartbeat" bill is making its way through Senate committees, but easily passed early hurdles. Tuesday's vote in the health committee means the bill moves on to a vote by the House of Representatives." 20. ^ Samuels, Brett (March 8, 2019). "Tennessee state House passes 'fetal heartbeat' abortion ban". The Hill. Retrieved March 8, 2019. "The Tennessee House of Representatives passed a bill on Thursday that would outlaw abortions in the state after a fetus has a detectable heartbeat. . . The legislation passed 66-21." 21. ^ "Court: Tennessee can enforce Down syndrome abortion ban". AP NEWS. November 21, 2020. 22. ^ 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. 23. ^ 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 2019-05-23. 24. ^ businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved 2019-05-24. 25. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved 2019-05-23. 26. ^ 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. 27. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved 2019-05-24. 28. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics". Pew Research Center. Retrieved 2019-05-23. 29. ^ "No. of abortions among women aged 15–19, by state of residence, 2013 by racial group". Guttmacher Data Center. Retrieved 2019-05-24. 30. ^ "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Retrieved 2019-06-02. 31. ^ 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. 32. ^ 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. 33. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738. 34. ^ Larson, Jordan. "Timeline: The 200-Year Fight for Abortion Access". The Cut. Retrieved May 25, 2019. 35. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA TODAY. 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	Abortion in Tennessee	None	5,612	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Tennessee	2021-01-18T18:31:00	{"wikidata": ["Q64876955"]}
A rare temporomandibular joint anomaly characterized by progressive, asymmetrical, non-neoplastic overgrowth of a mandibular condyle. It is unilateral in most cases and leads to progressive facial asymmetry, mandibular deviation, articular dysfunction, and dental malocclusion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Primary condylar hyperplasia	None	5,613	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=477781	2021-01-23T17:13:01	{"synonyms": ["Type 1 condylar hyperplasia"]}
## Summary ### Clinical characteristics. G6PC3 deficiency is characterized by severe congenital neutropenia which occurs in a phenotypic continuum that includes the following: * Isolated severe congenital neutropenia (nonsyndromic) * Classic G6PC3 deficiency (severe congenital neutropenia plus cardiovascular and/or urogenital abnormalities) * Severe G6PC3 deficiency (classic G6PC3 deficiency plus involvement of non-myeloid hematopoietic cell lines, additional extra-hematologic features, and pulmonary hypertension; known as Dursun syndrome) Neutropenia usually presents with recurrent bacterial infections in the first few months of life. Intrauterine growth restriction (IUGR), failure to thrive (FTT), and poor postnatal growth are common. Other findings in classic and severe G6PC3 deficiency can include inflammatory bowel disease (IBD) resembling Crohn's disease, and endocrine disorders (growth hormone deficiency, hypogonadotropic hypogonadism, and delayed puberty). ### Diagnosis/testing. The diagnosis of G6PC3 deficiency is established in a proband with severe congenital neutropenia and biallelic (homozygous or compound heterozygous) G6PC3 pathogenic variants on molecular genetic testing. ### Management. Treatment of manifestations: Treatment with granulocyte colony stimulating factor (G-CSF) that maintains absolute neutrophil counts above 0.5x109/L reduces the number of infections and improves the quality of life. A few mildly affected individuals have been reported to be adequately managed with prophylactic antibiotics alone. Fevers and infections require prompt treatment with antibiotics. Routine management of congenital heart disease, renal and urinary tract malformations, and hormone deficiencies as needed. Prevention of secondary complications: Good dental hygiene, including careful brushing and flossing and regular visits to the dentist, helps decrease the potential for infection. Prophylactic antibiotics should be considered in those with uncorrected neutropenia undergoing dental procedures, especially in those with heart defects at increased risk for subacute bacterial endocarditis. Surveillance: Frequent follow up by a hematologist or immunologist to monitor infection frequency and neutrophil counts to ensure an adequate response to G-CSF. Monitor growth in children, pubertal development in adolescents, and development of varicose veins, especially in adults. Monitoring for osteopenia/osteoporosis. Evaluation of relatives at risk: It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early diagnosis and management of the hematologic, cardiac, renal, and endocrine abnormalities of G6PC3 deficiency. The genetic status of at-risk sibs can be clarified by molecular genetic testing (if the G6PC3 pathogenic variants in the family are known) or by clinical findings. ### Genetic counseling. G6PC3 deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the G6PC3 pathogenic variants have been identified in the family. ## Diagnosis Consensus diagnostic criteria for G6PC3 deficiency have not been established. ### Suggestive Findings G6PC3 deficiency should be suspected in individuals with the following: * Severe congenital neutropenia defined as an absolute neutrophil count <0.5 x 109/L which usually results in early-onset, frequent, severe bacterial infections Note: Although maturation arrest of myeloid cells was initially thought to be the typical finding on bone marrow examination [Boztug et al 2009], subsequent reports identified bone marrows that were hypercellular [McDermott et al 2010] and normocellular [Banka et al 2011b]. More recently, sequential bone marrow examinations have typically revealed normal maturation and only rarely arrested maturation [Desplantes et al 2014]. * A family history consistent with autosomal recessive inheritance [Banka & Newman 2013] To date all individuals with G6PC3 deficiency have had severe congenital neutropenia; the phenotypic spectrum is a continuum that ranges from nonsyndromic (isolated severe congenital neutropenia) to classic (severe congenital neutropenia plus cardiovascular and/or urogenital abnormalities) to severe (classic G6PC3 deficiency plus involvement of non-myeloid hematopoietic cell lines and additional extra-hematologic features). Nonsyndromic G6PC3 deficiency includes only hematologic findings –predominantly severe congenital neutropenia [Smith et al 2012, Banka et al 2013]. Classic G6PC3 deficiency (known as severe congenital neutropenia type 4) includes severe congenital neutropenia as well as additional features [Boztug et al 2009, Banka et al 2011a, Boztug et al 2012]: * Other hematologic abnormalities: intermittent thrombocytopenia (66%) * Cardiovascular defects * Congenital heart defects (~77%) (see Clinical Description) * Prominent superficial venous pattern (66%) which may not be visible at birth but tends to gradually develop with age * Urogenital defects (44%), especially in males in whom cryptorchidism is the most common anomaly Severe G6PC3 deficiency (Dursun syndrome) comprises the findings of classic G6PC3 deficiency as well as additional features: * Primary pulmonary hypertension (PPH) developing in the newborn period * Non-myeloid cell involvement: severe lymphopenia * Thymic hypoplasia ### Establishing the Diagnosis The diagnosis of G6PC3 deficiency is established in a proband with severe congenital neutropenia and identification of biallelic (homozygous or compound heterozygous) G6PC3 pathogenic variants on molecular genetic testing (see Table 1). Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Single-gene testing. Sequence analysis of G6PC3 followed by consideration of deletion/duplication analysis if only one or no pathogenic variant is found. It should be noted that to date no exon or whole-gene deletions/duplications have been reported. * A multigene panel that includes G6PC3 and other genes of interest (see Differential Diagnosis) may also be considered. Note: The genes included and sensitivity of multigene panels vary by laboratory and over time. 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, genome sequencing, and mitochondrial 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 G6PC3 deficiency. 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 G6PC3 Deficiency View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method G6PC3Sequence analysis 316/31 (43%) 4, 5 Gene-targeted deletion/duplication analysis 6None reported 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\. An estimate based on a single nonsystematic study in which Boztug et al [2012] sequenced G6PC3 in individuals with syndromic forms of congenital neutropenia. 5\. To date more than 91 individuals with molecularly confirmed G6PC3 deficiency have been reported [Alangari et al 2013, Banka & Newman 2013, Estévez et al 2013, Racek et al 2013, Desplantes et al 2014, Kaya et al 2014, Notarangelo et al 2014, Ozgül et al 2014, Tavil et al 2014, Yeshayahu et al 2014, Arikoglu et al 2015, Lebel et al 2015]. 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. ## Clinical Characteristics ### Clinical Description G6PC3 deficiency is highly variable in its severity and associated clinical features. Individuals with "nonsyndromic" disease have only severe congenital neutropenia. The majority of persons with G6PC3 deficiency have cardiovascular and/or urogenital features (so-called classic G6PC3 deficiency). Of those with classic disease, a subset is more severely affected (so-called Dursun syndrome), because of the additional involvement of myeloid cells, primary pulmonary hypertension developing in the newborn period, and minor dysmorphic features. While it is estimated that nearly 10% of G6CP3 deficiency is the nonsyndromic form, this could be an underestimate due to ascertainment bias (i.e., selection of more severe phenotypes for testing of G6PC3 in previous studies) [Banka & Newman 2013]. It is also possible that some patients who initially present with the nonsyndromic form may develop features of the classic form in later life [Notarangelo et al 2014]. G6PC3 deficiency usually presents in the first few months of life with recurrent bacterial infections. A range of bacterial infections have been reported [Desplantes et al 2014]; respiratory tract infections, otitis media, stomatitis, urinary tract infections, pyelonephritis, skin abscesses, cellulitis, and sepsis are particularly common. The first serious infection can occur at any age, ranging from immediately after birth to adulthood. Hematologic. Persistent severe neutropenia is present in all affected individuals and is the core phenotype of the condition. Intermittent thrombocytopenia is seen frequently but usually does not cause symptoms. Lymphopenia associated with hypoplasia of the thymus can be seen in more severely affected individuals [Dursun et al 2009, Banka et al 2010, Ozgül et al 2014]. Cardiovascular. Congenital heart defects are common. In their recent review, Banka & Newman [2013] found that 44 (77%) of 57 of individuals with G6PC3 deficiency described in the literature had congenital cardiac defects. By far the most common anomaly was atrial septal defect. Other rare heart anomalies include patent foramen ovale; cor triatriatum; patent ductus arteriosus; critical pulmonary stenosis and hypoplastic left ventricle; mitral valve prolapse, insufficiency, and/ or regurgitation; tricuspid insufficiency; and bicuspid aortic and pulmonary valves. A prominent superficial venous pattern begins to emerge between late infancy and early childhood in most affected children [Banka et al 2011a]. This pattern can be seen on the trunk, extremities, and sometimes on the head. Experience with adults is limited but older patients have a tendency to develop varicose veins and venous ulcers. In Dursun syndrome early-onset primary pulmonary hypertension can be difficult to control [Dursun et al 2009]. In a few individuals primary pulmonary hypertension may be detected later in life [McDermott et al 2010, Fernandez et al 2012]. Urogenital anomalies are more common in males than females [Banka & Newman 2013]. In males the most common feature is cryptorchidism. Hydronephrosis, poor renal cortico-medullary differentiation, small kidneys, and vesico-uretric reflux are observed in some patients. Other features include inguinal hernia, ambiguous genitalia in undervirilized males, and urachal fistula. Inflammatory bowel disease (IBD) resembling Crohn's disease has been described in a few individuals [Cullinane et al 2011, Fernandez et al 2012, Smith et al 2012, Bégin et al 2013, Desplantes et al 2014, Kaya et al 2014]. Treatment that improves neutrophil counts can also help resolve the bowel disease [Kaya et al 2014]. Endocrine. Growth hormone deficiency has been described in two affected individuals [Boztug et al 2012]. Hypogonadotropic hypogonadism and delayed puberty have been reported in both males and females [Germeshausen et al 2010, Banka et al 2011a, Boztug et al 2012, Aytekin et al 2013]. One male, who had no detectable gonadal structures in the scrotum, inguinal canals, or abdomen, had a low testosterone level (unresponsive to HCG stimulation) and extremely high LH and FSH levels [Yeshayahu et al 2014]. Hypothyroidism has been reported in three individuals [Banka et al 2011a, Desplantes et al 2014]. Growth. Intrauterine growth restriction (IUGR), failure to thrive (FTT), and poor postnatal growth are common. The basis of growth problems is not known. It could be secondary to repeated infections or part of the primary phenotype of G6PC3 deficiency. Other findings * Minor dysmorphic features in some young children, such as a triangular face, depressed nasal bridge, thick lips, and prognathism [Dursun et al 2009, Banka et al 2011a, Boztug et al 2012, Desplantes et al 2014] * Neurodevelopmental involvement: * Mild learning difficulties were initially described in four affected individuals from a single family [Banka et al 2011a], although it was not clear whether the findings were attributable to G6PC3 deficiency. * Recently a study from the French Neutropenia Registry reported neurodevelopmental difficulties in seven of 14 individuals with pathogenic variants in G6CP3. Notably, one was said to have major developmental problems with bilateral atrophy on MRI [Desplantes et al 2014]. * Skeletal involvement, such as scoliosis and pectus carinatum [Dursun et al 2009, Boztug et al 2012] * Cutis laxa, described in at least seven patients [Boztug et al 2012, Desplantes et al 2014] * Microcephaly [Boztug et al 2009, Germeshausen et al 2010, McDermott et al 2010], which could be an effect of overall poor growth * Myopathy: * One patient with a single episode of myositis [Smith et al 2012] * One sib pair with proximal muscle weakness [McDermott et al 2010], one of whom developed at age 2.5 years recurrent episodes of proximal muscle pain and cramps; muscle histology suggested glycogen accumulation. * Two individuals reported with nonspecific myopathy but no clinical details [Boztug et al 2009, Desplantes et al 2014] Rarer features (some of which could be coincidental associations) * Myelodysplasia followed by acute myelogeneous leukemia with translocation (18, 21) (with no exposure to G-CSF) reported in one affected individual age 14 years [Desplantes et al 2014] * Mild to moderate bilateral sensorineural hearing loss which may be asymptomatic and is sometimes only detected on audiometry [McDermott et al 2010, Gatti et al 2011, Boztug et al 2012, Desplantes et al 2014]. The age of onset is not clear from the published reports. * Congenital ptosis [Boztug et al 2012] * Cleft palate [Boztug et al 2009] and Pierre Robin sequence [Desplantes et al 2014]. * Low HDL serum levels and persistently increased amylase activity described in one individual [Banka et al 2011a] Disease course. When neutropenia is treated (see Management), most patients have a good prognosis with reduced rate and severity of infections. If neutropenia is untreated, G6PC3 deficiency can lead to death in early childhood from infections [Alizadeh et al 2011] or severe respiratory distress [Dursun et al 2009]. One adult who was noncompliant with treatment died at age 37 years of bacterial endocarditis [Fernandez et al 2012]. Four deaths in the 14 individuals in the French Severe Congenital Neutropenia Registry were reported: one at age five years with sepsis, one at age 19 years from pulmonary insufficiency, and two from sudden death of unknown cause during sleep at age 30 years. ### Genotype-Phenotype Correlations No obvious genotype-phenotype correlations explain the difference between the marked cellularity of myeloid cells in the bone marrow of patients with G6PC3 deficiency [Banka et al 2011b]. Based on limited data certain pathogenic variants (e.g., p.Phe44Ser) appear to be more often (or only) associated with nonsyndromic neutropenia [Banka et al 2013]. ### Prevalence To date more than 91 individuals with the molecularly proven diagnosis of G6PC3 deficiency have been reported [Alangari et al 2013, Banka & Newman 2013, Estévez et al 2013, Racek et al 2013, Desplantes et al 2014, Kaya et al 2014, Notarangelo et al 2014, Ozgül et al 2014, Tavil et al 2014, Yeshayahu et al 2014, Arikoglu et al 2015, Lebel et al 2015]. The prevalence is likely to vary significantly from population to population based on the presence of founder variants in certain populations [Smith et al 2012, Banka & Newman 2013] and cultural practices such as consanguinity. For example, G6PC3 deficiency was found to be the most common cause of severe congenital neutropenia in Israel, accounting for the diagnosis in 25% of patients [Lebel et al 2015]. The French Neutropenia Registry has estimated incidence at birth at 0.4:1,000,000 [Desplantes et al 2014]. ## Differential Diagnosis Severe congenital neutropenia is genetically heterogeneous [Klein 2009, Donadieu et al 2011, Klein 2011]. The differential diagnosis of G6PC3 deficiency can be divided into inherited conditions in which neutropenia predominates and those in which neutropenia may be a part of a multisystem disorder. Inherited conditions in which neutropenia predominates Severe congenital neutropenia type 1 (SCN1), an autosomal dominant disorder caused by mutation of ELANE, is the most common genetic cause of congenital neutropenia. ELANE-related congenital neutropenia is characterized by recurrent fever, skin and oropharyngeal inflammation (i.e., mouth ulcers, gingivitis, sinusitis, and pharyngitis), and cervical adenopathy [Dale et al 2000]. Mutation of ELANE also causes cyclic neutropenia, a less severe disorder. Severe congenital neutropenia type 2 (SCN2) (OMIM 613107), an autosomal dominant disorder caused by mutation of GFI1, is characterized by an increased susceptibility to bacterial infections [Person et al 2003]. Mutation of GFI1 also causes chronic non-autoimmune neutropenia which manifests as monocytosis in adults. Kostmann disease (severe congenital neutropenia type 3) (OMIM 610738), an autosomal recessive disorder caused by mutation of HAX1, is characterized by neutropenia, maturation arrest of the promyelocyte or myelocyte stage with or without seizures, and developmental delay [Klein et al 2007]. Severe congenital neutropenia type 5 (SCN5) (OMIM 615285), an autosomal recessive disorder caused by mutation of VPS45, is characterized by neutropenia, neutrophil dysfunction, bone marrow fibrosis, and nephromegaly resulting from renal extramedullary hematopoiesis [Vilboux et al 2013]. Severe congenital neutropenia, X-linked (XLN), caused by mutation of WAS, is characterized in males by recurrent bacterial infections, persistent neutropenia, and arrested development of the bone marrow at the promyelocyte/myelocyte stage in the absence of other clinical findings of Wiskott-Aldrich syndrome. JAGN1-related severe congenital neutropenia (severe congenital neutropenia type 6) (OMIM 616022), an autosomal recessive disorder, is characterized by severe congenital neutropenia, increased susceptibility to bacterial infections, maturation arrest at the promyelocyte/myelocyte stage in the bone marrow, and poor response to treatment with human granulocyte colony-stimulating factor (rhG-CSF) [Boztug et al 2014]. Occasionally abnormalities are observed in bone, pancreas, and/or teeth. Inherited conditions in which neutropenia may be part of a multisystem disorder * Barth syndrome * Cartilage-hair hypoplasia * Charcot-Marie-Tooth disease caused by mutation of DNM2 (OMIM 606482) * Chediak-Higashi syndrome * Clericuzio poikiloderma with neutropenia * Cohen syndrome * Glycogen storage disease type 1b * Griscelli syndrome type 2 (OMIM 607624) * Hermansky-Pudlak syndrome type 2 * Immunodeficiency due to defect in MAPBP-interacting protein (P14 deficiency) (OMIM 610798) * Pearson syndrome * Shwachman-Diamond syndrome * WHIM syndrome (OMIM 193670) * Wiskott-Aldrich syndrome ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with G6PC3 deficiency, the following evaluations are recommended: * Full blood count to look for evidence of other hematologic involvement (i.e., intermittent thrombocytopenia and/or lymphopenia) * Immunologic evaluation for T-cell subsets in individuals with a more severe presentation and unusual non-bacterial infections * Consultation with a cardiologist to evaluate for congenital heart disease * Renal and pelvic ultrasound examination to look for urogenital malformations * Growth parameters in children and pubertal development in adolescents * Age appropriate endocrine assessment for evidence of the hormone deficiencies reported (i.e., growth hormone, gonadotropins, thyroid hormone) * Biochemical investigations to look for abnormalities in the lipid profile * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Neutropenia. Treatment with granulocyte colony stimulating factor (G-CSF) improves neutrophil numbers, reduces the number of infections, and improves the quality of life [Boztug et al 2009, McDermott et al 2010, Boztug et al 2012]. Of note, the dose required to keep absolute neutrophil counts above 0.5x109/L can vary greatly among patients. In some patients G-CSF -- even in large doses -- may fail to control infections [Smith et al 2012]. A few mildly affected individuals have been reported to be adequately managed with prophylactic antibiotics alone [Banka et al 2013]. However, prophylactic antibiotics have a limited use for preventing severe infections or bronchiectasis and inflammatory bowel disease. Fevers and infections require prompt treatment with antibiotics. Other ### Prevention of Secondary Complications Good dental hygiene, including careful brushing and flossing and regular visits to the dentist, helps decrease the potential for infection. Prophylactic antibiotics should be considered with dental procedures, including routine dental repair and cleaning, especially in individuals with heart defects. ### Surveillance The following are appropriate: * Routine management of congenital heart disease, renal and urinary tract malformations * Routine management of hormone deficiencies * Consideration of oral steroids for inflammatory bowel disease [Desplantes et al 2014] or anti-TNF treatment [Bégin et al 2013]. Some complications of IBD such as bowel stenosis may require appropriate surgical intervention. * Consideration of pancreatic enzyme supplementation if steatorrhea is present [Desplantes et al 2014] * Chemotherapy and hematopoietic stem cell transplantation for acute myelogeneous leukemia * Frequent follow up by a hematologist or immunologist to monitor infection frequency and neutrophil counts to ensure an adequate response to G-CSF (i.e., absolute neutrophil counts above 0.5x109/L) * Monitoring of growth in children and pubertal development in adolescents * Biochemical profile including lipid profile * Monitoring for development of varicose veins, especially in adults * Monitoring for osteopenia/osteoporosis * If the G6PC3 pathogenic variants in the family are known, molecular genetic testing can be used to clarify the genetic status of at-risk sibs. * If the G6PC3 pathogenic variants in the family are not known, the following evaluations can be used to help clarify the disease status of at-risk sibs: full blood count, bone marrow examination (if persistent severe neutropenia is detected on full blood count), directed general examination for prominence of superficial veins, echocardiogram, and a renal and pelvic ultrasound examination. ### Evaluation of Relatives at Risk It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early diagnosis and management of the hematologic, cardiac, renal, and endocrine abnormalities of G6PC3 deficiency. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	G6PC3 Deficiency	None	5,614	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK285321/	2021-01-18T21:24:57	{"synonyms": ["Ubiquitous Glucose-6-Phosphatase Deficiency"]}
A rare subtype of acute myeloid leukemia with recurrent genetic abnormalities characterized by clonal proliferation of poorly differentiated myeloid blasts in the bone marrow, blood, or other tissues in patients who present the t(6;9)(p23;q34) translocation. Frequently associated with multilineage bone marrow dysplasia, it usually presents with anemia, thrombocytopenia (often pancytopenia), and other nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Basophilia, as well as poor response to chemotherapy, has been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Acute myeloid leukemia with t(6;9)(p23;q34)	None	5,615	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=402014	2021-01-23T18:32:49	{"icd-10": ["C92.0"], "synonyms": ["AML with t(6;9)(p23;q34)"]}
Long face syndrome, also referred to as skeletal open bite,[1] is a relatively common condition characterised by excessive vertical facial development.[2] Its causes may be either genetic or environmental. Long face syndrome is "a common dentofacial abnormality."[3]:369[4] Its diagnosis, symptomology and treatments are complex and controversial. Indeed, even its existence as a "syndrome" is disputed. ## Contents * 1 Definition and treatment * 2 Notable people * 3 See also * 4 Notes * 5 References ## Definition and treatment[edit] One dental textbook defines it as: "Dolicofacial, there is excess of lower facial height usually associated with lower occlusal and mandibular plane angles." This is often associated "with vertical maxillary excess and mandibular hypoplasia."[5] Luc P. M. Tourne, a Fellow in the Department of TMJ and Craniofacial Pain at the University of Minnesota School of Dentistry, noted: "There is a clinically recognizable facial morphology, the long face syndrome, which has been incompletely described in the literature," However, her study of 31 adults with this syndrome, which included "analysis of esthetics, skeletal morphology, and occlusion" confirmed "this basic dentofacial deformity" has associations " with excessive vertical growth of the maxilla." She reported that closed bite and dental open are two of the syndrome's variants.[A][7] The treatment for young patients troubled by long face syndrome is to halt and control descent of the lower jaw and to prevent the eruption of posterior teeth. In severe cases of deformity, a mixture of orthodontics and orthognathic surgery may be the only effective solution.[8][9] The long-term (more than 6 years) effectiveness of surgical treatments for long face syndrome has been subject to study.[10] "In the American literature, the terms long-face syndrome and short-face syndrome are often used." To be sure, there are reported "long and the short face anomalies" and open bite cases. However, in the opinion of Hugo Obwegeser, there is no medical justification for naming them as a "syndrome" — the signs and symptoms do not meet the definitional threshold.[11]:22 There is controversy concerning the use of the descriptor "long-face syndrome." While increased anterior "total and lower face height" in many ages, combined with vertical maxillary excess in adults has been observed, the causes are controversial. Specifically, there is disagreement about possible potential environmental influences on genetic components.[12] Anecdotally, it was said to be a genetic condition, which could only be corrected with "massive amounts" of debilitating, frequent and long dental and facial reconstructive surgery.[13] For children, there is a concern that mouth breathing can contribute to the development of long face syndrome. A recent study finds that it is a growing problem which should be treated as "it won't just go away."[14] In addition to mouth breathing, it may be associated with sleep apnea.[15] Because of long face syndrome's sometime association with pediatric obstructive sleep apnea (OSA) and allergic reactions, it is essential that treating physicians differentiate the conditions and the treatments; treating one may not cure the other.[16][17] Multilevel coblation surgery is sometimes used to correct moderate to severe OSA, and long face syndrome can be a rare factor in considering surgery.[18] ## Notable people[edit] Actor and screenwriter Craig Chester says he has suffered from the condition.[13] ## See also[edit] * Adenoid facies * Facies (medical) * Mouth breathing ## Notes[edit] 1. ^ "Experimental evidence suggests that altered muscular function can influence craniofacial morphology. The switch from a nasal to an oronasal breathing pattern induces functional adaptations that include an increase in total anterior face height and vertical development of the lower anterior face. While some animal studies have suggested predictable growth patterns may occur, studies in human subjects have been much more controversial. Therefore, individual variations in response should be expected from the alteration of a long face syndrome patient's breathing mode."[6] ## References[edit] 1. ^ Carano, Aldo; Siciliani, Giuseppe; Bowman, S. Jay (September 2005). "Treatment of skeletal open bite with a device for rapid molar intrusion: a preliminary report". Angle Orthodontist. 75 (5): 736–746. doi:10.1043/0003-3219(2005)75[736:TOSOBW]2.0.CO;2 (inactive 2021-01-11). PMID 16283813.CS1 maint: DOI inactive as of January 2021 (link) 2. ^ Schendel, S. A.; Eisenfeld, J.; Bell, W. H.; Epker, B. N.; Mishelevich, D. J. (October 1976). "The long face syndrome: vertical maxillary excess". American Journal of Orthodontics. 70 (4): 398–408. doi:10.1016/0002-9416(76)90112-3. ISSN 0002-9416. PMID 1067758. 3. ^ Taub, Daniel I.; Jacobs, Jordan M. S.; Jacobs, Jonathan S. (2013). "Chapter 16: Anthropometry, cephalometry, and orthognathic surgery". In Neligan, Peter C. (ed.). Plastic surgery. Volume 2: Aesthetic. Warren, Richard J., volume editor. (3rd ed.). New York: Elsevier Saunders. pp. 354–372. ISBN 978-1-4557-4049-9. 4. ^ Prittinen, Jim (1996). "Orthodontic diagnosis of long face syndrome". General Dentistry. 44 (4): 348–351. PMID 8957832. Archived from the original on January 27, 2018. Retrieved December 18, 2017. 5. ^ Borle, Rajiv M. (February 28, 2014). Textbook of Oral and Maxillofacial Surgery. JP Medical Ltd. ISBN 9789351520092. Archived from the original on February 10, 2018. 6. ^ Tourne, Luc P. M. (September 1990). "The long face syndrome and impairment of the nasopharyngeal airway". The Angle Orthodontist. 60 (3): 167–176. doi:10.1043/0003-3219(1990)060<0167:TLFSAI>2.0.CO;2 (inactive 2021-01-11). PMID 2202236. Retrieved December 18, 2017.CS1 maint: DOI inactive as of January 2021 (link) 7. ^ See Schendel, Steven; Bell, William Harrison; Eisenfeld, Jerome; Miselevich, David; Epker, William (1976). "The long face syndrome: Vertical maxillary excess". American Journal of Orthodontics and Dentofacial Orthopedics. 70 (4): 398–408. doi:10.1016/0002-9416(76)90112-3. PMID 1067758. Archived from the original on February 10, 2018. Retrieved December 18, 2017. 8. ^ Angelillo, J. C.; Dolan, E. A. (January 1982). "The surgical correction of vertical maxillary excess (long face syndrome)". Annals of Plastic Surgery. 8 (1): 64–70. doi:10.1097/00000637-198201000-00010. ISSN 0148-7043. PMID 7073194. S2CID 38905192. 9. ^ Bell, William H.; Creekmore, Thomas D.; Alexander, R. G. (January 1977). "Surgical correction of the long face syndrome". American Journal of Orthodontics. 71 (1): 40–67. doi:10.1016/0002-9416(77)90176-2. ISSN 0002-9416. PMID 264364. 10. ^ Gallego-Romero, David; Llamas-Carrera, José M.; Torres-Lagares, Daniel; Paredes, Vanessa; Espinar, Eduardo; Guevara, Eduardo; Gutiérrez-Pérez5, José L. (May 2012). "Long-term stability of surgical-orthodontic correction of class III malocclusions with long-face syndrome". Med Oral Patol Oral Cir Bucal. 17 (3): 435–441. doi:10.4317/medoral.17647. PMC 3476084. PMID 22143741. 11. ^ Obwegeser, Hugo L. (2001). Mandibular growth anomalies: terminology – aetiology – diagnosis – greatment. Berlin: Springer. doi:10.1007/978-3-662-04534-3. ISBN 978-3-642-08655-7. Archived from the original on 2018-02-10. 12. ^ Krishnan, Vinod; Davidovitch, Ze'ev (March 18, 2004). Pediatric Endocrinology: Mechanisms, Manifestations, and Management. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins. ISBN 9780781740593. Archived from the original on February 10, 2018. 13. ^ a b Chester, Craig (April 1, 2004). Why the Long Face?: The Adventures of a Truly Independent Actor. New York: St. Martin's Press. p. 77. ISBN 9781429971980. Archived from the original on February 10, 2018. 14. ^ Holohan, Ellin (May 5, 2010). "Study says a mouthful about kids' breathing". Chicago Sun-Times. Chicago, Illinois. Archived from the original on February 10, 2018. Retrieved December 17, 2017 – via HighBeam Research. "Breathing through the mouth instead of the nose can lead to more than just dry tongues and palates. Chronic mouth breathers, most often children with allergies, have problems getting enough oxygen into their blood, which affects their size, weight, sleep and even school performance..." 15. ^ Morgan, Rachel (August 14, 2017). "Symptoms: Mouth Breathing". Live Strong. Archived from the original on July 29, 2017. Retrieved December 18, 2017. 16. ^ Li, Kasey K. (January 1, 2006). "Study says a mouthful about kids' breathing: Examining pediatric OSA surgery: although useful for many, the popular adenotonsillectomy treatment is not a cure-all". Sleep Review. Archived from the original on December 22, 2017. Retrieved December 18, 2017 – via HighBeam. 17. ^ "Allergic rhinitis in children; allergic rhinitis is the most common chronic disorder affecting children". The Pediatric OSA Airway. September 2010. Archived from the original on December 22, 2017. Retrieved December 19, 2017 – via HighBeam Research. "In addition, it is important to appreciate that many children with OSA have dentofacial abnormalities such as maxillomandibular constriction, maxillomandibular deficiency, and long face syndrome." 18. ^ Merugumala, Srinivasa (September 2, 2011). "Multilevel Coblation Therapy of OSA in Long Face Syndrome". Otolaryngology–Head and Neck Surgery. 145 (2_suppl): P273–P274. doi:10.1177/0194599811415823a457. S2CID 73149714. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Long face syndrome	c0399520	5,616	wikipedia	https://en.wikipedia.org/wiki/Long_face_syndrome	2021-01-18T18:34:27	{"umls": ["C0399520"], "wikidata": ["Q17120920"]}
An X-linked syndromic intellectual disability characterized by developmental delay, intellectual disability (ID) with severe speech impairment, and short stature. Variable additional clinical features have been associated, including behavioral disturbances, gait abnormalities, tremor, seizures, hypogonadism, truncal obesity, unspecific facial dysmorphism, and small hands and feet. ## Epidemiology The prevalence of Cabezas syndrome (CS) is unknown. It is estimated that CS accounts for 3% of X-linked intellectual disability. To date, around 120 cases have been reported in the literature. Males are predominantly affected. ## Clinical description CS typically presents in childhood and the penetrance of CS is age-dependent, with less specific clinical features in early childhood which progress over time. It is characterized by mild to severe intellectual disability with disproportionate, severe speech impairment. Other neurologic problems include behavioural disturbances (mainly hyperactivity and aggressive behaviour), gait abnormalities, tremors, seizures (more common in young children), and variable and unspecific cerebral abnormalities (such as malformations of cortical development, including polymicrogyria, ventriculomegaly, and decreased white matter volume). Most of the described patients also have short stature, truncal obesity, hypogonadism, and small hands and feet. The facial phenotype is unspecific and evolves with age. The most frequent facial dysmorphisms are prominent lower lip and low-set ears. Additional features include urogenital anomalies (such as undescended and/or small testes, hypospadias, and small penis), gynecomastia, kyphosis, pes cavus and sandal gap. Females are mainly asymptomatic but in rare cases can present learning disability, attention deficit disorder, or tremor. ## Etiology This syndrome is caused by pathogenic variants in CUL4B gene (Xq24), encoding a scaffold protein of the cullin 4B-RING ubiquitin ligase (E3) complex, which is crucial in the regulation of the degradation of cellular proteins. ## Diagnostic methods Molecular genetic testing approaches can include a combination of chromosomal microarray and Next Generation Sequencing-based multigene panel or a comprehensive genomic testing (whole-exome sequencing or genome sequencing). ## Differential diagnosis Differential diagnosis includes Börjeson-Forssman-Lehmann syndrome, Wilson-Turner syndrome and Smith-Fineman-Myers syndrome. ## Antenatal diagnosis Prenatal diagnosis can be offered if the disease-causing mutation has been identified in a family member. ## Genetic counseling Genetic counselling should be proposed to parents of affected individuals. It is inherited in an X-linked manner. If the mother is a carrier of the pathogenic variant, the chance of transmitting the pathogenic variant at each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers. Female carriers are usually asymptomatic but in rare cases can exhibit a mild phenotype. ## Management and treatment Management is symptomatic and should be multidisciplinary, usually addressing developmental delay. It can include physical, occupational and speech therapy, including nonverbal methods of communication. In patients with seizures, anticonvulsant medication is needed. Medication may also be required in patients with behavioural disturbances and/or hypogonadism. ## Prognosis Longitudinal data are insufficient to determine life expectancy. However, it is not a life-threatening condition and survival into adulthood is expected. Autonomy is limited and depends on the severity of intellectual disability. * 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	X-linked intellectual disability, Cabezas type	c1845861	5,617	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85293	2021-01-23T19:01:22	{"mesh": ["C567069"], "omim": ["300354"], "umls": ["C1845861"], "icd-10": ["Q87.8"], "synonyms": ["Cabezas syndrome"]}
## Summary ### Clinical characteristics. The 1q21.1 recurrent microdeletion itself does not appear to lead to a clinically recognizable syndrome as some persons with the deletion have no obvious clinical findings and others have variable findings that most commonly include microcephaly (50%), mild intellectual disability (30%), mildly dysmorphic facial features, and eye abnormalities (26%). Other findings can include cardiac defects, genitourinary anomalies, skeletal malformations, and seizures (~15%). Psychiatric and behavioral abnormalities can include autism spectrum disorders, attention deficit hyperactivity disorder, autistic features, and sleep disturbances. ### Diagnosis/testing. The distal 1.35-Mb 1q21.1 recurrent microdeletion can be detected by any number of molecular methods that determine the copy number of sequences within the deleted region, including chromosomal microarray analysis (CMA) using oligonucleotides or polymorphic DNA markers (i.e., SNPs). Fluorescence in situ hybridization (FISH) analysis may be used to test relatives of a proband known to have this deletion. ### Management. Treatment of manifestations: Routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed. Surveillance: Routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues. ### Genetic counseling. The recurrent distal 1.35-Mb 1q21.1 microdeletion is inherited in an autosomal dominant manner. Between 18% and 50% of deletions occur de novo. The microdeletion can be inherited from either parent; a parent with the microdeletion may show a normal phenotype or an abnormal phenotype that is similar to but usually less severe than that of his/her child. Recurrence risk for future pregnancies for parents who do not have the microdeletion is low (probably <1%) but greater than that of the general population because of the possibility of germline mosaicism. ## Diagnosis Because of the variability of the phenotypic features, the diagnosis of the 1q21.1 recurrent microdeletion is often made during chromosomal microarray analysis (CMA). ### Suggestive Findings 1q21.1 recurrent microdeletion should be suspected in individuals with the following features: * Developmental delays * Mild-to-moderate intellectual disability * Mild dysmorphic facial features (frontal bossing, deep-set eyes, bulbous nose) * Microcephaly ### Establishing the Diagnosis The diagnosis of the 1q21.1 recurrent microdeletion is established by detection of the recurrent distal 1.35-Mb heterozygous microdeletion at the approximate position of 145-146.35 Mb in the reference genome (NCBI Build 36). Note: The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the 1q21.1 recurrent microdeletion (see Genetically Related Disorders). Although several genes of interest (PRKAB2, CHD1L, BCL9, GJA5, GJA8) are within the distal 1.35-Mb recurrent microdeletion, no single gene in which pathogenic variants are causative has been identified (see Molecular Genetics for genes of interest in the deleted region). Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA) or targeted deletion analysis by fluorescence in situ hybridization (FISH). Note: The 1q21.1 recurrent microdeletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques. * Chromosomal microarray (CMA) using oligonucleotide arrays or SNP genotyping arrays can detect the common deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 1q21.1 region. Note: (1) Most individuals with the 1q21.1 recurrent microdeletion are identified by CMA performed in the context of developmental delay, intellectual disability, or autism spectrum disorders. (2) Prior to 2008 many CMA platforms did not include coverage of the 1q21.1 region and thus may not have detected this deletion. * Targeted deletion analysis. FISH analysis, quantitative PCR (qPCR), multiplex ligation-dependent probe amplification (MLPA) or other targeted quantitative methods may be used to test relatives of a proband known to have the1q21.1 recurrent microdeletion. Note: (1) Targeted deletion testing is not appropriate for an individual in whom the 1q21.1 recurrent microdeletion was not detected by CMA designed to target this region. (2) It is not possible to size the deletion routinely by use of targeted methods. ### Table 1. Molecular Genetic Testing Used Detect the 1q21.1 Recurrent Microdeletion View in own window Deletion 1ISCA ID 2Region Location 3, 4MethodSensitivity ProbandAt-risk family member ~1.35-Mb heterozygous deletion at 1q21.1ISCA-37421GRCh38/hg38 chr1:147,105,904-147,922,392CMA 5100%100% Targeted deletion analysis 6Not applicable 6100% 1\. See Molecular Genetics for details of the deletion. 2\. Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays (ISCA) Consortium) 3\. Genomic coordinates represent the minimum deletion size associated with the 1q21.1 recurrent microdeletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the microdeletion as calculated from these genomic positions may differ from the expected deletion size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller microdeletions within this region may be clinically distinct from the 1q21.1 recurrent microdeletion (see Genetically Related Disorders). 4\. See Molecular Genetics for genes of interest included in this region. 5\. Chromosome microarray analysis (CMA) using oligonucleotide arrays or SNP genotyping arrays. CMA designs in current clinical use target the 1q21.1 region. Note: the 1q21.1 recurrent microdeletion may not have been detectable by older oligonucleotide or BAC platforms. 6\. Targeted deletion analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods. Targeted deletion analysis is not appropriate for an individual in whom the 1q21.1 recurrent microdeletion was not detected by CMA designed to target this region. Evaluating at-risk relatives. FISH, qPCR, or other quantitative methods of targeted deletion analysis can be used to identify the 1q21.1 recurrent microdeletion in at-risk relatives of the proband. Testing parental samples is important in determining recurrence risk (see Genetic Counseling). ## Clinical Characteristics ### Clinical Description Individuals with the 1q21.1 recurrent microdeletion may have a wide range of clinical manifestations. The most common findings include developmental delay and mildly dysmorphic facies. However, there is not a clinically recognizable syndrome, as a subset of persons with the deletion do not have obvious clinical findings. Clinical information from three reports involving 55 probands with the 1q21.1 recurrent microdeletion is summarized in Table 2 [Brunetti-Pierri et al 2008, Mefford et al 2008, Bernier et al 2015]. ### Table 2. Features Present in 55 Persons with the 1q21.1 Recurrent Microdeletion View in own window FrequencyFeatures >75%Variable/mild dysmorphic facial features 50%-75%Mild-moderate developmental delay (includes speech & motor delays) 25%-50% * Eye abnormalities * Intellectual disability * Microcephaly * Short stature 10%-25% * Attention-deficit/hyperactivity disorder * Cardiac abnormalities * Failure to thrive * Hypotonia * Seizures <10% * Autism/autistic features * Brain malformations * Genitourinary abnormalities * Sensorineural deafness Clinical data shown is summarized from 55 probands with the 1q21.1 recurrent microdeletion using chromosomal microarray [Mefford et al 2008, Brunetti-Pierri et al 2008, Bernier et al 2015]. The majority of persons with the 1q21.1 recurrent microdeletion have developmental delay. Most delays are mild and may involve global or specific areas, particularly gross motor development. Some may also have generalized learning disabilities throughout life. Mild intellectual and learning disabilities are seen in approximately 30% of affected individuals. Dysmorphic craniofacial features are a common finding but are highly variable and therefore not easily recognizable. The facial features may include frontal bossing, deep-set eyes, epicanthal folds, prominent and/or large nasal bridge with bulbous tip, long philtrum, and highly arched palate. Microcephaly is described in 39% of individuals with the 1q21.1 recurrent microdeletion. Eye abnormalities are seen in 33% of individuals and may include strabismus, chorioretinal and iris colobomas, microphthalmia, hypermetropia, Duane anomaly, and various types of cataracts (e.g., congenital, nuclear pulverulent). Several reported individuals with the 1q21.1 recurrent microdeletion have cardiac defects, including patent ductus arteriosus, truncus arteriosus, ventricular and atrial septal defects, tetralogy of Fallot, bicuspid aortic valve, dilation of ascending aorta, aortic insufficiency, coarctation of the aorta, interrupted aortic arch, anomalous origin of the right coronary artery, pulmonary valve stenosis, and transposition of the great vessels in individuals with 1q21.1 deletions [Digilio et al 2013]. Genitourinary anomalies include vesicoureteral reflux, hydronephrosis, inguinal hernia, and cryptorchidism. Two individuals with the deletion had Mayer-Rokitansky-Kuster-Hauser syndrome [Chen et al 2015]. Skeletal malformations are variable and include craniosynostosis, scoliosis, joint laxity, brachydactyly with or without short distal phalanges, broad thumbs, clinodactyly of the fifth finger, clubfoot, small feet, pes planus, broad or duplicated/bifid great toes, overlapping or syndactyly of the toes, and polydactyly of the hands or feet. Most affected individuals have a normal neurologic physical examination, but hypotonia and tremors are fairly common features. Seizures (e.g., tonic-clonic, absence) are seen in approximately 16% and often begin during the first year of life. Brain malformations that have been described include hydrocephalus and agenesis of the corpus callosum. Sensorineural hearing loss has been reported in five individuals. Psychiatric and behavioral abnormalities that may be present include autism spectrum disorders, attention deficit hyperactivity disorder, anxiety and mood disorders, and sleep disturbances. In addition, distal 1q21.1 microdeletions have been identified in 0.2%-0.6% of persons with schizophrenia [International Schizophrenia Consortium 2008, Stefansson et al 2008, Walsh et al 2008, Rees et al 2014]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations are observed in those with the 1q21.1 recurrent microdeletion. ### Penetrance Little information is available regarding penetrance of the 1q21.1 recurrent microdeletion. Similar to several other recurrent microdeletions (e.g., 16p11.2, 15q13.3), the 1q21.1 recurrent microdeletion can be inherited from a parent with minimally abnormal or completely normal clinical findings. In addition, several relatives of probands (e.g., sibs, cousins) with the same 1q21.1 microdeletion have a normal phenotype or only mild manifestations [Christiansen et al 2004; Shaffer et al 2006; Brunetti-Pierri et al 2008; Mefford et al 2008; Bernier et al 2015; Authors, personal observation]. This suggests that the 1q21.1 recurrent microdeletion has reduced penetrance and variable expressivity. ### Prevalence The frequency of the 1q21.1 recurrent microdeletion is approximately 0.2% (46/22,563) of individuals with developmental delays, intellectual disabilities, and/or congenital anomalies evaluated by CMA [Brunetti-Pierri et al 2008, Mefford et al 2008]. ## Differential Diagnosis The 22q11.2 microdeletion syndrome is the most common microdeletion syndrome and has several features that overlap with those seen in individuals with the 1q21.1 recurrent microdeletion: developmental delays, learning disabilities (though the predominant nonverbal learning disability seen in 22q11.2 microdeletions is not seen in the 1q21.1 recurrent microdeletion), intellectual disability, behavioral abnormalities, short stature, eye abnormalities, cardiac defects, and schizophrenia. However, persons with the recurrent 1q21.1 microdeletion do not have the typical facial characteristics seen in the 22q11.2 microdeletion syndrome. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with the 1q21.1 recurrent microdeletion, the following evaluations should be considered: * Ophthalmologic examination if there are concerns about vision * Cardiac evaluation if there are suggestive features clinically or on physical examination * Brain imaging if microcephaly, macrocephaly, and/or neurologic findings are present * Renal ultrasound examination * Comprehensive developmental assessment for motor and language delays, which may include evaluations for autism spectrum disorders, intellectual disability, ADHD, and hearing loss * Neurology consultation if significant hypotonia, seizures, tics, or tremors are present * Psychiatric evaluation if evidence of mental illness is present * Consultation with a medical geneticist and/or genetic counselor ### Treatment of Manifestations The following are indicated: * Routine treatment of ophthalmologic, cardiac, and neurologic findings * Speech, occupational, and physical therapies, as appropriate * Specialized learning programs to meet individual needs No specific antiepileptic or antipsychotic medications are indicated. ### Surveillance Appropriate surveillance includes the following: * Routine pediatric care * Routine developmental and learning assessments * Monitoring of any specific medical issues that are identified ### Evaluation of Relatives at Risk Using genomic testing that will detect the 1q21.1 recurrent microdeletion found in the proband, it is appropriate to evaluate the sibs of a proband in order to identify as early as possible those who would benefit from close assessment/monitoring of developmental milestones in childhood. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. 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	1q21.1 Recurrent Microdeletion	None	5,618	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK52787/	2021-01-18T20:46:33	{"synonyms": []}
## Description Progesterone prepares the endometrium for blastocyst implantation and allows maintenance of pregnancy. The major sources of progesterone are the corpus luteum during the second half of the menstrual cycle and at the beginning of pregnancy, and the placenta. The main hormones responsible for stimulation of progesterone secretion are luteinizing hormone (LH) for the corpus luteum of the menstrual cycle and chorionic gonadotropin for the corpus luteum of pregnancy. Complete end-organ resistance to progesterone would be incompatible with reproductive competence in females. Males would not be expected to be affected since progesterone has no known function in men. Failure of the uterus to respond to progesterone would lead to the development of a 'constantly proliferative' endometrium incompatible with blastocyst implantation. Partial resistance to progesterone, on the other hand, would be expected to be associated with various degrees of incomplete maturation of the endometrium, perhaps expressed clinically as infertility or early abortions. The syndrome would present with the clinical and histologic picture of a luteal phase defect in which the life span of the corpus luteum and the plasma progesterone concentrations would be normal or elevated. Clinical Features The first report of a well-studied patient with progesterone resistance was by Keller et al. (1979). Their patient was an infertile woman with a normal menstrual cycle, a normal luteal phase duration, and normal plasma immunoreactive LH and progesterone concentrations. The endometrium was histologically immature. A decreased concentration of endometrial progesterone receptors (PGR; 607311) on day 14 of the luteal phase of the menstrual cycle was suggested by the studies. Chrousos et al. (1986) stated that the patient of Keller et al. (1979) was the only one in whom progesterone receptors had been examined; however, a similar defect had been proposed in other patients. Compensated progesterone resistance due to reduced progesterone receptor concentrations has been found in female squirrel monkeys and other New World primate species (Chrousos et al., 1986). Molecular Genetics Although the progesterone resistance syndrome may be due to mutations in the progesterone receptor gene, Chrousos (2002) stated that none such had been identified to that time. GU \- Female infertility \- Normal menstrual cycle \- Normal luteal phase duration Lab \- Normal plasma immunoreactive LH and progesterone \- Histologically immature endometrium \- Decreased endometrial progesterone receptors 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	PROGESTERONE RESISTANCE	c1849699	5,619	omim	https://www.omim.org/entry/264080	2019-09-22T16:23:16	{"mesh": ["C564871"], "omim": ["264080"], "synonyms": ["Alternative titles", "PSEUDOCORPUS LUTEUM INSUFFICIENCY"]}
A rare genetic neurological disorder characterized by progressive spastic paraparesis and delayed gross motor development with an onset in infancy or early childhood. Patients also show variable degrees of intellectual disability, speech delay, and dysarthria. Other reported features include microcephaly, seizures, bifid uvula with or without cleft palate, and ocular anomalies. Brain imaging shows white matter abnormalities in the periventricular and other regions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Autosomal recessive complex spastic paraplegia due to Kennedy pathway dysfunction	None	5,620	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=506353	2021-01-23T17:02:27	{"omim": ["618768"], "synonyms": ["Autosomal recessive complex SPG due to Kennedy pathway dysfunction"]}
Disseminated superficial actinic porokeratosis (DSAP) is a skin condition that causes dry, scaly patches. It is characterized by a large number of small, brownish patches with a distinctive border, found most commonly on sun-exposed areas of the skin (particularly the lower arms and legs). DSAP usually starts during the third or fourth decade of life and rarely affects children. Lesions generally are more prominent in the summer and less prominent in the winter. While it is usually benign (not cancerous), squamous cell carcinoma or Bowen’s disease may occasionally develop within patches. DSAP may be inherited in an autosomal dominant matter or may occur sporadically (in people with no family history of DSAP). Some cases are caused by a change (mutation) in the MVK or SART3 genes. There is no standard treatment for DSAP, and treatment is generally not effective long-term. Sun avoidance may reduce the development of new patches. Treatments that have been beneficial in some people include topical imiquimod cream, topical 5-fluorouracil, and topical vitamin D analogs such as tacalcitol and calcipotriol. Other therapies that have been tested with varying results include cryotherapy, electrodessication (using electrical currents to remove patches), laser ablation, and photodynamic therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Disseminated superficial actinic porokeratosis	c0265970	5,621	gard	https://rarediseases.info.nih.gov/diseases/10983/disseminated-superficial-actinic-porokeratosis	2021-01-18T18:00:51	{"mesh": ["D017499"], "orphanet": ["79152"], "synonyms": ["DSAP"]}
Lipschütz ulcer One of the first published cases of Lipschütz ulcer[1] Lipschütz ulcer, ulcus vulvae acutum or reactive non-sexually related acute genital ulcers (English: acute ulceration of the vulva) is a rare disease characterized by painful genital ulcers, fever, and lymphadenopathy, occurring most commonly, but not exclusively, in adolescents and young women.[2] Previously, it was described as being more common in virgins.[3] It is not a sexually transmitted disease, and is often misdiagnosed,[4][5] sometimes as a symptom of Behçet's disease.[6] Lipschütz ulcer is named after Benjamin Lipschütz, who first described it in 1912.[1][5] The cause is still unknown, although it has been associated with several infectious causes, including paratyphoid fever, cytomegalovirus, Mycoplasma pneumoniae and Epstein-Barr virus infection[7][8][9][10] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 History * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The most common presentation is a single large, deep ulcer (although several smaller ulcers may occur) in the internal surface of one or both labia minora.[11] The labia majora may be affected, as may the vagina and urethra. The ulcer develops very quickly, and is usually preceded by sudden onset of fever and malaise.[11] ## Diagnosis[edit] The diagnosis is mainly clinical and centred in eliminating other more common causes for vulvar ulcers. Nevertheless, it has been proposed that Epstein-Barr detection using polymerase chain reaction for virus genome can help to reach sooner a diagnosis.[7] ## Treatment[edit] Treatment is symptomatic, and usually of little value; in most cases, the ulcer heals spontaneously within four to six weeks, sometimes leaving scars. Topical analgesics and anesthetics, as well as topical application of disinfectants/astringents such as potassium permanganate (in sitz baths), is commonly used.[11] In severe cases, a combination of systemic glucocorticoids and broad-spectrum antibiotics has been recommended. ## Epidemiology[edit] The disorder typically appears among young girls and adolescents but cases in children as young as 17 months have been reported.[7] ## History[edit] The disease was first described in October 1912 by Galician-born Austrian dermatologist and microbiologist Benjamin Lipschütz, who published a series of four cases in girls aged 14 to 17.[1] He initially ascribed the ulcer to infection with "Bacillus crassus" (Lactobacillus acidophilus).[1][5] ## See also[edit] * Vulvovaginal health ## References[edit] 1. ^ a b c d Lipschütz B (October 1912). "Über eine eigenartige Geschwürsform des weiblichen Genitales (Ulcus vulvae acutum)". Arch Dermatol Res (in German). 114 (1): 363–96. doi:10.1007/BF01973166. S2CID 11890180. 2. ^ Vieira-Baptista, Pedro; Lima-Silva, Joana; Beires, Jorge; Martinez-de-Oliveira, José (2016-03-01). "Lipschütz ulcers: should we rethink this? An analysis of 33 cases". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 198: 149–152. doi:10.1016/j.ejogrb.2015.07.016. ISSN 1872-7654. PMID 26297242. 3. ^ Török L, Domján K, Faragó E (2000). "Ulcus vulvae acutum". Acta Dermatovenereologica Alpina, Pannonia et Adriatica. 9 (1). ISSN 1581-2979. 4. ^ Kluger N, Garcia C, Guillot B (October 2009). "[Lipschütz acute genital ulcer]". J Gynecol Obstet Biol Reprod (Paris) (in French). 38 (6): 528–30. doi:10.1016/j.jgyn.2009.08.005. PMID 19744804. 5. ^ a b c Lipschütz' ulcer at Who Named It? Retrieved on 2009-12-04. 6. ^ Braun-Falco O, Plewig G, Wolff HH, Burgdorf WH, Landthaler M, eds. (2005). "Erkrankungen des weiblichen Genitales". Dermatologie und Venereologie (in German). Berlin: Springer. p. 1030. ISBN 978-3-540-40525-2. 7. ^ a b c Burguete Archel E, Ruiz Goikoetxea M, Recari Elizalde E, Beristain Rementería X, Gómez Gómez L, Iceta Lizarraga A (May 2013). "Lipschütz ulcer in a 17-month-old girl: a rare manifestation of Epstein-Barr primoinfection". Eur. J. Pediatr. 172 (8): 1121–3. doi:10.1007/s00431-013-2013-8. PMID 23636284. S2CID 189872655. 8. ^ Pelletier F, Aubin F, Puzenat E, et al. (2003). "Lipschütz genital ulceration: a rare manifestation of paratyphoid fever". Eur J Dermatol. 13 (3): 297–8. PMID 12804994. 9. ^ Martín JM, Godoy R, Calduch L, Villalon G, Jordá E (2008). "Lipschütz acute vulval ulcers associated with primary cytomegalovirus infection". Pediatr Dermatol. 25 (1): 113–5. doi:10.1111/j.1525-1470.2007.00597.x. PMID 18304169. 10. ^ Vieira-Baptista, Pedro; Machado, Luísa; Costa, Ana Rosa; Beires, Jorge; Martinez-de-Oliveira, José (2013-07-01). "Mycoplasma pneumoniae: a rare cause of vulvar ulcers or an undiagnosed one?". Journal of Lower Genital Tract Disease. 17 (3): 330–334. doi:10.1097/LGT.0b013e3182710896. ISSN 1526-0976. PMID 23486069. S2CID 145823. 11. ^ a b c Heller DS, Wallach RC (2007). Vulvar disease: a clinicopathological approach. Informa Healthcare. pp. 51–2. ISBN 978-0-8493-3793-2. ## External links[edit] Classification D * ICD-9-CM: 616.50 * v * t * e Female diseases of the pelvis and genitals Internal Adnexa Ovary * Endometriosis of ovary * Female infertility * Anovulation * Poor ovarian reserve * Mittelschmerz * Oophoritis * Ovarian apoplexy * Ovarian cyst * Corpus luteum cyst * Follicular cyst of ovary * Theca lutein cyst * Ovarian hyperstimulation syndrome * Ovarian torsion Fallopian tube * Female infertility * Fallopian tube obstruction * Hematosalpinx * Hydrosalpinx * Salpingitis Uterus Endometrium * Asherman's syndrome * Dysfunctional uterine bleeding * Endometrial hyperplasia * Endometrial polyp * Endometriosis * Endometritis Menstruation * Flow * Amenorrhoea * Hypomenorrhea * Oligomenorrhea * Pain * Dysmenorrhea * PMS * Timing * Menometrorrhagia * Menorrhagia * Metrorrhagia * Female infertility * Recurrent miscarriage Myometrium * Adenomyosis Parametrium * Parametritis Cervix * Cervical dysplasia * Cervical incompetence * Cervical polyp * Cervicitis * Female infertility * Cervical stenosis * Nabothian cyst General * Hematometra / Pyometra * Retroverted uterus Vagina * Hematocolpos / Hydrocolpos * Leukorrhea / Vaginal discharge * Vaginitis * Atrophic vaginitis * Bacterial vaginosis * Candidal vulvovaginitis * Hydrocolpos Sexual dysfunction * Dyspareunia * Hypoactive sexual desire disorder * Sexual arousal disorder * Vaginismus * Urogenital fistulas * Ureterovaginal * Vesicovaginal * Obstetric fistula * Rectovaginal fistula * Prolapse * Cystocele * Enterocele * Rectocele * Sigmoidocele * Urethrocele * Vaginal bleeding * Postcoital bleeding Other / general * Pelvic congestion syndrome * Pelvic inflammatory disease External Vulva * Bartholin's cyst * Kraurosis vulvae * Vestibular papillomatosis * Vulvitis * Vulvodynia Clitoral hood or clitoris * Persistent genital arousal disorder [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Lipschütz ulcer	c0276086	5,622	wikipedia	https://en.wikipedia.org/wiki/Lipsch%C3%BCtz_ulcer	2021-01-18T18:28:09	{"icd-9": ["616.50"], "wikidata": ["Q6557016"]}
## Description Hydroa vacciniforme (HV) is a rare photodermatosis characterized by acute vesiculation and crusting and scarring following sun exposure (Gupta et al., 1999). Clinical Features Hydroa vacciniforme is usually sporadic, with onset in childhood The eruption tends to be worse during the spring and summer months, with lesions appearing in a sun-exposed distribution, especially the malar areas, bridge of the nose, lips, ears, and dorsa of the hands and forearms. Patients usually develop an itchy, stinging, erythematous rash 15 minutes to 24 hours after sun exposure, progressing to tender papules, which undergo vesiculation and form crusts. Healing occurs in 1 to 6 weeks with fine varioliform scars. In severe cases, the subject may show fever, malaise, and ocular signs such as conjunctival involvement, photophobia, lacrimation, and even corneal ulceration and scarring. The disorder usually remits spontaneously during adolescence but may persist into adult life in rare cases (Sonnex and Hawk, 1988; summary by Gupta et al., 1999). Although the pathogenesis of HV is unknown, repeated exposure of patients to artificial ultraviolet (UV) A is known to produce symptoms followed by the development of lesions that are clinically and histologically indistinguishable from those produced by sun exposure (Eramo et al., 1986). The major differential diagnosis of this disorder includes erythropoietic protoporphyria (177000), hereditary polymorphic light eruption (174770), Hartnup disease (234500), and some forms of xeroderma pigmentosum (see 278700) (Gupta et al., 1999). Inheritance Gupta et al. (1999) described the disorder in a 7-year-old boy and his 6-year-old sister. The father was said to have been similarly affected but was unavailable for study. The mother had no photodermatosis. Gupta et al. (1999) cited a previous report of 3 affected sibs (Annamalai, 1971). History Hydroa vacciniforme was first described by Bazin (1862). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	HYDROA VACCINIFORME, FAMILIAL	c1863533	5,623	omim	https://www.omim.org/entry/603794	2019-09-22T16:12:40	{"mesh": ["C536077"], "omim": ["603794"]}
The association of mesomelic shortness of the upper limbs (mainly due to hypoplastic ulna), clubfeet, and anonychia congenita was described by Kohn et al. (1989, 1995) in 2 males born of an inbred Arab couple. Lower limbs showed limitation of movement at the knees, severe varus deformity, and absence of all toenails. The arms showed limitation of movement at the elbows and absence of all fingernails. One child, who was severely mentally retarded, died at the age of 3 years; the other child died at age 6 months. Ultrasound examination during the next pregnancy revealed a fetus with bilaterally short forearms. The pregnancy was terminated, and a female fetus with similar malformations was delivered. Autopsy showed no internal anomalies. Kohn et al. (1995) suggested that this association is a 'new' syndrome with autosomal recessive inheritance. Joints \- Limited knee movement \- Severe varus deformity \- Limited elbow movement Limbs \- Bilateral symmetrical ulnar hypoplasia \- Clubfoot Neuro \- Profound mental retardation Nails \- Absent toenails \- Absent fingernails 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	ULNAR HYPOPLASIA WITH MENTAL RETARDATION	c1848650	5,624	omim	https://www.omim.org/entry/276821	2019-09-22T16:21:26	{"mesh": ["C564757"], "omim": ["276821"], "orphanet": ["2249"], "synonyms": ["Alternative titles", "MESOMELIA OF THE UPPER LIMBS, ANONYCHIA CONGENITA, CLUBFEET, AND MENTAL RETARDATION"]}
A number sign (#) is used with this entry because of evidence that pontocerebellar hypoplasia type 2E (PCH2E) is caused by compound heterozygous mutation in the VPS53 gene (615850) on chromosome 17p13. Description Pontocerebellar hypoplasia type 2E is an autosomal recessive neurodegenerative disorder characterized by profound mental retardation, progressive microcephaly, spasticity, and early-onset epilepsy (summary by Feinstein et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470). Clinical Features Feinstein et al. (2014) reported 10 individuals from 4 nonconsanguineous families of Jewish Moroccan descent with a severe neurodevelopmental disorder. Two of the families had previously been reported by Ben-Zeev et al. (2003). The patients were noted to have mild hypotonia and irritability in the first months of life, but psychomotor retardation did not become apparent until 3 to 5 months of age. The patients had normal head circumference at birth, but showed progressive deceleration, resulting in microcephaly by age 18 months. All developed progressive spastic quadriplegia with opisthotonic posturing and severe multifocal contractures. Generalized and myoclonic seizures began around ages 2 to 2.5 years. Other features included a sleep disorder, short stature, osteoporosis, and scoliosis. Brain imaging showed progressive diffuse cerebellar atrophy as early as 11 months of age, followed by cerebral atrophy and thin corpus callosum. All had profound mental retardation and gained almost no developmental milestones except visual tracking and smiling. Inheritance The transmission pattern of PCH2E in the families reported by Feinstein et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In 10 affected individuals from 4 nonconsanguineous families of Jewish Moroccan descent with pontocerebellar hypoplasia, Feinstein et al. (2014) identified compound heterozygous mutations in the VPS53 gene (615850.0001 and 615850.0002). The mutations were found using a combination of genomewide linkage analysis and whole-exome sequencing. Patient fibroblasts showed CD63 (155740)-positive swollen vesicles, suggesting disruption of the Golgi-associated retrograde protein (GARP) complex, but the patients had no evidence of a lysosomal storage disorder. There was a carrier frequency of 1 in 37 for each of the mutations in the local control Jewish Moroccan population, consistent with a founder effect. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly, progressive SKELETAL \- Joint contractures \- Osteoporosis Spine \- Scoliosis MUSCLE, SOFT TISSUES \- Hypotonia, neonatal NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Lack of developmental milestones \- Mental retardation, profound \- Irritability \- Seizures \- Spastic quadriplegia, progressive \- Opisthotonus \- Cerebellar atrophy, progressive \- Cerebral atrophy, progressive \- Thin corpus callosum MISCELLANEOUS \- Onset in infancy \- Progressive disorder \- Reported in individuals of Jewish Moroccan ancestry MOLECULAR BASIS \- Caused by mutation in the homolog of the S. cerevisiae vacuolar protein sorting 53 gene (VPS53, 615850.0001 ) ▲ 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	PONTOCEREBELLAR HYPOPLASIA, TYPE 2E	c4014488	5,625	omim	https://www.omim.org/entry/615851	2019-09-22T15:50:49	{"doid": ["0060271"], "omim": ["615851"], "orphanet": ["247198"], "synonyms": ["PCCA"]}
A sialocele is a localized, subcutaneous cavity containing saliva.[1][2] It is caused by trauma (e.g. violence, accident or surgery) or infection.[1] They most commonly develop about 8–14 days after injury.[3] They are a relatively common complication following surgery to the salivary glands,[4] commonly parotidectomy (removal of the parotid gland).[5] In this case the sialocele is the result of saliva draining out of remaining parotid tissue, and occurs about 5 to 10% of cases of superficial (partial) parotidectomy.[5][6] It is usually not painful,[6] and a mild and self-limiting complication,[5] and is managed by repeated aspiration (draining) of the swelling via a needle after the skin has been disinfected with an antibacterial.[5][6] The fluid is usually a clear yellow, and contains amylase (in contrast to fluid from a seroma).[6] Pressure dressings do not tend to be used.[6] They are rarely chronic, however if persistent a surgical drain may be required.[6] Botulinum toxin injections have also been used to manage this condition.[3] ## See also[edit] * Mucocele * Ranula ## References[edit] 1. ^ a b Araujo, MR; Centurion, BS; Albuquerque, DF; Marchesano, LH; Damante, JH (Jul–Aug 2010). "Management of a parotid sialocele in a young patient: case report and literature review". Journal of Applied Oral Science. 18 (4): 432–6. doi:10.1590/s1678-77572010000400019. PMC 5349079. PMID 20835582. 2. ^ Hupp JR, Ellis E, Tucker MR (2008). Contemporary oral and maxillofacial surgery (5th ed.). St. Louis, Mo.: Mosby Elsevier. p. 417. ISBN 9780323049030. 3. ^ a b Carlson E; Ord R (16 March 2009). Textbook and Color Atlas of Salivary Gland Pathology: Diagnosis and Management. John Wiley & Sons. p. 290. ISBN 978-0-8138-0652-5. 4. ^ Capaccio, P; Paglia, M; Minorati, D; Manzo, R; Ottaviani, F (July 2004). "Diagnosis and therapeutic management of iatrogenic parotid sialocele". Annals of Otology, Rhinology, and Laryngology. 113 (7): 562–4. doi:10.1177/000348940411300709. PMID 15274417. 5. ^ a b c d Myers EN; Ferris RL (14 August 2007). Salivary Gland Disorders. Springer Science & Business Media. p. 244. ISBN 978-3-540-47072-4. 6. ^ a b c d e f Eisele D; Smith RV (31 October 2008). Complications in Head and Neck Surgery. Elsevier Health Sciences. ISBN 978-1-4377-1963-5. * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Sialocele	c0026686	5,626	wikipedia	https://en.wikipedia.org/wiki/Sialocele	2021-01-18T18:47:46	{"umls": ["C0026686"], "wikidata": ["Q17000199"]}
For a phenotypic description and a discussion of genetic heterogeneity of susceptibility loci for dyslexia, see DYX1 (127700). Mapping Using genomewide parametric linkage analysis in a large Dutch family recruited for a linkage study of dyslexia through an advertisement campaign in newspapers and magazines, de Kovel et al. (2004) found evidence for a dyslexia susceptibility locus on Xq27.3 (multipoint lod score = 3.68 at theta = 0 for marker DXS8043), close to a locus described by Fisher et al. (2002). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	DYSLEXIA, SUSCEPTIBILITY TO, 9	c1845296	5,627	omim	https://www.omim.org/entry/300509	2019-09-22T16:20:09	{"omim": ["300509"]}
A number sign (#) is used with this entry because of evidence that type II primary hyperoxaluria (HP2) is caused by homozygous or compound heterozygous mutation in the glyoxylate reductase/hydroxypyruvate reductase gene (GRHPR; 604296) on chromosome 9p13. For a discussion of genetic heterogeneity of primary hyperoxaluria, see 259900. Clinical Features Seargeant et al. (1991) reported 8 HP2 patients who belonged to 3 Saulteaux-Ojibway Canadian Indian families living in 2 isolated communities in northwestern Ontario. All had increased urinary oxalic acid and L-glyceric acid. Four patients presented with symptoms resulting from calcium oxalate nephrolithiasis, including dysuria, hematuria, and urinary tract infections in infancy or early childhood; 3 did not have recurrences. The other 4 affected patients were free of symptoms, suggesting that HP2 may be a much milder disease with a better long-term prognosis for renal function than HP1 (259900). Seargeant et al. (1991) noted that 7 of 8 previously reported patients (Williams and Smith, 1968 and Chalmers et al., 1984) had renal calculi between 18 months and 24 years of age. One patient seemed to have had no symptoms and was identified only because his younger brother had the disorder (Chalmers et al., 1984). Kemper et al. (1997) stated that only 24 patients with primary hyperoxaluria type II had been reported, and noted that the disorder should be considered in any patient presenting with urolithiasis or nephrocalcinosis due to hyperoxaluria. The metabolic defect is deficiency of D-glycerate dehydrogenase/glyoxylate reductase leading to characteristic hyperoxaluria and excretion of L-glycerate, the cornerstone of diagnosis of this form of primary hyperoxaluria. Although development of terminal renal failure may be less common than in type I primary hyperoxaluria, chronic as well as terminal renal insufficiency has been described. Therefore, specific therapeutic measures should aim at reduction of urinary calcium oxalate saturation by potassium citrate or pyrophosphate to reduce the incidence of nephrolithiasis and nephrocalcinosis and thus improve renal survival. Secondary complications (obstruction, urinary tract infections, and pyelonephritis) must be avoided. In patients with terminal renal failure, renal transplantation seems to carry a high risk of disease recurrence. Takayama et al. (2014) reported 4 Japanese patients with HP2. The patients developed symptoms of hematuria or urinary tract infection between 10 months and 3 years of age. All developed stones in the kidney or bladder, but only 1 patient showed renal parenchymal calcifications. Laboratory studies showed increased urinary oxalate and L-glycerate. All patients had normal renal function at follow-up between 7 and 25 years of age. Biochemical Features Williams and Smith (1971) presented evidence that in HP2, hydroxypyruvate, present in excess because of deficiency in the enzyme that converts it to D-glycerate, stimulates oxidation of glycolate to oxalate, and decreases reduction of glyoxylate to glycolate. This is a novel explanation for the phenotypic consequences of a garrodian inborn error of metabolism. Van Schaftingen et al. (1989) presented evidence that D-glycerate dehydrogenase should be considered an NADPH-linked reductase. This property accounts for the function of the enzyme, which is to maintain the cytosolic concentration of hydroxypyruvate and glyoxylate at a very low level, thus preventing the formation of oxalate. In patients with HP2, Seargeant et al. (1991) demonstrated combined deficiencies of D-glycerate dehydrogenase and glyoxylate reductase, which are attributable to a single enzyme. Deficiency of D-glycerate dehydrogenase activity presumably causes accumulation of its substrate, hydroxypyruvate, which is then converted to L-glycerate by the action of L-lactate dehydrogenase. Deficiency of glyoxylate reductase activity presumably causes impaired conversion of glyoxylate to glycolate. Conversion of glyoxylate to oxalate by L-lactate dehydrogenase would explain the observed hyperoxaluria. Inheritance The transmission pattern of HP2 in the families reported by Takayama et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics Cramer et al. (1999) found homozygosity for an identical mutation in the GRHPR gene (604296.0001) in 2 pairs of sibs from unrelated families with type II primary hyperoxaluria. Webster et al. (2000) identified 5 other mutations in patients with type II hyperoxaluria. Ten of 11 patients that they had genotyped were homozygous for 1 of the 6 known mutations. In the case of two-thirds of the patients, the parents were related. Genotyping also showed the possible presence of a founder effect for the 2 most common mutations: 103delG and R99X (604296.0002). In 4 Japanese patients with HP2, Takayama et al. (2014) identified homozygous or compound heterozygous mutations in the GRHPR gene (604296.0003-604296.0005). Three of the patients were homozygous for the same mutation (c.864delTG; 604296.0003). Population Genetics Takayama et al. (2014) found the GRHPR c.103delG mutation (604296.0001) only in Caucasian patients of northern European or American origin, and the c.864delTG mutation (604296.0003) only in patients of Japanese or Chinese origin. INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Calcium oxalate urolithiasis \- Nephrocalcinosis \- Hematuria \- Renal failure (in some patients) LABORATORY ABNORMALITIES \- Increased urinary oxylate \- Increased urinary L-glycerate \- Decreased GRHPR activity MISCELLANEOUS \- Onset usually in infancy or early childhood \- Variable severity \- Some patients may be asymptomatic MOLECULAR BASIS \- Caused by mutation in the glyoxylate reductase/hydroxypyruvate reductase gene (GRHPR, 604296.0001 ) ▲ 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	HYPEROXALURIA, PRIMARY, TYPE II	c0268165	5,628	omim	https://www.omim.org/entry/260000	2019-09-22T16:23:48	{"doid": ["2977"], "mesh": ["C536415"], "omim": ["260000"], "orphanet": ["93599", "416"], "synonyms": ["Alternative titles", "OXALOSIS II", "GLYCERIC ACIDURIA", "GLYOXYLATE REDUCTASE/HYDROXYPYRUVATE REDUCTASE DEFICIENCY", "D-GLYCERATE DEHYDROGENASE DEFICIENCY"], "genereviews": ["NBK2692"]}
MiT family translocation renal cell carcinoma (t-RCC) is a rare subtype of renal cell carcinoma with recurrent genetic abnormalities, harboring rearrangements of the TFE3 (Xp11 t-RCC) or TFEB [t(6;11) t-RCC] genes. The t(6;11) t-RCC has distinctive histologic features of biphasic appearance with larger epitheloid and smaller eosinophilic cells. The symptoms are usually non-specific and include hematuria, flank pain, palpable abdominal mass and/or systemic symptoms of anemia, fatigue and fever. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	MiT family translocation renal cell carcinoma	c3275446	5,629	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319308	2021-01-23T18:50:15	{"omim": ["300854"], "icd-10": ["C64"], "synonyms": ["Carcinoma associated with MITF/TFE translocation", "Translocation renal cell carcinoma"]}
A number sign (#) is used with this entry because of evidence that paragangliomas-6 (PGL6) is caused by heterozygous germline mutation in the SLC25A11 gene (604165) on chromosome 17p13. Description Paragangliomas-6 (PGL6) is an adult-onset tumor predisposition syndrome in which affected individuals develop neuroendocrine neoplasms, known as paragangliomas. Many tumors arise in the abdomen, although some may arise in other regions, including the head and neck. Some of the tumors may secrete biologically active normetanephrines, resulting in secondary hypertension. Tumors may be benign or malignant, and some may metastasize (summary by Buffet et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of familial paragangliomas, see PGL1 (168000). Clinical Features Buffet et al. (2018) reported 7 unrelated patients with onset of paragangliomas (PGL) between 32 and 87 years of age. All but 1 patient had abdominal PGLs; 1 patient had a head-and-neck PGL (in the carotid body). Five of the 7 patients had tumors that secreted normetanephrines and catecholamines, and all of these patients also had metastatic disease. Those with secreting tumors tended to have arterial hypertension and other associated features, such as palpitations, headaches, or sweating. One patient had a significant paternal family history of various types of cancers, but details and tissues from these patients were not available. None of the other 6 patients had a family history of PGL. Molecular Genetics In a patient with PGL6, Buffet et al. (2018) identified a germline heterozygous missense mutation in the SLC25A11 gene (P239T; 604165.0001). The mutation, which was found by whole-genome sequencing, was confirmed by Sanger sequencing. Tumor tissue derived from the patient showed homozygosity for the mutation. Subsequent direct Sanger sequencing of the SLC25A11 gene in 639 patients with paragangliomas, in whom mutations in other known PGL-associated genes had been excluded, identified 6 patients with germline heterozygous SLC25A11 mutations (e.g., 604165.0002-604165.0005). Mutation types included missense, splice site, frameshift, and a silent change; none were found in the dbSNP or ExAC databases. The missense mutations affected highly conserved residues in the signature protein sequence or alpha matrix helix. Five of the 7 patients had metastatic disease. Available tumor tissue derived from the patients showed loss of heterozygosity (LOH) for SLC25A11. Immunohistochemical studies of the tumor tissue showed absence of the SLC25A11 protein and hypermethylation of DNA and histones compared to controls. Knockdown of the Slc25a11 gene in immortalized mouse chromaffin cells resulted in a hypermethylated and pseudohypoxic phenotype, and the cells showed increased adhesion and migration compared to controls, suggesting the acquisition of metastatic properties. These defects could be rescued by wildtype Slc25a11. The cells also showed lower levels of 2-oxoglutarate compared to controls, and treatment with 2-oxoglutarate reversed the migratory phenotype. Succinate levels were normal in these cells and in patient tumor cells, but aspartate and glutamate were increased. Buffet et al. (2018) noted that somatic mutations or copy-number alterations affecting the SLC25A11 gene have been identified in various types of cancer, suggesting that SLC25A11 can act as a tumor-suppressor gene. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Hypertension NEOPLASIA \- Paragangliomas LABORATORY ABNORMALITIES \- Increased catecholamines (in some patients) MISCELLANEOUS \- Adult-onset (range 32 to 87 years) \- High risk for metastatic disease MOLECULAR BASIS \- Caused by mutation in the solute carrier family 25 (mitochondrial carrier, oxoglutarate carrier), member 11 gene (SLC25A11, 604165.0001 ) ▲ 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	PARAGANGLIOMAS 6	None	5,630	omim	https://www.omim.org/entry/618464	2019-09-22T15:41:46	{"omim": ["618464"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant familial hypercholesterolemia-2 (FCHL2) is caused by heterozygous mutation in the APOB gene (107730) on chromosome 2p24. Clinical Features Higgins et al. (1975) described father and daughter with hypercholesterolemia which appeared to be due to an abnormality in LDL such that it did not interact properly with the receptor. The proband's leukocytes showed normal suppression of HMG CoA reductase activity when exposed to lipoprotein from sources other than the 2 patients. Vega and Grundy (1986) showed that some patients with hypercholesterolemia have reduced clearance of LDL not because of decreased activity of LDL receptors but because of a defect in the structure (or composition) of LDL that reduces its affinity for receptors. In 5 of 15 patients, turnover rates indicated that clearance of autologous LDL was significantly lower than for homologous normal LDL. In these 5 patients, autologous LDL appeared to be a poor ligand for LDL receptors. The authors did not carry the investigations far enough to determine whether abnormality in the primary structure of apoB100 accounted for the poor binding to receptors. Innerarity et al. (1987) found that moderate hypercholesterolemia could be attributed to defective receptor binding of a genetically altered apoB100 to the LDL receptor; they designated the disorder 'familial defective apolipoprotein B100.' The proband of the family studied by Innerarity et al. (1987) was described earlier by Vega and Grundy (1986). A finding of the same abnormality in several of the proband's first-degree relatives indicated the inherited nature of the defect. Weisgraber et al. (1988) found an antibody with an isotope between residues 3350 and 3506 of apoB that distinguished abnormal LDL from normal LDL in this disorder; the antibody MB47 bound with a higher affinity to abnormal LDL. Thus, an assay was provided for screening large populations for this disorder. Goldstein (1987) stated that an abnormality in LDL was not confirmed in his or in a second laboratory. The putatively abnormal LDL tested normal in all of their culture systems and also tested normal when injected into animals. Myant et al. (1976) found that the putatively abnormal LDL behaved in a normal fashion in various in vivo and in vitro assays. Goldstein (1987) stated further that although no documented cases of hypercholesterolemia due to mutations in the apoB gene were known, he 'would not be surprised if such cases were discovered any time--now that cDNA probes for the apoB of LDL are widely available.' The prophecy was fulfilled by the demonstration of familial hypercholesterolemia due to defective apoB-100. Illingworth et al. (1992) found that LDL cholesterol was reduced after administration of lovastatin in 12 hypercholesterolemic patients from 10 unrelated families with familial defective apoB100. Hansen et al. (1997) attempted to identify determinants of phenotypic variation in patients heterozygous for familial defective apolipoprotein B in 205 patients: 73 from Germany, 87 from the Netherlands, and 45 from Denmark. In addition, they attempted to assess whether the clinical phenotype of familial defective apoB differs from that of familial hypercholesterolemia. Besides age, sex, and geographic origin, variation in the LDLR gene was found to be the most powerful determinant of variation in total cholesterol and LDL cholesterol levels. Polymorphic variation in the LDLR gene was associated with total cholesterol and LDL variation in women. The expected association of APOE genotypes with cholesterol concentrations was also seen. With regard to clinical expression, familial defective APOB patients had lower total cholesterol and LDL cholesterol levels and a lower prevalence of cardiovascular disease than did 101 Danish patients with familial hypercholesterolemia. Molecular Genetics Goldstein and Brown (1974) showed that the classic form of familial hypercholesterolemia (143890) results from defects in the cell surface receptor that removes LDL particles from plasma (LDLR; 606945). Innerarity et al. (1987) demonstrated the genetic heterogeneity of autosomal dominant hypercholesterolemia by reporting hypercholesterolemic patients with normal LDLR activity and defective apolipoprotein B-100 (APOB; 107730) that displayed low affinity for its receptor. This novel form of the disorder was called familial ligand-defective apolipoprotein B-100, or type B familial hypercholesterolemia, because mutations were identified in the APOB gene (e.g., R3500Q; 107730.0009). Classic FH and the ligand-defective form (type B) map to chromosomes 19 and 2, respectively. In a 46-year-old woman of Celtic and Native American ancestry with primary hypercholesterolemia and pronounced peripheral vascular disease, Pullinger et al. (1995) identified heterozygosity for a missense mutation in the APOB gene (R3531C; 107730.0017). Screening of 1,560 individuals revealed an unrelated man of Italian ancestry with coronary heart disease and elevated triglyceride and LDL cholesterol levels who carried the same R3531C mutation; the mutation was also detected in 8 other members of the families of the 2 patients. LDL from R3531C-positive individuals had an affinity for the LDL receptor that was 63% of that of control LDL, compared to 91% for unaffected family members and 36% for patients heterozygous for the R3500Q mutation (107730.0009). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Corneal arcus \- Xanthelasma CARDIOVASCULAR Heart \- Coronary artery disease SKIN, NAILS, & HAIR Skin \- Tendinous xanthomas \- Planar xanthomas (in homozygotes) LABORATORY ABNORMALITIES \- Hypercholesterolemia \- Abnormal LDL MOLECULAR BASIS \- Caused by mutation in the apolipoprotein B gene (APOB, 107730.0001 ) ▲ 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	HYPERCHOLESTEROLEMIA, FAMILIAL, 2	c1704417	5,631	omim	https://www.omim.org/entry/144010	2019-09-22T16:40:01	{"mesh": ["D006938"], "omim": ["144010"], "icd-10": ["E78.2"], "synonyms": ["Alternative titles", "HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, TYPE B", "APOLIPOPROTEIN B-100, FAMILIAL LIGAND-DEFECTIVE", "HYPERCHOLESTEROLEMIA, FAMILIAL, DUE TO LIGAND-DEFECTIVE APOLIPOPROTEIN B", "APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE"], "genereviews": ["NBK174884"]}
A number sign (#) is used with this entry because the disorder is caused by mutation in the COX4I2 gene (607976). Clinical Features Shteyer et al. (2009) reported 3 brothers from a consanguineous Arab Muslim family with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis. They presented with steatorrhea, failure to thrive, and anemia soon after birth. Supplementation with pancreatic enzymes improved the steatorrhea, but growth was not normal until about 4 years of age. Red blood cell transfusions improved the anemia in 2 patients, but not in the third, who developed hepatosplenomegaly and episodic jaundice associated with mild indirect hyperbilirubinemia. He also improved by 4 years of age. All 3 brothers had a large, box-shaped skull with a bony groove between the frontal and occipital fontanelles. Other features included a localized scaly skin rash over the perineum, small hyperpigmented lesions, bronchial asthma, maldentition, and severe dental caries. A skeletal survey showed delayed bone age and osteopenia. Two girls from another consanguineous Arab Muslim family had a similar disorder with slightly variable features. One girl had failure to thrive, pancreatic exocrine insufficiency, and anemia, but not calvarial hyperostosis or skin rash. She had had delayed psychomotor development, which improved with pancreatic enzyme supplementation. The other girl had anemia, hepatosplenomegaly, a box-shaped skull, and failure to thrive, but her stools were of normal consistency with no evidence of a coagulopathy. CT scan showed pancreatic atrophy with massive fatty infiltration. She also had allergic rhinitis and severe asthma and was easily fatigued. Speech and comprehension were age appropriate, but she was doing poorly at school. Two additional infants from this family had died with severe jaundice, anemia, and hepatosplenomegaly. Bone marrow biopsies from all affected individuals showed erythroid hyperplasia with megaloblastic change and bi- and multi-nucleated red cell precursors, consistent with dyserythropoietic anemia. Glucose-tolerance tests were normal. Molecular Genetics In 5 affected individuals from 2 Arab Muslim families with pancreatic exocrine insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, Shteyer et al. (2009) identified a homozygous mutation in the COX4I2 gene (607976.0001). INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive \- Poor growth due to malnutrition HEAD & NECK Nose \- Allergic rhinitis Teeth \- Maldentition \- Dental caries RESPIRATORY Airways \- Asthma ABDOMEN Liver \- Hepatomegaly Pancreas \- Pancreatic exocrine deficiency \- Pancreatic atrophy \- Fatty infiltration of the pancreas Spleen \- Splenomegaly Gastrointestinal \- Steatorrhea SKELETAL \- Osteopenia \- Delayed bone age Skull \- Calvarial hyperostosis \- Large box-shaped skull \- Thickened parietal bones SKIN, NAILS, & HAIR Skin \- Scaly skin rash over the perineum \- Hyperpigmented lesions, 0.2-0.5 cm \- Jaundice NEUROLOGIC Central Nervous System \- Delayed psychomotor development, mild (in 3 of 5 patients) \- Difficulties in school HEMATOLOGY \- Dyserythropoietic anemia \- Impaired coagulation due to malnutrition MISCELLANEOUS \- Onset in infancy \- Five patients reported (as of March 2009) MOLECULAR BASIS \- Caused by mutation in the cytochrome c oxidase, subunit IV, isoform 2 gene (COX4I2, 607976.0001 ) ▲ 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	EXOCRINE PANCREATIC INSUFFICIENCY, DYSERYTHROPOIETIC ANEMIA, AND CALVARIAL HYPEROSTOSIS	c2675184	5,632	omim	https://www.omim.org/entry/612714	2019-09-22T16:00:43	{"mesh": ["C567195"], "omim": ["612714"], "orphanet": ["199337"]}
An accessory toenail on a right foot The accessory nail of the fifth toe is a physical trait of the small toe, where a minuscule "sixth toenail" is present in the outer corner of the nail situated on the smallest toe. ## Contents * 1 Trait * 2 Removal * 3 Legend * 4 See also * 5 References ## Trait[edit] The trait can be observed on either one or both feet, where there is a separation of the toenail situated on the smallest toe. The separated part of the nail forms a smaller "sixth toenail" on the corner of the larger, or "main" section of the toenail, on the outermost side of the foot, which protrudes outwards from the corner of the larger nail. The additional "nail" can be cut with a nail clipper, just like any other nail. ## Removal[edit] Many people do not request or seek out removal, as the accessory nail typically does not cause symptoms.[1] Surgical or chemical matricectomy, or complete removal or destruction of the nail matrix, has been used for successful removal of the accessory toenail.[2][1][3] ## Legend[edit] While it was thought to be a prevalent feature amongst Han Chinese,[2] it is observed in people from all ethnicities and races. Chinese mythology follows that during the time of the Yellow Emperor, there were two types of people living in China, those who were the descendants of the Yellow Emperor, and those who were nomadic Qiang people. As the Henan people attacked the Qiang, led by Yin Wang, they abducted a Qiang woman, who later tried to escape. After Yin Wang stabbed her in the abdomen as she tried to escape, she gave birth to two children with a scar on the small toe of the foot. The children were taken back by Yin Wang for adoption, and their descendants were born with double nails on their small toes.[4] ## See also[edit] * Dominance (genetics) * Mongolian spot * Epicanthal fold * Congenital malformations of the dermatoglyphs * List of cutaneous conditions ## References[edit] 1. ^ a b Haneke E (May 2016). "Double Nail of the Little Toe". Skin Appendage Disorders. 1 (4): 163–7. doi:10.1159/000443378. PMC 4908446. PMID 27386457. 2. ^ a b Chi CC, Wang SH (August 2004). "Inherited accessory nail of the fifth toe cured by surgical matricectomy". Dermatologic Surgery. 30 (8): 1177–9. doi:10.1111/j.1524-4725.2004.30351.x. PMID 15274716. 3. ^ "Definition of Matricectomy". MedicineNet. Retrieved 2018-02-27. 4. ^ "关于小脚趾两瓣趾甲的传说]" [Regarding the myth of the double toenail] (in Chinese). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Accessory nail of the fifth toe	c1852023	5,633	wikipedia	https://en.wikipedia.org/wiki/Accessory_nail_of_the_fifth_toe	2021-01-18T18:49:34	{"gard": ["9672"], "mesh": ["C565090"], "umls": ["C1852023"], "wikidata": ["Q4672539"]}
Kennedy disease is a gradually progressive, neuromuscular disorder characterized by wasting of the proximal muscles (those closer to the trunk) and bulbar muscles (those of the face and throat).The condition mainly affects males, with onset between the ages of 30 and 60. Early symptoms may include tremor, muscle cramps, and muscle twitching. This is followed by progressive muscle weakness and wasting, which may manifest in a variety of ways. Affected people may also have gynecomastia, testicular atrophy (reduction in size or function of the testes), and reduced fertility as a result of mild androgen insensitivity. Kennedy disease is caused by a mutation in the androgen receptor (AR) gene and is inherited in an X-linked recessive manner. Treatment may include physiotherapy and rehabilitation; medications to alleviate tremor and muscle cramps; and hormone therapy or surgical treatment for gynecomastia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Kennedy disease	c0393547	5,634	gard	https://rarediseases.info.nih.gov/diseases/6818/kennedy-disease	2021-01-18T17:59:37	{"mesh": ["D009134"], "omim": ["313200"], "orphanet": ["481"], "synonyms": ["Spinal and bulbar muscular atrophy", "X-linked spinal and bulbar muscular atrophy", "Bulbospinal muscular atrophy", "X-linked bulbospinal amyotrophy", "Spinobulbar muscular atrophy", "SBMA"]}
The arrow indicates a fusion beat on this ECG. A fusion beat occurs when electrical impulses from different sources act upon the same region of the heart at the same time.[1] If it acts upon the ventricular chambers it is called a ventricular fusion beat, whereas colliding currents in the atrial chambers produce atrial fusion beats. Ventricular fusion beats can occur when the heart's natural rhythm and the impulse from a pacemaker coincide to activate the same part of a ventricle at the same time, causing visible variation in configuration and height of the QRS complex of an electrocardiogram reading of the heart's activity.[2] This contrasts with the pseudofusion beat wherein the pacemaker impulse does not affect the complex of the natural beat of the heart. Pseudofusion beats are normal. Rare or isolated fusion beats caused by pacemakers are normal as well, but if they occur too frequently may reduce cardiac output and so can require adjustment of the pacemaker.[3] ## References[edit] 1. ^ Understanding Electrocardiography 8 Ed. Elsevier Health Sciences. 2003. p. 245. ISBN 978-0-323-01905-7. 2. ^ Huff, Jane (October 2005). ECG Workout: Exercises in Arrhythmia Interpretation. Lippincott Williams & Wilkins. p. 247. ISBN 978-0-7817-8230-2. 3. ^ Catalano, Joseph T. (2002). Guide to Ecg Analysis. Lippincott Williams & Wilkins. p. 289. ISBN 978-0-7817-2930-7. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Fusion beat	c0232213	5,635	wikipedia	https://en.wikipedia.org/wiki/Fusion_beat	2021-01-18T18:28:42	{"umls": ["C0232213"], "wikidata": ["Q5510271"]}
Glycine encephalopathy is an inherited metabolic disease characterized by abnormally high levels of an amino acid called glycine. Glycine is a chemical messenger that transmits signals in the brain. According to the symptoms the disease onset, glycine encephalopathy may be divided in: * Classical neonatal form (most common): Symptoms start within a few days of life and may include poor feeding, lack of energy (lethargy), weak muscle tone (hypotonia), hiccups, breathing problems, seizures, hiccups, and coma. * Infantile form: Symptoms start only after 6 months of age, as intellectual disability, abnormal movements, and behavioral problems * Late onset: Symptoms include tightness or stiffness of the legs or arms (spastic diplegia), and vision loss due to a damage of the eye nerve (optic atrophy). * Transient form: Symptoms are similar to the classic form, but glycine levels decrease and the symptoms may improve within time. Glycine encephalopathy is caused by changes (mutations) in the AMT, GLDC or GCSH genes which result in a deficiency of the enzyme that break-up the glycine. Diagnosis is based in the symptoms, the high glycine levels and the enzyme deficiency, as well as genetic testing. Inheritance is autosomal recessive. Treatment may include sodium benzoate to reduce the levels of glycine, N-methyl D-aspartate (NMDA) receptor site antagonists, anti-seizure drugs and ketogenic diet. About half of the babies with the classic form, die within a few weeks of life and the survivors may have motor delay, very small head, seizures and stiffness. In the transient form symptoms may improve with time. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Glycine encephalopathy	c0751748	5,636	gard	https://rarediseases.info.nih.gov/diseases/7219/glycine-encephalopathy	2021-01-18T18:00:17	{"mesh": ["D020158"], "omim": ["605899"], "umls": ["C0751748"], "orphanet": ["407"], "synonyms": ["Hyperglycinemia nonketotic", "Nonketotic hyperglycinemia", "Glycine synthase deficiency", "Non-ketotic hyperglycinemia"]}
Pulmonary veno-occlusive disease (PVOD) is characterized by the blockage (occlusion) of the blood vessels that carry oxygen-rich (oxygenated) blood from the lungs to the heart (the pulmonary veins). The occlusion is caused by a buildup of abnormal fibrous tissue in the small veins in the lungs, which narrows the vessels and impairs blood flow. Because blood flow through the lungs is difficult, pressure rises in the vessels that carry blood that needs to be oxygenated to the lungs from the heart (the pulmonary arteries). Increased pressure in these vessels is known as pulmonary arterial hypertension. The problems with blood flow in PVOD also impair the delivery of oxygenated blood to the rest of the body, which leads to the signs and symptoms of the condition. Shortness of breath (dyspnea) and tiredness (fatigue) during exertion are the most common symptoms of this condition. Other common features include dizziness, a lack of energy (lethargy), difficulty breathing when lying down, and a cough that does not go away. As the condition worsens, affected individuals can develop a bluish tint to the skin (cyanosis), chest pains, fainting spells, and an accumulation of fluid in the lungs (pulmonary edema). Certain features commonly seen in people with PVOD can be identified using a test called a CT scan. One of these features, which is seen in the lungs of affected individuals, is an abnormality described as centrilobular ground-glass opacities. Affected individuals also have abnormal thickening of certain tissues in the lungs, which is described as septal lines. In addition, lymph nodes in the chest (mediastinal lymph nodes) are abnormally enlarged in people with PVOD. PVOD can begin at any age, and the blood flow problems worsen over time. Because of the increased blood pressure in the pulmonary arteries, the heart must work harder than normal to pump blood to the lungs, which can eventually lead to fatal heart failure. Most people with this severe disorder do not live more than 2 years after diagnosis. ## Frequency The exact prevalence of PVOD is unknown. Many cases are likely misdiagnosed as idiopathic pulmonary arterial hypertension, which is increased blood pressure in the pulmonary arteries without a known cause. Research suggests that 5 to 25 percent of people diagnosed with idiopathic pulmonary arterial hypertension have PVOD. Based on these numbers, PVOD is thought to affect an estimated 1 to 2 per 10 million people. ## Causes The primary genetic cause of PVOD is mutations in the EIF2AK4 gene. Mutations in other genes may cause a small percentage of cases. Other suspected causes of PVOD include viral infection and exposure to toxic chemicals, including certain chemotherapy drugs. The protein produced from the EIF2AK4 gene helps cells respond appropriately to changes that could damage the cell. For example, when the level of protein building blocks (amino acids) in a cell falls too low, the activity of the EIF2AK4 protein helps reduce the production of other proteins, which conserves amino acids. The EIF2AK4 gene mutations involved in PVOD likely eliminate functional EIF2AK4 protein; however, it is unknown how absence of this protein's function leads to the pulmonary vessel abnormalities that underlie PVOD. ### Learn more about the genes associated with Pulmonary veno-occlusive disease * BMPR2 * EIF2AK4 ## Inheritance Pattern When caused by mutations in the EIF2AK4 gene, PVOD 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. In contrast, when caused by mutations in another gene, the condition can have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, one parent of an affected individual typically has increased blood pressure in the vessels of the lungs. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Pulmonary veno-occlusive disease	c3887658	5,637	medlineplus	https://medlineplus.gov/genetics/condition/pulmonary-veno-occlusive-disease/	2021-01-27T08:25:20	{"gard": ["10153"], "omim": ["265450", "234810"], "synonyms": []}
Autoimmune polyendocrine syndrome Other namesAutoimmune polyglandular syndromes (APSs) The autoimmune regulator protein (from the AIRE gene, which causes autoimmune polyendocrine syndrome type 1 when non-functional) SpecialtyEndocrinology TypesAPS type1, APS type 2, IPEX syndrome CausesFOXP3 gene is involved in the mechanism [1] Diagnostic methodEndoscopic, CT scan[2] TreatmentDepends on type Autoimmune polyendocrine syndromes (APSs), also called polyglandular autoimmune syndromes (PGASs)[3] or polyendocrine autoimmune syndromes (PASs), are a heterogeneous group[4] of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. There are three types of APS, and there are a number of other diseases which involve endocrine autoimmunity.[2][5][6] ## Contents * 1 Types * 2 Cause * 3 Diagnosis * 3.1 Differential diagnosis * 4 Management * 5 See also * 6 References * 7 Further reading * 8 External links ## Types[edit] * Autoimmune polyendocrine syndrome type 1,[2] an autosomal recessive syndrome due to mutation of the AIRE gene resulting in hypoparathyroidism, adrenal insufficiency, hypogonadism, vitiligo, candidiasis and others. * Autoimmune polyendocrine syndrome type 2,[7] an autosomal dominant syndrome due to multifactorial gene involvement resulting in adrenal insufficiency plus hypothyroidism and/or type 1 diabetes. * Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX syndrome) is X-linked recessive due to mutation of the FOXP3 gene on the X chromosome. Most develop diabetes and diarrhea and many die due to autoimmune activity against many organs. Boys are affected, while girls are carriers and might suffer mild disease.[2][8][9][10] ## Cause[edit] Each "type" of this condition has a different genetic cause. IPEX syndrome is inherited in males by an x-linked recessive process. The FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of the IPEX condition.[11][1] ## Diagnosis[edit] CT scan Diagnosis for type 1 of this condition for example, sees that the following methods/tests are available:[2] * Endoscopic * CT scan * Histologic test ### Differential diagnosis[edit] For this condition, differential diagnosis sees that the following should be considered:[12] * CD25 deficiency * STAT5B deficiency * Severe combined immunodeficiency * X linked thrombocytopenia ## Management[edit] Ketoconazole Immunosuppressive therapy may be used in type I of this condition.[13] Ketoconazole can also be used for type I under certain conditions.[2] The component diseases are managed as usual; the challenge is to detect the possibility of any of the syndromes and to anticipate other manifestations. For example, in a person with known type 2 autoimmune polyendocrine syndrome but no features of Addison's disease, regular screening for antibodies against 21-hydroxylase may prompt early intervention and hydrocortisone replacement to prevent characteristic crises[medical citation needed] ## See also[edit] * Immunosuppression ## References[edit] 1. ^ a b Reference, Genetics Home. "FOXP3 gene". Genetics Home Reference. Retrieved 2017-05-11. 2. ^ a b c d e f "Type I Polyglandular Autoimmune Syndrome: Background, Pathophysiology, Epidemiology". 2017-01-06. Cite journal requires `\|journal=` (help) 3. ^ Dittmar, Manuela; Kahaly, George J. (2003). "Polyglandular Autoimmune Syndromes: Immunogenetics and Long-Term Follow-Up". The Journal of Clinical Endocrinology & Metabolism. 88 (7): 2983–2992. doi:10.1210/jc.2002-021845. PMID 12843130. Retrieved 1 July 2013. 4. ^ Eisenbarth GS, Gottlieb PA (2004). "Autoimmune polyendocrine syndromes". N. Engl. J. Med. 350 (20): 2068–79. doi:10.1056/NEJMra030158. PMID 15141045. 5. ^ "Type III Polyglandular Autoimmune Syndrome: Background, Pathophysiology, Epidemiology". 2017-05-03. Cite journal requires `\|journal=` (help) 6. ^ "Type II Polyglandular Autoimmune Syndrome: Background, Pathophysiology, Epidemiology". 2017-05-03. Cite journal requires `\|journal=` (help) 7. ^ "Autoimmune polyglandular syndrome type 2 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-04-20. 8. ^ "IPEX syndrome". Genetics Home Reference. Retrieved 2017-04-20. 9. ^ "Immunodysregulation, polyendocrinopathy and enteropathy X-linked \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-04-20. 10. ^ Wildin, R. S.; Smyk-Pearson, S.; Filipovich, A. H. (1 August 2002). "Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome". Journal of Medical Genetics. 39 (8): 537–545. doi:10.1136/jmg.39.8.537. ISSN 0022-2593. PMC 1735203. PMID 12161590. Retrieved 1 January 2018. 11. ^ Reference, Genetics Home. "IPEX syndrome". Genetics Home Reference. Retrieved 2017-05-11. 12. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Immune dysregulation polyendocrinopathy enteropathy X linked syndrome". www.orpha.net. Retrieved 2017-05-11. 13. ^ Weiler, Fernanda Guimarães; Dias-da-Silva, Magnus R.; Lazaretti-Castro, Marise (2012-02-01). "Autoimmune polyendocrine syndrome type 1: case report and review of literature". Arquivos Brasileiros de Endocrinologia & Metabologia. 56 (1): 54–66. doi:10.1590/S0004-27302012000100009. ISSN 0004-2730. PMID 22460196. ## Further reading[edit] * Improda, Nicola; Capalbo, Donatella; Cirillo, Emilia; Cerbone, Manuela; Esposito, Andrea; Pignata, Claudio; Salerno, Mariacarolina (1 November 2014). "Cutaneous vasculitis in patients with autoimmune polyendocrine syndrome type 1: report of a case and brief review of the literature". BMC Pediatrics. 14: 272. doi:10.1186/1471-2431-14-272. ISSN 1471-2431. PMC 4286916. PMID 25361846. * Shoenfeld, Yehuda; Cervera, Ricard; Gershwin, M. Eric (2008). Diagnostic Criteria in Autoimmune Diseases. Springer Science & Business Media. ISBN 9781603272858. ## External links[edit] * Diseases Database (DDB): 29690 * PubMed Classification D * ICD-10: E31.0 * ICD-9-CM: 258.1 * OMIM: 240300 269200 * MeSH: D016884 * DiseasesDB: 29212 External resources * eMedicine: med/1867 med/1868 Scholia has a topic profile for Autoimmune polyendocrine syndrome. * v * t * e Disorders involving multiple endocrine glands * Autoimmune polyendocrine syndrome * APS1 * APS2 * Carcinoid syndrome * Multiple endocrine neoplasia * 1 * 2A * 2B * Progeria * Werner syndrome * Acrogeria * Metageria * Woodhouse–Sakati syndrome * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Autoimmune polyendocrine syndrome	c0085409	5,638	wikipedia	https://en.wikipedia.org/wiki/Autoimmune_polyendocrine_syndrome	2021-01-18T18:53:20	{"mesh": ["D016884"], "umls": ["C0085409"], "orphanet": ["282196"], "wikidata": ["Q675311"]}
Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance. People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation. IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness. Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy). Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5. ## Frequency More than 20 individuals with IOSCA have been identified in Finland. A few individuals with similar symptoms have been reported elsewhere in Europe. ## Causes Mutations in the TWNK gene cause IOSCA. The TWNK gene provides instructions for making two very similar proteins called Twinkle and Twinky. These proteins are found in the mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. The Twinkle protein is involved in the production and maintenance of mtDNA. The function of the Twinky protein is unknown. The TWNK gene mutations that cause IOSCA interfere with the function of the Twinkle protein and result in reduced quantities of mtDNA (mtDNA depletion). Impaired mitochondrial function in the nervous system, muscles, and other tissues that require a large amount of energy leads to neurological dysfunction and the other problems associated with IOSCA. ### Learn more about the gene associated with Infantile-onset spinocerebellar ataxia * TWNK ## 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	Infantile-onset spinocerebellar ataxia	c1849096	5,639	medlineplus	https://medlineplus.gov/genetics/condition/infantile-onset-spinocerebellar-ataxia/	2021-01-27T08:25:07	{"gard": ["4062"], "mesh": ["C535523"], "omim": ["271245"], "synonyms": []}
Arteritic anterior ischemic optic neuropathy SpecialtyOphthalmology Arteritic anterior ischemic optic neuropathy (AAION or arteritic AION) is the cause of vision loss that occurs in temporal arteritis (aka giant-cell arteritis). Temporal arteritis is an inflammatory disease of medium-sized blood vessels that happens especially with advancing age. AAION occurs in about 15-20 percent of patients with temporal arteritis. Damage to the blood vessels supplying the optic nerves leads to insufficient blood supply (ischemia) to the nerve and subsequent optic nerve fiber death. Most cases of AAION result in nearly complete vision loss first to one eye. If the temporal arteritis is left untreated, the fellow eye will likely suffer vision loss as well within 1–2 weeks. Arteritic AION falls under the general category of anterior ischemic optic neuropathy, which also includes non-arteritic AION. AION is considered an eye emergency, immediate treatment is essential to rescue remaining vision. An exhaustive review article published in March 2009 described the latest information on arteritic and non-arteritic ischemic optic neuropathy, both anterior (A-AION and NA-AION) and posterior (A-PION, NA-PION, and surgical).[1] ## Contents * 1 Symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 References ## Symptoms[edit] There are several constitutional symptoms of temporal arteritis that may aid in diagnosis of AAION such as jaw claudication (spasms of the jaw muscle), scalp tenderness, unintentional weight loss, fatigue, myalgias and loss of appetite. However, many cases are asymptomatic. There are also elevations in three blood tests that help identify AAION: erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and platelet count (thrombocytosis). A related rheumatic disease called polymyalgia rheumatica has a 15 percent incidence of giant cell arteritis. ## Cause[edit] This section is empty. You can help by adding to it. (September 2017) ## Diagnosis[edit] Prompt diagnosis is critical, since the sudden blindness in the one eye is often followed, within days, by similar sudden blindness in the second eye. Treatment may prevent further damage (see below). Any patient diagnosed with non-arteritic AION over the age of 50 must be asked about the constitutional symptoms mentioned above. Furthermore, AION patients over the age of 75 should often be blood tested regardless. ## Treatment[edit] AAION requires urgent and critical intervention with a very long course of corticosteroids to prevent further damage. While this treatment is in itself problematic, non-treatment leads to bilateral blindness and strokes.[citation needed] There is much research currently underway looking at ways to protect the nerve (neuroprotection) or even regenerate new fibers within the optic nerve.[citation needed] ## References[edit] * Myron Yanoff et al., Ophthalmology, 2nd ed. (C.V. Mosby, 2004), chapt. 191. * UpToDate article "Clinical manifestations and diagnosis of giant cell (temporal) arteritis" 1. ^ Sohan Hayreh, "Ischemic optic neuropathy", Progress in Retinal and Eye Research (2009) 28(1):34-62. [1] * 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	Arteritic anterior ischemic optic neuropathy	c2242711	5,640	wikipedia	https://en.wikipedia.org/wiki/Arteritic_anterior_ischemic_optic_neuropathy	2021-01-18T18:28:26	{"wikidata": ["Q4797551"]}
Coffin-Lowry syndrome is a genetic condition that affects many parts of the body. The signs and symptoms and severity vary from person to person; however, males are typically more severely affected than females. Signs and symptoms may include distinct facial findings, short stature, microcephaly, kyphoscoliosis, other skeletal abnormalities, stimulus-induced drop episodes, intellectual disability and delayed development. Mutations in the RPS6KA3 gene cause the syndrome. It is inherited in an X-linked dominant fashion. Treatment is symptomatic. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Coffin-Lowry syndrome	c0265252	5,641	gard	https://rarediseases.info.nih.gov/diseases/6123/coffin-lowry-syndrome	2021-01-18T18:01:14	{"mesh": ["D038921"], "omim": ["303600"], "orphanet": ["192"], "synonyms": ["Mental retardation with osteocartilaginous abnormalities", "CLS", "Coffin syndrome"]}
A number sign (#) is used with this entry because of evidence that amyotrophic lateral sclerosis-12 (ALS12) is caused by homozygous or heterozygous mutation in the optineurin gene (OPTN; 602432) on chromosome 10p13. Primary open angle glaucoma-1E (POAG; see 137760) is an allelic disorder caused by distinct missense mutations and segregating in an autosomal dominant manner. For a general phenotypic description and discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400). Clinical Features Of 6 Japanese individuals from consanguineous marriages who had ALS, Maruyama et al. (2010) identified 3 with mutations in the OPTN gene. Two were sibs. One member of the sib pair developed muscle weakness of her left arm at 33 years of age that progressed to dysphagia requiring endotracheal intubation. She was bedridden by age 34 and died at age 57. Her brother also had onset with left arm weakness at 36 years of age and 1 year later developed dysphagia, dysarthria, and tongue fasciculations. He likewise required endotracheal intubation, was bedridden by age 37, and died at the age of 55. The third patient from a consanguineous family developed dysarthria at 52 years of age and had muscle weakness of her left upper and lower extremities starting at 54 years of age. Her deep tendon reflex was exaggerated, but there was no pathologic reflex. She was still breathing independently at 60 years of age. These 3 individuals were homozygous for mutation in OPTN; 4 other heterozygous individuals identified in a separate analysis had onset in their 50s with slow progression. All individuals with mutations of OPTN showed onset from 30 to 60 years of age. Most of them showed a relatively slow progression and long duration before respiratory failure, although the clinical phenotypes were not homogeneous. Inheritance The transmission pattern of ALS12 in some of the families reported by Maruyama et al. (2010) was consistent with autosomal recessive inheritance, whereas other families showed autosomal dominant inheritance. Pottier et al. (2015) reported a deceased patient (Case B) showing digenic inheritance of a neurodegenerative disorder: whole-exome sequencing identified heterozygous mutations in the OPTN (G538EfsX27) and TBK1 (604834; R117X) genes. He presented with rapidly progressive cognitive and language difficulties at age 68 years, becoming almost mute by age 69. Other features included trouble swallowing, jerky movements of the hands, and slow movements, but there was no obvious clinical evidence of motor neuron disease. The patient showed symptoms of frontal dementia and was diagnosed with primary progressive aphasia. He died at age 72. Postmortem examination showed severe focal cortical atrophy of the frontal lobe, atrophy of the amygdala and hippocampus, loss of pigment in the substantia nigra, and midbrain atrophy. There were p62- (601530) and TDP43 (605078)-positive neuronal and glial inclusions. There was no neuronal loss in the motor cortex or brainstem. He had no family history of a similar disorder. Mapping Using homozygosity mapping in 4 Japanese subjects from consanguineous marriages with ALS, Maruyama et al. (2010) identified a candidate region for the disorder on chromosome 10 containing 17 genes. Molecular Genetics Among 8 Japanese patients with ALS, Maruyama et al. (2010) identified homozygosity for 2 null mutations in the OPTN gene, one a deletion of exon 5 (602432.0005) in 2 sibs and the other a nonsense mutation (Q398X; 602432.0006) in 2 individuals thought to be unrelated but who shared a haplotype for a 0.9-Mb region containing the OPTN gene. The authors also identified heterozygosity for a missense mutation (E478G; 602432.0007) within the OPTN ubiquitin-binding domain in 4 individuals from 2 families. The pedigree of one of these families suggested that the disorder is an autosomal dominant trait with incomplete penetrance. Although these 2 families were not known to be related, all affected individuals shared their haplotype for 2.3 Mb on chromosome 10 around the OPTN gene. Neither the Q398X nor the E478G mutations were observed in 781 healthy Japanese volunteers or in over 6,800 (including 1,728 Japanese) individuals in glaucoma studies, in which the entire coding region of the gene was investigated. Collectively, the mutation was absent over a total of 5,000 Japanese chromosomes. The deletion mutation was also absent in 200 Japanese, and not reported in the over 6,800 glaucoma individuals. Pathogenesis In cell transfection assays, Maruyama et al. (2010) observed that nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa-B (NFKB; see 164011) and that E478G (602432.0007) mutant OPTN had a cytoplasmic distribution different from that of wildtype OPTN or OPTN carrying a mutation resulting in primary open angle glaucoma (POAG; see 137760). A case with the E478G mutation showed OPTN-immunoreactive cytoplasmic inclusions. Furthermore, TDP43 (605078)- or SOD1 (147450)-positive inclusions in sporadic and familial cases of ALS were also noticeably immunolabeled by anti-OPTN antibodies. Ito et al. (2016) found that OPTN actively suppressed receptor-interacting kinase-1 (RIPK1; 613435)-dependent signaling by regulating its turnover. Loss of OPTN led to progressive dysmyelination and axonal degeneration through engagement of necroptotic machinery in the CNS, including RIPK1, RIPK3 (605817), and mixed lineage kinase domain-like protein (MLKL; 615153). Furthermore, RIPK1- and RIPK3-mediated axonal pathology was commonly observed in SOD1(G93A) (147450.0008) transgenic mice and pathologic samples from human ALS patients. Thus, RIPK1 and RIPK3 play a critical role in mediating progressive axonal degeneration. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	AMYOTROPHIC LATERAL SCLEROSIS 12	c0002736	5,642	omim	https://www.omim.org/entry/613435	2019-09-22T15:58:49	{"doid": ["0060203"], "mesh": ["D000690"], "omim": ["613435"], "orphanet": ["803"], "genereviews": ["NBK1450"]}
A number sign (#) is used with this entry because hereditary folate malabsorption is caused by homozygous or compound heterozygous mutation in the SLC46A1 gene (611672) on chromosome 17q11. Description Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system (summary by Qiu et al., 2006). Clinical Features Luhby et al. (1965) observed affected sisters, and Lanzkowsky (1970) described a sporadic case in a 20-year-old. The patients had an isolated defect in intestinal absorption of folic acid and a defect in transport of folic acid across the blood-brain barrier. Recurrent megaloblastic anemia, mental retardation, convulsions, and movement disorder (ataxia in Luhby's cases, athetosis in Lanzkowsky's) were manifestations. Basal ganglion calcification was described in Lanzkowsky's cases. The seizures were said to be reduced by folic acid in Luhby's cases but aggravated by folic acid in Lanzkowsky's. Parenteral folic acid corrected the anemia. Corbeel et al. (1985) reported a patient in whom oral folic acid cured the anemia, diarrhea, and susceptibility to infections, but failed to prevent convulsions and the development of mental retardation and cerebral calcifications. (Cases of dihydropteridine reductase deficiency (261630) in which treatment with folinic acid is not given also develop intracranial calcification (Woody et al., 1989).) Corbeel et al. (1985) were prompted to give methionine along with vitamin B12 and folic acid because of low plasma methionine; the convulsions were controlled. In a male patient, Steinschneider et al. (1990) confirmed improvement in the peripheral neuropathy with intramuscular folinic acid therapy as had been reported by Su (1976). Rosenblatt and Fenton (2001) stated that this disorder had been described in fewer than 20 patients, mostly females. Jebnoun et al. (2001) reported a large family of 8 children (6 males and 2 females) affected by congenital folate malabsorption. The first 5 children (4 boys and 1 girl) died within the first few months of life with diarrhea, vomiting, drowsiness, pallor, and glossitis. The 3 surviving children (1 girl and 2 boys) developed the same symptoms within the first weeks of life. In the surviving girl, studied at 3 months of age, blood cell count showed severe pancytopenia with an aregenerative normocytic anemia, leukopenia, and thrombocytopenia. The peripheral blood smear revealed hypersegmented neutrophils. Bone marrow was hypercellular with an excess of megaloblastic erythroblasts. Folate deficiency was confirmed in serum, red cells, and cerebrospinal fluid (CSF). Methylfolate was undetectable. Congenital malabsorption of folate was confirmed by a folic acid loading test that showed a peak serum folate of 8 microg/liter 2 hours after oral administration of 40 microg/liter folic acid and body saturation 2 days before the test with an injection of 5 mg folinic acid. Intramuscular administration of folinic acid achieved detectable CSF folate levels in a dose-dependent manner. With intermittent folinic acid administration the child had normal growth and hematologic parameters but developed epilepsy at age 4 years and had a low IQ. Geller et al. (2002) reported 2 Puerto Rican sibs with hereditary folate malabsorption. The female proband presented at 6.5 months of age with recurrent diarrhea, gastroesophageal reflux, frequent upper respiratory infections, bilateral pneumonia, urinary tract infection, eosinophilia, anemia, anorexia, poor weight gain, and oral ulcers. She continued to have infections and diarrhea and required blood and platelet transfusions for anemia and thrombocytopenia. Folate deficiency was diagnosed at age 8 months, and she responded well to folate therapy. Her younger sister was diagnosed with the disorder at age 2 months and responded well to proper treatment. Family history revealed that a deceased sister had also experienced recurrent diarrhea, pulmonary disease, eosinophilia, and seizures; she died from sepsis at age 4 months. Qiu et al. (2006) noted that the sisters reported by Geller et al. (2002) developed normally and remained completely well on folate supplements at ages 9 and 6 years, respectively. Zhao et al. (2007) reported a male infant of Spanish/Brazilian/Mexican origin with hereditary folate malabsorption. He presented at age 4 months with severe macrocytic anemia and thrombocytopenia. He subsequently developed Pneumocystis carinii pneumonia. He had low serum folate and immunoglobulins. Treatment with folate replacement led to clinical improvement. An older sister had developed pancytopenia at age 3 months and died due to cytomegalovirus pneumonia. Molecular analysis identified compound heterozygosity for 2 mutations in the SLC46A1 gene (611672.0004 and 611672.0005). Sofer et al. (2007) reported an Arab Israeli infant, born of consanguineous parents, with folate malabsorption. He presented at age 15 months with generalized and focal seizures and a decline in mental status. Laboratory tests revealed low folate levels in blood and CSF, accompanied by pancytopenia. Bone marrow aspiration confirmed the presence of megaloblastic anemia. Treatment with high-dose intravenous folinic acid led to normalization of CSF folate levels. Shin et al. (2011) reported an English boy with hereditary folate malabsorption. The child developed Pneumocystis jiroveci pneumonia associated with anemia and undetectable plasma folate at age 2 months. He later showed delayed motor development, hyperreflexia, jerky movements, tremor, and proximal muscle wasting. Brain MRI at 3 years 9 months showed a slight delay in myelination. He improved neurologically with treatment, but had mild difficulty in fine motor skills and reading but good math skills. He developed occipital seizures at age 5 years. Shin et al. (2011) also reported an 8-year-old Tunisian boy, born of consanguineous parents, with hereditary folate malabsorption. The patient developed macrocytic anemia with low serum folate at age 2.5 months. He was treated with leucovorin, which corrected the anemia and axial hypertonia. EEG and head CT scan were normal. Two affected sibs had died. Inheritance Parental consanguinity was noted in the families reported by Lanzkowsky et al. (1969), Santiago-Borrero et al. (1973), and Urbach et al. (1987), supporting autosomal recessive inheritance. Molecular Genetics In 2 sisters with hereditary folate malabsorption (Geller et al., 2002), Qiu et al. (2006) identified a homozygous mutation in the SLC46A1 gene (611672.0001). In 5 infants with hereditary folate malabsorption, Zhao et al. (2007) identified 6 different biallelic mutations in the SLC46A1 gene (see, e.g., 611672.0002-611672.0005). One of the patients had been reported by Corbeel et al. (1985) (R113S; 611672.0003). In an affected patient reported by Sofer et al. (2007), Lasry et al. (2008) identified a homozygous mutation in the SLC46A1 gene (611672.0006). In a Tunisian patient, born of consanguineous parents, with hereditary folate malabsorption, previously reported by Jebnoun et al., 2001, Shin et al. (2011) identified a homozygous mutation in the SLC46A1 gene (611672.0007). They also identified compound heterozygosity for 2 mutations in the SLC46A1 gene (611672.0008 and 611672.0009) in an English boy with the disorder and identified a homozygous mutation (611672.0010) in another unrelated Tunisian patient. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Mouth \- Oral ulcers ABDOMEN Gastrointestinal \- Poor feeding \- Diarrhea \- Folate malabsorption NEUROLOGIC Central Nervous System \- Hypotonia \- Head lag \- Delayed development if untreated \- Mental retardation if untreated \- Ataxia \- Seizures \- Athetosis \- Dyskinesias \- Basal ganglion calcifications Peripheral Nervous System \- Peripheral neuropathy Behavioral Psychiatric Manifestations \- Irritability HEMATOLOGY \- Megaloblastic anemia, folate-responsive \- Thrombocytopenia \- Neutropenia \- Leukopenia IMMUNOLOGY \- Recurrent infections \- Increased susceptibility to pneumocystis and cytomegalovirus infections \- Hypoimmunoglobulinemia LABORATORY ABNORMALITIES \- Decreased serum folate \- Decreased CSF folate \- Low plasma methionine \- Increased urinary formiminoglutamic acid (FIGLU) MISCELLANEOUS \- Onset in infancy \- Early diagnosis and proper treatment with folate replacement therapy can avoid neurologic sequelae MOLECULAR BASIS \- Caused by mutation in the solute carrier family 46 (folate transporter), member 1 gene (SLC46A1, 611672.0001 ) ▲ 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	FOLATE MALABSORPTION, HEREDITARY	c0342705	5,643	omim	https://www.omim.org/entry/229050	2019-09-22T16:27:48	{"mesh": ["C562799"], "omim": ["229050"], "orphanet": ["90045"], "genereviews": ["NBK1673"]}
A number sign (#) is used with this entry because of evidence that Reynolds syndrome is caused by heterozygous mutation in the LBR gene (600024) on chromosome 1q42. One such patient has been reported. Clinical Features Reynolds et al. (1971) reported 6 unrelated women, ranging in age from 38 to 51 years, with a constellation of clinical features, including liver disease, telangiectasia, Raynaud phenomenon, and variable features of scleroderma (181750). The liver disease was characterized by pruritus, jaundice, hepatomegaly, increased serum alkaline phosphatase, and positive serum mitochondrial autoantibodies, all consistent with primary biliary cirrhosis (PBC; 109720). Liver biopsies showed variable subtle features of PBC, including absence of cholangioles and inflammatory cells, in most patients. Telangiectases were present on the fingerpads of all patients, on the lips in 5, and in the gastrointestinal tract in at least 2. Most patients described pain and blanching of the hands upon cold exposure, and all except 1 patient had sclerodactyly of the hands and forearms. Two had decreased esophageal motility, and 3 had areas of calcinosis cutis. These findings were reminiscent of CREST syndrome (see 181750). Three patients had upper gastrointestinal bleeding, which was related to telangiectasia or esophageal varices. Nonspecific symptoms included fatigue and generalized increase in skin pigmentation. None had a family history of the disorder. The association of PBC with a form of scleroderma suggested to Reynolds et al. (1971) an immunologic etiology for the liver disease. Murray-Lyon et al. (1970) reported 2 unrelated women in their sixties with scleroderma affecting the hands and esophagus associated with PBC, telangiectasia, and Raynaud disease. One also had areas of calcinosis of the skin. Both had mitochondrial autoantibodies. Gaudy-Marqueste et al. (2010) reported a 76-year-old Caucasian woman with Reynolds syndrome. She had a long history of Raynaud phenomenon, telangiectasia, and mild cholestasis. Laboratory studies showed autoimmune markers, such as increased erythrocyte sedimentation rate, antimitochondrial autoantibodies, and antinuclear antibodies. She had limited cutaneous scleroderma, and was diagnosed with PBC. Molecular Genetics In a 76-year-old Caucasian woman with Reynolds syndrome, Gaudy-Marqueste et al. (2010) identified a heterozygous mutation in the LBR gene (R372C; 600024.0007). Studies of patient lymphoblastoid cells did not show abnormalities, but patient fibroblasts showed decreased LBR and decreased levels of lamin proteins, as well as dysmorphic nuclei with mottled chromatin. These findings suggested that the R372C mutation exerted a dominant-negative effect on LBR-interacting proteins, perhaps resulting from decreased stabilization of the mutant protein and increased proteasome-mediated degradation. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Telangiectasia of the lips ABDOMEN Liver \- Hepatomegaly \- Primary biliary cirrhosis \- Absence of cholangioles \- Inflammatory cell infiltrate \- Destruction of the limiting plate Spleen \- Splenomegaly Gastrointestinal \- Decreased esophageal peristalsis \- Upper gastrointestinal bleeding \- Steatorrhea, mild SKIN, NAILS, & HAIR Skin \- Jaundice \- Pruritis \- Telangiectasia, particularly of the fingerpads and lips \- Sclerodactyly \- Calcinosis cutis \- Raynaud phenomenon \- Blanching of the fingers in response to cold \- Numbness, pain, and tingling of the fingers in response to cold \- Generalized darkening of the skin \- Tight, shiny skin over the forearms and hands LABORATORY ABNORMALITIES \- Increased serum alkaline phosphatase \- Hyperbilirubinemia \- Increased serum cholesterol \- Abnormal liver function tests \- Serum mitochondrial autoantibodies MISCELLANEOUS \- More common in women \- A mutation in the LBR gene has been identified in 1 patient (as of July 2010) MOLECULAR BASIS \- Caused by mutation in the lamin B receptor gene (LBR, 600024.0007 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	REYNOLDS SYNDROME	c0748397	5,644	omim	https://www.omim.org/entry/613471	2019-09-22T15:58:34	{"omim": ["613471"], "orphanet": ["779"], "synonyms": ["Alternative titles", "PRIMARY BILIARY CIRRHOSIS, SCLERODERMA, RAYNAUD DISEASE, AND TELANGIECTASIA"]}
Disease of the kidney "Berger's disease" redirects here. It is not to be confused with Buerger's disease. Berger's disease (IgA nephropathy) Other namesIgA nephritis Immunoglobulin A dimer SpecialtyNephrology Rheumatology Oncology IgA nephropathy (IgAN), also known as Berger's disease (/bɛərˈʒeɪ/) (and variations), or synpharyngitic glomerulonephritis, is a disease of the kidney (or nephropathy) and the immune system; specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney. Aggressive Berger's disease (a rarer form of the disease) can attack other major organs, such as the liver, skin and heart. IgA nephropathy is the most common glomerulonephritis worldwide; however, aggressive Berger's disease is on the NORD list of rare diseases.[1] Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. There are other diseases associated with glomerular IgA deposits, the most common being IgA vasculitis (formerly known as Henoch–Schönlein purpura [HSP]), which is considered by many to be a systemic form of IgA nephropathy.[2] IgA vasculitis presents with a characteristic purpuric skin rash, arthritis, and abdominal pain, and occurs more commonly in young adults (16–35 years old). HSP is associated with a more benign prognosis than IgA nephropathy. In non-aggressive IgA nephropathy there is traditionally a slow progression to chronic kidney failure in 25–30% of cases during a period of 20 years. ## Contents * 1 Signs and symptoms * 2 Morphology * 3 Pathophysiology * 3.1 Natural history * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 Epidemiology * 7.1 Genetics * 8 History * 9 References * 10 External links ## Signs and symptoms[edit] The classic presentation for the non-aggressive form (in 40–50% of the cases) is episodic hematuria, which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic), as opposed to post-streptococcal glomerulonephritis, which occurs some time (weeks) after initial infection. With both aggressive and non-aggressive Berger's disease loin pain can also occur. The gross hematuria may resolve after a few days, though microscopic hematuria will persist, it is however more common with aggressive Berger's disease for gross hematuria to persist rather than microscopic hematuria. Renal function usually remains normal with non-aggressive Berger's disease, though rarely acute kidney failure may occur (see below). This presentation is more common in younger adults. The following is a basic list of symptoms taken primarily from Mayo clinic; * Severe flank/abdominal pain * High blood pressure * Hematuria (gross, frank, microscopic) * Compromised immune system * Edema in hands and feet * Cola- or tea-colored urine A smaller proportion (20–30%), usually the older population, have microscopic hematuria and proteinuria (less than 2 gram/day). These patients may be asymptomatic and only picked up due to urinalysis. Hence, the disease is more commonly diagnosed in situations where screening of urine is compulsory (e.g., schoolchildren in Japan). Very rarely (5% each), the presenting history is: * Nephrotic syndrome (3–3.5 grams of protein loss in the urine, associated with a poorer prognosis) * Acute kidney failure (either as a complication of the frank hematuria, when it usually recovers, or due to rapidly progressive glomerulonephritis which often leads to chronic kidney failure) * Chronic kidney failure (no previous symptoms, presents with anemia, hypertension and other symptoms of kidney failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria) A variety of systemic diseases are associated with aggressive IgA nephropathy (Berger's disease) such as liver failure, cancer, celiac disease, systemic lupus erythematosus, rheumatoid arthritis, heart failure, reactive arthritis, ankylosing spondylitis and HIV. Diagnosis of Berger's disease and a search for any associated disease occasionally reveals such an underlying serious systemic disease. Occasionally, there are simultaneous symptoms of Henoch–Schönlein purpura; see below for more details on the association. Some HLA alleles have been suspected along with complement phenotypes as being genetic factors. Non-aggressive Berger's disease may also be associated with any of the above systemic diseases, however this is rare. ## Morphology[edit] Histologically, IgA nephropathy may show mesangial widening and focal and segmental inflammation. Diffuse mesangial proliferation or crescentic glomerulonephritis may also be present. Immunoflourescence shows mesangial deposition of IgA often with C3 and properdin and smaller amounts of other immunoglobulins (IgG or IgM). Early components of the classical complement pathway (C1q or C4) are usually not seen. Electron microscopy confirms electron-dense deposits in the mesangium that may extend to the subendothelial area of adjacent capillary walls in a small subset of cases, usually those with focal proliferation. ## Pathophysiology[edit] Immunostaining showing IgA in the glomerulus of a patient with Henoch-Schönlein nephritis. Play media The pathophysiology, signs and symptoms, and treatment of IgA nephropathy. The disease derives its name from deposits of immunoglobulin A (IgA) in a granular pattern in the mesangium (by immunofluorescence), a region of the renal glomerulus. The mesangium by light microscopy may be hypercellular and show increased deposition of extracellular matrix proteins. In terms of the renal manifestation of Henoch–Schönlein purpura, it has been found that although it shares the same histological spectrum as IgA nephropathy, a greater frequency of severe lesions such as glomerular necrosis and crescents were observed. Correspondingly, HSP nephritis has a higher frequency of glomerular staining for fibrin compared with IgAN, but with an otherwise similar immunofluorescence profile.[3] There is no clear known explanation for the accumulation of the IgA. Exogenous antigens for IgA have not been identified in the kidney, but it is possible that this antigen has been cleared before the disease manifests itself. It has also been proposed that IgA itself may be the antigen. A recently advanced theory focuses on abnormalities of the IgA1 molecule. IgA1 is one of the two immunoglobulin subclasses (the other is IgD) that is O-glycosylated on a number of serine and threonine residues in a special proline-rich hinge region. Aberrant glycosylation of IgA appears to lead to polymerisation of the IgA molecules in tissues, especially the glomerular mesangium.[4] A similar mechanism has been claimed to underlie Henoch–Schönlein purpura, a vasculitis that mainly affects children and can feature renal involvement that is almost indistinguishable from IgA nephritis. However, human studies have found that degalactosylation of IgA1 occurs in patients with IgA nephropathy in response only to gut antigen exposures (not systemic), and occurs in healthy people to a lesser extent.[5] This strongly suggests degalactosylation of IgA1 is a result of an underlying phenomenon (abnormal mucosal antigen handling) and not the ultimate cause of IgA nephropathy. Prevailing evidence suggests that both galactose-deficient o-glycans in the hinge region of IgA1 and synthesis and binding of antibodies against IgA1 are required for immunoglobulin complexes to form and accumulate in glomeruli.[6] From the fact that IgAN can recur after renal transplant, it can be postulated that the disease is caused by a problem in the immune system rather than the kidney itself. Remarkably, the IgA1 that accumulates in the kidney does not appear to originate from the mucosa-associated lymphoid tissue (MALT), which is the site of most upper respiratory tract infections, but from the bone marrow. This, too, suggests an immune pathology rather than direct interference by outside agents. ### Natural history[edit] Since IgA nephropathy commonly presents without symptoms through abnormal findings on urinalysis, there is considerable possibility for variation in any population studied depending upon the screening policy. Similarly, the local policy for performing kidney biopsy assumes a critical role; if it is a policy to simply observe patients with isolated bloody urine, a group with a generally favourable prognosis will be excluded. If, in contrast, all such patients are biopsied, then the group with isolated microscopic hematuria and isolated mesangial IgA will be included and ‘improve’ the prognosis of that particular series. Nevertheless, IgA nephropathy, which was initially thought to be a benign disease, has been shown to not be a benign disease, particularly if the patient presents with an aggressive form. Though most reports describe Berger's disease as having an indolent evolution towards either healing or renal damage, a more aggressive course is occasionally seen associated with extensive crescents, and presenting as acute kidney failure. In general, the entry into chronic kidney failure is slow as compared to most other glomerulonephritides – occurring over a time scale of 30 years or more (in contrast to the 5 to 15 years in other glomerulonephritides), however in aggressive Berger's disease the time scale is within 5–10 years and often sooner. This may reflect the earlier diagnosis made due to frank hematuria. Complete remission of aggressive Berger's disease, occurs rarely in adults. In about 5% of cases, however, there is a higher chance of remission with non-aggressive Berger's disease (this is estimated to be around 7.4% of cases). There is a high chance of relapse particularly with aggressive Berger's disease. However, given the evolution of this disease, the longer term (10–20 years) outcome of such patients is not yet established. Overall, the current 10 year survival rate for aggressive Berger's disease is 25% and 73% for non-aggressive Berger's disease. ## Diagnosis[edit] For an adult patient with isolated hematuria, tests such as ultrasound of the kidney and cystoscopy are usually done first to pinpoint the source of the bleeding. These tests would rule out kidney stones and bladder cancer, two other common urological causes of hematuria. In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy. A kidney biopsy is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium, with IgA deposits on immunofluorescence and electron microscopy. However, patients with isolated microscopic hematuria (i.e. without associated proteinuria and with normal kidney function) are not usually biopsied since this is associated with an excellent prognosis. A urinalysis will show red blood cells, usually as red cell urinary casts. Proteinuria, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement membrane disease and Alport syndrome, the latter being a hereditary disease associated with hearing impairment and eye problems. Other blood tests done to aid in the diagnosis include CRP or ESR, complement levels, ANA, and LDH. Protein electrophoresis and immunoglobulin levels can show increased IgA in 50% of all patients. ## Treatment[edit] The ideal treatment for IgAN would remove IgA from the glomerulus and prevent further IgA deposition. This goal still remains a remote prospect. There are a few additional caveats that have to be considered while treating IgA nephropathy. IgA nephropathy has a very variable course, ranging from a benign recurrent hematuria up to a rapid progression to chronic kidney failure and failure of other major organs. Hence the decision on which patients to treat should be based on the prognostic factors and the risk of progression. Also, IgA nephropathy recurs in transplants despite the use of ciclosporin, azathioprine or mycophenolate mofetil, cyclophosphamide, Isotretinoin and steroids in these patients. There are persisting uncertainties, due to the limited number of patients included in the few controlled, randomized, studies performed to date. These studies hardly produce statistically significant evidence regarding the heterogeneity of IgA nephropathy patients, the diversity of study treatment protocols, and the length of follow-up. In cases where tonsillitis is the precipitating factor for episodic hematuria, a tonsillectomy has been claimed to reduce the frequency of those episodes. However, it does not reduce the incidence of progressive kidney failure.[7] Dietary gluten restriction, used to reduce mucosal antigen challenge, also has not been shown to preserve kidney function. Phenytoin has also been tried without any benefit.[8] A subset of IgA nephropathy patients, who have minimal change disease on light microscopy and clinically have nephrotic syndrome, show an exquisite response to steroids, behaving more or less like minimal change disease. In other patients, the evidence for steroids is not compelling. Short courses of high dose steroids have been proven to lack benefit. However, in patients with aggressive Berger's disease 6 months regimen of steroids in addition to other medications may lessen proteinuria and preserve renal function.[9] The study had 10 years of patient follow-up data, and did show a benefit for steroid therapy; there was a lower chance of reaching end-stage renal disease (renal function so poor that dialysis was required) in the steroid group. Importantly, angiotensin-converting enzyme inhibitors were used in both groups equally. Cyclophosphamide (traded as endoxan & cytoxan) and Isotretinoin have commonly been used, often with anti-platelet/anticoagulants in patients with Aggressive Berger's disease, however, the side effect profile of these drugs, including long term risk of malignancy and sterility, made them an unfavorable choice for use in young adults. However, one recent study, in a carefully selected high risk population of patients with declining GFR, showed that a combination of steroids and cyclophosphamide for the initial 3 months followed by azathioprine for a minimum of 2 years resulted in a significant preservation of renal function.[10] Other agents such as mycophenolate mofetil, ciclosporin and mizoribine have also been tried with varying results. A study from Mayo Clinic did show that long term treatment with omega-3 fatty acids results in slight reduction of progression to kidney failure, without, however, reducing proteinuria in a subset of patients with high risk of worsening kidney function.[11] However, these results have not been reproduced by other study groups and in two subsequent meta-analyses.[12][13] However, fish oil therapy does not have the drawbacks of immunosuppressive therapy. Also, apart from its unpleasant taste and abdominal discomfort, it is relatively safe to consume. The events that tend to progressive kidney failure are not unique to IgA nephropathy and non-specific measures to reduce the same would be equally useful. These include low-protein diet and optimal control of blood pressure. The choice of the antihypertensive agent is open as long as the blood pressure is controlled to desired level. However, Angiotensin converting enzyme inhibitors and Angiotensin II receptor antagonists are favoured due to their anti-proteinuric effect. ## Prognosis[edit] Male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidemia, older age, familial disease and elevated creatinine concentrations are markers of a poor outcome. Frank hematuria has shown discordant results with most studies showing a better prognosis, perhaps related to the early diagnosis, except for one group which reported a poorer prognosis. Proteinuria and hypertension are the most powerful prognostic factors in this group.[14] There are certain other features on kidney biopsy such as interstitial scarring which are associated with a poor prognosis. ACE gene polymorphism has been recently shown to have an impact with the DD genotype associated more commonly with progression to kidney failure. ## Epidemiology[edit] Men are affected three times as often as women. There is also marked geographic variation in the prevalence of IgA nephropathy throughout the world. It is the most common glomerular disease in the Far East and Southeast Asia, accounting for almost half of all the patients with glomerular disease.[citation needed] However, it accounts for only about 25% of the proportion in Europeans and about 10% among North Americans, with African–Americans having a very low prevalence of about 2%.[citation needed] A confounding factor in this analysis is the existing policy of screening and use of kidney biopsy as an investigative tool. School children in Japan undergo routine urinalysis (as do army recruits in Singapore) and any suspicious abnormality is pursued with a kidney biopsy, which might partly explain the high observed incidence of IgA nephropathy in those countries. ### Genetics[edit] Though various associations have been described, no consistent pattern pointing to a single susceptible gene has been identified to date. Associations described include those with C4 null allele, factor B Bf alleles, MHC antigens and IgA isotypes. ACE gene polymorphism (D allele) is associated with progression of kidney failure, similar to its association with other causes of chronic kidney failure. However, more than 90% of cases of IgA nephropathy are sporadic, with a few large pedigrees described from Kentucky and Italy (Online Mendelian Inheritance in Man (OMIM): 161950). ## History[edit] Dr Jean Berger William Heberden, the elder, first described the disease in 1801 in a 5-year-old child with abdominal pain, hematuria, hematochezia, and purpura of the legs.[15] In 1837, Johann Lukas Schönlein described a syndrome of purpura associated with joint pain and urinary precipitates in children. Eduard Heinrich Henoch, a student of Schönlein's, further associated abdominal pain and renal involvement with the syndrome. In 1968, Jean Berger (1930–2011), a pioneering French nephrologist, with co-author, the electron microscopist Nicole Hinglais, was the first to describe IgA deposition in this form of glomerulonephritis and therefore it is sometimes called Berger’s disease.[16] ## References[edit] 1. ^ D'Amico, G (1987). "The commonest glomerulonephritis in the world: IgA nephropathy". Q J Med. 64 (245): 709–27. PMID 3329736. 2. ^ C, Davin J (2001). "What is the difference between IgA nephropathy and Henoch-Schönlein purpura nephritis?". Kidney International. 59 (3): 823–34. doi:10.1046/j.1523-1755.2001.059003823.x. PMID 11231337. 3. ^ Magistroni, Riccardo (2015). "New developments in the genetics, pathogenesis, and therapy of IgA nephropathy". Kidney International. 88 (5): 974–89. doi:10.1038/ki.2015.252. PMC 4653078. PMID 26376134. 4. ^ Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity". J Autoimmun. 57 (6): 1–13. doi:10.1016/j.jaut.2014.12.002. PMC 4340844. PMID 25578468. 5. ^ Smith AC, Molyneux K, Feehally J, Barratt J (2006). "O-glycosylation of serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy". J Am Soc Nephrol. 17 (12): 3520–28. doi:10.1681/ASN.2006060658. PMID 17093066. 6. ^ Suzuki, Hitoshi; Kiryluk, Krzysztof; Novak, Jan; Moldoveanu, Zina; Herr, Andrew; Renfrow, Matthew; Wyatt, Robert; Scolari, Francesco; Mestecky, Jiri; Gharavi, Ali; Julian, Bruce (October 1, 2011). "The Pathophysiology of IgA Nephropathy". Journal of the American Society of Nephrology. 22 (10): 1795–1803. doi:10.1681/ASN.2011050464. PMC 3892742. PMID 21949093. 7. ^ Xie Y, Chen X, Nishi S, Narita I, Gejyo F (2004). "Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy". Kidney Int. 65 (4): 1135–44. doi:10.1111/j.1523-1755.2004.00486.x. PMID 15086452. 8. ^ Clarkson AR, Seymour AE, Woodroffe AJ, McKenzie PE, Chan YL, Wootton AM (1980). "Controlled trial of phenytoin therapy in IgA nephropathy". Clin. Nephrol. 13 (5): 215–18. PMID 6994960. 9. ^ Kobayashi Y, Hiki Y, Kokubo T, Horii A, Tateno S (1996). "Steroid therapy during the early stage of progressive IgA nephropathy. A 10-year follow-up study". Nephron. 72 (2): 237–42. doi:10.1159/000188848. PMID 8684533. 10. ^ Ballardie FW, Roberts IS (2002). "Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy". J. Am. Soc. Nephrol. 13 (1): 142–48. PMID 11752031. 11. ^ Donadio JV, Bergstralh EJ, Offord KP, Spencer DC, Holley KE (1994). "A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group". N. Engl. J. Med. 331 (18): 1194–99. doi:10.1056/NEJM199411033311804. PMID 7935657. 12. ^ Strippoli GF, Manno C, Schena FP (2003). "An "evidence-based" survey of therapeutic options for IgA nephropathy: assessment and criticism". Am. J. Kidney Dis. 41 (6): 1129–39. doi:10.1016/S0272-6386(03)00344-5. PMID 12776264. 13. ^ Dillon JJ (1997). "Fish oil therapy for IgA nephropathy: efficacy and interstudy variability". J. Am. Soc. Nephrol. 8 (11): 1739–44. PMID 9355077. 14. ^ Bartosik LP, Lajoie G, Sugar L, Cattran DC (2001). "Predicting progression in IgA nephropathy". Am. J. Kidney Dis. 38 (4): 728–35. doi:10.1053/ajkd.2001.27689. PMID 11576875. 15. ^ Heberden W. Commentarii Di Morborium Historia et Curatione. London: Payne, 1801. 16. ^ Berger J, Hinglais N (1968). "Les depots intercapillaires d'IgA-IgG". J Urol Nephrol. 74: 694–95. ## External links[edit] * IGA Nephropathy on National Institute of Diabetes and Digestive and Kidney Diseases Classification D * ICD-10: N02.8 * ICD-9-CM: 583.9 * OMIM: 161950 * MeSH: D005922 * DiseasesDB: 1353 External resources * MedlinePlus: 000466 * eMedicine: med/886 * v * t * e Disease of the kidney glomerules Primarily nephrotic Non-proliferative * Minimal change * Focal segmental * Membranous Proliferative * Mesangial proliferative * Endocapillary proliferative * Membranoproliferative/mesangiocapillary By condition * Diabetic * Amyloidosis Primarily nephritic, RPG Type I RPG/Type II hypersensitivity * Goodpasture syndrome Type II RPG/Type III hypersensitivity * Post-streptococcal * Lupus * diffuse proliferative * IgA Type III RPG/Pauci-immune * Granulomatosis with polyangiitis * Microscopic polyangiitis * Eosinophilic granulomatosis with polyangiitis General * glomerulonephritis * glomerulonephrosis Authority control * NDL: 01219636 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	IgA nephropathy	c0017661	5,645	wikipedia	https://en.wikipedia.org/wiki/IgA_nephropathy	2021-01-18T18:31:18	{"gard": ["863"], "mesh": ["D005922"], "umls": ["C0017661"], "wikidata": ["Q1146454"]}
Goldenhar syndrome Other namesOculo-auriculo-vertebral spectrum (OAVS), oculo-auriculo-vertebral dysplasia (OAV), expanded spectrum of hemifacial microsomia, facioauriculovertebral dysplasia Female with Goldenhar syndrome, showing preauricular skin tags SpecialtyMedical genetics Goldenhar syndrome is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip and mandible on usually one side of the body. Common clinical manifestations include limbal dermoids, preauricular skin tags and strabismus.[1] It is associated with anomalous development of the first branchial arch and second branchial arch.[2] The term is sometimes used interchangeably with hemifacial microsomia, although this definition is usually reserved for cases without internal organ and vertebrae disruption. It affects between 1 in 3,500 and 1 in 5,600 live births, with a male-to-female ratio of 3:2.[3] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 Eponym * 7 References * 8 External links ## Signs and symptoms[edit] Limbal dermoid as seen in Goldenhar syndrome This condition can be inherited in an autosomal dominant manner. Chief markers of Goldenhar syndrome are incomplete development of the ear, nose, soft palate, lip, and mandible on usually one side of the body. Additionally, some patients will have growing issues with internal organs, especially heart, kidneys and lungs. Typically, the organ will either not be present on one side or will be underdeveloped. Note that while it is more usual for there to be problems on only one side, it has been known for defects to occur bilaterally (approximate incidence 10% of confirmed GS cases).[citation needed] Other problems can include severe scoliosis (twisting of the vertebrae), limbal dermoids and hearing loss (see hearing loss with craniofacial syndromes), and deafness or blindness in one or both ears/eyes. Granulosa cell tumors may be associated as well.[citation needed] ## Causes[edit] The cause of Goldenhar syndrome is largely unknown. However, it is thought to be multifactorial, although there may be a genetic component, which would account for certain familial patterns. It has been suggested that there is a branchial arch development issue late in the first trimester.[citation needed] An increase in Goldenhar syndrome in the children of Gulf War veterans has been suggested, but the difference was shown to be statistically insignificant.[4] ## Diagnosis[edit] Diagnosis is based on clinical features. General features include unilateral facial asymmetry. Ocular abnormalities include limbal dermoids, strabismus. Otorhinolaryngological features include microtia, partial to complete atresia of external acoustic meatus, preauricular skin tags, deafness, macrosomia. Skeletal abnormalities include mandibular deformities, scoliosis. Other organ abnormalities include cardiac defects and renal abnormalities.[citation needed] ## Treatment[edit] Treatment is usually confined to such surgical intervention as may be necessary to help the child to develop e.g. jaw distraction/bone grafts, ocular dermoid debulking (see below), repairing cleft palate/lip, repairing heart malformations or spinal surgery. Some patients with Goldenhar syndrome will require assistance as they grow by means of hearing aids or glasses.Stem cell grafting (womb tissue grafting) has been successfully used to "reprogram" eye dermoids, effectively halting the regrowth of eye dermoids. These tissues that grow on the eye are "mis-programmed" cells (sometimes tooth or nail cells instead of eye cells).[citation needed] ## Epidemiology[edit] Prevalence ranges from 1 in 3,500 to 5,600 live births. Male-female ratio is found to be 3:2.[5] ## Eponym[edit] The condition was documented in 1952 by Belgian–American ophthalmologist Maurice Goldenhar (1924–2001).[6][7] ## References[edit] 1. ^ Zaka-ur-Rab Z, Mittal S (2007). "Optic Nerve Head Drusen in Goldenhar Syndrome" (PDF). JK Science. 9 (1): 33–34.[1] 2. ^ Touliatou V, Fryssira H, Mavrou A, Kanavakis E, Kitsiou-Tzeli S (2006). "Clinical manifestations in 17 Greek patients with Goldenhar syndrome". Genet. Couns. 17 (3): 359–70. PMID 17100205. 3. ^ Sudarshan P Gaurkar; Khushboo D Gupta; Kirti S Parmar & Bela J Shah (2013). "Goldenhar Syndrome: A Report of 3 Cases". Indian Journal of Dermatology. 58 (3): 244. doi:10.4103/0019-5154.110876. PMC 3667321. PMID 23723509. 4. ^ Araneta MR, Moore CA, Olney RS, et al. (1997). "Goldenhar syndrome among infants born in military hospitals to Gulf War veterans". Teratology. 56 (4): 244–251. doi:10.1002/(SICI)1096-9926(199710)56:4<244::AID-TERA3>3.0.CO;2-Z. PMID 9408975. 5. ^ Kokavec, R (September 2006). "Goldenhar syndrome with various clinical manifestations". The Cleft Palate-Craniofacial Journal. 43 (5): 628–34. doi:10.1597/05-094. PMID 16986988. S2CID 42914089. 6. ^ synd/2300 at Who Named It? 7. ^ M. Goldenhar. Associations malformatives de l’oeil et de l’oreille, en particulier le syndrome dermoïde epibulbaire-appendices auriculaires-fistula auris congenita et ses relations avec la dysostose mandibulo-faciale. Journal de génétique humaine, Genève, 1952, 1: 243-282. ## External links[edit] Classification D * ICD-10: Q87.0 * OMIM: 164210 * MeSH: D006053 * DiseasesDB: 31292 External resources * Orphanet: 374 * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Goldenhar syndrome	c0265240	5,646	wikipedia	https://en.wikipedia.org/wiki/Goldenhar_syndrome	2021-01-18T19:02:01	{"gard": ["6540"], "mesh": ["D006053"], "umls": ["C0432130"], "orphanet": ["374"], "wikidata": ["Q769988"]}
Familial dysfibrinogenemia is a coagulation disorder characterized by a bleeding tendency due to a functional anomaly of circulating fibrinogen. ## Epidemiology Prevalence is unknown but dysfibrinogenemia is more frequent than afibrinogenemia which has a prevalence of 1/1,000,000. ## Clinical description Most patients with dysfibrinogenemia are asymptomatic. The others may have mild bleeding symptoms or even thrombosis. ## Etiology The deficiency is due to various mutations in the FGA, FGB, or FGG genes. ## Genetic counseling Transmission is mainly autosomal dominant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Familial dysfibrinogenemia	c0272350	5,647	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98881	2021-01-23T18:55:25	{"gard": ["2004"], "mesh": ["C562727"], "omim": ["616004"], "umls": ["C0272350"], "icd-10": ["D68.2"]}
A number sign (#) is used with this entry because the Guion-Almeida type of mandibulofacial dysostosis (MFDGA) is caused by heterozygous mutation in the EFTUD2 gene (603892) on chromosome 17q21. Description Mandibulofacial dysostosis with microcephaly is a rare syndrome comprising progressive microcephaly, midface and malar hypoplasia, micrognathia, microtia, dysplastic ears, preauricular skin tags, significant developmental delay, and speech delay. Many patients have major sequelae, including choanal atresia that results in respiratory difficulties, conductive hearing loss, and cleft palate (summary by Lines et al., 2012). Clinical Features Guion-Almeida et al. (2000) reported 2 Brazilian boys with mental and growth retardation, microcephaly, trigonocephaly, preauricular skin tags, and cleft palate. Guion-Almeida et al. (2006) reevaluated these patients and reported 2 additional patients, a Brazilian boy and girl. In addition to the features noted by Guion-Almeida et al. (2000), all 4 patients had zygomatic arch hypoplasia and accentuated micrognathia, and all had severe language and speech delay. Guion-Almeida et al. (2006) concluded that this combination of signs represents a novel form of mandibulofacial dysostosis. Ozkan et al. (2006) reported a male infant with esophageal atresia and distal tracheoesophageal fistula, micrognathia, U-shaped cleft palate, low-set right ear with microtia, glossoptosis, and right congenital radioulnar synostosis. The authors stated that the association of Pierre Robin sequence (261800) with congenital radioulnar synostosis and esophageal atresia had not previously been reported. Wieczorek et al. (2007) described a sister and brother with esophageal atresia, microcephaly, hypoplasia of the zygomatic arch, microcephaly, micrognathia, cup-shaped ears, congenital heart defect, and mental retardation. The brother was more severely affected, with more pronounced facial dysmorphism, progression of microcephaly with age, and bilateral absence of the zygomatic arch. Their mother was mildly affected, with only right-sided hypoplasia of the zygomatic complex with partial aplasia of the zygomatic arch. Wieczorek et al. (2009) reported 3 unrelated patients with sporadic occurrence of a mandibulofacial dysostosis syndrome with microcephaly and developmental delay. The children were born to unrelated parents of Turkish, German, and Spanish origin, respectively. Microcephaly (-2.2 to 3.7 SD) was apparent at birth, as were microtia, upturned nose, choanal atresia, malar hypoplasia, and micrognathia. Ears were dysplastic or hypoplastic with atresia or stenosis of the external auditory canal resulting in conductive hearing loss, preauricular tags, and hypoplasia of the upper part of the helix. Choanal atresia resulted in breathing difficulties. One patient had downslanting palpebral fissures and 2 had upslanting palpebral fissures. One had mild pulmonary stenosis, and another had atrial septal defect and cleft palate. All had delayed psychomotor development. Brain MRI of 1 patient at age 12 months showed delayed myelination, and bone scan at age 15 months showed retarded bone age. This patient developed seizures at age 7 years. Another patient had short neck and slender fingers with proximally located thumbs. Molecular studies excluded mutations in the TCOF1 (606847), HOXA2 (604685), and CHD7 (608892) genes in all patients. Wieczorek et al. (2009) noted similarities between these patients and the 2 sisters reported by Megarbane et al. (2005) (see 221300) and the sister and brother described by Wieczorek et al. (2007), although none of the sibs had choanal atresia. Lines et al. (2012) reported follow-up of the patients reported by Guion-Almeida et al. (2006) and those of Wieczorek et al. (2009), as well as 7 additional patients with a similar phenotype. The patients ranged in age from 1 to 13 years; none had a family history of the disorder. Most were full-term infants, with microcephaly at birth, which progressed after birth to -3.0 to 6 SD. Other common features included malar hypoplasia, micrognathia, oblique palpebral fissures, and microtia, usually resulting in conductive hearing loss. Preauricular tags were found in most. Six patients had choanal atresia, 6 patients had a cleft palate, and 1 had bifid uvula. All had mild to moderate global developmental delay, with delayed walking and delayed or absent speech. Five developed seizures. More variable features included cardiac septal defects (6), proximally placed thumbs (4), and cryptorchidism (2). Vincent et al. (2016) sequenced the EFTUD2 gene in 11 patients with suspected MFDM or MFD Guion-Almeida type 1 and identified mutations in 4 of those patients. All 4 patients had microcephaly, intellectual disability, malar and mandibular hypoplasia, deafness, and downward slanting palpebral fissures. Of 2 patients examined, both had microtia. One patient presented with esophageal atresia and 1 with complex cardiac malformation involving an atrial septal defect, patent ductus arteriosus, and bicuspid aortic valve. Notably, none of them had coloboma of the lower lid, projection of scalp hair onto the lateral cheek, renal malformation, or anomaly of the limbs. Inheritance Lines et al. (2012) found that all 12 molecularly confirmed cases of MFDM occurred de novo. However, Guion-Almeida et al. (2009) reported 1 instance of a Brazilian mother and son with variable manifestations of a similar disorder; molecular analysis was not performed. The boy had microcephaly, mandibulofacial dysostosis, S-shaped palpebral fissures, unusual ears with skin tags, micrognathia, cleft palate, and mental retardation with speech delay. The ears were small and cup-shaped with an atretic meatus, and he had conductive hearing loss. He had respiratory difficulties at birth. His mother had a similar craniofacial phenotype, with microcephaly, S-shaped palpebral fissures, zygomatic arch hypoplasia, micrognathia, malformed ears, and preauricular skins tags, but without cleft palate, mental retardation, or speech delay. However, in infancy she had mild motor developmental delay and learning difficulties. Molecular Genetics In 12 unrelated patients with mandibulofacial dysostosis with microcephaly, Lines et al. (2012) identified heterozygous de novo mutations in or deletions involving the EFTUD2 gene (see, e.g., 603892.0001-603892.0005). A range of mutations, including deletion, frameshift, splice site, nonsense, and missense mutations, were identified, consistent with haploinsufficiency as the disease mechanism. The mutations were found by exome capture and high-throughput sequencing of 4 unrelated affected individuals, followed by analysis of EFTUD2 in 8 additional patients. All 3 patients reported by Wieczorek et al. (2009) had mutations, as did the 2 Brazilian patients reported by Guion-Almeida et al. (2006). Because of the overlap in features between the Nager type of acrofacial dysostosis (AFD1; 154400), which is caused by mutation in the SF3B4 gene (605593), and MFDM, Bernier et al. (2012) analyzed the EFTUD2 gene in AFD patients who were negative for mutation in SF3B4 and identified a nonsense mutation in EFTUD2 in 1 patient (603892.0006). The authors noted that in retrospect the patient exhibited microcephaly, suggesting that MFDM rather than Nager syndrome was the appropriate diagnosis. Need et al. (2012) performed whole-exome sequencing in 12 unrelated patients with unexplained and apparently genetic conditions, along with their unaffected parents. In 2 of the trios, in which the offspring had microcephaly, facial dysmorphism, dysplastic ears, and hearing loss, among other features, Need et al. (2012) identified a splice site and a frameshift insertion/deletion in the EFTUD2 gene, respectively. Analysis of mRNA from the proband with the splice site mutation and his parents did not reveal altered splicing or expression level. Need et al. (2012) concluded that EFTUD2 was a leading candidate for explaining the conditions in these children, and noted that both showed similarities to the patients studied by Lines et al. (2012). Gordon et al. (2012) analyzed the EFTUD2 gene in 3 groups of patients: 17 cases with isolated esophageal atresia, 19 cases with oculoauriculovertebral spectrum (OAVS; see 164210), and 14 patients with mandibulofacial dysostosis and esophageal atresia and/or microcephaly. No mutations were found in the first 2 groups, but 10 of the patients in the last group had pathogenic EFTUD2 mutations (see, e.g., 603892.0007 and 603892.0008) or deletions. Of the 10 patients with pathogenic EFTUD2 mutations, 8 presented with esophageal atresia as a component of the phenotype; Gordon et al. (2012) concluded that esophageal atresia is an additional malformation caused by heterozygous EFTUD2 loss-of-function mutations. The authors noted that microcephaly might not be a consistent feature in this syndrome and proposed designating the entity 'MFD Guion-Almeida type.' They also suggested that the 2 patients with OAVS and esophageal atresia reported by Sutphen et al. (1995) (see hemifacial microsomia, 164210), and possibly the familial cases described by Wieczorek et al. (2007) and the patient reported by Ozkan et al. (2006), might represent additional cases of this syndrome. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (of varying degrees) HEAD & NECK Head \- Microcephaly, progressive (-3 to 6 SD) \- Trigonocephaly Face \- Midface hypoplasia \- Malar hypoplasia \- Prominent philtrum \- Micrognathia \- Buccal tags Ears \- Microtia \- Preauricular skin tags \- External auditory meatus atresia \- Low-set ears \- Overfolded helices \- Hypoplasia of the upper part of the helix \- Dysplastic ears \- Conductive hearing loss Eyes \- Upslanting palpebral fissures \- Downslanting palpebral fissures \- Epicanthal folds \- Telecanthus Nose \- Choanal atresia (in some patients) \- Upturned nose \- Short nose \- Anteverted nares Mouth \- Cleft palate (in some patients) CARDIOVASCULAR Heart \- Atrial septal defect \- Ventricular septal defect (in some patients) RESPIRATORY \- Breathing difficulties due to choanal atresia ABDOMEN Gastrointestinal \- Esophageal atresia (in some patients) \- Feeding problems SKELETAL Hands \- Preaxial polydactyly \- Slender fingers \- Proximally placed thumbs (in some patients) NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Severe speech delay \- Seizures (in some patients) MISCELLANEOUS \- De novo mutation resulting in haploinsufficiency of EFTUD2 ( 603892 ) MOLECULAR BASIS \- Caused by mutation in the elongation factor Tu GTP-binding domain-containing 2 gene (EFTUD2, 603892.0001 ) ▲ 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	MANDIBULOFACIAL DYSOSTOSIS, GUION-ALMEIDA TYPE	c1864652	5,648	omim	https://www.omim.org/entry/610536	2019-09-22T16:04:23	{"doid": ["0080196"], "mesh": ["C537405"], "omim": ["610536"], "orphanet": ["79113"], "synonyms": ["Alternative titles", "MANDIBULOFACIAL DYSOSTOSIS WITH MICROCEPHALY", "GROWTH AND MENTAL RETARDATION, MANDIBULOFACIAL DYSOSTOSIS, MICROCEPHALY, AND CLEFT PALATE"], "genereviews": ["NBK214367"]}
For the glacial landform sometimes spelled eschar, see Esker. Look up eschar in Wiktionary, the free dictionary. An eschar (/ˈɛskɑːr/; Greek: eschara) is a slough[1] or piece of dead tissue that is cast off from the surface of the skin, particularly after a burn injury, but also seen in gangrene, ulcer, fungal infections, necrotizing spider bite wounds, tick bites associated with spotted fevers, and exposure to cutaneous anthrax. The term "eschar" is not interchangeable with "scab". An eschar contains necrotic tissue, whereas a scab is composed of dried blood and exudate. Eschar on the back of the knee on a patient with lymphangitis caused by Rickettsia sibirica Black eschars are most frequently attributed in medicine to cutaneous anthrax (infection by Bacillus anthracis), which may be contracted through herd animal exposure, but can also be obtained from Pasteurella multocida exposure in cats and rabbits. A newly-identified human rickettsial infection, R. parkeri rickettsiosis, can be differentiated from Rocky Mountain spotted fever by the presence of an eschar at the site of inoculation.[2] Eschar is sometimes called a black wound because the wound is covered with thick, dry, black necrotic tissue. Eschar may be allowed to slough off naturally, or it may require surgical removal (debridement) to prevent infection, especially in immunocompromised patients (e.g. if a skin graft is to be conducted). If eschar is on a limb, it is important to assess peripheral pulses of the affected limb to make sure blood and lymphatic circulation is not compromised. If circulation is compromised, an escharotomy, or surgical incision through the eschar, may be indicated. ## Contents * 1 Escharotic * 2 See also * 3 References * 4 External links ## Escharotic[edit] An escharotic is a substance that kills unwanted or diseased tissue, usually skin or superficial growths like warts, leaving them to slough off. Examples include: * inorganic reagents, such as strong acids and alkalis, or cytotoxic salts of heavy metals, for example zinc or silver * organic compounds such as sanguinarine, salicylic acid, and certain medicines like imiquimod * irritant or corrosive fluids from plants, such as latex or resins from various species of Ficus, Euphorbia, Carica, or Taraxacum * refrigerants, which kill the tissue by freezing; examples include liquid nitrogen, solid carbon dioxide, and its solution in ether Escharotics have long been used in medicine. In conventional modern practice some still are useful for topical treatment of growths such as warts. For lack of anything better in the past, escharotics once were more widely used, and for example, popular products included so-called black salves, with ingredients such as zinc chloride, plus sanguinarine in the form of bloodroot extract. These and others were traditional as topical treatments for localised skin cancers in herbal medicine. They combined unreliability in eradication of the cancer, with harmful effects such as scarring, serious injury, and disfigurement. Consequently escharotic salves now are strictly regulated in most western countries, and available on prescription only. Some prosecutions have been pursued over unlicensed sales of escharotic products such as Cansema. ## See also[edit] * Wound healing ## References[edit] 1. ^ "eschar" at Dorland's Medical Dictionary 2. ^ Paddock, C. D.; Finley, R. W.; Wright, C. S.; Robinson, H. N.; Schrodt, B. J.; Lane, C. C.; Ekenna, O.; Blass, M. A.; Tamminga, C. L.; Ohl, C. A.; McLellan, S. L. F.; Goddard, J.; Holman, R. C.; Openshaw, J. J.; Sumner, J. W.; Zaki, S. R.; Eremeeva, M. E. (2008). "Rickettsia parkeri Rickettsiosis and Its Clinical Distinction from Rocky Mountain Spotted Fever". Clinical Infectious Diseases. 47 (9): 1188–1196. doi:10.1086/592254. PMID 18808353. ## External links[edit] Classification D * ICD-10: R23.4 External resources * MedlinePlus: 002355 * Medical Separation of the Eschar [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Eschar	c0521172	5,649	wikipedia	https://en.wikipedia.org/wiki/Eschar	2021-01-18T18:30:58	{"wikidata": ["Q2478746"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-46 (MRD46) is caused by heterozygous mutation in the KCNQ5 gene (607357) on chromosome 6q14. Clinical Features Lehman et al. (2017) reported 2 unrelated boys with delayed psychomotor development, mild to moderate intellectual disability with limited speech, and hypotonia. Both achieved walking at 18 months of age. Neither had seizures and both had normal brain imaging. One patient had a sleep disorder. ### Clinical Variability Lehman et al. (2017) reported 2 unrelated patients with early-onset intractable seizures at ages 2 years and 5 months, respectively. Both had severe intellectual disability with absent speech. The patient with onset of seizures at age 2 years had mainly focal or absence seizures with normal brain imaging and was able to walk with an unstable ataxic gait. The patient with onset of seizures at age 5 months had profound intellectual disability and was nonambulatory with axial hypotonia and limb spasticity at age 10 years. She had hypsarrhythmia on EEG and progressive cerebral atrophy, consistent with epileptic encephalopathy. Molecular Genetics In 4 unrelated patients with MRD46, Lehman et al. (2017) identified de novo heterozygous missense mutations in the KCNQ5 gene (607357.0001-607357.0004). The mutations were found by exome sequencing and confirmed by Sanger sequencing. Electrophysiologic studies in Xenopus oocytes showed that 3 of the mutations resulted in a loss of function, whereas 1 resulted in a gain of function. The loss-of-function mutations were predicted to cause a lowered seizure threshold as a result of decreased repolarization reserve. The gain-of-function mutation (P369R; 607357.0004) was found in the most severely affected patient, who had epileptic encephalopathy. INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability, variably severity \- Impaired coordination \- Unsteady gait \- Lack of ambulation \- Poor or absent speech \- Seizures (in some patients) \- Sleep disorder (in some patients) \- Epileptic encephalopathy (1 patient) MISCELLANEOUS \- Variable severity \- De novo mutation \- Four unrelated patients have been reported (last curated August 2017) MOLECULAR BASIS \- Caused by mutation in the potassium channel, voltage-gated, KQT-like subfamily, member 5 gene (KCNQ5, 607357.0001 ) ▲ 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	MENTAL RETARDATION, AUTOSOMAL DOMINANT 46	c4539851	5,650	omim	https://www.omim.org/entry/617601	2019-09-22T15:45:32	{"omim": ["617601"]}
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: "Isovaleric acidemia" – news · newspapers · books · scholar · JSTOR (August 2008) (Learn how and when to remove this template message) Isovaleric acidemia Other namesIsovaleric aciduria, Isovaleric acid CoA dehydrogenase deficiency[1] Isovaleric acid SpecialtyEndocrinology Isovaleric acidemia is a rare autosomal recessive[2] metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.[3] ## Contents * 1 Symptoms and signs * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 5 Screening * 6 Treatment * 7 Prognosis * 8 Epidemiology * 9 See also * 10 References * 11 External links ## Symptoms and signs[edit] A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet.[4] This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.[5] In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.[citation needed] ## Genetics[edit] Isovaleric acidemia has an autosomal recessive pattern of inheritance. The disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.[citation needed] Mutations in both copies of the IVD gene result in isovaleric acidemia.[citation needed] ## Pathophysiology[edit] The enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase (EC 1.3.99.10), plays an essential role in breaking down proteins from the diet. Specifically, the enzyme is responsible for the third step in processing leucine, an essential amino acid. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, isovaleric acid and related compounds build up to toxic levels, damaging the brain and nervous system.[citation needed] ## Diagnosis[edit] The urine of newborns can be screened for isovaleric acidemia using mass spectrometry,[3] allowing for early diagnosis. Elevations of isovalerylglycine in urine and of isovalerylcarnitine in plasma are found. ## Screening[edit] On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four further genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including isovaleric acidemia.[6] ## Treatment[edit] Treatment consists of dietary protein restriction, particularly leucine. During acute episodes, glycine is sometimes given, which conjugates with isovalerate forming isovalerylglycine, or carnitine which has a similar effect. Elevated 3-hydroxyisovaleric acid is a clinical biomarker of biotin deficiency. Without biotin, leucine and isoleucine cannot be metabolized normally and results in elevated synthesis of isovaleric acid and consequently 3-hydroxyisovaleric acid, isovalerylglycine, and other isovaleric acid metabolites as well. Elevated serum 3-hydroxyisovaleric acid concentrations can be caused by supplementation with 3-hydroxyisovaleric acid, genetic conditions, or dietary deficiency of biotin. Some patients with isovaleric acidemia may benefit from supplemental biotin.[7] Biotin deficiency on its own can have severe physiological and cognitive consequences[8] that closely resemble symptoms of organic acidemias. ## Prognosis[edit] A 2011 review of 176 cases found that diagnoses made early in life (within a few days of birth) were associated with more severe disease and a mortality of 33%. Children diagnosed later, and who had milder symptoms, showed a lower mortality rate of ~3%.[9] ## Epidemiology[edit] Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States.[10] ## See also[edit] * Maple syrup urine disease * Methylmalonic acidemia * Propionic acidemia ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 243500 2. ^ Lee, Yw; Lee, Dh; Vockley, J; Kim, Nd; Lee, Yk; Ki, Cs (September 2007). "Different spectrum of mutations of isovaleryl-CoA dehydrogenase (IVD) gene in Korean patients with isovaleric acidemia". Molecular Genetics and Metabolism. 92 (1–2): 71–7. doi:10.1016/j.ymgme.2007.05.003. PMC 4136440. PMID 17576084. 3. ^ a b Dionisi-Vici, C; Deodato, F; Röschinger, W; Rhead, W; et al. (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis. 29 (2–3): 383–389. doi:10.1007/s10545-006-0278-z. PMID 16763906. S2CID 19710669. 4. ^ Tokatli A, Oskun T, Ozalp I (1998). "Isovaleric acidemia. Clinical presentation of 6 cases". The Turkish Journal of Pediatrics. 40 (1): 111–119. PMID 9673537. 5. ^ "Isovaleric Acidemia". National Organization for Rare Disorders. 6. ^ "New screening will protect babies from death and disability". screening.nhs.uk. Archived from the original on 2015-06-10. 7. ^ http://www.ommbid.com/OMMBID/the_online_metabolic_and_molecular_bases_of_inherited_disease/b/abstract/part9/ch93 8. ^ "Genova Diagnostics (GDX) - Diagnostic Laboratory Testing for Wellness & Preventive Medicine". metametrix.com. 9. ^ Grünert, Sarah C.; Wendel, Udo; Lindner, Martin; Leichsenring, Michael; Schwab, K. Otfried; Vockley, Jerry; Lehnert, Willy; Ensenauer, Regina (2012-01-01). "Clinical and neurocognitive outcome in symptomatic isovaleric acidemia". Orphanet Journal of Rare Diseases. 7: 9. doi:10.1186/1750-1172-7-9. ISSN 1750-1172. PMC 3292949. PMID 22277694. 10. ^ "Isovaleric acidemia". Genetics Home Reference. 4 May 2015. ## External links[edit] * Isovaleric acidemia at NLM Genetics Home Reference * GeneReviews: The Organic Acidemias Classification D * ICD-10: E71.1 * ICD-9-CM: 270.3 * OMIM: 243500 * MeSH: C538167 * DiseasesDB: 29840 External resources * Orphanet: 33 * v * t * e Inborn error of amino acid metabolism K→acetyl-CoA Lysine/straight chain * Glutaric acidemia type 1 * type 2 * Hyperlysinemia * Pipecolic acidemia * Saccharopinuria Leucine * 3-hydroxy-3-methylglutaryl-CoA lyase deficiency * 3-Methylcrotonyl-CoA carboxylase deficiency * 3-Methylglutaconic aciduria 1 * Isovaleric acidemia * Maple syrup urine disease Tryptophan * Hypertryptophanemia G G→pyruvate→citrate Glycine * D-Glyceric acidemia * Glutathione synthetase deficiency * Sarcosinemia * Glycine→Creatine: GAMT deficiency * Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine * Carnosinemia * Histidinemia * Urocanic aciduria Proline * Hyperprolinemia * Prolidase deficiency Glutamate/glutamine * SSADHD G→propionyl-CoA→ succinyl-CoA Valine * Hypervalinemia * Isobutyryl-CoA dehydrogenase deficiency * Maple syrup urine disease Isoleucine * 2-Methylbutyryl-CoA dehydrogenase deficiency * Beta-ketothiolase deficiency * Maple syrup urine disease Methionine * Cystathioninuria * Homocystinuria * Hypermethioninemia General BC/OA * Methylmalonic acidemia * Methylmalonyl-CoA mutase deficiency * Propionic acidemia G→fumarate Phenylalanine/tyrosine Phenylketonuria * 6-Pyruvoyltetrahydropterin synthase deficiency * Tetrahydrobiopterin deficiency Tyrosinemia * Alkaptonuria/Ochronosis * Tyrosinemia type I * Tyrosinemia type II * Tyrosinemia type III/Hawkinsinuria Tyrosine→Melanin * Albinism: Ocular albinism (1) * Oculocutaneous albinism (Hermansky–Pudlak syndrome) * Waardenburg syndrome Tyrosine→Norepinephrine * Dopamine beta hydroxylase deficiency * reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine * aspartate) * Argininemia * Argininosuccinic aciduria * Carbamoyl phosphate synthetase I deficiency * Citrullinemia * N-Acetylglutamate synthase deficiency * Ornithine transcarbamylase deficiency/translocase deficiency Transport/ IE of RTT * Solute carrier family: Cystinuria * Hartnup disease * Iminoglycinuria * Lysinuric protein intolerance * Fanconi syndrome: Oculocerebrorenal syndrome * Cystinosis Other * 2-Hydroxyglutaric aciduria * Aminoacylase 1 deficiency * Ethylmalonic encephalopathy * Fumarase deficiency * Trimethylaminuria [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Isovaleric acidemia	c0268575	5,651	wikipedia	https://en.wikipedia.org/wiki/Isovaleric_acidemia	2021-01-18T18:50:01	{"gard": ["465"], "mesh": ["C538167"], "umls": ["C0268575"], "icd-9": ["270.3"], "orphanet": ["33"], "wikidata": ["Q3278042"]}
Duverney fracture SpecialtyOrthopedic Duverney fractures are isolated pelvic fractures involving only the iliac wing. They are caused by direct trauma to the iliac wing, and are generally stable fractures as they do not disrupt the weight bearing pelvic ring.[1] The fracture is named after the French surgeon Joseph Guichard Duverney who described the injury in his book Maladies des Os which was published posthumously in 1751.[2] ## Contents * 1 Presentation * 1.1 Complications * 2 Diagnosis * 3 Management * 4 References ## Presentation[edit] ### Complications[edit] Malunion and deformity of the iliac wing can occur. Injury to the internal iliac artery can occur, leading to hypovolaemic shock. Perforation of the bowel can occur, leading to sepsis.[3] Damage to the adjacent nerves of the lumbosacral plexus has also been described.[2] ## Diagnosis[edit] Duverney fractures can usually be seen on pelvic X-rays, but CT scans are required to fully delineate the fracture and to look for associated fractures involving the pelvic ring.[3] ## Management[edit] Since fractures that do not involve the weight bearing part of the pelvic ring tend to be stable fractures, they can often be managed without surgery. These fractures tend to be very painful, so walking aids such as crutches or walking frames may be needed until the pain settles.[3] Open reduction internal fixation is sometimes required to correct deformity,[4] and surgery may be required if there is damage to blood vessels, nerves or organs, or if the fracture is open.[3] ## References[edit] 1. ^ "Duverney fracture". Medcyclopaedia. GE. 2. ^ a b Amr, SM; Abdel-Meguid, KMS; Kholeif, AM (February 2002). "Neurologic injury caused by fracture of the iliac wing (Duverney's Fracture): Case report". Journal of Trauma-Injury Infection & Critical Care. 52 (2): 370–6. doi:10.1097/00005373-200202000-00027. 3. ^ a b c d Iliac wing fractures at Orthopaedia.com 4. ^ Tile, Marvin; David Helfet; James Kellam (2003). Fractures of the Pelvis and Acetabulum. Lippincott Williams & Wilkins. pp. 263–4. ISBN 978-0-7817-3213-0. * v * t * e Fractures and cartilage damage General * Avulsion fracture * Chalkstick fracture * Greenstick fracture * Open fracture * Pathologic fracture * Spiral fracture Head * Basilar skull fracture * Blowout fracture * Mandibular fracture * Nasal fracture * Le Fort fracture of skull * Zygomaticomaxillary complex fracture * Zygoma fracture Spinal fracture * Cervical fracture * Jefferson fracture * Hangman's fracture * Flexion teardrop fracture * Clay-shoveler fracture * Burst fracture * Compression fracture * Chance fracture * Holdsworth fracture Ribs * Rib fracture * Sternal fracture Shoulder fracture * Clavicle * Scapular Arm fracture Humerus fracture: * Proximal * Supracondylar * Holstein–Lewis fracture Forearm fracture: * Ulna fracture * Monteggia fracture * Hume fracture * Radius fracture/Distal radius * Galeazzi * Colles' * Smith's * Barton's * Essex-Lopresti fracture Hand fracture * Scaphoid * Rolando * Bennett's * Boxer's * Busch's Pelvic fracture * Duverney fracture * Pipkin fracture Leg Tibia fracture: * Bumper fracture * Segond fracture * Gosselin fracture * Toddler's fracture * Pilon fracture * Plafond fracture * Tillaux fracture Fibular fracture: * Maisonneuve fracture * Le Fort fracture of ankle * Bosworth fracture Combined tibia and fibula fracture: * Trimalleolar fracture * Bimalleolar fracture * Pott's fracture Crus fracture: * Patella fracture Femoral fracture: * Hip fracture Foot fracture * Lisfranc * Jones * March * Calcaneal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Duverney fracture	c0272578	5,652	wikipedia	https://en.wikipedia.org/wiki/Duverney_fracture	2021-01-18T18:58:53	{"umls": ["C0272578"], "wikidata": ["Q5317627"]}
Familial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints. These episodes are often accompanied by fever and sometimes a rash or headache. Occasionally inflammation may occur in other parts of the body, such as the heart; the membrane surrounding the brain and spinal cord; and in males, the testicles. In about half of affected individuals, attacks are preceded by mild signs and symptoms known as a prodrome. Prodromal symptoms include mildly uncomfortable sensations in the area that will later become inflamed, or more general feelings of discomfort. The first episode of illness in familial Mediterranean fever usually occurs in childhood or the teenage years, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity. The length of time between attacks is also variable and can range from days to years. During these periods, affected individuals usually have no signs or symptoms related to the condition. However, without treatment to help prevent attacks and complications, a buildup of protein deposits (amyloidosis) in the body's organs and tissues may occur, especially in the kidneys, which can lead to kidney failure. ## Frequency Familial Mediterranean fever primarily affects populations originating in the Mediterranean region, particularly people of Armenian, Arab, Turkish, or Jewish ancestry. The disorder affects 1 in 200 to 1,000 people in these populations. It is less common in other populations. ## Causes Mutations in the MEFV gene cause familial Mediterranean fever. The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin), which is found in white blood cells. This protein is involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this process is complete, the body stops the inflammatory response to prevent damage to its own cells and tissues. Mutations in the MEFV gene reduce the activity of the pyrin protein, which disrupts control of the inflammation process. An inappropriate or prolonged inflammatory response can result, leading to fever and pain in the abdomen, chest, or joints. Normal variations in the SAA1 gene may modify the course of familial Mediterranean fever. Some evidence suggests that a particular version of the SAA1 gene (called the alpha variant) increases the risk of amyloidosis among people with familial Mediterranean fever. ### Learn more about the genes associated with Familial Mediterranean fever * MEFV * SAA1 ## Inheritance Pattern Familial Mediterranean fever is almost always inherited in an autosomal recessive pattern, which means both copies of the MEFV 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. In rare cases, this condition appears to be inherited in an autosomal dominant pattern. An autosomal dominant inheritance pattern describes cases in which one copy of the altered gene in each cell is sufficient to cause the disorder. In autosomal dominant inheritance, affected individuals often inherit the mutation from one affected parent. However, another mechanism is believed to account for some cases of familial Mediterranean fever that were originally thought to be inherited in an autosomal dominant pattern. A gene mutation that occurs frequently in a population may result in a disorder with autosomal recessive inheritance appearing in multiple generations in a family, a pattern that mimics autosomal dominant inheritance. If one parent has familial Mediterranean fever (with mutations in both copies of the MEFV gene in each cell) and the other parent is an unaffected carrier (with a mutation in one copy of the MEFV gene in each cell), it may appear as if the affected child inherited the disorder only from the affected parent. This appearance of autosomal dominant inheritance when the pattern is actually autosomal recessive is called pseudodominance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Familial Mediterranean fever	c0031069	5,653	medlineplus	https://medlineplus.gov/genetics/condition/familial-mediterranean-fever/	2021-01-27T08:25:42	{"gard": ["6421"], "mesh": ["D010505"], "omim": ["249100", "134610"], "synonyms": []}
Reticular dysgenesis Other namesAK2 deficiency, Congenital aleukocytosis, De Vaal disease, Generalized hematopoietic hypoplasia, SCID with leukopenia Reticular dysgenesis is inherited in an autosomal recessive manner SpecialtyHematology Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in immunodeficiency.[1] Individuals with RD have mutations in both copies of the AK2 gene.[1] Mutations in this gene lead to absence of AK2 protein.[2] AK2 protein allows hematopoietic stem cells to differentiate and proliferate.[2] Hematopoietic stem cells give rise to blood cells.[2] Differentiation and proliferation of hematopoietic stem cells require a lot of energy and this energy is supplied by the mitochondria.[2] The energy metabolism of mitochondria is regulated by the AK2 protein.[2] If there is a mutation in the protein, that means that the mitochondria metabolism most likely will be altered and will not be able to provide enough energy to the hematopoietic stem cells.[2] As a result, hematopoietic stem cells will not be able to differentiate or proliferate.[2] The immune system consists of specialized cells that work together to fight off bacteria, fungi and viruses.[3] These cells include T lymphocytes (T cells), that primarily mediate the immune system, B lymphocytes (B cells) and Natural Killer cells.[3] Patients with RD have a genetic defect that affects the T cells and at least one other type of immune cell.[4] Since more than one type of immune cell is affected, this disease is classified as a severe combined immunodeficiency disease (SCID).[3] A weakened immune system leaves patients susceptible to different kinds of infection. Commonly, patients who are diagnosed with RD also have bacterial sepsis and/or pneumonia.[4]The annual incidence has been estimated at 1/3,000,000-1/5,000,000 and both females and males are affected.[5] ## Contents * 1 Signs and symptoms * 2 Risk factors * 3 Diagnosis * 4 Treatment * 4.1 Hematopoietic Stem Cell Transplantation * 4.2 Cytokine Therapy * 5 Prognosis * 6 Research * 6.1 Gene Therapy * 7 References * 8 External links ## Signs and symptoms[edit] Signs and Symptoms Approximate Number of Patients Affected Abnormality of mitochondria metabolism 90% Abnormality of Neutrophils 90% Anemia 90% Aplasia/Hypoplasia of the thymus 90% Cellular immunodeficiency 90% Decreased antibody level in blood 90% Diarrhea 90% Hearing Impairment 90% Recurrent respiratory infection 90% Sepsis 90% Abnormality of temperature regulation 50% Malabsorption 50% Weight Loss 50% Dehydration 7.5% Skin rash 7.5% Skin Ulcer 7.5% [6] ## Risk factors[edit] * Condition follows an autosomal recessive pattern[7] * The mutated gene must be inherited from both the mother and father[7] * Both males and females must have an equal frequency of inheritance[7] ## Diagnosis[edit] Health professionals must look at a person's history, symptoms, physical exam and laboratory test in order to make a diagnosis. If the results show patients with low levels of lymphocytes, absence of granulocytes or absence of thymus then the patient may be suspected to have RD.[4] ## Treatment[edit] RD can only be treated temporarily through Hematopoietic stem cell transplantation (HSCT) and Cytokine Therapy.[4][8][9] ### Hematopoietic Stem Cell Transplantation[edit] Transplantation of stem cells are taken from the bone marrow, peripheral blood or umbilical cord of healthy, matched donors.[10] Hematopoietic Stem Cell Transplantation (HSCT) involves intravenous infusion of stem cells to those who have either a damaged bone marrow or defective immune system.[4][10] Transplantation is a simple process. Bone marrow product is infused through a central vein over a period of several hours.[10] The hematopoietic cells are able to go to the bone marrow through tracking mechanisms.[10] Patients who suffer from RD will now have more stem cells that can differentiate into immune cells.[citation needed] ### Cytokine Therapy[edit] Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) can be used as a temporary cure.[8] GM-CSF stimulates production of white blood cells.[8] This cure is commonly used in patients who are awaiting bone marrow transplantation.[8] Response to this cure can vary.[8] Those with a more severe combined immunodeficiency may have no response to this therapy.[8] ## Prognosis[edit] The survival range is estimated to be 3 days to 17 weeks without treatment.[8] Patients die due to bacterial or viral infections.[8] Aggressive treatment with antibiotics is required and bone marrow transplant is common.[8] Patients undergoing bone marrow transplant, specifically from a matched sibling, have a higher 5 year survival rate than those receiving a transplant from other donors.[10] ## Research[edit] ### Gene Therapy[edit] Gene therapy is a relatively new concept in the field of SCID.[11] This therapy is currently undergoing clinical trial and has cured a small number of children suffering from X-linked SCID and recessive allele SCID.[11] Gene therapy aims to correct the underlying genetic abnormality in SCID.[11] In the case of RD, the genetic abnormality would be AK2 malfunction.[2] Stem cells are taken from an affected child's blood or bone marrow.[11] Then in laboratory conditions the stem cells are manipulated and corrected with gene technology.[11] They are then injected back into the patient.[11] Similarly, in bone transplant, stem cells are able to find their way back through tracking mechanisms.[10][11] ## References[edit] 1. ^ a b Pannicke, Ulrich; Hönig, Manfred; Hess, Isabell; Friesen, Claudia; Holzmann, Karlheinz; Rump, Eva-Maria; Barth, Thomas F; Rojewski, Markus T; Schulz, Ansgar (2009). "Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2". Nature Genetics. 41 (1): 101–105. doi:10.1038/ng.265. PMID 19043417. S2CID 205347130. 2. ^ a b c d e f g h Six, E.; Lagresle-Peyrou, C.; Susini, S.; De Chappedelaine, C.; Sigrist, N.; Sadek, H.; Chouteau, M.; Cagnard, N.; Fontenay, M. (2015-08-13). "AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages". Cell Death & Disease. 6 (8): e1856. doi:10.1038/cddis.2015.211. PMC 4558504. PMID 26270350. 3. ^ a b c "The Immune System and Primary Immunodeficiency \| Immune Deficiency Foundation". primaryimmune.org. Retrieved 2016-11-20. 4. ^ a b c d e Bertrand, Y.; Müller, S. M.; Casanova, J. L.; Morgan, G.; Fischer, A.; Friedrich, W. (2002-05-01). "Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patients". Bone Marrow Transplantation. 29 (9): 759–762. doi:10.1038/sj.bmt.1703531. ISSN 0268-3369. PMID 12040473. 5. ^ "Reticular dysgenesis: epidemiology". rarediseases. Genetic and rare diseases information center. Retrieved 17 April 2018. 6. ^ "Reticular dysgenesis". GARD. 7. ^ a b c "Severe Combined Immunodeficiency - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2016-11-20. 8. ^ a b c d e f g h i Calhoun, Christensen, DA, RD (1998). "Recent advances in the pathogenesis and treatment of nonimmune neutropenias in the neonate". Current Opinion in Hematology. 5 (1): 37–41. doi:10.1097/00062752-199801000-00007. PMID 9515201. S2CID 37329390. 9. ^ Scheinfeld, Noah (2019-08-05). "Intravenous Immunoglobulin". Intravenous Immunoglobulin. Medscape. 10. ^ a b c d e f Perumbeti, Ajay (2018-08-06). "Hematopoietic Stem Cell Transplantation". Medscape. 11. ^ a b c d e f g "Severe combined immunodeficiency (SCID)". Retrieved 2016-11-20. ## External links[edit] Classification D * ICD-10: D81.0 * MeSH: C538361 C538361, C538361 External resources * Orphanet: 33355 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Reticular dysgenesis	c1282908	5,654	wikipedia	https://en.wikipedia.org/wiki/Reticular_dysgenesis	2021-01-18T19:03:27	{"gard": ["8625"], "mesh": ["C538361"], "umls": ["C1282908"], "icd-10": ["D81.0"], "orphanet": ["33355"], "wikidata": ["Q7316718"]}
A number sign (#) is used with this entry because adolescent nephropathic cystinosis is caused by mutation in the gene encoding cystinosin (606272), which maps to chromosome 17p13. See also 219800 for general information about nephropathic cystinosis and the infantile type of the disorder. Clinical Features Adolescent nephropathic cystinosis manifests itself first at age 10 to 12 years with proteinuria due to glomerular damage rather than with the manifestations of tubular damage that occur first in infantile cystinosis. There is no excess amino aciduria and stature is normal. Photophobia, late development of pigmentary retinopathy, and chronic headaches are features. White cells show high cystine content in heterozygotes for this form of cystinosis, just as they do in infantile cystinosis. Spear et al. (1971) described glomerular changes in renal biopsies from a case of late-onset nephropathic cystinosis. Clinically the disorder shows a slowly progressive glomerular insufficiency rather than the prominent Fanconi syndrome, electrolyte and water disturbances, growth arrest, and rickets typical of infantile cystinosis. The patient was the only affected person in the family and the parents were not related (as one would expect if juvenile cystinosis is the genetic compound of infantile cystinosis and adult cystinosis). Molecular Genetics Attard et al. (1999) identified a mutation in the CTNS gene (606272.0008) in a patient with late-onset juvenile nephropathic cystinosis. Thoene et al. (1999) described 2 sibs in Taiwan with intermediate cystinosis who had linear growth and weight gain within 2 standard deviations of the mean for their ethnic group until the ages of 13 and 14 years when their plasma creatinine concentrations were 1.2 mg per deciliter and 3.3 mg per deciliter, respectively. They were found to be homozygous for a missense mutation in the CTNS gene substitution of lysine for the conserved asparagine at position 323 (N323K; 606272.0016). Presumably, this mutation allowed for some residual cystine transport, accounting for the mild clinical presentation. In 2 unrelated Spanish patients with juvenile-onset cystinosis, Macias-Vidal et al. (2009) identified compound heterozygosity for a missense mutation (S139F; 606272.0018) and truncating mutations (606272.0004 and 606272.0005, respectively). The S139F mutation had previously been identified in a patient with 'nonclassic' cystinosis (see 219800), with onset before age 7 years but a milder course of disease than the infantile nephropathic form, by Attard et al. (1999), who suggested that the mutation might allow production of functional protein or be located in a region of cystinosin that was not functionally important. INHERITANCE \- Autosomal recessive GROWTH Height \- Normal stature HEAD & NECK Eyes \- Corneal crystals \- Retinopathy GENITOURINARY Kidneys \- End stage renal disease SKELETAL \- Rickets LABORATORY ABNORMALITIES \- Proteinuria \- Elevated white blood cell cystine MISCELLANEOUS \- Onset of symptoms usually between 12-15 years \- Three type of cystinosis are recognized - infantile nephropathic ( 219800 ), juvenile or adolescent nephropathic ( 219900 ), and adult nonnephropathic ( 219750 ) MOLECULAR BASIS \- Caused by mutations in the cystinosis gene (CTNS, 219800.0008 ) ▲ 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	CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE	c0268626	5,655	omim	https://www.omim.org/entry/219900	2019-09-22T16:29:00	{"doid": ["1064"], "mesh": ["C562683"], "omim": ["219900"], "orphanet": ["411634", "213"], "synonyms": ["Alternative titles", "CYSTINOSIS, INTERMEDIATE"], "genereviews": ["NBK1400"]}
A number sign (#) is used with this entry because FG syndrome-2 (FGS2) is caused by mutation in the gene encoding filamin A (FLNA; 300017) on chromosome Xq28. Description Although the phenotypic spectrum and severity of FG syndrome is wide, the cardinal features include congenital hypotonia, delayed speech development, relative macrocephaly, dysmorphic facies, and anal anomalies or severe constipation (Unger et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (305450). Clinical Features Briault et al. (1999) reported a French boy with FG syndrome. His maternal uncle was mentally retarded. The proband had mental retardation, facial anomalies, prominent forehead, hypotonia, failure to thrive, constipation, and anteriorly placed anus, while his maternal uncle had mental retardation, facial anomalies, constipation, and bronchopulmonary infections, but no macrocephaly, frontal bossing, or anal anomalies. Unger et al. (2007) reported an 18-month-old German boy with severe constipation, large rounded forehead, prominent ears, frontal hair upsweep, and mild delay in language acquisition. The parents declined brain MRI studies. Mapping In a French boy with FG syndrome and in his mentally retarded maternal uncle, Briault et al. (1999) identified an X-chromosome inversion, inv(X)(q12q28). Using FISH in further studies of this family, Briault et al. (2000) identified 2 clones that crossed the breakpoints, one located at Xq11.2 and the other at Xq28 (FGS2). Molecular Genetics In a German boy with FGS2, Unger et al. (2007) identified a hemizygous mutation in the FLNA gene (P1291L; 300017.0028). His asymptomatic mother also carried the mutation, which was absent in 100 control chromosomes. Unger et al. (2007) also suggested that a patient reported by Hehr et al. (2006) with a FLNA mutation (300017.0024) and periventricular heterotopia, facial dysmorphism, and constipation may have also had FGS2. INHERITANCE \- X-linked GROWTH Weight \- Low weight HEAD & NECK Face \- Prominent forehead \- Rounded forehead Ears \- Prominent ears \- Hypoplasia of the upper crus of the antihelix Mouth \- Relatively small mouth ABDOMEN Gastrointestinal \- Constipation \- Normal placement of anus SKELETAL Feet \- Broad halluces SKIN, NAILS, & HAIR Hair \- Frontal upsweep of hair with cowlick NEUROLOGIC Central Nervous System \- Language delay, mild LABORATORY ABNORMALITIES \- Normal karyotype MISCELLANEOUS \- Based on report of 1 patient MOLECULAR BASIS \- Caused by mutation in the filamin A gene (FLNA, 300017.0028 ) ▲ 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	FG SYNDROME 2	c1845902	5,656	omim	https://www.omim.org/entry/300321	2019-09-22T16:20:33	{"mesh": ["C537923"], "omim": ["300321"]}
Benign childhood occipital epilepsy, Panayiotopoulos type is a rare, genetic neurological disorder characterized by late infancy to early-adolescence onset of prolonged, nocturnal seizures which begin with autonomic features (e.g. vomiting, pallor, sweating) and associate tonic eye deviation, impairment of consciousness and may evolve to a hemi-clonic or generalized convulsion. Autonomic status epilepticus may be the only clinical event in some cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid *[pop.]: population	Benign childhood occipital epilepsy, Panayiotopoulos type	c0393676	5,657	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98815	2021-01-23T19:06:31	{"mesh": ["D004828"], "icd-10": ["G40.0"], "synonyms": ["Early-onset benign childhood occipital epilepsy", "Panayiotopoulos syndrome"]}
OSLAM syndrome Other namesOsteosarcoma-limb anomalies-erythroid macrocytosis syndrome OSLAM syndrome is inherited in an autosomal dominant manner OSLAM syndrome is a rare autosomal dominant hereditary disorder. Its name is an initialism of "osteosarcoma, limb anomalies, and erythroid macrocytosis with megaloblastic marrow syndrome". OSLAM syndrome was recognised and described by Mulvilhill et al. as a syndrome that increases susceptibility to tumours and is characterised by an impaired regulation of bone and marrow development.[1][2] Individuals with OSLAM syndrome have an elevated risk of bone cancer, limb abnormalities, and enlarged red blood cells. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] * Bone cancer * Curved fifth fingers (clinodactyly) with brachymesophalangy (shortened phalanges of the toes and/or fingers (digits)) * Absence of one digital ray of the foot (a digit and corresponding metacarpal or metatarsal bone) * Bilateral radioulnar synostosis * Enlarged red blood cells * Dental decay * Short stature ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (August 2017) ## See also[edit] * Li-Fraumeni syndrome ## References[edit] 1. ^ Mulvihill J.J., Gralnick H.R., Whang-Peng J., Leventhal B.G. (1977.) Multiple childhood osteosarcomas in an American Indian family with erythoid macrocytosis and skeletal anomalies, Cancer, 40(6):3115–3122. 2. ^ Weber G.F. (2007.) Molecular Mechanisms of Cancer, Springer, pg. 558. ## External links[edit] Classification D * ICD-10: C41.9 * OMIM: 165660 * MeSH: C537138 External resources * Orphanet: 2760 This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	OSLAM syndrome	c1833792	5,658	wikipedia	https://en.wikipedia.org/wiki/OSLAM_syndrome	2021-01-18T18:58:18	{"gard": ["4129"], "mesh": ["C537138"], "umls": ["C1833792"], "orphanet": ["2760"], "wikidata": ["Q7073028"]}
A number sign (#) is used with this entry because this form of hypomaturation amelogenesis imperfecta (AI) is caused by homozygous mutation in the WDR72 gene (613214). For a phenotypic description and a discussion of genetic heterogeneity of the hypomaturation type of AI, see AI2A1 (204700). Clinical Features El-Sayed et al. (2009) studied 10 families with autosomal recessive hypomaturation amelogenesis imperfecta originating from Pakistan or Oman. The largest pedigree was Pakistani and had generalized AI with involvement of the primary and secondary dentitions. Radiographic appearance prior to eruption and clinical appearance upon eruption were consistent with near-normal enamel matrix volume formation; however, at the time of eruption, the enamel was creamier and more opaque than that of normal teeth. Once in the mouth, the enamel soon began to undergo posteruptive changes, including variable degrees of brown discoloration and loss of enamel tissue. In some instances enamel chipped away, but attrition was also evident. Variable malocclusions were observed, and 1 affected individual also had anterior open bite. Teeth were sensitive to thermal and physical stimuli. No other health problems segregated with AI. Lee et al. (2010) described 2 families with hypomaturation amelogenesis imperfecta. The teeth in the 3 affected sisters in a Mexican family (family 1) had rough, stained enamel that deteriorated after eruption. The enamel layer displayed reduced radiodensity. The 2 affected brothers in a Turkish family (family 2) had a milder phenotype but the same reduced rediodensity of the enamel layer. Mapping In a large Pakistani family segregating autosomal recessive AI, El-Sayed et al. (2009) identified a large region of homozygosity on chromosome 15; multipoint linkage analysis yielded a maximum lod score of 4.1 at D15S1016. Additional genotyping refined the locus to a 3-cM (4.4-Mb) interval on chromosome 15q21.3 between D15S1016 and D15S998, containing 16 annotated genes. Molecular Genetics In a large Pakistani family segregating autosomal recessive amelogenesis imperfecta mapping to chromosome 15q21.3, El-Sayed et al. (2009) sequenced 16 candidate genes and identified a nonsense mutation in the WDR72 gene (613214.0001). Analysis of the WDR72 gene in 4 Pakistani AI families and 5 Omani AI families revealed homozygosity for the same mutation in another Pakistani AI family with a similar clinical phenotype; in addition, 2 different WDR72 mutations were identified in 2 Omani AI families (613214.0002 and 613214.0003, respectively). The mutations all cosegregated consistently with the phenotype and were not found in controls. No mutations were detected in the 6 remaining AI families, indicating further genetic heterogeneity of hypomaturation AI. By whole-exome sequencing of the WDR72 gene in a Mexican family and a Turkish family segregating autosomal recessive amelogenesis imperfecta, Lee et al. (2010) identified the same homozygous 2-bp deletion (c.1467_1468delAT; 613214.0004) that segregated with the disorder in both families. INHERITANCE \- Autosomal recessive HEAD & NECK Teeth \- Amelogenesis imperfecta \- Opaque enamel at time of eruption \- Creamy enamel at time of eruption \- Posteruptive loss of surface enamel \- Rough enamel \- Discolored enamel \- Enamel layer shows reduced radiodensity \- Sensitive teeth (thermal and physical stimuli) \- Variable malocclusions (in some patients) MOLECULAR BASIS \- Caused by mutation in the WD repeat-containing protein 72 gene (WDR72, 613214.0001 ) ▲ 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)	AMELOGENESIS IMPERFECTA, HYPOMATURATION TYPE, IIA3	c0399372	5,659	omim	https://www.omim.org/entry/613211	2019-09-22T15:59:20	{"doid": ["0110061"], "mesh": ["C536606"], "omim": ["613211"], "orphanet": ["100033", "88661"]}
Childhood apraxia of speech occurs in children and is present from birth. It appears to be more common in boys than girls. Children with this condition have difficulty planning and producing the precise, refined, and specific movements of the tongue, lips, jaw, and palate that are necessary for intelligible speech. In many cases, the underlying cause of childhood apraxia of speech is unknown (idiopathic). Some cases are associated with a known neurological cause (such as intrauterine or early childhood stroke, infection, trauma, brain cancer or tumor resection, traumatic brain injury, etc.), and other cases occur as part of a complex neurobehavioral disorder (such as autism, epilepsy, fragile X syndrome, galactosemia, Rett syndrome, Prader-Willi syndrome or certain types of chromosome abnormalities). In some cases, researchers have found alterations (mutations) in the FOXP2 gene or loss of genetic material involving this gene. Treatment of childhood apraxia of speech involves speech therapy with a speech-language pathologist. Those with more severe cases will require more therapy than those with mild cases. The goal of therapy is to increase speech production and intelligibility. In some cases, augmentative and alternative forms of communication may be needed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Childhood apraxia of speech	c0750927	5,660	gard	https://rarediseases.info.nih.gov/diseases/12889/childhood-apraxia-of-speech	2021-01-18T18:01:29	{"mesh": ["D001072"], "omim": ["602081"], "orphanet": ["209908"], "synonyms": ["Developmental apraxia of speech", "Speech and language disorder with orofacial dyspraxia", "CAS", "Speech-language disorder type 1", "Speech-language disorder-1", "Developmental verbal dyspraxia", "DAS", "Articulatory apraxia", "Developmental verbal apraxia"]}
A rare genetic neurological disorder characterized by infantile or childhood onset of recurrent acute encephalopathic episodes with cerebellar and extrapyramidal involvement following febrile illnesses. During the episodes, patients typically show sudden onset of truncal ataxia, occasionally accompanied by lethargy and impairment of speech, as well as choreic and athetoid movements, seizures, loss of deep tendon reflexes, and presence of pathological reflexes. Episodes last from day to weeks and may leave residual symptoms such as speech impairment and poor coordination. There have been no further descriptions in the literature since 1983. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Neuhauser-Eichner-Opitz syndrome	c1851708	5,661	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2672	2021-01-23T18:14:02	{"gard": ["3949"], "mesh": ["C536407"], "omim": ["130950"], "umls": ["C1851708"], "synonyms": ["Recurrent encephalophathy of childhood"]}
Palatal myoclonus Play media Palatal myoclonus Palatal myoclonus is a rapid spasm of the palatal (roof of the mouth) muscles, which results in clicking or popping in the ear. The movements of the palate vary in rate between 40 and 200 beats per minute. Chronic clonus is often due to lesions of the central tegmental tract (which connects the red nucleus to the ipsilateral inferior olivary nucleus). Uniquely, the clicking noise does not subside when the patient sleeps. When associated with eye movements, it is known as oculopalatal myoclonus ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Classifications * 3 Treatment * 3.1 Drugs * 4 General references * 5 References * 6 External links ## Signs and symptoms[edit] Signs and symptoms of Palatal Myoclonus include: Rhythmic, jerky movements in the face, eyeballs, tongue, jaw, vocal cord or extremities (mostly hands).[1] ## Diagnosis[edit] ### Classifications[edit] physiologic, essential, epileptic, and symptomatic ## Treatment[edit] ### Drugs[edit] Drugs used to treat palatal myoclonus include clonazepam, carbamazepine, baclofen, anticholinergics, tetrabenazine, valproic acid, phenytoin, lamotrigine, sumatriptan, and PIR ## General references[edit] * http://www.tchain.com/otoneurology/disorders/central/opm.html * https://www.hindawi.com/journals/criot/2013/231505/ * "NINDS Tremor Information Page". National Institute of Neurological Disorders and Stroke. July 20, 2007. Archived from the original on October 6, 2007. Retrieved 2007-10-08. [2] [3] ## References[edit] 1. ^ Kim, Jong S.; Caplan, Louis R. (2016). "26 Vertebrobasilar Disease". Stroke (Sixth ed.). Elsevier. pp. 413–448.e7. doi:10.1016/B978-0-323-29544-4.00026-8. ISBN 9780323295444. "Occasionally, rhythmic, jerky movements are also observed in the face, eyeballs, tongue, jaw, vocal cord or extremities (mostly hands); they may not be synchronous with palatal movements. The movements of the palate vary in rate between 40 and 200 beats per minute. The movements may involve the Eustachian tube and make a click that the patient can hear." 2. ^ Zadikoff C, Lang AE, Klein C. (29 November 2005). "The 'essentials' of essential palatal tremor: a reappraisal of the nosology". Brain. 129 (4): 832–840. doi:10.1093/brain/awh684. PMID 16317025.CS1 maint: uses authors parameter (link) 3. ^ Saeed SR1, Brookes GB. (1993). "The use of clostridium botulinum toxin in palatal myclonus. A preliminary report". Journal of Laryngology & Otology. 107 (3): 208–210. doi:10.1017/S0022215100122650. PMID 8509697.CS1 maint: uses authors parameter (link) ## External links[edit] Classification D * ICD-9-CM: 333.2 External resources * MedlinePlus: 001637 This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Palatal myoclonus	c0030214	5,662	wikipedia	https://en.wikipedia.org/wiki/Palatal_myoclonus	2021-01-18T19:01:41	{"mesh": ["D009207"], "umls": ["C0030214"], "icd-9": ["333.2"], "wikidata": ["Q7126771"]}
"Fear of Flying" redirects here. For other uses, see Fear of flying (disambiguation). Human disease A Boeing 747 aeroplane Fear of flying is a fear of being on an aeroplane, or other flying vehicle, such as a helicopter, while in flight. It is also referred to as flying anxiety, flying phobia, flight phobia, aviophobia, or aerophobia (although the last also means a fear of drafts or of fresh air).[1] Acute anxiety caused by flying can be treated with anti-anxiety medication. The condition can be treated with exposure therapy, which works better when combined with cognitive behavioral therapy.[2][3] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Classification * 4 Management * 4.1 Virtual reality exposure therapy * 5 Outcomes * 6 Epidemiology * 7 History * 8 Society and culture * 9 Research directions * 10 See also * 11 References ## Signs and symptoms[edit] Play media Video explaining what fear of flying means and what sufferers can do to control the physical symptoms. People with fear of flying experience intense, persistent fear or anxiety when they consider flying, as well as during flying. They will avoid flying if they can, and the fear, anxiety, and avoidance cause significant distress and impair their ability to function.[4] Take-off, bad weather, and turbulence appear to be the most anxiety provoking aspects of flying.[4] The most extreme manifestations can include panic attacks or vomiting at the mere sight or mention of an aircraft or air travel.[2] Around 60% of people with fear of flying report having some other anxiety disorder.[4] ## Cause[edit] The causes of flight phobia and the mechanisms by which it is maintained were not well understood as of 2016.[4][5] It is not clear if it is really one condition; it appears to be heterogenous. It appears that some people get aerophobia from being or having claustrophobia to the small spaces inside the fuselage of the plane or helicopter.[6] ## Diagnosis[edit] The diagnosis is clinical. It is often difficult to determine if the specific phobia of fear of flight should be the primary diagnosis, or if fear of flying is a symptom of a generalized anxiety disorder or another anxiety disorder such as agoraphobia or claustrophobia.[6] ### Classification[edit] Fear of flying is a specific phobia classified as such in the DSM-5.[4] ## Management[edit] Acute anxiety caused by flying can be treated with anti-anxiety medication. The condition can be treated with exposure therapy, including use of virtual reality equipment, which works better when combined with cognitive behavioral therapy. Relaxation techniques and education about aviation safety can also be helpful in combination with other approaches.[2][3] A new and advanced treatment for aviophobia is virtual reality exposure therapy. This type of treatment uses computer technology where the patient enters a virtual reality of flying.[7] ### Virtual reality exposure therapy[edit] Effective treatment for phobias such as fear of flying would be one that activates and modifies the fear structure.[8] Activation of the fear structure can be achieved by exposing the patient to the feared stimuli, flying in this case, to elicit the fearful response.[8] Modification of the fear structure can be achieved by the processes of habituation and extinction after eliciting the fearful response several times.[8] A new and advanced treatment for aviophobia is virtual reality exposure therapy (VRET). This type of treatment uses computer technology where the patient virtually experiences flying.[9] This experience includes visual, auditory, and motion stimuli to imitate flying in a plane as close as possible.[9] Thus, VRET is considered an effective treatment for aviophobia. While it can be argued that vivo exposure treatment, patients being exposed to an aircraft, is the most effective way of treatment, but VRET is more cost-effective, accessible,[9] less time consuming, and requires less organization.[10] Another advantage of VRET over vivo exposure treatment is that it focuses on the main reason that elicits fear of flying easily. For example, if the patient's most anxiety-inducing-component is takeoff, in VRET the patient would be exposed to a plane takeoff repeatedly while in vivo exposure the patient would have to wait for the plane to land and then take off again.[11] ## Outcomes[edit] Studies of interventions like CBT have reported rates of reduction in anxiety of around 80%; however, there is little evidence that any treatment can completely eliminate fear of flying.[3] ## Epidemiology[edit] Estimates for prevalence have ranged between 2.5% and 40%; estimates on the lower end are probably generated through studies where the condition is diagnosed by a professional, and the higher end probably includes people who have diagnosed themselves.[4] ## History[edit] Fear of flying was first discussed in the biomedical literature by a doctor in the UK at the end of World War I, who called it "aero-neurosis" and was describing pilots and crew who were or became anxious about flying. It was not much discussed until the 1950s and rise of commercial air travel and the vogue in psychoanalysis. Starting in the 1970s fear of flying was addressed through behavioral and cognitive approaches.[6] ## Society and culture[edit] Immediately after the September 11 attacks, Americans chose to travel more by car instead of flying; because of the extra traffic, around 350 more people died in traffic accidents than would have normally occurred.[12] A number of famous celebrities have suffered from a fear of flying, including former Arsenal FC and Netherlands footballer Dennis Bergkamp, famously dubbed the “non-flying Dutchman.” ## Research directions[edit] As of 2016, the causes of fear of flying as well as the psychological mechanisms through which it were persists had not been well researched. A few studies had looked at whether mechanisms like illusory correlation and expectancy bias were present in all or most people with fear of flying as well as other specific phobias; these studies have not led to clear outcomes.[4][5] Research into the most effective ways to treat or manage fear of flying is difficult (as it is with other counselling or behavioral interventions) due to the inability to include a placebo or other control arm in such studies.[3] ## See also[edit] * List of phobias * Health hazards of air travel * Flight shame ## References[edit] Wikivoyage has a travel guide for Fear of flying. 1. ^ "aerophobia". Merriam-Webster. Retrieved July 20, 2014. 2. ^ a b c Mulcahy, RA; Blue, RS; Vardiman, JL; Castleberry, TL; Vanderploeg, JM (2016). "Screening and Mitigation of Layperson Anxiety in Aerospace Environments". Aerospace Medicine and Human Performance. 87 (10): 882–889. doi:10.3357/AMHP.4536.2016. PMID 27662351. 3. ^ a b c d Oakes, M; Bor, R (November 2010). "The psychology of fear of flying (part II): a critical evaluation of current perspectives on approaches to treatment". Travel Medicine and Infectious Disease. 8 (6): 339–63. doi:10.1016/j.tmaid.2010.10.002. PMID 21071281. 4. ^ a b c d e f g Clark, GI; Rock, AJ (2016). "Processes Contributing to the Maintenance of Flying Phobia: A Narrative Review". Frontiers in Psychology. 7: 754. doi:10.3389/fpsyg.2016.00754. PMC 4887486. PMID 27313550. 5. ^ a b Wiemer, J; Pauli, P (August 2016). "Fear-relevant illusory correlations in different fears and anxiety disorders: A review of the literature". Journal of Anxiety Disorders. 42: 113–28. doi:10.1016/j.janxdis.2016.07.003. PMID 27454587. 6. ^ a b c Oakes, M; Bor, R (November 2010). "The psychology of fear of flying (part I): a critical evaluation of current perspectives on the nature, prevalence and etiology of fear of flying". Travel Medicine and Infectious Disease. 8 (6): 327–38. doi:10.1016/j.tmaid.2010.10.001. PMID 21050826. 7. ^ Czerniak, Efrat; Caspi, Asaf; Litvin, Michal; Amiaz, Revital; Bahat, Yotam; Baransi, Hani; Sharon, Hanania; Noy, Shlomo; Plotnik, Meir (April 1, 2016). "A Novel Treatment of Fear of Flying Using a Large Virtual Reality System". Aerospace Medicine and Human Performance. 87 (4): 411–416. doi:10.3357/AMHP.4485.2016. 8. ^ a b c Rothbaum, Barbara Olasov; Hodges, Larry; Smith, Samantha; Lee, Jeong Hwan; Price, Larry (2000). "A controlled study of virtual reality exposure therapy for the fear of flying". Journal of Consulting and Clinical Psychology. 68 (6): 1020–1026. doi:10.1037/0022-006X.68.6.1020. ISSN 1939-2117. 9. ^ a b c Czerniak, Efrat; Caspi, Asaf; Litvin, Michal; Amiaz, Revital; Bahat, Yotam; Baransi, Hani; Sharon, Hanania; Noy, Shlomo; Plotnik, Meir (April 1, 2016). "A Novel Treatment of Fear of Flying Using a Large Virtual Reality System". Aerospace Medicine and Human Performance. 87 (4): 411–416. doi:10.3357/AMHP.4485.2016. ISSN 2375-6314. 10. ^ Wechsler, Theresa F.; Kümpers, Franziska; Mühlberger, Andreas (September 10, 2019). "Inferiority or Even Superiority of Virtual Reality Exposure Therapy in Phobias?—A Systematic Review and Quantitative Meta-Analysis on Randomized Controlled Trials Specifically Comparing the Efficacy of Virtual Reality Exposure to Gold Standard in vivo Exposure in Agoraphobia, Specific Phobia, and Social Phobia". Frontiers in Psychology. 10: 1758. doi:10.3389/fpsyg.2019.01758. ISSN 1664-1078. PMC 6746888. PMID 31551840. 11. ^ Maltby, Nicholas; Kirsch, Irving; Mayers, Michael; Allen, George J. (2002). "Virtual reality exposure therapy for the treatment of fear of flying: A controlled investigation". Journal of Consulting and Clinical Psychology. 70 (5): 1112–1118. doi:10.1037/0022-006X.70.5.1112. ISSN 1939-2117. 12. ^ "Afraid to Fly After 9/11, Some Took a Bigger Risk - In Cars". Wall Street Journal. March 23, 2004. Retrieved October 11, 2013. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Fear of flying	c0344318	5,663	wikipedia	https://en.wikipedia.org/wiki/Fear_of_flying	2021-01-18T18:53:35	{"umls": ["C0344318"], "wikidata": ["Q1127417"]}
Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal anomaly characterized by multiple mosaic aneuploidies that leads to a variety of phenotypic abnormalities and cancer predisposition. ## Epidemiology To date, 41 cases of MVA have been described in the literature. ## Clinical description The most common clinical features are growth retardation of prenatal onset, microcephaly, developmental delay, structural central nervous system and ophthalmological anomalies (e.g. cataract, corneal opacities, microphthalmia and glaucoma), and mild dysmorphic features, including triangular facies, micrognathia, and epicanthic folds. Additional features include oligohydramnios, ventricular dilatation, Dandy-Walker malformation, fetal ascites, and increased nuchal translucency. Cancer occurs in approximately 1/3 of individuals. Wilms tumor, rhabdomyosarcoma, acute lymphoblastic leukemia, and granulosa cell malignant tumor of the ovary (see these terms) all occur before the age of 5 years. In one individual, carcinoma of the ampulla of Vater and of the colon occurred in adulthood. ## Etiology MVA is due to defective cell division, leading to aberrant disjunction of chromosomes during mitosis. This results in a high proportion (>10%) of aneuploid cells. Mutations of the BUB1B and CEP57 genes have been identified in individuals with MVA. BUB1B encodes BUBR1, a key protein in the mitotic spindle checkpoint. CEP57 is a centrosomal protein involved in nucleating and stabilizing microtubules. Individuals with BUB1B mutations have a high incidence of cancer (approximately 75%). No individual with a CEP57 mutation has thus far been diagnosed with cancer. ## Diagnostic methods Diagnosis of MVA is based on cytogenetic analysis showing variable aneuploidy. ## Differential diagnosis Aneuploidy can be a feature of chromosomal instability syndromes including Roberts syndrome, ataxia telangiectasia, xeroderma pigmentosum, Bloom syndrome, Werner syndrome and Nijmegen breakage syndrome. Microcephaly with chromosome instability can occur in Fanconi anemia (see these terms). ## Antenatal diagnosis Prenatal karyotype can be undertaken by chorionic villus sampling or amniocentesis. This allows prenatal diagnosis of familial recurrence or investigation of abnormal sonographic findings consistent with MVA. ## Genetic counseling MVA is inherited in an autosomal recessive manner. The parents of an affected child are obligate carriers. Recurrence risk to siblings is 25%. Carrier testing for at-risk family members of individuals with biallelic BUB1B or CEP57 mutations is possible. ## Management and treatment Clinical management depends on the affected individual's specific needs (e.g.: growth hormone therapy for the treatment of growth failure). Cases with a cytogenetic confirmation of MVA syndrome and/or demonstrated BUB1B mutations should be offered Wilms tumor surveillance with renal ultrasonography every three to four months until five years. ## Prognosis Prognosis is related to the nature of the malformations and the risk of malignancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Mosaic variegated aneuploidy syndrome	c1850343	5,664	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1052	2021-01-23T17:08:12	{"gard": ["3007"], "mesh": ["C536987"], "omim": ["257300", "614114", "617598"], "umls": ["C1850343", "C2931286"], "icd-10": ["Q99.8"], "synonyms": ["Warburton-Anyane-Yeboa syndrome"]}
Occurs when there is a sudden lack of blood flow to a limb Acute limb ischaemia Other namesAcute limb ischemia Acute embolism to the right femoral artery resulting in ischemia SymptomsCold, painful, pulseless limb that cannot move CausesEmbolism, thrombosis TreatmentThrombectomy, embolectomy, thrombolysis MedicationThrombolytic drugs Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb.[1] Acute limb ischaemia is caused by embolism or thrombosis, or rarely by dissection or trauma.[2] Thrombosis is usually caused by peripheral vascular disease (atherosclerotic disease that leads to blood vessel blockage), while an embolism is usually of cardiac origin.[3] In the United States, ALI is estimated to occur in 14 out of every 100,000 people per year.[4] With proper surgical care, acute limb ischaemia is a highly treatable condition; however, delayed treatment (beyond 6 to 12 hours) can result in permanent disability, amputation, and/or death. In contrast to acute limb ischemia, chronic limb threatening ischemia results from peripheral artery disease that develops over time. While limbs in both acute and chronic limb ischemia may be pulseless, a chronically ischemic limb is typically warm and pink due to a well-developed collateral artery network and does not need emergency intervention to avoid limb loss.[5] The New Latin term ischaemia as written, is a British version of the word ischemia, and stems from the Greek terms ischein 'to hold'; and haima 'blood'.[6] In this sense, ischaemia refers to the inhibition of blood flow to/through the limb. ## Contents * 1 Signs and symptoms * 1.1 Related conditions * 2 Diagnosis * 3 Treatment * 3.1 Surgery * 3.2 Medications * 3.3 Mechanical thrombolysis * 3.4 Considerations in treatment * 4 Epidemiology * 5 References * 6 External links ## Signs and symptoms[edit] Acute limb ischaemia can occur in patients through all age groups. People who smoke tobacco cigarettes and have diabetes mellitus are at a higher risk of developing acute limb ischaemia. Most cases involve people with atherosclerosis problems.[7] Symptoms of acute limb ischaemia include: * Pain * Pallor (pale appearance of the limb) * Paresthesias (abnormal sensations in the limb) * Perishingly cold * Pulselessness * Paralysis These symptoms are called "the six P's'";[8][9][10] they are commonly mis-attributed to compartment syndrome. One more symptom would be the development of gangrene. Immediate medical attention should be sought with any of the symptoms.[1] In late stages, paresthesia is replaced by anesthesia (numbness) due to death of nerve cells. In some cases, gangrene can occur within six hours of ischaemia. ### Related conditions[edit] When a limb is ischaemic in the non-acute (chronic) setting, the condition is alternatively called peripheral artery disease or critical limb ischaemia, rather than ALI. In addition to limb ischaemia, other organs can become ischaemic, causing: * Renal ischemia (nephric ischaemia) * Mesenteric ischaemia * Cerebral ischaemia * Cardiac ischaemia ## Diagnosis[edit] Acute occlusion of the axillary artery resulting in an ischemic limb as seen on CT angiography In order to treat acute limb ischaemia there are a series of things that can be done to determine where the occlusion is located, the severity, and what the cause was. To find out where the occlusion is located one of the things that can be done is simply a pulse examination to see where the heart rate can be detected and where it stops being sensed. Also there is a lower body temperature below the occlusion as well as paleness. A Doppler evaluation is used to show the extent and severity of the ischaemia by showing flow in smaller arteries. Other diagnostical tools are duplex ultrasonography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). The CTA and MRA are used most often because the duplex ultrasonography although non-invasive is not precise in planning revascularization. CTA uses radiation and may not pick up on vessels for revascularization that are distal to the occlusion, but it is much quicker than MRA.[1] In treating acute limb ischaemia time is everything. In the worst cases acute limb ischaemia progresses to critical limb ischaemia, and results in death or limb loss. Early detection and steps towards fixing the problem with limb-sparing techniques can salvage the limb. Compartment syndrome can occur because of acute limb ischaemia because of the biotoxins that accumulate distal to the occlusion resulting in edema.[1] ## Treatment[edit] ### Surgery[edit] The primary intervention in acute limb ischaemia is emergency embolectomy using a Fogarty Catheter, providing the limb is still viable within the 4-6h timeframe.[11] Other options include a vascular bypass to route blood flow around the clot.[12] Angiograph before and after thrombolytic treatment of acute limb ischemia. ### Medications[edit] Those unsuitable for surgery may receive thrombolytics. In the past, streptokinase was the main thrombolytic chemical. More recently, drugs such as tissue plasminogen activator, urokinase, and anisterplase have been used in its place. Mechanical methods of injecting the thrombolytic compounds have improved with the introduction of pulsed spray catheters—which allow for a greater opportunity for patients to avoid surgery.[13][14] Pharmacological thrombolysis requires a catheter to be inserted into the affected area, attached to the catheter is often a wire with holes to allow for a wider dispersal area of the thrombolytic agent. These agents lyse the ischemia-causing thrombus quickly and effectively.[15] However, the efficacy of thrombolytic treatment is limited by hemorrhagic complications. Plasma fibrinogen level has been proposed as a predictor of these hemorrhagic complications. However, based on a systematic review of the available literature until January 2016, the predictive value of plasma is unproven.[16] ### Mechanical thrombolysis[edit] Another type of thrombolysis disrupts the clot mechanically using either saline jets or, more recently, ultrasound waves. Saline jets dislodge the clot using the Bernoulli effect. Ultrasound waves, emitted at low frequency, create a physical fragmentation of the thrombus.[17] ### Considerations in treatment[edit] The best course of treatment varies from case to case. The physician must take into account the details in the case before deciding on the appropriate treatment. No treatment is effective for every patient. Treatment depends on many factors, including: * Location of lesions * Anatomy of lesions * Individual risk factors * Procedural risk * Clinical presentation of symptoms * Duration of symptoms * etc.[13] ## Epidemiology[edit] The major cause of acute limb ischaemia is arterial embolism (80%), while arterial thrombosis is responsible for 20% of cases. In rare instances, arterial aneurysm of the popliteal artery has been found to create a blood clot or embolism resulting in ischaemia.[18] ## References[edit] 1. ^ a b c d Walker T. Gregory (2009). "Acute Limb Ischemia". Techniques in Vascular and Interventional Radiology. 12 (2): 117–129. doi:10.1053/j.tvir.2009.08.005. PMID 19853229. 2. ^ Creager, Mark A.; Kaufman, John A.; Conte, Michael S. (2012). "Acute Limb Ischemia". New England Journal of Medicine. 366 (23): 2198–2206. doi:10.1056/NEJMcp1006054. PMID 22670905. 3. ^ Klonaris, C; Georgopoulos, S; Katsargyris, A; Tsekouras, N; Bakoyiannis, C; Giannopoulos, A; Bastounis, E (March 2007). "Changing patterns in the etiology of acute lower limb ischemia". International Angiology : A Journal of the International Union of Angiology. 26 (1): 49–52. PMID 17353888. 4. ^ Dormandy J, Heeck L, Vig S (June 1999). "Acute limb ischemia". Semin Vasc Surg. 12 (2): 148–53. PMID 10777242. 5. ^ Farber, A (12 July 2018). "Chronic Limb-Threatening Ischemia". The New England Journal of Medicine. 379 (2): 171–180. doi:10.1056/NEJMcp1709326. PMID 29996085. 6. ^ "Ischaemia." Merriam-Webster. Last modified 2012. http://www.merriam-webster.com/dictionary/ischemia?show=0&t=1334804041 7. ^ Brooks Marcus; Jenkins Michael P (2008). "Acute and chronic ischaemia of the limb". Surgery (Oxford). 26 (1): 17–20. doi:10.1016/j.mpsur.2007.10.012. 8. ^ Brearley, S (May 8, 2013). "Acute leg ischaemia". BMJ (Clinical Research Ed.). 346: f2681. doi:10.1136/bmj.f2681. PMID 23657181. 9. ^ "CKS is only available in the UK". NICE. Retrieved 2020-10-15. 10. ^ "Acute Limb Ischaemia - Clinical Features - Management". TeachMeSurgery. Retrieved 2020-10-15. 11. ^ Goldberg, Andrew (2012). Surgical Talk: Lecture Notes in Undergraduate Surgery. Imperial College Press. p. 234. ISBN 978-1-84816-6141. 12. ^ Bowley, Douglas, and Andrew Kingsnorth, eds. Fundamentals of Surgical Practice: A Preparation Guide for the Intercollegiate Mrcs Examination. 3rd ed. N.p.: Cambridge University Press, 2011. 506-11. Web. 20 Apr. 2012. 13. ^ a b Andaz S.; Shields D.A.; Scurr J.H.; Smith P.D. Coleridge (1993). "Thrombolysis in acute lower limb ischaemia". European Journal of Vascular Surgery. 7 (6): 595–603. doi:10.1016/S0950-821X(05)80702-9. PMID 8270059. 14. ^ ABC of Arterial and Venous Disease: Acute Limb Ischaemia Ken Callum and Andrew Bradbury BMJ: British Medical Journal, Vol. 320, No. 7237 (Mar. 18, 2000), pp. 764-767 15. ^ Wardlaw J.M.; Warlow C.P. (1992). "Thrombolysis in acute ischemic stroke: does it work?". Stroke. 23 (12): 1826–1839. doi:10.1161/01.str.23.12.1826. 16. ^ Poorthuis, Michiel H. F.; Brand, Eelco C.; Hazenberg, Constantijn E. V. B.; Schutgens, Roger E. G.; Westerink, Jan; Moll, Frans L.; de Borst, Gert J. (2017-03-05). "Plasma fibrinogen level as a potential predictor of hemorrhagic complications after catheter-directed thrombolysis for peripheral arterial occlusions". Journal of Vascular Surgery. 65 (5): 1519–1527.e26. doi:10.1016/j.jvs.2016.11.025. ISSN 1097-6809. PMID 28274749. 17. ^ Sean P. Lyden, Endovascular Treatment of Acute Limb Ischemia: Review of Current Plasminogen Activators and Mechanical Thrombectomy Devices PERSPECT VASC SURG ENDOVASC THER December 2010 22: 219-222, first published on March 16, 2011 18. ^ Mitchell ME, Carpenter JP. Overview of acute arterial occlusion of the extremities (acute limb ischemia). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-acute-arterial-occlusion-of-the-extremities-acute-limb-ischemia?source=search_result&search=Classification%20of%20acute%20extremity%20ischemia&selectedTitle=1∼90#H506059593. Last updated May 31, 2016. Accessed December 13, 2016. ## External links[edit] Classification D * ICD-9-CM: 459.9 * DiseasesDB: 7480 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Acute limb ischaemia	c4049535	5,665	wikipedia	https://en.wikipedia.org/wiki/Acute_limb_ischaemia	2021-01-18T18:53:21	{"icd-9": ["459.9"], "wikidata": ["Q3155223"]}
A chick with two beaks and three eyes Diprosopus (Greek διπρόσωπος, "two-faced", from δι-, di-, "two" and πρόσωπον, prósopon [neuter], "face", "person"; with Latin ending), also known as craniofacial duplication (cranio- from Greek κρανίον, "skull", the other parts Latin), is an extremely rare congenital disorder whereby parts (accessories) or all of the face are duplicated on the head.[1][2][3][4][5][6] ## Contents * 1 Development * 2 Occurrences * 2.1 Humans * 2.1.1 Lali Singh * 2.1.2 Faith and Hope Howie * 2.2 Other animals * 3 See also * 4 References * 5 External links ## Development[edit] Although classically considered conjoined twinning (which it resembles), diprosopus is not normally due to the fusion or incomplete separation of two embryos. It is the result of abnormal activity by the protein SHH (sonic hedgehog).[7][8][9] (The name of this protein was inspired by the Sonic the Hedgehog video game character and is part of an idiosyncratic naming tradition in molecular biology research.)[10][11] SHH and its corresponding gene have been found to play an important role in signaling craniofacial patterning during embryonic development. Among other things, SHH governs the width of facial features. In excess it leads to widening of facial features and to duplication of facial structures.[7] The greater the widening, the more structures are duplicated, often in a mirror image form. This has been demonstrated in the laboratory by introducing pellets of the SHH protein into chicken embryos, resulting in chickens with duplicate beaks. Inadequate amounts of that protein lead to opposite conditions such as cyclopia where facial features are insufficiently developed.[12] Healthy brain development is also dependent on the signaling function of SHH.[13] During embryonic development, SHH directs embryonic cells to organize in specific areas that later become specialized neural tissues, thus controlling the size and shape of brain structures. ## Occurrences[edit] Diprosopus often occurs in combination with other congenital disorders, particularly anencephaly, neural tube defect and cardiac malformations.[14] When present, the brain may show abnormalities ranging from partial to complete duplication of brain structures, and/or underdevelopment of brain tissues.[15][16] ### Humans[edit] Most human infants with diprosopus are stillborn. Known instances of humans with diprosopus surviving for longer than minutes to hours past birth are very rare; only a few are recorded. In 2002 and 2003, two living male infants with partial diprosopus were described in the medical literature in separate case reports.[17][18] One infant was born with duplication of the nose and the cerebral frontal lobes, two widely spaced eyes, a small, underdeveloped central eye socket, and a large, asymmetric mouth. The other infant was born with duplication of the upper and lower jaw, two tongues arising from the same base, cleft palate, a slightly divided tip of the nose, and two widely spaced eyes, as well as absence of the corpus callosum, duplication of the pituitary gland and stalk, and abnormalities in the midbrain. Because they were born with a milder, partial form of diprosopus, both infants were considered candidates for surgical correction of their abnormal facial features. #### Lali Singh[edit] Lali Singh[2] (10 March – 10 May 2008) was born to Sushma and Vinod Singh in Saini, Sunpura Sohanpur village, near Delhi; the birth was delayed by dystocia caused by her large head, and her birth in a hospital was facilitated by her mother's receiving an episiotomy. She was one of the very few infants with diprosopus to survive well past birth. She might have been the only known living individual with complete facial duplication. Her facial features included two pairs of eyes, two noses, and two mouths (but only one pair of ears). She was seen as the reincarnation of the goddess Durga, who is sometimes depicted with many limbs and eyes. Sushma and Vinod Singh declined an offer from local doctors to evaluate their daughter through CT or MRI scanning. Without diagnostic imaging, it was not possible to know the full extent to which the child's condition might have affected her brain and other vital structures in her head and neck. Thus, any estimation of her ability to thrive or even survive could be only speculative, though Lali's family described her as functioning normally. It is also unknown whether neurosurgeons or craniofacial surgeons, if consulted, would have had feasible solutions to offer with respect to corrective surgery. A local doctor told reporters that the baby should be considered a healthy child who currently was living a normal life, a previously unknown occurrence among sufferers of the disorder.[19] Lali's two middle eyes suffered from corneal opacity due to abnormal anatomy of the facial muscles, which prevented her from properly closing those eyes. (Initially, this was wrongly blamed on camera flashes.) A cleft palate caused difficulty in her feeding under village conditions. A poor diet of bottle-fed sugar solution and diluted milk, allowed to drip down her throat, as she could not suck properly due to her cleft palate, weakened her condition, and vomiting and infection started. Admission to hospital was delayed by discussion (including taking her back home from hospital) among her extended family and her village's headman. Finally, her parents, alarmed at her illness and dehydration, defied her other relatives and took her back to hospital, where under proper medical treatment including antibiotic and a saline drip she started to improve, stopped vomiting, started drinking milk and defecating normally; but six hours later, at two months old to the day, she died of a heart attack.[20] She was buried in her village, as is usual in Hinduism with children who die very young. Later a temple was built at the village in her memory.[citation needed] #### Faith and Hope Howie[edit] Faith Daisy and Hope Alice Howie (8 May – 27 May 2014) were born in Sydney, Australia, to parents Simon Howie and Renee Young. Faith and Hope shared one body and skull, but had complete duplication of the facial features, as well as duplication of the brain; both brains joined to one brain stem. Young and Howie had learned at nineteen weeks gestation of their children's condition, but opted not to terminate the pregnancy. The children were born six weeks prematurely and appeared to be doing well, able to breathe unaided several days after their birth, and they were observed to sleep and cry at different times.[21] They died nineteen days following their birth due to unknown causes, although some sources indicated that the girls died following an operation for unknown reasons. ### Other animals[edit] Janus, a goat with two faces on one body, survived from April 5 to May 5, 2020 in Wittenberg, Wisconsin.[22] Few two-faced animals have survived due to associated internal organ abnormalities and brain abnormalities. One of the most famous was Ditto, a pig.[23] Ditto was raised to adulthood, but died of pneumonia caused by food inhalation when breathing through one muzzle while eating with the other. Cats with the condition are known as 'Janus cats', after the Roman god.[24] In July 2006, a six-year-old male Janus cat called "Frank and Louie" from Millbury, Massachusetts, USA, received publicity. In their case, only one esophagus (and possibly only one trachea) were functional; this aided survival. In September 2011, when Frank and Louie were twelve years old, it was announced that they would appear in the 2012 Guinness Book of World Records as the longest-surviving Janus cat on record.[25] In 2014, Frank and Louie died at the age of fifteen.[26] ## See also[edit] * Conjoined twins * Craniopagus parasiticus * Cyclopia * Durga, a three-eyed Hindu goddess * Edward Mordake, a disputed story of a 19th-century man with a face on the back of his head * Futakuchi-onna, a female Japanese yokai with mouth on back of her head/hair * Janus, a Roman god with two faces * Kara Mia, a Philippine TV series that tells the story of a young woman with two faces divided in one body. * Polycephaly ## References[edit] 1. ^ Definition of diprosopus at MedicineNet. Accessed 8 January 2006. 2. ^ a b 'Miracle baby' is feted in India at BBC News. Accessed 10 April 2008. 3. ^ al Muti Zaitoun A, Chang J, Booker M (1999). "Diprosopus (partially duplicated head) associated with anencephaly: a case report". Pathol Res Pract. 195 (1): 45–50. doi:10.1016/s0344-0338(99)80094-6. PMID 10048094. 4. ^ Borzabadi-Farahani A, Yen SL, Yamashita DD, Sanchez-Lara PA (2012). "Bilateral maxillary duplication: case report and literature review". Oral Surg Oral Med Oral Pathol Oral Radiol. 113 (5): e29–32. doi:10.1016/j.tripleo.2011.06.017. PMID 22676989. 5. ^ Borzabadi-Farahani A, Gross J, Sanchez-Lara PA, Yen SL (2013). "An unusual accessory mandible and a submucosal cleft palate-a case report and review of the literature". Cleft Palate Craniofacial J. 50 (3): 369–75. doi:10.1597/11-032. PMID 22404912. 6. ^ Borzabadi-Farahani A, Yen SL, Francis C, Lara-Sanchez PA, Hammoudeh J (2013). "A rare case of accessory maxilla and bilateral Tessier no. 7 clefts, a 10-year follow-up". J Craniomaxillofac Surg. 41 (6): 527–31. doi:10.1016/j.jcms.2012.11.019. PMID 23333494. 7. ^ a b Hu D, Helms JA (1 November 1999). "The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis". Development. 126 (21): 4873–84. PMID 10518503. 8. ^ Ruiz i Altaba, Ariel (2006). Hedgehog-Gli Signaling in Human Disease. New York, NY: Springer Science+Business Media, Inc. ISBN 978-0-387-33777-7. Retrieved March 12, 2014. 9. ^ Brugmann, S.A.; Helms, J.A. (2007). "Chapter 30: Craniofacial formation and congenital defects". In Moody, Sally A. (ed.). Principles of Developmental Genetics. Burlington, MA: Academic Press, an imprint of Elsevier Inc. ISBN 9780123695482. Retrieved March 12, 2014. 10. ^ Donahue JK (July 2006). "Gene therapy, angiogenesis, Sonic Hedgehog: Sonic the Hedgehog to the rescue?". Gene Ther. 13 (13): 998–9. doi:10.1038/sj.gt.3302748. PMID 17262905. 11. ^ Cameron, David (2012). "Express Yourself (Space Savers issue). Our chromosomes bear creative, even outlandish, names. Who knew?". Harvard Medical School News. 85 (2). Archived from the original on 2012-10-31. Retrieved 2012-10-22. 12. ^ Young DL, Schneider RA, Hu D, Helms JA (2000). "Genetic and teratogenic approaches to craniofacial development". Crit. Rev. Oral Biol. Med. 11 (3): 304–17. CiteSeerX 10.1.1.542.1906. doi:10.1177/10454411000110030201. PMID 11021632. 13. ^ Sonic Hedgehog shapes the brain. ScienceDaily, 13 March 2001. 14. ^ al Muti Zaitoun A, Chang J, Booker M (1999). "Diprosopus (partially duplicated head) associated with anencephaly: a case report". Pathol. Res. Pract. 195 (1): 45–50, discussion 51–2. doi:10.1016/s0344-0338(99)80094-6. PMID 10048094. 15. ^ Koseoglu K, Gok C, Dayanir Y, Karaman C (1 March 2003). "CT and MR imaging findings of a rare craniofacial malformation: diprosopus". AJR Am J Roentgenol. 180 (3): 863–4. doi:10.2214/ajr.180.3.1800863. PMID 12591714. 16. ^ Angtuaco TL, Angtuaco EJ, Quirk JG (1 January 1999). "US case of the day. Complete brain duplication with fusion at the posterior fossa (diprosopus tetraophthalmos)". Radiographics. 19 (1): 260–3. doi:10.1148/radiographics.19.1.g99ja15260. PMID 9925407. 17. ^ Hähnel S, Schramm P, Hassfeld S, Steiner HH, Seitz A (January 2003). "Craniofacial duplication (diprosopus): CT, MR imaging, and MR angiography findings case report". Radiology. 226 (1): 210–3. doi:10.1148/radiol.2261011754. PMID 12511692. 18. ^ Wu J, Staffenberg DA, Mulliken JB, Shanske AL (December 2002). "Diprosopus: a unique case and review of the literature" (PDF). Teratology. 66 (6): 282–7. doi:10.1002/tera.10102. PMID 12486761. 19. ^ Two-Faced Baby Triggers Shock and Awe ABC report. Accessed 21 April 2008. 20. ^ Channel 4 UK television program Body Shock, 10 pm to 11.10 pm Tuesday 16 September 2008 21. ^ "Conjoined twins Hope and Faith have distinct personalities, say parents". 2014-05-19. 22. ^ Melissa Siegler, Wausau Daily Herald (May 5, 2020) 'He will surely be missed': Two-headed goat born on Wittenberg farm dies 23. ^ Armand Marie Leroi (2005). Mutants: on the form, varieties and errors of the human body. New York, N.Y: Harper Perennial. ISBN 978-0-00-653164-7. 24. ^ Wilson, Cherry (30 September 2011). "Two-faced cat is a record breaker". The Guardian. London. 25. ^ Ngowi, Roderique (Sep 29, 2011). "Meet Frank and Louie, the longest surviving two-faced cat". thestar.com. Toronto Star. Retrieved 16 October 2011. 26. ^ "Frank and Louie, the world's oldest two-faced cat, dies at 15". Cox Media Group. December 5, 2014. Archived from the original on December 9, 2014. Retrieved December 5, 2014. ## External links[edit] Wikimedia Commons has media related to Diprosopus. * Armand Marie, Leroi (2005). Mutants: On Genetic Variety and the Human Body. New York, NY: Penguin Books. ISBN 9780142004821. Retrieved March 13, 2014. * Howie, Sarah; Fisher, Carolyn Elaine, eds. (2010). Shh and Gli Signalling in Development. New York, NY: Springer Science+Business Media, Inc. ISBN 978-0-387-39957-7. Retrieved March 13, 2014. * Tapadia MD, Cordero DR, Helms JA (November 2005). "It's all in your head: new insights into craniofacial development and deformation". J. Anat. 207 (5): 461–77. doi:10.1111/j.1469-7580.2005.00484.x. PMC 1571563. PMID 16313388. * ‘Sonic Hedgehog’ sounded funny, at first. New York Times, 12 November 2006. * Rediscovering biology: Unit 7, Genetics of development. Expert interview transcripts, interview with John Incardona, PhD. explanation of the discovery and naming of the sonic hedgehog gene * Page for sonic hedgehog homolog (SHH) at The Human Genome Organisation (HUGO) * Two-faced kitten has image problem at Channel4000 * Two-faced kitten shocks owner, veterinarian at OregonNews.com * Two-faced cat sets record as oldest living "Janus" cat at Reuters * diprosopus kitten * diprosopus piglet * diprosopus calf * Rescue Kitten Was Born With Two Face Who Rejected By Her Cat Mom diprosopus kitten * Baby with 2 faces born in north India MSNBC * Image:Diprosopus Authority control * GND: 4326904-7 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Diprosopus	c0266731	5,666	wikipedia	https://en.wikipedia.org/wiki/Diprosopus	2021-01-18T18:44:42	{"gard": ["1876"], "orphanet": ["1681"], "synonyms": ["Craniofacial duplication", "Diprosopia"], "wikidata": ["Q32744"]}
Cutaneous T-cell lymphomas (CTCLs) are a group of disorders characterized by an abnormal accumulation of cancerous T-cells (a type of white blood cells) in the skin resulting in an itchy, red rash that can thicken or form a tumor. CTCLs belong to a larger group of disorders known asnon-Hodgkin's lymphomas. The most common types are mycosis fungoides and Sézary syndrome. In some cases, cancerous T-cells may spread to the lymph nodes and eventually to other body tissues and organs, potentially resulting in life-threatening complications. The specific signs and symptoms vary from person to person. The exact cause of these conditions is unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Cutaneous T-cell lymphoma	c0079773	5,667	gard	https://rarediseases.info.nih.gov/diseases/6226/cutaneous-t-cell-lymphoma	2021-01-18T18:01:00	{"mesh": ["D016410"], "umls": ["C0079773"], "orphanet": ["171901"], "synonyms": ["CTCL"]}
An autosomal dominant cerebellar ataxia type 1 that is characterized by ataxia and cognitive impairment. Azoospermia is a typical feature in affected males. ## Epidemiology Spinocerebellar ataxia type 32 (SCA32) has been reported in one Chinese family to date. ## Clinical description Disease onset occurs in adulthood with females more affected than males. Manifestations include ataxia, cognitive impairment and, in males, azoospermia. Cerebellar atrophy is visible with magnetic resonance imaging. ## Etiology The causal gene of SCA32 has not yet been identified but it is located to chromosome 7q32-q33. ## Diagnostic methods Diagnosis is based on the characteristic clinical findings and family history of the disease. ## Differential diagnosis Differential diagnosis includes other types of ADCA. ## Genetic counseling SCA32 is inherited in an autosomal dominant manner and genetic counseling is possible. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. ## Management and treatment There is no cure for SCA32 and treatment is supportive. Physical therapy, as well as the use of canes and walkers, should be offered in order to maximize strength and maintain activity. Wheelchairs are eventually necessary. Speech therapy and communication devices may be useful to those with dysarthria. Dysphagia should be monitored to decrease the risk of aspiration pneumonia. Annual neurological examinations are recommended to monitor disease progression. ## Prognosis Precise prognosis is unknown due to limited number of patients reported. Mean age when aid walking needed is about 34 years. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Spinocerebellar ataxia type 32	c3151343	5,668	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276183	2021-01-23T18:21:53	{"omim": ["613909"], "icd-10": ["G11.8"], "synonyms": ["Cerebellar ataxia with azoospermia and intellectual disability", "SCA32"]}
Glycogen storage disease type 0 Glycogen storage disease type 0 has defect in glycogen synthase SpecialtyMedical genetics Glycogen storage disease type 0 is a disease characterized by a deficiency in the glycogen synthase enzyme (GSY). Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a glycogen storage disease because it is another defect of glycogen storage and can cause similar problems. There are two isoforms (types) of glycogen synthase enzyme; GSY1 in muscle and GSY2 in liver, each with a corresponding form of the disease.[1] Mutations in the liver isoform (GSY2), causes fasting hypoglycemia, high blood ketones, increased free fatty acids and low levels of alanine and lactate. Conversely, feeding in these patients results in hyperglycemia and hyperlactatemia. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnostic * 4.1 Laboratory Studies * 4.2 Imaging Studies * 4.3 Other Tests * 4.4 Procedures * 4.5 Histologic Findings * 4.6 Differential Diagnoses * 4.7 Types * 5 Treatment * 6 Epidemiology * 6.1 Mortality/Morbidity * 6.2 Sex * 6.3 Age * 7 References * 8 External links ## Signs and symptoms[edit] The most common clinical history in patients with glycogen-storage disease type 0 (GSD-0) is that of an infant or child with symptomatic hypoglycemia or seizures that occur before breakfast or after an inadvertent fast. In affected infants, this event typically begins after they outgrow their nighttime feeds. In children, this event may occur during acute GI illness or periods of poor enteral intake. Mild hypoglycemic episodes may be clinically unrecognized, or they may cause symptoms such as drowsiness, sweating, lack of attention, or pallor. Uncoordinated eye movements, disorientation, seizures, and coma may accompany severe episodes.[2] Glycogen-storage disease type 0 affects only the liver. Growth delay may be evident with height and weight percentiles below average. Abdominal examination findings may be normal or reveal only mild hepatomegaly.[citation needed] Signs of acute hypoglycemia may be present, including the following:[2] * Lethargy * Apathy * Jitteriness * Diaphoresis * Tachycardia * Pallor * Nausea and vomiting * Headache * Mental confusion * Visual disturbances * Dysarthria * Hypotonia * Ataxia * Seizures * Coma ## Causes[edit] Glycogen-storage disease type 0 is caused by genetic defects in the gene that codes for liver glycogen synthetase (GYS2), which is located on chromosome band 12p12.2. Glycogen synthetase catalyzes the rate-limiting reaction for glycogen synthesis in the liver by transferring glucose units from uridine 5'-diphosphate (UDP)-glucose to a glycogen primer. Its action is highly regulated by a mechanism of phosphorylation and dephosphorylation and modulated by counter-regulatory hormones including insulin, epinephrine, and glucagon. Mutations in the gene for liver glycogen synthetase (GYS2, 138571) result in decreased or absent activity of liver glycogen synthetase and moderately decreased amounts of structurally normal glycogen in the liver. Mutational studies of patients with glycogen-storage disease type 0 do not demonstrate correlations between genotype and phenotype. [3] A different gene (GYS1, 138570) encodes muscle glycogen synthetase, which has normal activity in patients with glycogen-storage disease type 0A.[2] ## Pathophysiology[edit] In the early stages of fasting, the liver provides a steady source of glucose from glycogen breakdown (or glycogenolysis). With prolonged fasting, glucose is generated in the liver from noncarbohydrate precursors through gluconeogenesis. Such precursors include alanine (derived from the breakdown of proteins in skeletal muscle) and glycerol (derived from the breakdown of triacylglycerols in fat cells). In patients with glycogen-storage disease type 0, fasting hypoglycemia occurs within a few hours after a meal because of the limited stores of hepatic glycogen and inadequate gluconeogenesis to maintain normoglycemia. Feeding characteristically results in postprandial hyperglycemia and glucosuria, in addition to increased blood lactate levels, because glycogen synthesis is limited, and excess glucose is preferentially converted to lactate by means of the glycolytic pathway.[2] ## Diagnostic[edit] Important clinical criteria to consider in the evaluation of a child with hypoglycemia and suspected glycogen-storage disease type 0 (GSD-0) include (1) the presence or absence of hepatomegaly; (2) the characteristic schedule of hypoglycemia, including unpredictable, postprandial, short fast, long fast, or precipitating factors; (3) the presence or absence of lactic acidosis; (4) any associated hyperketosis or hypoketosis; and (5) any associated liver failure or cirrhosis. The differential diagnosis also includes ketotic hypoglycemia. Patients with ketotic hypoglycemia have a normal response to glucagon in the fed state. Patients with glycogen-storage disease type 0 have normal-to-increased response to glucagon in the fed state, with hyperglycemia and lactic acidemia.[2] ### Laboratory Studies[edit] Serum glucose levels are measured to document the degree of hypoglycemia. Serum electrolytes calculate the anion gap to determine presence of metabolic acidosis; typically, patients with glycogen-storage disease type 0 (GSD-0) have an anion gap in the reference range and no acidosis. See the Anion Gap calculator. Serum lipids (including triglyceride and total cholesterol) may be measured. In patients with glycogen-storage disease type 0, hyperlipidemia is absent or mild and proportional to the degree of fasting. Urine (first voided specimen with dipstick test for ketones and reducing substances) may be analyzed. In patients with glycogen-storage disease type 0, urine ketones findings are positive, and urine-reducing substance findings are negative. However, urine-reducing substance findings are positive (fructosuria) in those with fructose 1-phosphate aldolase deficiency (fructose intolerance). Serum lactate is in reference ranges in fasting patients with glycogen-storage disease type 0. Liver function studies provide evidence of mild hepatocellular damage in patients with mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.[citation needed]Plasma amino-acid analysis shows plasma alanine levels as in reference ranges during a fast. ### Imaging Studies[edit] Skeletal radiography may reveal osteopenia. ### Other Tests[edit] Evaluation of a patient with suspected glycogen-storage disease type 0 requires monitored assessment of fasting adaptation in an inpatient setting. Patients typically have hypoglycemia and ketosis, with lactate and alanine levels in the low or normal part of the reference range approximately 5–7 hours after fasting. A glucagon tolerance test may be needed if the fast fails to elicit the expected rise in plasma glucose. Lactate and alanine levels are in the reference range. By contrast, a glucagon challenge test after a meal causes hyperglycemia, with increased levels of plasma lactate and alanine. Oral loading of glucose, galactose, or fructose results in a marked rise in blood lactate levels. ### Procedures[edit] Liver biopsy for microscopic analysis and enzyme assay is required for definitive diagnosis. Diagnosis may include linkage analysis in families with affected members and sequencing of the entire coding region of the GSY2 gene for mutations. ### Histologic Findings[edit] Histologic analysis of liver tissue demonstrates moderately decreased amounts of periodic acid-Schiff (PAS)–positive, diastase-sensitive glycogen stores. Evidence of increased fat accumulation in the liver may be observed, as in other glycogen-storage diseases. Electron microscopic analysis of liver sections shows normal glycogen structure. Muscle glycogen stores are normal.[2] ### Differential Diagnoses[edit] * Acute Hypoglycemia * Fructose 1-Phosphate Aldolase Deficiency (Hereditary fructose intolerance). ### Types[edit] There are two types of this\\\e condition glycogen storage disease type 0 to be considered, they are:[3][4] * Glycogen storage disease due to liver glycogen synthase deficiency * Glycogenosis due to muscle and heart glycogen synthase deficiency ## Treatment[edit] The goal for treatment of Glycogen-storage disease type 0 is to avoid hypoglycemia. This is accomplished by avoiding fasting by eating every 1–2 hours during the day. At night, uncooked corn starch can be given because it is a complex glucose polymer. This will be acted on slowly by pancreatic amylase and glucose will be absorbed over a 6-hour period. ## Epidemiology[edit] The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. The identification of asymptomatic and oligosymptomatic siblings in several glycogen-storage disease type 0 families has suggested that glycogen-storage disease type 0 is underdiagnosed.[2] ### Mortality/Morbidity[edit] The major morbidity is a risk of fasting hypoglycemia, which can vary in severity and frequency. Major long-term concerns include growth delay, osteopenia, and neurologic damage resulting in developmental delay, intellectual deficits, and personality changes.[2] ### Sex[edit] No sexual predilection is observed because the deficiency of glycogen synthetase activity is inherited as an autosomal recessive trait.[2] ### Age[edit] Glycogen-storage disease type 0 is most commonly diagnosed during infancy and early childhood.[2] ## References[edit] 1. ^ Orho M, Bosshard NU, Buist NR, et al. (August 1998). "Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0". J. Clin. Invest. 102 (3): 507–15. doi:10.1172/JCI2890. PMC 508911. PMID 9691087. 2. ^ a b c d e f g h i j Lynne Ierardi-Curto and others. "Glycogen-Storage Disease Type 0" 3. ^ "Orphanet: Glycogen storage disease due to hepatic glycogen synthase deficiency". www.orpha.net. Retrieved 2017-05-31. 4. ^ "Orphanet: Glycogen storage disease due to muscle and heart glycogen synthase deficiency". www.orpha.net. Retrieved 2017-05-31. ## External links[edit] * Media related to Glycogen storage disease type 0 at Wikimedia Commons Classification D * OMIM: 240600 611556 * DiseasesDB: 31944 External resources * eMedicine: ped/873 * 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)	Glycogen storage disease type 0	c0342748	5,669	wikipedia	https://en.wikipedia.org/wiki/Glycogen_storage_disease_type_0	2021-01-18T18:47:45	{"orphanet": ["308520"], "synonyms": ["GSD due to glycogen synthase deficiency", "Glycogenosis due to glycogen synthase deficiency"], "wikidata": ["Q5572606"]}
Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome is a rare genetic ectodermal dysplasia syndrome characterized by short stature, nail dystrophy and/or nail loss, oral mucosa and/or tongue hyperpigmentation, dentition abnormalities (delayed teeth eruption, hypodontia, enamel hypoplasia), keratoderma on the margins of the palms and soles and focal hyperkeratosis on the dorsum of the hands and feet. Additionally, dysphagia with esophageal strictures, sensorineural deafness, bronchial asthma and severe iron-deficiency anemia have been observed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome	c4014987	5,670	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=423454	2021-01-23T18:57:37	{"omim": ["616029"], "icd-10": ["Q82.8"], "synonyms": ["Ectodermal dysplasia-short stature syndrome", "Short stature-nail dysplasia-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome"]}
Four males with the same mother and 2 different fathers showed leukopenia and 'partial' Pelger-Huet anomaly (pseudo-Pelger anomaly) of the neutrophils as well as clinical and cytologic evidence of involvement of the lymphatic system (Heyne, 1976). The mother, clinically normal, showed Pelger-Huet-like changes in neutrophils. At least 1 of the fathers was hematologically normal. Severe varicella and generalized vaccinia, as well as severe bacterial infections, occurred. Heyne (1976) suggested X-linked inheritance. Other X-linked conditions, including Swiss type agammaglobulinemia (300400) and reticuloendotheliosis (312500), share some features with this disorder, but it is probably a separate entity. Inheritance \- X-linked Immunology \- Myelolymphatic insufficiency \- Susceptibility to bacterial and viral infections Heme \- Leukopenia \- Pelger-Huet anomaly ▲ 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)	MYELOLYMPHATIC INSUFFICIENCY	c1839650	5,671	omim	https://www.omim.org/entry/310350	2019-09-22T16:17:36	{"omim": ["310350"], "synonyms": ["Alternative titles", "PELGER-LIKE ANOMALY WITH LEUKOPENIA AND SUSCEPTIBILITY TO INFECTIONS"]}
Encephalitis lethargica (EL) is a disease characterized by high fever, headache, double vision, delayed physical and mental response, extreme tiredness (lethargy), and sometimes coma. Patients may also experience abnormal eye movements, upper body weakness, muscle pain, tremors, neck rigidity, and behavioral changes including psychosis. A worldwide epidemic of EL occurred from 1917 to 1928 with more than one million reported cases. Although occasional cases are reported with similar symptoms, EL epidemics have not recurred. The cause of this condition is unknown, but a viral origin is suspected. Treatment depends on a person's symptoms. Levodopa and other antiparkinson drugs may be effective in alleviating some symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Encephalitis lethargica	c0014040	5,672	gard	https://rarediseases.info.nih.gov/diseases/6332/encephalitis-lethargica	2021-01-18T18:00:43	{"umls": ["C0014040"], "orphanet": ["83600"], "synonyms": ["Von Economo’s disease", "Von Economo encephalitis"]}
A number sign (#) is used with this entry because of evidence that this form of pigmented hypomaturation-type amelogenesis imperfecta (AI2A1) is caused by homozygous mutation in the kallikrein-4 gene (KLK4; 603767) on chromosome 19q13. Description Autosomal recessive amelogenesis imperfecta pigmented hypomaturation type is characterized by enamel of normal thickness that is hypomineralized and has a mottled appearance. The slightly soft enamel detaches easily from the dentin, and radiographs show a lack of contrast between enamel and dentin (Witkop, 1989). ### Genetic Heterogeneity of the Hypomaturation Type of Amelogenesis Imperfecta See also AI2A2 (612529), caused by mutation in the MMP20 gene (604629); AI2A3 (613211), caused by mutation in the WDR72 gene (613214); and AI2A4 (614832), caused by mutation in the C4ORF26 gene (614829). Clinical Features Witkop (1965) reported 2 families with autosomal recessive pigmented hypomaturation AI. In 1 of the families, a brother and sister were affected. The disorder involved both the primary and the secondary dentitions. The teeth had a shiny agar jelly appearance and the enamel was softer than normal. The usual radiographic contrast between enamel and dentin was lacking. Histologically a brown pigment, which was probably not derived from blood pigments, was demonstrable in the middle layers of enamel. The parents, who were first cousins once removed, and more remote relatives were unaffected. Witkop et al. (1973) reported 2 sisters with autosomal recessive pigmented hypomaturation AI. Hart et al. (2004) reported 2 African American female sibs with hypomaturation AI. Both primary and permanent dentitions were affected, showing a yellow-brown discoloration. The teeth were excessively sensitive to hot and cold, making it painful to masticate. Radiographically the teeth appeared morphologically normal, indicating that the enamel was of normal thickness. The enamel showed only a slightly increased opacity compared with the dentin, indicative of a decreased enamel mineral content. Enamel had fractured from the occlusal surfaces of the primary molars, consistent with a decreased mineral content. One child had an anterior dental open bite. Wang et al. (2013) described a 9-year-old girl from Turkey with an isolated hypomaturation form of amelogenesis imperfecta. The girl's parents were first cousins and had normal-appearing enamel. The proband's teeth appeared normal in size and shape but showed brown discoloration and chipping. She was secondarily affected with dental caries but had no anterior open bite. Radiographically, the enamel was of normal thickness and showed slight contrast with dentin. ### Comparison of AI2A1 and AI2A2 Kim et al. (2005) compared the dental phenotypes of the KLK4 (Hart et al., 2004) and MMP20 (their study) probands and noted many similar features. The enamel crowns are normal in size and shape, have a rougher, duller, less reflective surface than normal enamel, appear to be more brittle in that they show a tendency to fracture or chip, but do not appear to be particularly susceptible to dental caries. The radiodensity of the defective enamel is generally less than that of normal enamel, but can still be distinguished from the underlying dentin on radiographs. The coloration of the teeth is different, but extrinsic staining since tooth eruption could have contributed to the current appearance. The KLK4 teeth have a more homogeneous dark yellow hue, while the MMP20 teeth have an irregular grayish brown discoloration and are a little more glossy. Overall, the dental phenotypes in the KLK4 and MMP20 probands are remarkably similar. Molecular Genetics In 2 African American sibs with AI2A1, Hart et al. (2004) identified a homozygous nonsense mutation in the KLK4 gene (W153X; 603767.0001). Wright et al. (2011) identified the same mutation in 2 affected members of an unrelated African American family with amelogenesis imperfecta. In a 9-year-old Turkish girl with AI2A1, Wang et al. (2013) identified a homozygous deletion in the KLK4 gene (603767.0002) Her first-cousin parents were heterozygous for the mutation. INHERITANCE \- Autosomal recessive HEAD & NECK Teeth \- Yellow brown discolored teeth \- Normal size and shape of teeth \- Enamel is of normal thickness \- Excessive sensitivity to hot and cold \- Enamel is prone to chipping \- Caries \- Enamel is slightly more opaque than dentin on radiograph \- Anterior openbite (in one patient) MISCELLANEOUS \- Detailed clinical information provided for 2 KLK-mutation-positive families (last curated March 2015) MOLECULAR BASIS \- Caused by mutation in the kallikrein-4 gene (KLK4, 603767.0001 ) ▲ 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)	AMELOGENESIS IMPERFECTA, HYPOMATURATION TYPE, IIA1	c0399372	5,673	omim	https://www.omim.org/entry/204700	2019-09-22T16:31:10	{"doid": ["0110057"], "mesh": ["C536606"], "omim": ["204700"], "orphanet": ["100033", "88661"], "synonyms": ["Alternative titles", "AMELOGENESIS IMPERFECTA, PIGMENTED HYPOMATURATION TYPE, 1"]}
A rare neuro-opthalmological disease characterized by severe microcephaly of prenatal onset (with diminutive anterior fontanelle and sutural ridging), growth retardation, global developmental delay and intellectual disability (ranging from mild to profound), dysmorphic features (sloping forehead, micro/retrognathia, prominent ears) and visual impairments (including microphthalmia to anophtalmia, generalized retinopathy or multiple punched-out retinal lesions, retinal folds with retinal detachment, optic nerve hypoplasia, strabismus, nystagmus). Brain MRI may show reduced cortical size, cerebral hemispheres, corpus callosum, pachygyria, symplified gyral folding or normal pattern. Other associated features include epilepsy and neurological deficits. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Autosomal recessive chorioretinopathy-microcephaly syndrome	c3502492	5,674	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2518	2021-01-23T17:02:34	{"mesh": ["C565379"], "omim": ["251270", "616335"], "umls": ["C3502492"], "icd-10": ["Q87.8"], "synonyms": ["Autosomal recessive chorioretinopathy-microcephaly-intellectual disability syndrome"]}
For other uses, see Locura (disambiguation). Locura, which translates to "madness" in Spanish,[1][2] is a mental disorder characterized as severe chronic psychosis.[2][3][4] The term refers to a culture-bound syndrome, found mostly in Latin America and Latin Americans in the United States.[5][6][3][7] Also referred to as ataques de locura (meaning "madness attacks"),[6] it is categorized as a more severe form of nervios[7] ataque de nervios[6][3] with symptoms appearing similar to those of schizophrenia.[2][3] As the term may have multiple meanings in multiple environments, research on locura is limited and conflicting.[7] The term can be used loosely in Spanish when discussing madness in other psychological meaning, specifically describing a "deviance from the norm due to mental illness."[7] Besides for the implications found in the DSM-IV, the word is not used in English.[4] ## Contents * 1 Classification * 2 Signs and symptoms * 3 History * 4 See also * 5 References ## Classification[edit] In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), locura is classified as a culture-bound syndrome. Culture-bound syndromes can be found in an appendix of the manual named, Outline for Cultural Formulation and Glossary of Culture-Bound Syndromes.[4] However, the DSM - 5 does not include locura in its equivalent appendix named, Glossary of Cultural Concepts of Distress.[8] One author chooses to describe the symptoms as correlating to a somatoform disorder of conversive type.[6] ## Signs and symptoms[edit] Locura is thought to develop during times of stress or vulnerability in one's life, as well as the accumulation of difficulties or traumas.[3][7][4] Another possible cause is through the manifestation of supernatural maneuvers,[7] or maleficios (meaning "curses").[6][9] The DSM-IV includes symptoms of incoherence, agitation, inability to follow rules of social interaction, unpredictability, and possible violence.[4] Other sources include headache, fainting, convulsive attacks, difficulty in breathing, an urge to run away, hallucinations, and visions of people, visions, or demons.[2][6][7] ## History[edit] Locura has been examined in an indigenous group in Colombia called Embera.[6] After four members of the Embera community began exhibiting symptoms later described as, "repetitive episodes of what resembled a dissociative fugue disorder,"[6] a local shaman explained that the outbreak could be attributed to a shaman from a different region. The local shaman attempted their own treatment, but the affected member's symptoms continued and after six months, they eventually chose to seek help in the closest province. Soon after they arrived, their local relatives began to develop the same symptoms. After five more individuals presented similarly, all nine members began seeking forms of treatment including care from different types of religious healers, psychiatrists, and antipsychotic drugs. After none of these tactics proved successful, a shaman from the Chocó province in Columbia was brought to attempt treatment. The shaman's treatments reportedly reduced the frequency of the symptoms greatly in all of the patients and eliminated symptoms completely in two patients.[6] ## See also[edit] * Ataques de nervios * Culture-bound syndrome ## References[edit] 1. ^ "Locura - Spanish to English Translation \| Spanish Central". www.spanishcentral.com. Merriam-Webster. Retrieved 2017-04-06. 2. ^ a b c d Colman, Andrew (2015). A Dictionary of Psychology. Oxford University Press. 3. ^ a b c d e Villarruel, Francisco (2009). Handbook of U.S. Latino psychology: developmental and community-based perspectives. Thousand Oaks, CA: SAGE. 4. ^ a b c d e Diagnostic and Statistical Manual of Mental Disorders (Fourth ed.). Washington, DC: American Psychiatric Association. 1994. pp. 843–847. 5. ^ Nogueira, Bruno; de Jesus Mari, Jair; Razzouk, Denise (2015). "Culture-bound syndromes in Spanish speaking Latin America: the case of Nervios, Susto and Ataques de Nervios". Archives of Clinical Psychiatry. 42.5-6 (6): 171–178. doi:10.1590/0101-60830000000070. 6. ^ a b c d e f g h i Piñeros, Marion; Rosselli, Diego; Calderon, Claudia (1998). "An epidemic of collective conversion and dissociation disorder in an indigenous group of Columbia: its relation to cultural change". Social Science and Medicine. 46 (11): 1425–1428. doi:10.1016/S0277-9536(97)10094-6. PMID 9665572. 7. ^ a b c d e f g Garcia Briggs, Mary Jo (2012). Loue, Sana; Sajatovic, Martha (eds.). Encyclopedia of Immigrant Health. New York, NY: Springer US. pp. 1025. 8. ^ Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Association. 2013. 9. ^ "Maleficio - Spanish to English Translation \| Spanish Central". www.spanishcentral.com. Retrieved 2017-04-13. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Locura	None	5,675	wikipedia	https://en.wikipedia.org/wiki/Locura	2021-01-18T18:56:43	{"wikidata": ["Q48996017"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive osteopetrosis-4 (OPTB4) is caused by homozygous or compound heterozygous mutation in the CLCN7 gene (602727) on chromosome 16p13. An autosomal dominant form of osteopetrosis (OPTA2; 166600) is also caused by mutation in CLCN7. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700). Clinical Features Cleiren et al. (2001) reported a girl, born to second-cousin parents of Chinese ancestry, who presented at 3 months of age with Bell palsy. Radiographic skeletal survey revealed severe osteopetrosis and several nondisplaced oblique fractures. She had anemia, reticulocytosis, hepatosplenomegaly, and mild optic nerve atrophy. The child underwent a mismatched allogeneic marrow transplant but died at age 18 months from sepsis and respiratory failure. Molecular Genetics Based on the similarity between the phenotype of patients with infantile malignant osteopetrosis and that of mice with targeted disruption of the Clcn7 gene (see 602727), which develop severe osteopetrosis and retinal degeneration, Kornak et al. (2001) searched for mutations in the human CLCN7 gene in 12 patients with infantile osteopetrosis. They identified compound heterozygosity for a nonsense (Q555X; 602727.0001) and a missense (R762Q; 602727.0002) mutation in the CLCN7 gene in 1 patient with infantile malignant osteopetrosis who had early visual impairment. No retinal histology was available. In a girl with severe autosomal recessive infantile osteopetrosis born to consanguineous parents of Chinese ancestry, Cleiren et al. (2001) identified homozygosity for a missense mutation (L766P; 602727.0003) in the CLCN7 gene. Her parents, who were heterozygous for the mutation, were asymptomatic, but radiographic skeletal survey was unavailable. Because OPTB4 patients are homozygous whereas patients with autosomal dominant osteopetrosis-2 (OPTA2; 166600) are heterozygous for mutations in CLCN7, the 2 disorders appear to be allelic. Cleiren et al. (2001) hypothesized that OPTA2 reflects a dominant-negative effect, since loss-of-function mutations in CLCN7 do not cause abnormalities in heterozygous individuals. Using whole-genome scans based on high density single-nucleotide polymorphism (SNP) microarray for homozygosity mapping, Lam et al. (2007) investigated a consanguineous Chinese family in which a sister and brother had malignant osteopetrosis. Mapping revealed that among the 3 possible causal loci, only the CLCN7 gene was located in an autozygous region. Sequencing of CLCN7 showed that the proband and her affected brother were homozygous for a novel missense mutation (I261F; 602727.0006). Their unaffected first-cousin parents and an unaffected brother were heterozygous for the mutation, which was not found in 50 Chinese controls. INHERITANCE \- Autosomal recessive GROWTH Other \- Growth retardation HEAD & NECK Eyes \- Visual impairment (early onset) \- Pale optic discs \- Optic nerve atrophy ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Severe osteopetrosis \- Segmentary osteosclerosis \- Generalized increased bone density \- Fractures with minor trauma \- Increased trabecular size \- Thickening of matrix \- Abnormal medullary bone formation \- Narrowing of medullary space Skull \- Sclerosis, particularly of the base of the skull Spine \- Increased bone density \- Sclerotic vertebral endplates ('rugger-jersey' spine) Pelvis \- Concentric arcs of sclerosis in iliac wings ('bone-within-bone' sign) Limbs \- Increased bone density in epiphyseal growth plates of long bones SKIN, NAILS, & HAIR Skin \- Generalized petechiae NEUROLOGIC Peripheral Nervous System \- Bell palsy HEMATOLOGY \- Anemia \- Reticulocytosis \- Thrombocytopenia MOLECULAR BASIS \- Caused by mutation in the chloride channel-7 gene (CLCN7, 602727.0001 ) ▲ 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)	OSTEOPETROSIS, AUTOSOMAL RECESSIVE 4	c1318518	5,676	omim	https://www.omim.org/entry/611490	2019-09-22T16:03:11	{"doid": ["0110944"], "omim": ["611490"], "orphanet": ["667"], "synonyms": ["Alternative titles", "OSTEOPETROSIS, INFANTILE MALIGNANT 2"], "genereviews": ["NBK1127"]}
"Infectious disease" redirects here. For the medical specialty, see infectious disease (medical specialty). For the journal, see Infectious Diseases (journal). For other uses, see Infection (disambiguation). Invasion of an organism's body tissues by disease-causing agents Infection False-colored electron micrograph showing a malaria sporozoite migrating through the midgut epithelium of a rat SpecialtyInfectious disease Causesbacterial, viral, parasitic, fungal An infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to the infectious agents and the toxins they produce.[1][2] An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection. Infections are caused by infectious agents (pathogens) including: * Viruses and related agents such as viroids (HIV, Rhinovirus, Lyssaviruses such as Rabies virus, Ebolavirus and Severe acute respiratory syndrome coronavirus 2) * Bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Clostridium botulinum, and Salmonella spp.) * Fungi, further subclassified into: * * Ascomycota, including yeasts such as Candida, filamentous fungi such as Aspergillus, Pneumocystis species, and dermatophytes, a group of organisms causing infection of skin and other superficial structures in humans.[3] * Basidiomycota, including the human-pathogenic genus Cryptococcus.[4] * prions (although they don't secrete toxins) * Parasites, which are usually divided into:[5] * Unicellular organisms (e.g. malaria, Toxoplasma, Babesia) * Macroparasites[6] (worms or helminths) including nematodes such as parasitic roundworms and pinworms, tapeworms (cestodes), and flukes (trematodes, such as schistosomiasis) * Arthropods such as ticks, mites, fleas, and lice, can also cause human disease, which conceptually are similar to infections, but invasion of a human or animal body by these macroparasites is usually termed infestation. (Diseases caused by helminths, which are also macroparasites, are sometimes termed infestations as well, but are sometimes called infections.) Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, often involving inflammation, followed by an adaptive response.[7] Specific medications used to treat infections include antibiotics, antivirals, antifungals, antiprotozoals, and antihelminthics. Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths).[8] The branch of medicine that focuses on infections is referred to as infectious disease.[9] ## Contents * 1 Classification * 1.1 Subclinical versus clinical (latent versus apparent) * 1.2 Primary versus opportunistic * 1.2.1 Primary pathogens * 1.2.2 Opportunistic pathogens * 1.2.3 Secondary infection * 1.2.4 Other types of infection * 1.3 Infectious or not * 1.4 Contagiousness * 1.5 By anatomic location * 2 Signs and symptoms * 2.1 Bacterial or viral * 3 Pathophysiology * 3.1 Colonization * 3.2 Disease * 3.3 Transmission * 4 Diagnosis * 4.1 Symptomatic diagnostics * 4.2 Microbial culture * 4.3 Microscopy * 4.4 Biochemical tests * 4.5 PCR-based diagnostics * 4.6 Metagenomic sequencing * 4.7 Indication of tests * 5 Prevention * 5.1 Immunity * 5.1.1 Host genetic factors * 6 Treatments * 7 Epidemiology * 7.1 Historic pandemics * 7.2 Emerging diseases * 8 Germ theory of disease * 8.1 Medical specialists * 9 Society and culture * 10 Fossil record * 11 Outer space * 12 See also * 13 References * 14 External links ## Classification[edit] ### Subclinical versus clinical (latent versus apparent)[edit] Symptomatic infections are apparent and clinical, whereas an infection that is active but does not produce noticeable symptoms may be called inapparent, silent, subclinical, or occult. An infection that is inactive or dormant is called a latent infection.[10] An example of a latent bacterial infection is latent tuberculosis. Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family.[11] The word infection can denote any presence of a particular pathogen at all (no matter how little) but also is often used in a sense implying a clinically apparent infection (in other words, a case of infectious disease).[12] This fact occasionally creates some ambiguity or prompts some usage discussion; to get around this it is common for health professionals to speak of colonization (rather than infection) when they mean that some of the pathogens are present but that no clinically apparent infection (no disease) is present. Different terms are used to describe infections. The first is an acute infection. An acute infection is one in which symptoms develop rapidly; its course can either be rapid or protracted.[13] The next is a chronic infection. A chronic infection is when symptoms develop gradually, over weeks or months, and are slow to resolve.[14] A subacute infection is one in which symptoms take longer to develop than in an acute infection but arise more quickly than a chronic infection. A latent infection is a type of infection that may occur after an acute episode; the organism is present but symptoms are not; after time the disease can reappear. A focal infection is defined as the initial site of infection from which organisms travel via the bloodstream to another area of the body.[15] ### Primary versus opportunistic[edit] See also: Coinfection Among the many varieties of microorganisms, relatively few cause disease in otherwise healthy individuals.[16] Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depend upon the ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. However, a host's immune system can also cause damage to the host itself in an attempt to control the infection. Clinicians, therefore, classify infectious microorganisms or microbes according to the status of host defenses - either as primary pathogens or as opportunistic pathogens: #### Primary pathogens[edit] Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts. #### Opportunistic pathogens[edit] Main article: Opportunistic infection Opportunistic pathogens can cause an infectious disease in a host with depressed resistance (immunodeficiency) or if they have unusual access to the inside of the body (for example, via trauma). Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridium difficile colitis) or from the environment as a result of traumatic introduction (as in surgical wound infections or compound fractures). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as Chronic granulomatous disease), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy), exposure to ionizing radiation, or as a result of an infectious disease with immunosuppressive activity (such as with measles, malaria or HIV disease). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host.[17] #### Secondary infection[edit] While a primary infection can practically be viewed as, the root cause of an individual's current health problem, a secondary infection is a sequela or complication of that root cause. For example, pulmonary tuberculosis is often a primary infection, but an infection that happened only because a burn or penetrating trauma (the root cause) allowed unusual access to deep tissues is a secondary infection. Primary pathogens often cause primary infection and also often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections (because immunodeficiency or injury was the predisposing factor). #### Other types of infection[edit] Other types of infection consist of mixed, iatrogenic, nosocomial, and community-acquired infection. A mixed infection is an infection that is caused by two or more pathogens. An example of this is Appendicitis, which is caused by Bacteroides fragilis and Escherichia coli. The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. A nosocomial infection is also one that occurs in a health care setting. Nosocomial infections are those that are acquired during a hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community.[15] ### Infectious or not[edit] One manner of proving that a given disease is infectious, is to satisfy Koch's postulates (first proposed by Robert Koch), which require that first, the infectious agent be identifiable only in patients who have the disease, and not in healthy controls, and second, that patients who contract the infectious agent also develop the disease. These postulates were first used in the discovery that Mycobacteria species cause tuberculosis. However, Koch's postulates cannot usually be tested in modern practice for ethical reasons. Proving them would require experimental infection of a healthy individual with a pathogen produced as a pure culture. Conversely, even clearly infectious diseases do not always meet the infectious criteria; for example, Treponema pallidum, the causative spirochete of syphilis, cannot be cultured in vitro – however the organism can be cultured in rabbit testes. It is less clear that a pure culture comes from an animal source serving as host than it is when derived from microbes derived from plate culture. Epidemiology, or the study and analysis of who, why and where disease occurs, and what determines whether various populations have a disease, is another important tool used to understand infectious disease. Epidemiologists may determine differences among groups within a population, such as whether certain age groups have a greater or lesser rate of infection; whether groups living in different neighborhoods are more likely to be infected; and by other factors, such as gender and race. Researchers also may assess whether a disease outbreak is sporadic, or just an occasional occurrence; endemic, with a steady level of regular cases occurring in a region; epidemic, with a fast arising, and unusually high number of cases in a region; or pandemic, which is a global epidemic. If the cause of the infectious disease is unknown, epidemiology can be used to assist with tracking down the sources of infection. ### Contagiousness[edit] Infectious diseases are sometimes called contagious diseases when they are easily transmitted by contact with an ill person or their secretions (e.g., influenza). Thus, a contagious disease is a subset of infectious disease that is especially infective or easily transmitted. Other types of infectious, transmissible, or communicable diseases with more specialized routes of infection, such as vector transmission or sexual transmission, are usually not regarded as "contagious", and often do not require medical isolation (sometimes loosely called quarantine) of victims. However, this specialized connotation of the word "contagious" and "contagious disease" (easy transmissibility) is not always respected in popular use. Infectious diseases are commonly transmitted from person to person through direct contact. The types of contact are through person to person and droplet spread. Indirect contact such as airborne transmission, contaminated objects, food and drinking water, animal person contact, animal reservoirs, insect bites, and environmental reservoirs are another way infectious diseases are transmitted.[18] ### By anatomic location[edit] Infections can be classified by the anatomic location or organ system infected, including: * Urinary tract infection * Skin infection * Respiratory tract infection * Odontogenic infection (an infection that originates within a tooth or in the closely surrounding tissues) * Vaginal infections * Intra-amniotic infection In addition, locations of inflammation where infection is the most common cause include pneumonia, meningitis and salpingitis. ## Signs and symptoms[edit] The symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue, loss of appetite, weight loss, fevers, night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes, coughing, or a runny nose. In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier. An infection is not synonymous with an infectious disease, as some infections do not cause illness in a host.[17] ### Bacterial or viral[edit] As bacterial and viral infections can both cause the same kinds of symptoms, it can be difficult to distinguish which is the cause of a specific infection.[19] Distinguishing the two is important, since viral infections cannot be cured by antibiotics whereas bacterial infections can.[20] Comparison of viral and bacterial infection Characteristic Viral infection Bacterial infection Typical symptoms In general, viral infections are systemic. This means they involve many different parts of the body or more than one body system at the same time; i.e. a runny nose, sinus congestion, cough, body aches etc. They can be local at times as in viral conjunctivitis or "pink eye" and herpes. Only a few viral infections are painful, like herpes. The pain of viral infections is often described as itchy or burning.[19] The classic symptoms of a bacterial infection are localized redness, heat, swelling and pain. One of the hallmarks of a bacterial infection is local pain, pain that is in a specific part of the body. For example, if a cut occurs and is infected with bacteria, pain occurs at the site of the infection. Bacterial throat pain is often characterized by more pain on one side of the throat. An ear infection is more likely to be diagnosed as bacterial if the pain occurs in only one ear.[19] A cut that produces pus and milky-colored liquid is most likely infected.[clarification needed][21] Cause Pathogenic viruses Pathogenic bacteria ## Pathophysiology[edit] There is a general chain of events that applies to infections.[22] The chain of events involves several steps – which include the infectious agent, reservoir, entering a susceptible host, exit and transmission to new hosts. Each of the links must be present in a chronological order for an infection to develop. Understanding these steps helps health care workers target the infection and prevent it from occurring in the first place.[23] ### Colonization[edit] Infection of an ingrown toenail; there is pus (yellow) and resultant inflammation (redness and swelling around the nail). Infection begins when an organism successfully enters the body, grows and multiplies. This is referred to as colonization. Most humans are not easily infected. Those with compromised or weakened immune systems have an increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections. Entrance to the host at host-pathogen interface, generally occurs through the mucosa in orifices like the oral cavity, nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids. Wound colonization refers to non-replicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue is injured.[24] All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon, and an example of the latter are the various species of staphylococcus that exist on human skin. Neither of these colonizations are considered infections. The difference between an infection and a colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and viridans streptococci, prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with the host, preventing infection and speeding wound healing. [25][26][27] This image depicts the steps of pathogenic infection. The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include: * the route of entry of the pathogen and the access to host regions that it gains * the intrinsic virulence of the particular organism * the quantity or load of the initial inoculant * the immune status of the host being colonized As an example, several staphylococcal species remain harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum, multiply without resistance and cause harm. An interesting fact that gas chromatography–mass spectrometry, 16S ribosomal RNA analysis, omics, and other advanced technologies have made more apparent to humans in recent decades is that microbial colonization is very common even in environments that humans think of as being nearly sterile. Because it is normal to have bacterial colonization, it is difficult to know which chronic wounds can be classified as infected and how much risk of progression exists. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in the Journal of the American Medical Association's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection.[28] The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11–20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64–0.88) does not rule out infection (summary LR 0.64–0.88). ### Disease[edit] Disease can arise if the host's protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis. Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected with polio develop disease.[29] On the other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease invariably kills all animals and people that are infected. Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain a persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise. Persistent infections cause millions of deaths globally each year.[30] Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries. ### Transmission[edit] Main article: Transmission (medicine) A southern house mosquito (Culex quinquefasciatus) is a vector that transmits the pathogens that cause West Nile fever and avian malaria among others. For infecting organisms to survive and repeat the infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Infection transmission can take place via many potential routes: * Droplet contact, also known as the respiratory route, and the resultant infection can be termed airborne disease. If an infected person coughs or sneezes on another person the microorganisms, suspended in warm, moist droplets, may enter the body through the nose, mouth or eye surfaces. * Fecal-oral transmission, wherein foodstuffs or water become contaminated (by people not washing their hands before preparing food, or untreated sewage being released into a drinking water supply) and the people who eat and drink them become infected. Common fecal-oral transmitted pathogens include Vibrio cholerae, Giardia species, rotaviruses, Entameba histolytica, Escherichia coli, and tape worms.[31] Most of these pathogens cause gastroenteritis. * Sexual transmission, with the resulting disease being called sexually transmitted disease * Oral transmission, Diseases that are transmitted primarily by oral means may be caught through direct oral contact such as kissing, or by indirect contact such as by sharing a drinking glass or a cigarette. * Transmission by direct contact, Some diseases that are transmissible by direct contact include athlete's foot, impetigo and warts * Vehicle transmission, transmission by an inanimate reservoir (food, water, soil).[32] * Vertical transmission, directly from the mother to an embryo, fetus or baby during pregnancy or childbirth. It can occur as a result of a pre-existing infection or one acquired during pregnancy. * Iatrogenic transmission, due to medical procedures such as injection or transplantation of infected material. * Vector-borne transmission, transmitted by a vector, which is an organism that does not cause disease itself but that transmits infection by conveying pathogens from one host to another.[33] The relationship between virulence versus transmissibility is complex; if a disease is rapidly fatal, the host may die before the microbe can be passed along to another host. ## Diagnosis[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. (December 2019) (Learn how and when to remove this template message) Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly.[34] In practice most minor infectious diseases such as warts, cutaneous abscesses, respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about the cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is benign. Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve the culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Other techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by a prion. ### Symptomatic diagnostics[edit] The diagnosis is aided by the presenting symptoms in any individual with an infectious disease, yet it usually needs additional diagnostic techniques to confirm the suspicion. Some signs are specifically characteristic and indicative of a disease and are called pathognomonic signs; but these are rare. Not all infections are symptomatic.[35] In children the presence of cyanosis, rapid breathing, poor peripheral perfusion, or a petechial rash increases the risk of a serious infection by greater than 5 fold.[36] Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C.[36] ### Microbial culture[edit] Four nutrient agar plates growing colonies of common Gram negative bacteria. Microbiological culture is a principal tool used to diagnose infectious disease. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Most pathogenic bacteria are easily grown on nutrient agar, a form of solid medium that supplies carbohydrates and proteins necessary for growth of a bacterium, along with copious amounts of water. A single bacterium will grow into a visible mound on the surface of the plate called a colony, which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit the growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of viruses: the medium, in this case, being cells grown in culture that the virus can infect, and then alter or kill. In the case of viral identification, a region of dead cells results from viral growth, and is called a "plaque". Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent. In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as Mycobacterium leprae and Treponema pallidum can be grown in animals, although serological and microscopic techniques make the use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent. Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of the causative agent, Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case, xenodiagnosis involves the use of the vector of the Chagas agent T. cruzi, an uninfected triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of T. cruzi within its gut. ### Microscopy[edit] Another principal tool in the diagnosis of infectious disease is microscopy. Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound light microscope, or with instruments as complex as an electron microscope. Samples obtained from patients may be viewed directly under the light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with biochemical staining techniques, and can be made exquisitely specific when used in combination with antibody based techniques. For example, the use of antibodies made artificially fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific antigens present on a pathogen. A fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly. Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with a number of basic dyes due to the electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as Giemsa stain or crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures is used in the taxonomic classification of microbes as well. Two methods, the Gram stain and the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Firmicutes and Actinobacteria, both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinobacterial genera Mycobacterium and Nocardia. ### Biochemical tests[edit] Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media. The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an enzyme and has no metabolic function. Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, S. pyogenes, that is retrieved from a patient's throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.[17] Complex serological techniques have been developed into what are known as Immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow the destruction of the virus. Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost-effective automated process for diagnosis of infectious disease. ### PCR-based diagnostics[edit] Technologies based upon the polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids in order to cause a disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers, are derived from the genomes of infectious agents, and with time those genomes will be known, if they are not already. Thus, the technological ability to detect any infectious agent rapidly and specifically are currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases (tetanus and botulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria. ### Metagenomic sequencing[edit] Given the wide range of bacteria, viruses, and other pathogens that cause debilitating and life-threatening illness, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis, a severe illness affecting the brain, remain undiagnosed, despite extensive testing using state-of-the-art clinical laboratory methods. Metagenomics is currently being researched for clinical use, and shows promise as a sensitive and rapid way to diagnose infection using a single all-encompassing test. This test is similar to current PCR tests; however, amplification of genetic material is unbiased rather than using primers for a specific infectious agent. This amplification step is followed by next-generation sequencing and alignment comparisons using large databases of thousands of organismic and viral genomes. Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised. An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally, the expression of symptoms is often atypical, making clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A broad, sensitive test for pathogens that detects the presence of infectious material rather than antibodies is therefore highly desirable. ### Indication of tests[edit] There is usually an indication for a specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of AZT for the treatment of AIDS, the course of the disease was closely followed by monitoring the composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of HIV in specific communities permitted the advancement of hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing the number of new infections. The specific serological diagnostic identification, and later genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the temporal and geographical origins of the virus, as well as a myriad of other hypothesis.[17] The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs. Molecular diagnostics are now commonly used to identify HIV in healthy people long before the onset of illness and have been used to demonstrate the existence of people who are genetically resistant to HIV infection. Thus, while there still is no cure for AIDS, there is great therapeutic and predictive benefit to identifying the virus and monitoring the virus levels within the blood of infected individuals, both for the patient and for the community at large. ## Prevention[edit] Main articles: Public health and Infection control Washing one's hands, a form of hygiene, is an effective way to prevent the spread of infectious disease.[37] Techniques like hand washing, wearing gowns, and wearing face masks can help prevent infections from being passed from one person to another. Aseptic technique was introduced in medicine and surgery in the late 19th century and greatly reduced the incidence of infections caused by surgery. Frequent hand washing remains the most important defense against the spread of unwanted organisms.[38] There are other forms of prevention such as avoiding the use of illicit drugs, using a condom, wearing gloves, and having a healthy lifestyle with a balanced diet and regular exercise. Cooking foods well and avoiding foods that have been left outside for a long time is also important. Antimicrobial substances used to prevent transmission of infections include: * antiseptics, which are applied to living tissue/skin * disinfectants, which destroy microorganisms found on non-living objects. * antibiotics, called prophylactic when given as prevention rather as treatment of infection. However, long term use of antibiotics leads to resistance of bacteria. While humans do not become immune to antibiotics, the bacteria does. Thus, avoiding using antibiotics longer than necessary helps preventing bacteria from forming mutations that aide in antibiotic resistance. One of the ways to prevent or slow down the transmission of infectious diseases is to recognize the different characteristics of various diseases.[39] Some critical disease characteristics that should be evaluated include virulence, distance traveled by victims, and level of contagiousness. The human strains of Ebola virus, for example, incapacitate their victims extremely quickly and kill them soon after. As a result, the victims of this disease do not have the opportunity to travel very far from the initial infection zone.[40] Also, this virus must spread through skin lesions or permeable membranes such as the eye. Thus, the initial stage of Ebola is not very contagious since its victims experience only internal hemorrhaging. As a result of the above features, the spread of Ebola is very rapid and usually stays within a relatively confined geographical area. In contrast, the Human Immunodeficiency Virus (HIV) kills its victims very slowly by attacking their immune system.[17] As a result, many of its victims transmit the virus to other individuals before even realizing that they are carrying the disease. Also, the relatively low virulence allows its victims to travel long distances, increasing the likelihood of an epidemic. Another effective way to decrease the transmission rate of infectious diseases is to recognize the effects of small-world networks.[39] In epidemics, there are often extensive interactions within hubs or groups of infected individuals and other interactions within discrete hubs of susceptible individuals. Despite the low interaction between discrete hubs, the disease can jump to and spread in a susceptible hub via a single or few interactions with an infected hub. Thus, infection rates in small-world networks can be reduced somewhat if interactions between individuals within infected hubs are eliminated (Figure 1). However, infection rates can be drastically reduced if the main focus is on the prevention of transmission jumps between hubs. The use of needle exchange programs in areas with a high density of drug users with HIV is an example of the successful implementation of this treatment method. [6][full citation needed] Another example is the use of ring culling or vaccination of potentially susceptible livestock in adjacent farms to prevent the spread of the foot-and-mouth virus in 2001.[41] A general method to prevent transmission of vector-borne pathogens is pest control. In cases where infection is merely suspected, individuals may be quarantined until the incubation period has passed and the disease manifests itself or the person remains healthy. Groups may undergo quarantine, or in the case of communities, a cordon sanitaire may be imposed to prevent infection from spreading beyond the community, or in the case of protective sequestration, into a community. Public health authorities may implement other forms of social distancing, such as school closings, to control an epidemic. ### Immunity[edit] Mary Mallon (a.k.a. Typhoid Mary) was an asymptomatic carrier of typhoid fever. Over the course of her career as a cook, she infected 53 people, three of whom died. Infection with most pathogens does not result in death of the host and the offending organism is ultimately cleared after the symptoms of the disease have waned.[16] This process requires immune mechanisms to kill or inactivate the inoculum of the pathogen. Specific acquired immunity against infectious diseases may be mediated by antibodies and/or T lymphocytes. Immunity mediated by these two factors may be manifested by: * a direct effect upon a pathogen, such as antibody-initiated complement-dependent bacteriolysis, opsonoization, phagocytosis and killing, as occurs for some bacteria, * neutralization of viruses so that these organisms cannot enter cells, * or by T lymphocytes, which will kill a cell parasitized by a microorganism. The immune system response to a microorganism often causes symptoms such as a high fever and inflammation, and has the potential to be more devastating than direct damage caused by a microbe.[17] Resistance to infection (immunity) may be acquired following a disease, by asymptomatic carriage of the pathogen, by harboring an organism with a similar structure (crossreacting), or by vaccination. Knowledge of the protective antigens and specific acquired host immune factors is more complete for primary pathogens than for opportunistic pathogens. There is also the phenomenon of herd immunity which offers a measure of protection to those otherwise vulnerable people when a large enough proportion of the population has acquired immunity from certain infections. Immune resistance to an infectious disease requires a critical level of either antigen-specific antibodies and/or T cells when the host encounters the pathogen. Some individuals develop natural serum antibodies to the surface polysaccharides of some agents although they have had little or no contact with the agent, these natural antibodies confer specific protection to adults and are passively transmitted to newborns. #### Host genetic factors[edit] The organism that is the target of an infecting action of a specific infectious agent is called the host. The host harbouring an agent that is in a mature or sexually active stage phase is called the definitive host. The intermediate host comes in contact during the larvae stage. A host can be anything living and can attain to asexual and sexual reproduction.[42] The clearance of the pathogens, either treatment-induced or spontaneous, it can be influenced by the genetic variants carried by the individual patients. For instance, for genotype 1 hepatitis C treated with Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in the treatment-induced clearance of the virus. This finding, originally reported in Nature,[43] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more possibly to achieve sustained virological response after the treatment than others. Later report from Nature[44] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus. ## Treatments[edit] When infection attacks the body, anti-infective drugs can suppress the infection. Several broad types of anti-infective drugs exist, depending on the type of organism targeted; they include antibacterial (antibiotic; including antitubercular), antiviral, antifungal and antiparasitic (including antiprotozoal and antihelminthic) agents. Depending on the severity and the type of infection, the antibiotic may be given by mouth or by injection, or may be applied topically. Severe infections of the brain are usually treated with intravenous antibiotics. Sometimes, multiple antibiotics are used in case there is resistance to one antibiotic. Antibiotics only work for bacteria and do not affect viruses. Antibiotics work by slowing down the multiplication of bacteria or killing the bacteria. The most common classes of antibiotics used in medicine include penicillin, cephalosporins, aminoglycosides, macrolides, quinolones and tetracyclines.[45][46] Not all infections require treatment, and for many self-limiting infections the treatment may cause more side-effects than benefits. Antimicrobial stewardship is the concept that healthcare providers should treat an infection with an antimicrobial that specifically works well for the target pathogen for the shortest amount of time and to only treat when there is a known or highly suspected pathogen that will respond to the medication.[47] ## Epidemiology[edit] Deaths due to infectious and parasitic diseases per million persons in 2012 28–81 82–114 115–171 172–212 213–283 284–516 517–1,193 1,194–2,476 2,477–3,954 3,955–6,812 Disability-adjusted life year for infectious and parasitic diseases per 100,000 inhabitants in 2004.[48] no data ≤250 250–500 500–1000 1000–2000 2000–3000 3000–4000 4000–5000 5000–6250 6250–12,500 12,500–25,000 25,000–50,000 ≥50,000 In 2010, about 10 million people died of infectious diseases.[49] The World Health Organization collects information on global deaths by International Classification of Disease (ICD) code categories. The following table lists the top infectious disease by number of deaths in 2002. 1993 data is included for comparison. Worldwide mortality due to infectious diseases[50][51] Rank Cause of death Deaths 2002 (in millions) Percentage of all deaths Deaths 1993 (in millions) 1993 Rank N/A All infectious diseases 14.7 25.9% 16.4 32.2% 1 Lower respiratory infections[52] 3.9 6.9% 4.1 1 2 HIV/AIDS 2.8 4.9% 0.7 7 3 Diarrheal diseases[53] 1.8 3.2% 3.0 2 4 Tuberculosis (TB) 1.6 2.7% 2.7 3 5 Malaria 1.3 2.2% 2.0 4 6 Measles 0.6 1.1% 1.1 5 7 Pertussis 0.29 0.5% 0.36 7 8 Tetanus 0.21 0.4% 0.15 12 9 Meningitis 0.17 0.3% 0.25 8 10 Syphilis 0.16 0.3% 0.19 11 11 Hepatitis B 0.10 0.2% 0.93 6 12–17 Tropical diseases (6)[54] 0.13 0.2% 0.53 9, 10, 16–18 Note: Other causes of death include maternal and perinatal conditions (5.2%), nutritional deficiencies (0.9%), noncommunicable conditions (58.8%), and injuries (9.1%). The top three single agent/disease killers are HIV/AIDS, TB and malaria. While the number of deaths due to nearly every disease have decreased, deaths due to HIV/AIDS have increased fourfold. Childhood diseases include pertussis, poliomyelitis, diphtheria, measles and tetanus. Children also make up a large percentage of lower respiratory and diarrheal deaths. In 2012, approximately 3.1 million people have died due to lower respiratory infections, making it the number 4 leading cause of death in the world.[55] ### Historic pandemics[edit] Great Plague of Marseille in 1720 killed 100,000 people in the city and the surrounding provinces With their potential for unpredictable and explosive impacts, infectious diseases have been major actors in human history.[56] A pandemic (or global epidemic) is a disease that affects people over an extensive geographical area. For example: * Plague of Justinian, from 541 to 542, killed between 50% and 60% of Europe's population.[57] * The Black Death of 1347 to 1352 killed 25 million in Europe over 5 years. The plague reduced the old world population from an estimated 450 million to between 350 and 375 million in the 14th century. * The introduction of smallpox, measles, and typhus to the areas of Central and South America by European explorers during the 15th and 16th centuries caused pandemics among the native inhabitants. Between 1518 and 1568 disease pandemics are said to have caused the population of Mexico to fall from 20 million to 3 million.[58] * The first European influenza epidemic occurred between 1556 and 1560, with an estimated mortality rate of 20%.[58] * Smallpox killed an estimated 60 million Europeans during the 18th century[59] (approximately 400,000 per year).[60] Up to 30% of those infected, including 80% of the children under 5 years of age, died from the disease, and one-third of the survivors went blind.[61] * In the 19th century, tuberculosis killed an estimated one-quarter of the adult population of Europe;[62] by 1918 one in six deaths in France were still caused by TB. * The Influenza Pandemic of 1918 (or the Spanish flu) killed 25–50 million people (about 2% of world population of 1.7 billion).[63] Today Influenza kills about 250,000 to 500,000 worldwide each year. ### Emerging diseases[edit] In most cases, microorganisms live in harmony with their hosts via mutual or commensal interactions. Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host. 1. Coevolution between parasite and host can lead to hosts becoming resistant to the parasites or the parasites may evolve greater virulence, leading to immunopathological disease. 2. Human activity is involved with many emerging infectious diseases, such as environmental change enabling a parasite to occupy new niches. When that happens, a pathogen that had been confined to a remote habitat has a wider distribution and possibly a new host organism. Parasites jumping from nonhuman to human hosts are known as zoonoses. Under disease invasion, when a parasite invades a new host species, it may become pathogenic in the new host.[64] Several human activities have led to the emergence of zoonotic human pathogens, including viruses, bacteria, protozoa, and rickettsia,[65] and spread of vector-borne diseases,[64] see also globalization and disease and wildlife disease: * Encroachment on wildlife habitats. The construction of new villages and housing developments in rural areas force animals to live in dense populations, creating opportunities for microbes to mutate and emerge.[66] * Changes in agriculture. The introduction of new crops attracts new crop pests and the microbes they carry to farming communities, exposing people to unfamiliar diseases. * The destruction of rain forests. As countries make use of their rain forests, by building roads through forests and clearing areas for settlement or commercial ventures, people encounter insects and other animals harboring previously unknown microorganisms. * Uncontrolled urbanization. The rapid growth of cities in many developing countries tends to concentrate large numbers of people into crowded areas with poor sanitation. These conditions foster transmission of contagious diseases. * Modern transport. Ships and other cargo carriers often harbor unintended "passengers", that can spread diseases to faraway destinations. While with international jet-airplane travel, people infected with a disease can carry it to distant lands, or home to their families, before their first symptoms appear. ## Germ theory of disease[edit] Main article: Germ theory of disease East German postage stamps depicting four antique microscopes. Advancements in microscopy were essential to the early study of infectious diseases. In Antiquity, the Greek historian Thucydides (c. 460 – c. 400 BCE) was the first person to write, in his account of the plague of Athens, that diseases could spread from an infected person to others.[67][68] In his On the Different Types of Fever (c. AD 175), the Greco-Roman physician Galen speculated that plagues were spread by "certain seeds of plague", which were present in the air.[69] In the Sushruta Samhita, the ancient Indian physician Sushruta theorized: "Leprosy, fever, consumption, diseases of the eye, and other infectious diseases spread from one person to another by sexual union, physical contact, eating together, sleeping together, sitting together, and the use of same clothes, garlands and pastes."[70][71] This book has been dated to about the sixth century BC.[72] A basic form of contagion theory was proposed by Persian physician Ibn Sina (known as Avicenna in Europe) in The Canon of Medicine (1025), which later became the most authoritative medical textbook in Europe up until the 16th century. In Book IV of the Canon, Ibn Sina discussed epidemics, outlining the classical miasma theory and attempting to blend it with his own early contagion theory. He mentioned that people can transmit disease to others by breath, noted contagion with tuberculosis, and discussed the transmission of disease through water and dirt.[73] The concept of invisible contagion was later discussed by several Islamic scholars in the Ayyubid Sultanate who referred to them as najasat ("impure substances"). The fiqh scholar Ibn al-Haj al-Abdari (c. 1250–1336), while discussing Islamic diet and hygiene, gave warnings about how contagion can contaminate water, food, and garments, and could spread through the water supply, and may have implied contagion to be unseen particles.[74] When the Black Death bubonic plague reached Al-Andalus in the 14th century, the Arab physicians Ibn Khatima (c. 1369) and Ibn al-Khatib (1313–1374) hypothesised that infectious diseases were caused by "minute bodies" and described how they can be transmitted through garments, vessels and earrings.[75] Ideas of contagion became more popular in Europe during the Renaissance, particularly through the writing of the Italian physician Girolamo Fracastoro.[76] Anton van Leeuwenhoek (1632–1723) advanced the science of microscopy by being the first to observe microorganisms, allowing for easy visualization of bacteria. In the mid-19th century John Snow and William Budd did important work demonstrating the contagiousness of typhoid and cholera through contaminated water. Both are credited with decreasing epidemics of cholera in their towns by implementing measures to prevent contamination of water.[77] Louis Pasteur proved beyond doubt that certain diseases are caused by infectious agents, and developed a vaccine for rabies. Robert Koch, provided the study of infectious diseases with a scientific basis known as Koch's postulates. Edward Jenner, Jonas Salk and Albert Sabin developed effective vaccines for smallpox and polio, which would later result in the eradication and near-eradication of these diseases, respectively. Alexander Fleming discovered the world's first antibiotic, Penicillin, which Florey and Chain then developed. Gerhard Domagk developed sulphonamides, the first broad spectrum synthetic antibacterial drugs. ### Medical specialists[edit] The medical treatment of infectious diseases falls into the medical field of Infectious Disease and in some cases the study of propagation pertains to the field of Epidemiology. Generally, infections are initially diagnosed by primary care physicians or internal medicine specialists. For example, an "uncomplicated" pneumonia will generally be treated by the internist or the pulmonologist (lung physician). The work of the infectious diseases specialist therefore entails working with both patients and general practitioners, as well as laboratory scientists, immunologists, bacteriologists and other specialists. An infectious disease team may be alerted when: * The disease has not been definitively diagnosed after an initial workup * The patient is immunocompromised (for example, in AIDS or after chemotherapy); * The infectious agent is of an uncommon nature (e.g. tropical diseases); * The disease has not responded to first line antibiotics; * The disease might be dangerous to other patients, and the patient might have to be isolated ## Society and culture[edit] A number of studies have reported associations between pathogen load in an area and human behavior. Higher pathogen load is associated with decreased size of ethnic and religious groups in an area. This may be due high pathogen load favoring avoidance of other groups, which may reduce pathogen transmission, or a high pathogen load preventing the creation of large settlements and armies that enforce a common culture. Higher pathogen load is also associated with more restricted sexual behavior, which may reduce pathogen transmission. It also associated with higher preferences for health and attractiveness in mates. Higher fertility rates and shorter or less parental care per child is another association that may be a compensation for the higher mortality rate. There is also an association with polygyny which may be due to higher pathogen load, making selecting males with a high genetic resistance increasingly important. Higher pathogen load is also associated with more collectivism and less individualism, which may limit contacts with outside groups and infections. There are alternative explanations for at least some of the associations although some of these explanations may in turn ultimately be due to pathogen load. Thus, polygyny may also be due to a lower male:female ratio in these areas but this may ultimately be due to male infants having increased mortality from infectious diseases. Another example is that poor socioeconomic factors may ultimately in part be due to high pathogen load preventing economic development.[78] ## Fossil record[edit] Main article: Paleopathology Herrerasaurus skull. Evidence of infection in fossil remains is a subject of interest for paleopathologists, scientists who study occurrences of injuries and illness in extinct life forms. Signs of infection have been discovered in the bones of carnivorous dinosaurs. When present, however, these infections seem to tend to be confined to only small regions of the body. A skull attributed to the early carnivorous dinosaur Herrerasaurus ischigualastensis exhibits pit-like wounds surrounded by swollen and porous bone. The unusual texture of the bone around the wounds suggests they were afflicted by a short-lived, non-lethal infection. Scientists who studied the skull speculated that the bite marks were received in a fight with another Herrerasaurus. Other carnivorous dinosaurs with documented evidence of infection include Acrocanthosaurus, Allosaurus, Tyrannosaurus and a tyrannosaur from the Kirtland Formation. The infections from both tyrannosaurs were received by being bitten during a fight, like the Herrerasaurus specimen.[79] ## Outer space[edit] Main articles: Effect of spaceflight on the human body, Medical treatment during spaceflight, and Space medicine A 2006 Space Shuttle experiment found that Salmonella typhimurium, a bacterium that can cause food poisoning, became more virulent when cultivated in space.[80] On April 29, 2013, scientists in Rensselaer Polytechnic Institute, funded by NASA, reported that, during spaceflight on the International Space Station, microbes seem to adapt to the space environment in ways "not observed on Earth" and in ways that "can lead to increases in growth and virulence".[81] More recently, in 2017, bacteria were found to be more resistant to antibiotics and to thrive in the near-weightlessness of space.[82] Microorganisms have been observed to survive the vacuum of outer space.[83][84] ## See also[edit] * Bioinformatics Resource Centers for Infectious Diseases * Biological hazard * Blood-borne disease * Coinfection * Copenhagen Consensus * Cordon sanitaire * Disease diffusion mapping * Epidemiological transition * Foodborne illness * Gene therapy * History of medicine * Hospital-acquired infection * Eradication of infectious diseases * Human Microbiome Project * Infection control * Isolation (health care) * List of bacterial vaginosis microbiota * List of causes of death by rate * List of diseases caused by insects * List of epidemics * List of infectious diseases * Mathematical modelling of infectious disease * Membrane vesicle trafficking * Multiplicity of infection * Neglected tropical diseases * Sentinel surveillance * Social distancing * Spatiotemporal Epidemiological Modeler (STEM) * Spillover infection * Threshold host density * Transmission (medicine) * Ubi pus, ibi evacua (Latin: "where there is pus, there evacuate it") * Vaccine-preventable diseases * Waterborne diseases ## References[edit] 1. ^ Definition of "infection" from several medical dictionaries – Retrieved on 2012-04-03 2. ^ "Utilizing antibiotics agents effectively will preserve present day medication". News Ghana. 21 November 2015. Retrieved 21 November 2015. 3. ^ "Types of Fungal Diseases". www.cdc.gov. 2019-06-27. Retrieved 2019-12-09. 4. ^ Mada, Pradeep Kumar; Jamil, Radia T.; Alam, Mohammed U. (2019), "Cryptococcus (Cryptococcosis)", StatPearls, StatPearls Publishing, PMID 28613714, retrieved 2019-12-09 5. ^ "About Parasites". www.cdc.gov. 2019-02-25. Retrieved 2019-12-09. 6. ^ Brown, Peter J. (1987). "Microparasites and Macroparasites". Cultural Anthropology. 2 (1): 155–71. doi:10.1525/can.1987.2.1.02a00120. JSTOR 656401. 7. ^ Alberto Signore (2013). "About inflammation and infection" (PDF). EJNMMI Research. 8 (3). 8. ^ GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442. 9. ^ "Infectious Disease, Internal Medicine". Association of American Medical Colleges. Archived from the original on 2015-02-06. Retrieved 2015-08-20. "Infectious disease is the subspecialty of internal medicine dealing with the diagnosis and treatment of communicable diseases of all types, in all organs, and in all ages of patients." 10. ^ Kayser, Fritz H; Kurt A Bienz; Johannes Eckert; Rolf M Zinkernagel (2005). Medical microbiology. Stuttgart: Georg Thieme Verlag. p. 398. ISBN 978-3-13-131991-3. 11. ^ Grinde, Bjørn (2013-10-25). "Herpesviruses: latency and reactivation – viral strategies and host response". Journal of Oral Microbiology. 5: 22766. doi:10.3402/jom.v5i0.22766. ISSN 0901-8328. PMC 3809354. PMID 24167660. 12. ^ Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier. 13. ^ "Acute infections (MPKB)". mpkb.org. Retrieved 2019-12-09. 14. ^ Boldogh, Istvan; Albrecht, Thomas; Porter, David D. (1996), Baron, Samuel (ed.), "Persistent Viral Infections", Medical Microbiology (4th ed.), University of Texas Medical Branch at Galveston, ISBN 978-0-9631172-1-2, PMID 21413348, retrieved 2020-01-23 15. ^ a b Foster, John (2018). Microbiology. New York: Norton. p. 39. ISBN 978-0-393-60257-9. 16. ^ a b This section incorporates public domain materials included in the text: Medical Microbiology Fourth Edition: Chapter 8 (1996). Baron, Samuel MD. The University of Texas Medical Branch at Galveston. Medical Microbiology. University of Texas Medical Branch at Galveston. 1996. ISBN 9780963117212. Archived from the original on June 29, 2009. Retrieved 2013-11-27.CS1 maint: bot: original URL status unknown (link) 17. ^ a b c d e f Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 978-0-8385-8529-0. 18. ^ Higurea & Pietrangelo 2016[page needed] 19. ^ a b c "Bacterial vs. Viral Infections – Do You Know the Difference?" National Information Program on Antibiotics 20. ^ Robert N. Golden; Fred Peterson (2009). The Truth About Illness and Disease. Infobase Publishing. p. 181. ISBN 978-1438126371. 21. ^ "Infection". Rencare. Archived from the original on March 5, 2012. Retrieved 4 July 2013. 22. ^ Infection Cycle – Retrieved on 2010-01-21 Archived May 17, 2014, at the Wayback Machine 23. ^ Understanding Infectious Diseases Archived 2009-09-24 at the Wayback Machine Science.Education.Nih.Gov article – Retrieved on 2010-01-21 24. ^ Negut, Irina; Grumezescu, Valentina; Grumezescu, Alexandru Mihai (2018-09-18). "Treatment Strategies for Infected Wounds". Molecules. 23 (9): 2392. doi:10.3390/molecules23092392. ISSN 1420-3049. PMC 6225154. PMID 30231567. 25. ^ Duerkop, Breck A; Hooper, Lora V (2013-07-01). "Resident viruses and their interactions with the immune system". Nature Immunology. 14 (7): 654–59. doi:10.1038/ni.2614. PMC 3760236. PMID 23778792. 26. ^ "Bacterial Pathogenesis at Washington University". StudyBlue. St. Louis. Retrieved 2016-12-02. 27. ^ "Print Friendly". www.lifeextension.com. Archived from the original on 2016-12-02. Retrieved 2016-12-02. 28. ^ Reddy M, Gill SS, Wu W, et al. (Feb 2012). "Does this patient have an infection of a chronic wound?". JAMA. 307 (6): 605–11. doi:10.1001/jama.2012.98. PMID 22318282. 29. ^ http://www.immunize.org/catg.d/p4215.pdf 30. ^ Chronic Infection Information Retrieved on 2010-01-14 Archived July 22, 2015, at the Wayback Machine 31. ^ Intestinal Parasites and Infection Archived 2010-10-28 at the Wayback Machine fungusfocus.com – Retrieved on 2010-01-21 32. ^ "Clinical Infectious Disease – Introduction". www.microbiologybook.org. Retrieved 2017-04-19. 33. ^ Pathogens and vectors Archived 2017-10-05 at the Wayback Machine. MetaPathogen.com. 34. ^ Seventer JM, Hochberg NS (October 2016). "Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control". International Encyclopedia of Public Health: 22–39. doi:10.1016/B978-0-12-803678-5.00516-6. ISBN 9780128037089. PMC 7150340. 35. ^ Ljubin-Sternak, Suncanica; Mestrovic, Tomislav (2014). "Review: Chlamydia trachonmatis and Genital Mycoplasmias: Pathogens with an Impact on Human Reproductive Health". Journal of Pathogens. 2014 (183167): 3. doi:10.1155/2014/183167. PMC 4295611. PMID 25614838. 36. ^ a b Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D (March 2010). "Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review". Lancet. 375 (9717): 834–45. doi:10.1016/S0140-6736(09)62000-6. PMID 20132979. S2CID 28014329. 37. ^ Bloomfield SF, Aiello AE, Cookson B, O'Boyle C, Larson EL (2007). "The effectiveness of hand hygiene procedures including hand-washing and alcohol-based hand sanitizers in reducing the risks of infections in home and community settings". American Journal of Infection Control. 35 (10): S27–S64. doi:10.1016/j.ajic.2007.07.001. PMC 7115270. 38. ^ ""Generalized Infectious Cycle" Diagram Illustration". science.education.nih.gov. Archived from the original on 2009-09-24. Retrieved 2010-01-21. 39. ^ a b Watts, Duncan (2003). Six degrees: the science of a connected age. London: William Heinemann. ISBN 978-0-393-04142-2. 40. ^ Preston, Richard (1995). The hot zone. Garden City, N.Y.: Anchor Books. ISBN 978-0-385-49522-6. 41. ^ Ferguson NM, Donnelly CA, Anderson RM (May 2001). "The foot-and-mouth epidemic in Great Britain: pattern of spread and impact of interventions". Science. 292 (5519): 1155–60. Bibcode:2001Sci...292.1155F. doi:10.1126/science.1061020. PMID 11303090. S2CID 16914744. 42. ^ Barreto ML, Teixeira MG, Carmo EH (2006). "Infectious diseases epidemiology". Journal of Epidemiology and Community Health. 60 (3): 192–95. doi:10.1136/jech.2003.011593. PMC 2465549. PMID 16476746. 43. ^ Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. Bibcode:2009Natur.461..399G. doi:10.1038/nature08309. PMID 19684573. S2CID 1707096. 44. ^ Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M (2009). "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus". Nature. 461 (7265): 798–801. Bibcode:2009Natur.461..798T. doi:10.1038/nature08463. PMC 3172006. PMID 19759533. 45. ^ Fair RJ, Tor Y (2014). "Antibiotics and Bacterial Resistance in the 21st Century". Perspectives in Medicinal Chemistry. 6: 25–64. doi:10.4137/PMC.S14459. PMC 4159373. PMID 25232278. Retrieved 13 May 2020. 46. ^ "Antibiotics: List of Common Antibiotics & Types". Drugs.com. Retrieved 2020-11-10. 47. ^ O'Brien, Deirdre J.; Gould, Ian M. (August 2013). "Maximizing the impact of antimicrobial stewardship". Current Opinion in Infectious Diseases. 26 (4): 352–58. doi:10.1097/QCO.0b013e3283631046. PMID 23806898. S2CID 5487584. 48. ^ World Health Organization (February 2009). "Age-standardized DALYs per 100,000 by cause, and Member State, 2004". 49. ^ "Could Ebola rank among the deadliest communicable diseases?". CBC News. 20 October 2014. 50. ^ "The World Health Report (Annex Table 2)" (PDF). 2004. 51. ^ "Table 5" (PDF). 1995. 52. ^ Lower respiratory infections include various pneumonias, influenzas and acute bronchitis. 53. ^ Diarrheal diseases are caused by many different organisms, including cholera, botulism, and E. coli to name a few. See also: Intestinal infectious diseases 54. ^ Tropical diseases include Chagas disease, dengue fever, lymphatic filariasis, leishmaniasis, onchocerciasis, schistosomiasis and trypanosomiasis. 55. ^ "WHO \| The top 10 causes of death". WHO. Retrieved 2015-09-24. 56. ^ Fauci AS, Morens DM (2012). "The perpetual challenge of infectious diseases". New England Journal of Medicine. 366 (5): 454–61. doi:10.1056/NEJMra1108296. PMID 22296079. 57. ^ "Infectious and Epidemic Disease in History" Archived July 12, 2012, at Archive.today 58. ^ a b Dobson AP, Carter ER (1996). "Infectious Diseases and Human Population History" (PDF). BioScience. 46 (2): 115–26. doi:10.2307/1312814. JSTOR 1312814. 59. ^ "Smallpox". North Carolina Digital History. 60. ^ Smallpox and Vaccinia. National Center for Biotechnology Information. Archived June 1, 2009, at the Wayback Machine 61. ^ Barquet, Nicolau (15 October 1997). "Smallpox: The Triumph over the Most Terrible of the Ministers of Death". Annals of Internal Medicine. 127 (8_Part_1): 635–42. doi:10.7326/0003-4819-127-8_Part_1-199710150-00010. PMID 9341063. S2CID 20357515. 62. ^ Multidrug-Resistant "Tuberculosis". Centers for Disease Control and Prevention. Archived March 9, 2010, at the Wayback Machine 63. ^ "Influenza of 1918 (Spanish Flu) and the US Navy". 20 February 2006. Archived from the original on 20 February 2006. 64. ^ a b Krauss H; Weber A; Appel M (2003). Zoonoses: Infectious Diseases Transmissible from Animals to Humans (3rd ed.). Washington, D.C.: ASM Press. ISBN 978-1-55581-236-2. 65. ^ Potter P (July 2013). "Summer buzz". Emerg Infect Dis. 19 (3): 1184. doi:10.3201/eid1907.AC1907. PMC 3903457. 66. ^ Peter Daszak; Andrew A. Cunningham; Alex D. Hyatt (27 January 2000). "Emerging Infectious Diseases of Wildlife – Threats to Biodiversity and Human Health". Science. 287 (5452): 443–49. Bibcode:2000Sci...287..443D. doi:10.1126/science.287.5452.443. PMID 10642539. 67. ^ Singer, Charles and Dorothea (1917) "The scientific position of Girolamo Fracastoro [1478?–1553] with especial reference to the source, character and influence of his theory of infection," Annals of Medical History, 1 : 1–34; see p. 14. 68. ^ Thucydides with Richard Crawley, trans., History of the Peloponnesian War (London: J.M. Dent & Sons, Ltd., 1910), Book III, § 51, pp. 131–32. 69. ^ Nutton, Vivian (1983) "The seeds of disease: an explanation of contagion and infection from the Greeks to the Renaissance," Medical History, 27 (1) : 1–34; see p. 10. Available at: U.S. National Library of Medicine, National Institutes of Health 70. ^ Rastogi, Nalin; Rastogi, R (1985-01-01). "Leprosy in ancient India". International Journal of Leprosy and Other Mycobacterial Diseases. 52 (4): 541–43. PMID 6399073. 71. ^ Susruta; Bhishagratna, Kunja Lal (1907–1916). An English translation of the Sushruta samhita, based on original Sanskrit text. Edited and published by Kaviraj Kunja Lal Bhishagratna. With a full and comprehensive introd., translation of different readings, notes, comparative views, index, glossary and plates. Gerstein – University of Toronto. Calcutta. 72. ^ Hoernle, A. F. Rudolf (August Friedrich Rudolf) (1907). Studies in the medicine of ancient India. Gerstein – University of Toronto. Oxford : At the Clarendon Press. 73. ^ Byrne, Joseph Patrick (2012). Encyclopedia of the Black Death. ABC-CLIO. p. 29. ISBN 978-1598842531. 74. ^ Reid, Megan H. (2013). Law and Piety in Medieval Islam. Cambridge University Press. pp. 106, 114, 189–90. ISBN 978-1107067110. 75. ^ Majeed, Azeem (22 December 2005). "How Islam changed medicine". BMJ. 331 (7531): 1486–87. doi:10.1136/bmj.331.7531.1486. ISSN 0959-8138. PMC 1322233. PMID 16373721. 76. ^ Beretta M (2003). "The revival of Lucretian atomism and contagious diseases during the renaissance". Medicina Nei Secoli. 15 (2): 129–54. PMID 15309812. 77. ^ Moorhead Robert (November 2002). "William Budd and typhoid fever". J R Soc Med. 95 (11): 561–64. doi:10.1258/jrsm.95.11.561. PMC 1279260. PMID 12411628. 78. ^ Nettle D (2009). "Ecological influences on human behavioural diversity: a review of recent findings". Trends Ecol. Evol. 24 (11): 618–24. doi:10.1016/j.tree.2009.05.013. PMID 19683831. 79. ^ Molnar, R. E., 2001, "Theropod paleopathology: a literature survey": In: Mesozoic Vertebrate Life, edited by Tanke, D. H., and Carpenter, K., Indiana University Press, pp. 337–63. 80. ^ Caspermeyer, Joe (23 September 2007). "Space flight shown to alter ability of bacteria to cause disease". Arizona State University. Retrieved 14 September 2017. 81. ^ Kim W, et al. (April 29, 2013). "Spaceflight Promotes Biofilm Formation by Pseudomonas aeruginosa". PLOS ONE. 8 (4): e6237. Bibcode:2013PLoSO...862437K. doi:10.1371/journal.pone.0062437. PMC 3639165. PMID 23658630. 82. ^ Dvorsky, George (13 September 2017). "Alarming Study Indicates Why Certain Bacteria Are More Resistant to Drugs in Space". Gizmodo. Retrieved 14 September 2017. 83. ^ Dose, K.; Bieger-Dose, A.; Dillmann, R.; Gill, M.; Kerz, O.; Klein, A.; Meinert, H.; Nawroth, T.; Risi, S.; Stridde, C. (1995). "ERA-experiment "space biochemistry"" (PDF). Advances in Space Research. 16 (8): 119–29. Bibcode:1995AdSpR..16..119D. doi:10.1016/0273-1177(95)00280-R. PMID 11542696.[permanent dead link] 84. ^ Horneck G.; Eschweiler, U.; Reitz, G.; Wehner, J.; Willimek, R.; Strauch, K. (1995). "Biological responses to space: results of the experiment "Exobiological Unit" of ERA on EURECA I". Adv. Space Res. 16 (8): 105–18. Bibcode:1995AdSpR..16..105H. doi:10.1016/0273-1177(95)00279-N. 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others)	Infection	c3714514	5,677	wikipedia	https://en.wikipedia.org/wiki/Infection	2021-01-18T18:49:04	{"mesh": ["D007239"], "wikidata": ["Q166231"]}
Bartter syndrome Other namesSalt-wasting nephropathy[1] Scheme of renal tubule and its vascular supply. SpecialtyEndocrinology Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia),[2] increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Related conditions * 4 Treatment * 5 Prognosis * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] In 90% of cases, neonatal Bartter syndrome is seen between 24 and 30 weeks of gestation with excess amniotic fluid (polyhydramnios). After birth, the infant is seen to urinate and drink excessively (polyuria, and polydipsia, respectively). Life-threatening dehydration may result if the infant does not receive adequate fluids. About 85% of infants dispose of excess amounts of calcium in the urine (hypercalciuria) and kidneys (nephrocalcinosis), which may lead to kidney stones. In rare occasions, the infant may progress to kidney failure.[citation needed] Patients with classic Bartter syndrome may have symptoms in the first two years of life, but they are usually diagnosed at school age or later. Like infants with the neonatal subtype, patients with classic Bartter syndrome also have polyuria, polydipsia, and a tendency to dehydration, but normal or just slightly increased urinary calcium excretion without the tendency to develop kidney stones. These patients also have vomiting and growth retardation. Kidney function is also normal if the disease is treated,[3] but occasionally patients proceed to end-stage kidney failure. Bartter syndrome consists of low levels of potassium in the blood, alkalosis, normal to low blood pressures, and elevated plasma renin and aldosterone. Numerous causes of this syndrome probably exist. Diagnostic pointers include high urinary potassium and chloride despite low serum values, increased plasma renin, hyperplasia of the juxtaglomerular apparatus on kidney biopsy, and careful exclusion of diuretic abuse. Excess production of prostaglandins by the kidneys is often found. Magnesium wasting may also occur. Homozygous patients suffer from severe hypercalciuria and nephrocalcinosis.[4] ## Pathophysiology[edit] Bartter syndrome is caused by mutations of genes encoding proteins that transport ions across renal cells in the thick ascending limb of the nephron also called as the ascending loop of Henle.[3] Specifically, mutations directly or indirectly involving the Na-K-2Cl cotransporter are key. The Na-K-2Cl cotransporter is involved in electroneutral transport of one sodium, one potassium, and two chloride ions across the apical membrane of the tubule. The basolateral calcium-sensing receptor has the ability to downregulate the activity of this transporter upon activation. Once transported into the tubule cells, sodium ions are actively transported across the basolateral membrane by Na+/K+-ATPases, and chloride ions pass by facilitated diffusion through basolateral chloride channels. Potassium, however, is able to diffuse back into the tubule lumen through apical potassium channels, returning a net positive charge to the lumen and establishing a positive voltage between the lumen and interstitial space. This charge gradient is obligatory for the paracellular reabsorption of both calcium and magnesium ions.[citation needed] Proper function of all of these transporters is necessary for normal ion reabsorption along the thick ascending limb, and loss of any component can result in functional inactivation of the system as a whole and lead to the presentation of Bartter syndrome. Loss of function of this reabsorption system results in decreased sodium, potassium, and chloride reabsorption in the thick ascending limb, as well as abolishment of the lumen-positive voltage, resulting in decreased calcium and magnesium reabsorption. Loss of reabsorption of sodium here also has the undesired effect of abolishing the hypertonicity of the renal medulla, severely impairing the ability to reabsorb water later in the distal nephron and collecting duct system, leading to significant diuresis and the potential for volume depletion. Finally, increased sodium load to the distal nephron elicits compensatory reabsorption mechanisms, albeit at the expense of potassium by excretion by principal cells and resulting hypokalemia. This increased potassium excretion is partially compensated by α-intercalated cells at the expense of hydrogen ions, leading to metabolic alkalosis.[citation needed] Bartter and Gitelman syndromes can be divided into different subtypes based on the genes involved:[5] Name Bartter type Associated gene mutations Defect neonatal Bartter's syndrome type 1 SLC12A1 (NKCC2) Na-K-2Cl symporter neonatal Bartter's syndrome type 2 ROMK/KCNJ1 thick ascending limb K+ channel classic Bartter's syndrome type 3 CLCNKB Cl− channel Bartter's syndrome with sensorineural deafness type 4 BSND[6] Cl− channel accessory subunit Bartter's syndrome associated with autosomal dominant hypocalcemia type 5 CASR[7] activating mutation of the calcium-sensing receptor Gitelman's syndrome - SLC12A3 (NCCT) Sodium-chloride symporter ## Diagnosis[edit] People suffering from Bartter syndrome present symptoms that are identical to those of patients who are on loop diuretics like furosemide, given that the loop diuretics target the exact transport protein that is defective in the syndrome (at least for type 1 Bartter syndrome). The other subtypes of the syndrome involve mutations in other transporters that result in functional loss of the target transporter. Patients often admit to a personal preference for salty foods.[citation needed] The clinical findings characteristic of Bartter syndrome are hypokalemia, metabolic alkalosis, and normal to low blood pressure. These findings may also be caused by other conditions, which may cause confusion. When diagnosing a Bartter's syndrome, the following conditions must be ruled out as possible causes of the symptomatology:[citation needed] * Chronic vomiting: These patients will have low urine chloride levels; they have relatively higher urine chloride levels. * Abuse of diuretic medications (water pills): The physician must screen urine for multiple diuretics before diagnosis is made. * Magnesium deficiency and calcium deficiency: These patients will also have low serum and urine magnesium and calcium. Patients with Bartter syndrome may also have elevated renin and aldosterone levels.[8] Prenatal Bartter syndrome can be associated with polyhydramnios.[9] ### Related conditions[edit] * Bartter and Gitelman syndromes are both characterized by low levels of potassium and magnesium in the blood, normal to low blood pressure, and hypochloremic metabolic alkalosis.[10] However, Bartter syndrome is also characterized by high renin, high aldosterone, hypercalciuria, and an abnormal Na+-K+-2Cl− transporter in the thick ascending limb of the loop of Henle, whereas Gitelman syndrome causes hypocalciuria and is due to an abnormal thiazide-sensitive transporter in the distal segment.[citation needed] Pseudo-Bartter’s syndrome is a syndrome of similar presentation as Bartter syndrome but without any of its characteristic genetic defects. Pseudo-Bartter's syndrome has been seen in cystic fibrosis,[11] as well as in excessive use of laxatives.[12] ## Treatment[edit] Medically supervised sodium, chloride and potassium supplementation is necessary, and spironolactone can be also used to reduce potassium loss.[2] Free and unqualified access to water is necessary to prevent dehydration, as patients maintain an appropriate thirst response.In severe cases where supplementation alone cannot maintain biochemical homeostasis, nonsteroidal anti-inflammatory drugs (NSAIDs) can be used to reduce glomerular filtration, and can be very useful, although may cause gastric irritation and should be administered alongside stomach acid suppression therapies. Angiotensin-converting enzyme (ACE) inhibitors can also be used to reduce glomerular filtration rate. In young babies and children, a low threshold to check serum electrolytes during periods of illness compromising fluid intake in necessary.[citation needed] Surveillance renal ultrasound should be employed to monitor for the development of nephrocalcinosis, a common complication which further augments urinary concentrating difficulty.[citation needed] ## Prognosis[edit] The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with classic Bartter Syndrome may improve growth and perhaps intellectual development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage kidney disease (kidney failure). With early treatment of the electrolyte imbalances, the prognosis for patients with classic Bartter Syndrome is good.[citation needed] ## History[edit] The condition is named after Dr. Frederic Bartter, who, along with Dr. Pacita Pronove, first described it in 1960 and in more patients in 1962.[8][13][14][15] ## References[edit] 1. ^ "Bartter syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 29 September 2019. 2. ^ a b "Bartter Syndrome: Tubular and Cystic Kidney Disorders: Merck Manual Home Edition". Archived from the original on 4 January 2008. Retrieved 2007-12-31. 3. ^ a b Rodriguez-Soriano J (1998). "Bartter and related syndromes: the puzzle is almost solved". Pediatr Nephrol. 12 (4): 315–27. doi:10.1007/s004670050461. PMID 9655365. S2CID 41782906. 4. ^ http://ajprenal.physiology.org/content/307/9/F991.long 5. ^ Naesens M, Steels P, Verberckmoes R, Vanrenterghem Y, Kuypers D (2004). "Bartter's and Gitelman's syndromes: from gene to clinic". Nephron Physiol. 96 (3): 65–78. doi:10.1159/000076752. PMID 15056980. S2CID 9649621. 6. ^ Zaffanello M, Taranta A, Palma A, Bettinelli A, Marseglia GL, Emma F (2006). "Type IV Bartter syndrome: report of two new cases". Pediatr. Nephrol. 21 (6): 766–70. doi:10.1007/s00467-006-0090-x. PMID 16583241. S2CID 34031819. 7. ^ Vezzoli G, Arcidiacono T, Paloschi V, et al. (2006). "Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome". J. Nephrol. 19 (4): 525–8. PMID 17048213. 8. ^ a b Bartter FC, Pronove P, Gill JR, MacCardle RC (1962). "Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome". Am J Med. 33 (6): 811–28. doi:10.1016/0002-9343(62)90214-0. PMID 13969763. Reproduced in Bartter FC, Pronove P, Gill JR, MacCardle RC (1998). "Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. 1962". J. Am. Soc. Nephrol. 9 (3): 516–28. PMID 9513916. 9. ^ Dane B, Yayla M, Dane C, Cetin A (2007). "Prenatal diagnosis of Bartter syndrome with biochemical examination of amniotic fluid: case report". Fetal Diagn. Ther. 22 (3): 206–8. doi:10.1159/000098719. PMID 17228161. S2CID 45890736. 10. ^ Gitelman HJ, Graham JB, Welt LG (1966). "A new familial disorder characterized by hypokalemia and hypomagnesemia". Trans Assoc Am Physicians. 79: 221–35. PMID 5929460. 11. ^ Royal Brompton & Harefield Hospital > Pseudo-Bartter’s syndrome Archived 2011-07-21 at the Wayback Machine Retrieved Mars, 2011 12. ^ Metyas, Samy; Rouman, Heba; Arkfeld, Daniel G. (2010). "Pregnancy in a Patient With Gouty Arthritis Secondary to Pseudo-Bartter Syndrome". Journal of Clinical Rheumatology. 16 (5): 219–220. doi:10.1097/RHU.0b013e3181e9312a. PMID 20661067. 13. ^ Proesmans W (2006). "Threading through the mizmaze of Bartter syndrome". Pediatr. Nephrol. 21 (7): 896–902. doi:10.1007/s00467-006-0113-7. PMID 16773399. S2CID 26270693. 14. ^ synd/2328 at Who Named It? 15. ^ "Bartter's syndrome". www.whonamedit.com. ## External links[edit] Classification D * ICD-10: E26.8 * ICD-9-CM: 255.13 * OMIM: 601678 241200 607364 602522 * MeSH: D001477 * DiseasesDB: 1254 * SNOMED CT: 707742001 External resources * MedlinePlus: 000308 * eMedicine: med/213 ped/210 * Orphanet: 93604 * v * t * e Adrenal gland disorder Hyperfunction Aldosterone * Hyperaldosteronism * Primary aldosteronism * Conn syndrome * Bartter syndrome * Glucocorticoid remediable aldosteronism * AME * Liddle's syndrome * 17α CAH * Pseudohypoaldosteronism Cortisol * Cushing's syndrome * Pseudo-Cushing's syndrome * Steroid-induced osteoporosis Sex hormones * 21α CAH * 11β CAH Hypofunction Aldosterone * Hypoaldosteronism * 21α CAH * 11β CAH Cortisol * CAH * Lipoid * 3β * 11β * 17α * 21α Sex hormones * 17α CAH * Inborn errors of steroid metabolism Adrenal insufficiency * Adrenal crisis * Adrenalitis * Xanthogranulomatous * Addison's disease * Waterhouse–Friderichsen syndrome * v * t * e Kidney disease Glomerular disease * See Template:Glomerular disease Tubules * Renal tubular acidosis * proximal * distal * Acute tubular necrosis * Genetic * Fanconi syndrome * Bartter syndrome * Gitelman syndrome * Liddle's syndrome Interstitium * Interstitial nephritis * Pyelonephritis * Balkan endemic nephropathy Vascular * Renal artery stenosis * Renal ischemia * Hypertensive nephropathy * Renovascular hypertension * Renal cortical necrosis General syndromes * Nephritis * Nephrosis * Renal failure * Acute renal failure * Chronic kidney disease * Uremia Other * Analgesic nephropathy * Renal osteodystrophy * Nephroptosis * Abderhalden–Kaufmann–Lignac syndrome * Diabetes insipidus * Nephrogenic * Renal papilla * Renal papillary necrosis * Major calyx/pelvis * Hydronephrosis * Pyonephrosis * Reflux nephropathy * v * t * e Diseases of ion channels Calcium channel Voltage-gated * CACNA1A * Familial hemiplegic migraine 1 * Episodic ataxia 2 * Spinocerebellar ataxia type-6 * CACNA1C * Timothy syndrome * Brugada syndrome 3 * Long QT syndrome 8 * CACNA1F * Ocular albinism 2 * CSNB2A * CACNA1S * Hypokalemic periodic paralysis 1 * Thyrotoxic periodic paralysis 1 * CACNB2 * Brugada syndrome 4 Ligand gated * RYR1 * Malignant hyperthermia * Central core disease * RYR2 * CPVT1 * ARVD2 Sodium channel Voltage-gated * SCN1A * Familial hemiplegic migraine 3 * GEFS+ 2 * Febrile seizure 3A * SCN1B * Brugada syndrome 6 * GEFS+ 1 * SCN4A * Hypokalemic periodic paralysis 2 * Hyperkalemic periodic paralysis * Paramyotonia congenita * Potassium-aggravated myotonia * SCN4B * Long QT syndrome 10 * SCN5A * Brugada syndrome 1 * Long QT syndrome 3 * SCN9A * Erythromelalgia * Febrile seizure 3B * Paroxysmal extreme pain disorder * Congenital insensitivity to pain Constitutively active * SCNN1B/SCNN1G * Liddle's syndrome * SCNN1A/SCNN1B/SCNN1G * Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated * KCNA1 * Episodic ataxia 1 * KCNA5 * Familial atrial fibrillation 7 * KCNC3 * Spinocerebellar ataxia type-13 * KCNE1 * Jervell and Lange-Nielsen syndrome * Long QT syndrome 5 * KCNE2 * Long QT syndrome 6 * KCNE3 * Brugada syndrome 5 * KCNH2 * Short QT syndrome * KCNQ1 * Jervell and Lange-Nielsen syndrome * Romano–Ward syndrome * Short QT syndrome * Long QT syndrome 1 * Familial atrial fibrillation 3 * KCNQ2 * BFNS1 Inward-rectifier * KCNJ1 * Bartter syndrome 2 * KCNJ2 * Andersen–Tawil syndrome * Long QT syndrome 7 * Short QT syndrome * KCNJ11 * TNDM3 * KCNJ18 * Thyrotoxic periodic paralysis 2 Chloride channel * CFTR * Cystic fibrosis * Congenital absence of the vas deferens * CLCN1 * Thomsen disease * Myotonia congenita * CLCN5 * Dent's disease * CLCN7 * Osteopetrosis A2, B4 * BEST1 * Vitelliform macular dystrophy * CLCNKB * Bartter syndrome 3 TRP channel * TRPC6 * FSGS2 * TRPML1 * Mucolipidosis type IV Connexin * GJA1 * Oculodentodigital dysplasia * Hallermann–Streiff syndrome * Hypoplastic left heart syndrome * GJB1 * Charcot–Marie–Tooth disease X1 * GJB2 * Keratitis–ichthyosis–deafness syndrome * Ichthyosis hystrix * Bart–Pumphrey syndrome * Vohwinkel syndrome) * GJB3/GJB4 * Erythrokeratodermia variabilis * Progressive symmetric erythrokeratodermia * GJB6 * Clouston's hidrotic ectodermal dysplasia Porin * AQP2 * Nephrogenic diabetes insipidus 2 See also: ion channels [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Bartter syndrome	c0004775	5,678	wikipedia	https://en.wikipedia.org/wiki/Bartter_syndrome	2021-01-18T19:00:02	{"gard": ["5893"], "mesh": ["D001477"], "umls": ["C0004775"], "orphanet": ["112"], "wikidata": ["Q790971"]}
Madras motor neuron disease (MMND) is characterized by weakness and atrophy of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. ## Epidemiology Less than 200 cases have be reported to date, predominantly from Southern India. Isolated MMND cases have been reported from Thailand and Italy. ## Clinical description Onset occurs at a young age (often before the age of 15), with a slight male preponderance or equal sex distribution. Parental consanguinity has been reported in some cases. Main clinical features include thin habitus, wasting and weakness predominantly of the distal limb muscles, involvement of facial and bulbar muscles, and pyramidal dysfunction. Multiple cranial nerve palsies particularly involve the 7th, and the 9th to 12th cranial nerves. Hearing impairment was described in all patients. Optic atrophy is reported in some patients. ## Etiology The etiopathogenesis of MMND remains unknown. The majority of cases are sporadic. A few familial cases have been reported, but the mode of inheritance is yet to be determined. Inflammation and/or environmental factors may play a role in the etiology of MMND. ## Diagnostic methods Diagnosis is clinical and is supported by the association of benign focal atrophy of the extremities with hearing impairment. Neuroimaging studies may help to distinguish MMND from other motor neuron diseases. ## Differential diagnosis Differential diagnoses include amyotrophic lateral sclerosis, spinocerebellar ataxia syndromes, Brown-Vialetto-Van Laere syndrome, progressive muscular atrophy, post-polio progressive muscular atrophy, and spinal muscular atrophy (see these terms). ## Management and treatment Currently, there is no cure for MMND. Management should involve a multidisciplinary team (neurologists, physical therapists, occupational therapists, palliative care specialists, specialist nurses and psychologists) and should focus on the relief of symptoms. Symptomatic treatment and supportive care can help patients to maintain their daily living activities. Patients should be offered hearing aids. ## Prognosis The disease shows a slowly progressive but benign course. Most of the reported patients survived for over 30 years after the onset of the 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)	Madras motor neuron disease	c0393551	5,679	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137867	2021-01-23T18:22:41	{"umls": ["C0393551"], "icd-10": ["G12.2"], "synonyms": ["MMND"]}
Pallister-Killian mosaic syndrome is a multi-system disorder that is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects. The signs and symptoms of Pallister-Killian mosaic syndrome can vary, although most documented cases of people with the syndrome have severe to profound intellectual disability and other serious health problems. Pallister-Killian mosaic syndrome is usually caused by the presence of an abnormal extra chromosome 12 called isochromosome 12p. An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 12p is a version of chromosome 12 made up of two p arms. Cells normally have two copies of each chromosome, one inherited from each parent. In people with Pallister-Killian mosaic syndrome, cells have the two usual copies of chromosome 12, but some cells also have the isochromosome 12p. These cells have a total of four copies of all the genes on the p arm of chromosome 12. The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder. Although Pallister-Killian mosaic syndrome is usually caused by an isochromosome 12p, other, more complex chromosomal changes involving chromosome 12 are responsible for the disorder in rare cases. Treatment depends upon the specific symptoms present in each individual. Treating medical and developmental problems early can help to optimize outcome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Pallister-Killian mosaic syndrome	c0265449	5,680	gard	https://rarediseases.info.nih.gov/diseases/8421/pallister-killian-mosaic-syndrome	2021-01-18T17:58:28	{"mesh": ["C538105"], "omim": ["601803"], "umls": ["C0265449"], "orphanet": ["884"], "synonyms": ["Chromosome 12, Isochromosome 12p syndrome", "Killian syndrome", "Killian Teschler-Nicola syndrome", "Pallister mosaic syndrome", "Teschler-Nicola Killian syndrome", "Tetrasomy 12p, mosaic", "Pallister Killian syndrome", "PKS"]}
A rare disorder characterized by the association of severe combined immunodeficiency (affecting mainly the humoral immune response) with progressive cerebellar ataxia. It is characterized by neurological signs, telangiectasia, increased susceptibility to infections and a higher risk of cancer. ## Epidemiology Average prevalence is estimated at 1/100,000 children. ## Clinical description The severity of the neurological, immune system and pulmonary manifestations varies widely between patients. Onset usually occurs between 1 and 2 years of age with abnormal head movements and loss of balance, followed by slurred speech and abnormal eye movements. Poor coordination and trembling of the extremities may appear towards 9-10 years of age and worsen progressively. Choreoathetosis is quite common. In the majority of cases, intelligence is normal: around 30% of patients have learning difficulties or moderate intellectual deficiency. Cutaneomucosal telangiectasias appear between 3 and 6 years of age, or during adolescence. The immunodeficiency causes repeated sinus and lung infections, and the latter may cause bronchiectasis. Growth delay is also fairly frequent. ## Etiology Ataxia-telangiectasia (A-T) is caused by inactivating mutations of the ATM gene (11q22.3). This gene is expressed ubiquitously and encodes a protein kinase playing a key role in the control of double-strand-break (DSB) DNA repair, notably in the Purkinje cells of the cerebellum and in cerebral, cutaneous and conjunctival endothelial cells. A-T-like disorder is a rare variant form of A-T caused by inactivation of the MRE11 gene (11q21), which also encodes a protein involved in DSB repair. ## Diagnostic methods Establishing the clinical diagnosis early in the disease course is problematic but quasi-constant increases in serum alpha-foetoprotein (AFP) levels and cytogenetic analysis may help confirm the diagnosis (7;14 translocations). Molecular diagnosis is sometimes necessary. ## Differential diagnosis The differential diagnosis should include Ataxia - oculomotor apraxia, types 1 and2 (see these terms). ## Antenatal diagnosis Prenatal diagnosis is possible once at least one inactivating ATM gene mutation has been identified in the index case. ## Genetic counseling A-T is an autosomal recessive disease. ## Management and treatment Management is symptomatic and involves physiotherapy, speech therapy and treatment of the infection and pulmonary complications. Beta-blockers may reduce trembling and improve performance of fine movements. As the cells of A-T patients show an increased susceptibility to X-rays, radiotherapy, together with some forms of chemotherapy, should be used with caution. Affected children often require a wheelchair by the age of 10-11. ## Prognosis The prognosis is severe as it reflects the occurrence of respiratory infections, neurodegeneration, accelerated cutaneomucosal ageing and an increased risk of cancer (35% of patients develop cancer by the age of 20). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Ataxia-telangiectasia	c0004135	5,681	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100	2021-01-23T17:33:44	{"gard": ["5862"], "mesh": ["D001260"], "omim": ["208900", "208910"], "umls": ["C0004135"], "icd-10": ["G11.3"], "synonyms": ["Louis-Bar syndrome"]}
Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes). Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder. The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability. Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums. Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism). Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome. Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects. ## Frequency Oral-facial-digital syndrome has an estimated incidence of 1 in 50,000 to 250,000 newborns. Type I accounts for the majority of cases of this disorder. The other forms of oral-facial-digital syndrome are very rare; most have been identified in only one or a few families. ## Causes Only one gene, OFD1, has been associated with oral-facial-digital syndrome. Mutations in this gene cause oral-facial-digital syndrome type I. OFD1 gene mutations were also found in an affected family whose disorder was classified as type VII; however, researchers now believe that type VII is the same as type I. The OFD1 gene provides instructions for making a protein whose function is not fully understood. It appears to play an important role in the early development of many parts of the body, including the brain, face, limbs, and kidneys. Mutations in the OFD1 gene prevent cells from making enough functional OFD1 protein, which disrupts the normal development of these structures. It is unclear how a shortage of this protein causes the specific features of oral-facial-digital syndrome type I. Researchers are actively searching for the genetic changes responsible for the other forms of oral-facial-digital syndrome. ### Learn more about the gene associated with Oral-facial-digital syndrome * OFD1 ## Inheritance Pattern Oral-facial-digital syndrome type I is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of OFD1 protein and other cells produce none. The resulting overall reduction in the amount of this protein leads to the signs and symptoms of oral-facial-digital syndrome type I. In males (who have only one X chromosome), mutations result in a total loss of the OFD1 protein. A lack of this protein is usually lethal very early in development, so very few males are born with oral-facial-digital syndrome type I. Affected males usually die before birth, although a few have lived into early infancy. Most of the other forms of oral-facial-digital syndrome are inherited in an autosomal recessive pattern, which suggests that both copies of a causative 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)	Oral-facial-digital syndrome	c0026363	5,682	medlineplus	https://medlineplus.gov/genetics/condition/oral-facial-digital-syndrome/	2021-01-27T08:25:07	{"gard": ["4121", "3701", "10692"], "mesh": ["D009958"], "omim": ["252100", "311200", "258850", "258860", "258865", "174300", "277170", "608518", "300484", "165590", "612913"], "synonyms": []}
Hereditary pancreatitis This condition is inherited in an autosomal dominant manner Hereditary pancreatitis (HP) is an inflammation of the pancreas due to genetic causes. It was first described in 1952 by Comfort and Steinberg[1] but it was not until 1996 that Whitcomb et al[2] isolated the first responsible mutation in the trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35). The term "hereditary pancreatitis" is used when a genetic biomarker is identified, and "familial pancreatitis" otherwise.[3] ## Contents * 1 Presentation * 2 Genetics * 3 Diagnosis * 4 Management * 5 Prognosis * 6 References * 7 External links ## Presentation[edit] HP is characterised by attacks of epigastric pain, which are often associated with nausea and vomiting. Symptoms may start shortly after birth but onset varies periodically, with some patients not exhibiting symptoms until adulthood. There is usually progression to chronic pancreatitis with endocrine and exocrine failure and a mortally increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54%[4][5][6] to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a scientific basis.[7] Some patients may choose to have their pancreas surgically removed to prevent pancreatic cancer from developing in the future.[8] The epidemiology of HP follows a similar pattern to alcohol-associated chronic pancreatitis, but there are important differences. For example, HP typically has an earlier age of pancreatitis onset; although malabsorption and diabetes mellitus occur at a later stage in the disease progression.[5] ## Genetics[edit] The vast majority of the cases of HP are caused by substitutions, at base 365 (c.365G>A) and base 86 of the cDNA (c.86A>T) on the PRSS1 gene. The nucleotide substitutions were discovered in the late 1990s by classical linkage analysis[2][9] and are now known as p.R122H and p.N29I respectively, according to the amino acid substitution and position in the protein sequence. These mutations are rarely identified in general screens of patients with idiopathic disease[10][11][12][13] and the phenotype of p.R122H and p.N29I is now well characterised[4][5][6] with the p.A16V mutation recently characterised for the first time.[14] There are many other rare mutations or polymorphisms of PRSS1 which remain less well understood[15][16] and not all HP families have had the responsible genetic mutation identified. The mechanism by which these genetic mutations cause pancreatitis is not yet known; but is likely to be the result of increased autoactivation[17] or reduced deactivation[18] of trypsinogen. However, a novel mechanism has recently been identified in a p.R116C kindred.[19] ## Diagnosis[edit] Families are defined as having HP,[5] if the phenotype is consistent with highly penetrant autosomal dominant inheritance. In simple terms, this would require two or more first degree relatives (or three or more second degree relatives) to have unexplained recurrent-acute or chronic pancreatitis in two or more generations. It is an autosomal dominant disease with penetrance that is generally accepted to be ≈80%.[1][20] ## Management[edit] Treatment of HP resemble that of chronic pancreatitis of other causes. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction.(PMC1774562)[citation needed] ## Prognosis[edit] A 2009 study which followed 189 patients found no excess mortality despite the increased risk of pancreatic cancer.[21] ## References[edit] 1. ^ a b Comfort MW, Steinberg AG (May 1952). "Pedigree of a family with hereditary chronic relapsing pancreatitis". Gastroenterology. 21 (1): 54–63. doi:10.1016/S0016-5085(52)80120-9. PMID 14926813. 2. ^ a b Whitcomb DC, Gorry MC, Preston RA, et al. (October 1996). "Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene". Nat. Genet. 14 (2): 141–5. doi:10.1038/ng1096-141. PMID 8841182. S2CID 21974705. 3. ^ Cheifetz, Adam S.; Brown, Alphonso; Curry, Michael; Alan C. Moss (2011-03-10). Oxford American Handbook of Gastroenterology and Hepatology. Oxford University Press US. pp. 223–. ISBN 978-0-19-538318-8. Retrieved 9 August 2011. 4. ^ a b Lowenfels AB, Maisonneuve P, DiMagno EP, et al. (March 1997). "Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group". J. Natl. Cancer Inst. 89 (6): 442–6. doi:10.1093/jnci/89.6.442. PMID 9091646. 5. ^ a b c d Howes N, Lerch MM, Greenhalf W, et al. (March 2004). "Clinical and genetic characteristics of hereditary pancreatitis in Europe". Clin. Gastroenterol. Hepatol. 2 (3): 252–61. doi:10.1016/S1542-3565(04)00013-8. PMID 15017610. 6. ^ a b Rebours V, Boutron-Ruault MC, Schnee M, et al. (January 2008). "Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series". Am. J. Gastroenterol. 103 (1): 111–9. PMID 18184119. 7. ^ Greenhalf W, Grocock C, Harcus M, Neoptolemos J (2009). "Screening of high-risk families for pancreatic cancer". Pancreatology. 9 (3): 215–22. doi:10.1159/000210262. PMID 19349734. S2CID 29100310. 8. ^ Wolfgang, CL; Herman, JM; Laheru, DA; Klein, AP; Erdek, MA; Fishman, EK; Hruban, RH (Sep 2013). "Recent progress in pancreatic cancer". CA: A Cancer Journal for Clinicians. 63 (5): 322–323. doi:10.3322/caac.21190. PMC 3769458. PMID 23856911. 9. ^ Gorry MC, Gabbaizedeh D, Furey W, et al. (October 1997). "Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis". Gastroenterology. 113 (4): 1063–8. doi:10.1053/gast.1997.v113.pm9322498. PMID 9322498. 10. ^ Chen JM, Piepoli Bis A, Le Bodic L, et al. (March 2001). "Mutational screening of the cationic trypsinogen gene in a large cohort of subjects with idiopathic chronic pancreatitis". Clin. Genet. 59 (3): 189–93. doi:10.1034/j.1399-0004.2001.590308.x. PMID 11260229. 11. ^ Lee KH, Yoon WJ, Ryu JK, Kim YT, Yoon YB, Kim CY (August 2004). "[Mutations of SPINK1 and PRSS1 gene in Korean patients with chronic pancreatitis]". Korean J Gastroenterol (in Korean). 44 (2): 93–8. PMID 15329520. 12. ^ O'Reilly DA, Yang BM, Creighton JE, Demaine AG, Kingsnorth AN (2001). "Mutations of the cationic trypsinogen gene in hereditary and non-hereditary pancreatitis". Digestion. 64 (1): 54–60. doi:10.1159/000048839. PMID 11549837. S2CID 21037146. 13. ^ Witt H, Luck W, Becker M (July 1999). "A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis". Gastroenterology. 117 (1): 7–10. doi:10.1016/s0016-5085(99)70543-3. PMID 10381903. 14. ^ Grocock CJ, Rebours V, Delhaye MN, et al. (March 2010). "The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families". Gut. 59 (3): 357–63. doi:10.1136/gut.2009.186817. PMID 19951905. S2CID 983450. 15. ^ Teich N, Rosendahl J, Tóth M, Mössner J, Sahin-Tóth M (August 2006). "Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis". Hum. Mutat. 27 (8): 721–30. doi:10.1002/humu.20343. PMC 2793115. PMID 16791840. 16. ^ Szmola R, Sahin-Tóth M (May 2010). "Uncertainties in the classification of human cationic trypsinogen (PRSS1) variants as hereditary pancreatitis-associated mutations". J. Med. Genet. 47 (5): 348–50. doi:10.1136/jmg.2009.072751. PMC 2930840. PMID 20452997. 17. ^ Sahin-Tóth M (June 2006). "Biochemical models of hereditary pancreatitis". Endocrinol. Metab. Clin. North Am. 35 (2): 303–12, ix. doi:10.1016/j.ecl.2006.02.002. PMC 1602208. PMID 16632094. 18. ^ Felderbauer P, Schnekenburger J, Lebert R, et al. (August 2008). "A novel A121T mutation in human cationic trypsinogen associated with hereditary pancreatitis: functional data indicating a loss-of-function mutation influencing the R122 trypsin cleavage site". J. Med. Genet. 45 (8): 507–12. doi:10.1136/jmg.2007.056481. PMID 18511571. S2CID 24473962. 19. ^ Kereszturi E, Szmola R, Kukor Z, et al. (April 2009). "Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism". Hum. Mutat. 30 (4): 575–82. doi:10.1002/humu.20853. PMC 2663013. PMID 19191323. 20. ^ Whitcomb DC (September 1999). "Hereditary pancreatitis: new insights into acute and chronic pancreatitis". Gut. 45 (3): 317–22. doi:10.1136/gut.45.3.317. PMC 1727629. PMID 10446089. 21. ^ Rebours, Vinciane; Boutron-Ruault, Marie-Christine; Jooste, Valérie; Bouvier, Anne-Marie; Hammel, Pascal; Ruszniewski, Philippe; Lévy, Philippe (2009-09-01). "Mortality rate and risk factors in patients with hereditary pancreatitis: uni- and multidimensional analyses". The American Journal of Gastroenterology. 104 (9): 2312–2317. doi:10.1038/ajg.2009.363. ISSN 1572-0241. PMID 19550412. S2CID 2555617. ## External links[edit] Classification D * ICD-10: K86.1 * OMIM: 167800 * DiseasesDB: 30026 * SNOMED CT: 68072000 External resources * Orphanet: 676 * 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 * t * e Congenital malformations and deformations of digestive system Upper GI tract Tongue, mouth and pharynx * Cleft lip and palate * Van der Woude syndrome * tongue * Ankyloglossia * Macroglossia * Hypoglossia Esophagus * EA/TEF * Esophageal atresia: types A, B, C, and D * Tracheoesophageal fistula: types B, C, D and E * esophageal rings * Esophageal web (upper) * Schatzki ring (lower) Stomach * Pyloric stenosis * Hiatus hernia Lower GI tract Intestines * Intestinal atresia * Duodenal atresia * Meckel's diverticulum * Hirschsprung's disease * Intestinal malrotation * Dolichocolon * Enteric duplication cyst Rectum/anal canal * Imperforate anus * Rectovestibular fistula * Persistent cloaca * Rectal atresia Accessory Pancreas * Annular pancreas * Accessory pancreas * Johanson–Blizzard syndrome * Pancreas divisum Bile duct * Choledochal cysts * Caroli disease * Biliary atresia Liver * Alagille syndrome * Polycystic liver disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Hereditary pancreatitis	c0238339	5,683	wikipedia	https://en.wikipedia.org/wiki/Hereditary_pancreatitis	2021-01-18T18:55:24	{"gard": ["6632"], "mesh": ["C537262"], "orphanet": ["676"], "wikidata": ["Q3361967"]}
## Description Familial multiple lipomatosis is a rare autosomal dominant disorder characterized by numerous encapsulated lipomas on the trunk and extremities (Keskin et al., 2002). Clinical Features Stephens and Isaacson (1959) observed 17 cases in 3 generations. Usually the condition did not become evident until the age of about 35 years, although in 1 case lipomas were present at age 9. The gastrointestinal tract may be involved (Lang et al., 1959). Golsch and Worret (1995) described a family with 9 cases of familial multiple lipomatosis in 3 generations. The oldest living member of the family suffered from a nonalcoholic peripheral neuropathy. Polyneuropathy has been described in association with multiple symmetric lipomatosis (151800) and may be an intrinsic part of that disorder. Its relationship to familial multiple lipomatosis is less clear. Keskin et al. (2002) reported a large family in which 8 members of 3 generations had multiple lipomatosis. In 1 patient, the lipomas occurred only on the neck, but in others they occurred on the trunk, the upper extremities, and the thighs. The lipomas arose in the third or fourth decade in all but 1, who had onset at age 14 years. Inheritance Keskin et al. (2002) reported multiple lipomas in 8 members of 3 generations of a family with male-to-male transmission. Cytogenetics Dal Cin et al. (1988) reported on the cytogenetic analysis of 3 different lipomas from a patient with multiple subcutaneous lipomas. Two distinct reciprocal translocations were observed, both with breakpoints at 12q14. The reciprocal translocation t(3;12)(q28;q14) was found in 2 lipomas from this patient; t(1;12)(q34.2;q14) was seen in the third. The authors noted that 2 previously described translocations involving chromosome 12q14 also had breakpoints in the region of 3q27-q28. Heim et al. (1988) concluded, on the basis of cytogenetic analysis of tumor cells from 50 lipomas, that 4 main cytogenetic subtypes can be recognized: (1) tumors with normal karyotype (18 cases); (2) tumors with rearrangements of 12q13-q14 (18 cases); (3) tumors with ring chromosomes (6 cases); and (4) tumors with other clonal changes (8 cases). All 6 tumors with ring marker chromosomes were histopathologically classified as atypical lipomas. All 7 multiple lipomas were karyotypically normal. Sreekantaiah et al. (1991) found abnormalities of chromosome 12 in 34 of 92 patients with lipomas. The distinctness of benign lipomas, including multiple lipomatosis, from myxoid liposarcoma (613488) was indicated by the findings of Mrozek et al. (1993) that the chromosome 12 breakpoint in myxoid liposarcoma is at 12q13.3, as reported by many others, but that the breakpoint in benign lipoma, including multiple lipomatosis, is more distally situated, at 12q15. They suggested that the more distal location is identical to that found in other benign tumors such as uterine leiomyoma (150699) and pleomorphic adenoma of the salivary gland (181030). In a note added in proof to their report of the HMGIC gene (600698) on chromosome 12 involved in soft tissue tumors with translocations of 12q15, Schoenmakers et al. (1995) referred to the isolation and sequencing of the lipoma-preferred-partner gene (LPP; 600700). Chromosome 3 is the preferred partner in lipomas resulting from translocation involving 12q15. Other translocation partners of 12q15 include chromosomes 1, 2, 4, 5, 6, 7, 10, 11, 13, 15, 17, 21, and X (Sreekantaiah et al., 1991). Ligon et al. (2005) reported an 8-year-old boy who had a de novo pericentric inversion of chromosome 12, with breakpoints at p11.22 and q14.3, and a phenotype that included extreme somatic overgrowth, advanced endochondral bone and dental ages, a cerebellar tumor, and multiple lipomas. At 27 months of age the patient showed macrocephaly, bilateral bowing and multiple lipomas of the lower extremities, and megaepiphyseal flaring of the femur and tibia at the knee joint. At the age of 4 years, the patient showed disorganized and advanced dental age of both erupted and unerupted teeth. Bone age was estimated at 13.5 years on a wrist radiograph taken at 8 years of age. The chromosomal inversion was found to truncate HMGA2 (600698), a gene that encodes an architectural factor involved in the etiology of many benign mesenchymal tumors and that maps to the 12q14.3 breakpoint. Similar truncations of mouse Hmga2 in transgenic mice result in somatic overgrowth and, in particular, increased abundance of fat and lipomas (Arlotta et al., 2000), features strikingly similar to those observed in the child. Prontera et al. (2009) described a 5-year-old girl with encephalocutaneous lipomatosis (ECCL; 613001) and a family history of multiple lipomatosis. The patient had lipomas on the face, alopecia areata, coloboma of iris, chorioretinitis, bilateral epibulbar dermoid, complex partial crises, moderate tricuspid valve insufficiency, increased pulmonary pressure, intracranial lipomas, leptomeningeal angiomatosis, intracranial calcification, hypoplastic corpus callosum, arachnoid cyst of the right temporal lobe, enlargement of the right ventricle, microgyria of the temporal and occipital right lobes, osteolytic lesion in the right jaw, including irregular zones of calcification, ossification and dental elements (odontogenic jaw tumor), moderate speech delay, and macrocephaly. Her father and her paternal grandmother had multiple benign lipomas affecting limbs and trunk that appeared during the second and third decade of life. Prontera et al. (2009) suggested that HMGA2 may be a good candidate for both FML and ECCL. They proposed that a germline mutation in the HMGA2 gene may be responsible for dominant FML and that a somatic mutation in this gene may be responsible for ECCL. Inheritance \- Autosomal dominant Lab \- Frequent rearrangements at 12q13 or 12q14 Skin \- Lipomatosis ▲ 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)	LIPOMATOSIS, MULTIPLE	c3489413	5,684	omim	https://www.omim.org/entry/151900	2019-09-22T16:38:49	{"doid": ["3315", "14116"], "mesh": ["D008067"], "omim": ["151900"], "orphanet": ["199276"], "synonyms": ["Alternative titles", "LIPOMATOSIS, FAMILIAL MULTIPLE", "LIPOMA"]}
Microsporidiosis is a parasitosis caused by microsporidia (protozoan parasites). ## Epidemiology The annual incidence of microsporidiosis is unknown and the geographical distribution of microsporidia remains to be defined. Immunodeficient patients (individuals with HIV, and patients who have undergone a bone marrow or organ transplant) are the main target. ## Clinical description The infection results in chronic diarrhea that leads to severe weight loss. ## Etiology Microsporidia are unicellular eukaryotic parasites without mitochondria and are responsible for opportunistic infections. Microsporidia are strictly intracellular parasites. The initial proliferative asexual stage (merogony) is followed by a disseminating stage (sporogony) that leads to spore development. Small spores (1 to 3 µm depending on the species) represent the most resistant and disseminating form and are characterized by a polar filament, which allows them to perforate the cell wall and inject nuclear material. They develop mainly in intestinal cells but may also develop in adipocytes, epithelium cells and blood cells. Several genera have been reported in humans, among which Encephalitozoon and Enterocytozoon are the most common. Contamination probably occurs after ingesting spores contained in water or food. Direct interhuman contamination is also likely. ## Diagnostic methods Diagnosis is based on the identification of spores through laboratory testing. ## Differential diagnosis Differential diagnoses include the other genera of microsporidia. ## Management and treatment Treatment with albendazole is well tolerated and successful, except for patients with Enterocytozoon bieneusi infections, for which only fumagillin is effective but hematotoxic. ## Prognosis The prognosis may be severe in immunodeficient patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Microsporidiosis	c0085407	5,685	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2552	2021-01-23T17:26:40	{"gard": ["3655"], "mesh": ["D016881"], "umls": ["C0085407"], "icd-10": ["B60.8"]}
A number sign (#) is used with this entry because of evidence that MIRAGE syndrome (MIRAGE) is caused by heterozygous mutation in the SAMD9 gene (610456) on chromosome 7q21. Description MIRAGE syndrome is a form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. The condition is often fatal within the first decade of life, usually as a result of invasive infection (Narumi et al., 2016). Clinical Features Narumi et al. (2016) studied 11 patients who exhibited strikingly similar phenotypes, including moderate to severe growth restriction both prenatally and postnatally. Intellectual development was variably affected; 4 of 8 patients who survived to 1 year of life were unable to hold their head up or say a word. Adrenal insufficiency was usually suspected because of skin hyperpigmentation, even before onset of symptoms of salt loss; adrenal hypoplasia was documented in the 7 patients who underwent ultrasonography. Six of 7 patients with a 46,XY karyotype exhibited genital underdevelopment, with microphallus, cryptorchidism, and hypospadias; 1 patient had completely female-appearing external genitalia at birth and had been assigned female. In early infancy, all patients experienced thrombocytopenia and/or anemia requiring transfusions, but these resolved spontaneously. Severe invasive infections, including sepsis, meningitis, and fungal infections, were invariably observed; 6 patients died before 2 years of age, chiefly as a result of invasive infection. Immunologic testing in 8 patients showed some abnormalities, including mild lymphopenia, but did not reveal a shared severe defect. In addition, 9 patients had chronic diarrhea with colonic dilation. Mosaic monosomy 7 (see 252270) was detected in 2 patients, who both developed myelodysplastic syndrome and died from the complication. Postmortem histologic analysis in 2 female patients showed very small adrenal glands that were highly disorganized, with the medulla only partially surrounded by cortex. The dysgenetic adrenocortical cells had a foamy appearance, and the layered architecture of the cortex was disturbed. Ovaries were also markedly hypoplastic, with few primordial follicles, and the thymus was hypoplastic with a decreased number of cortical lymphocytes. Narumi et al. (2016) proposed the designation MIRAGE syndrome. Molecular Genetics By whole-exome sequencing in 6 Japanese patients with suspected syndromic adrenal hypoplasia, Narumi et al. (2016) identified 3 different heterozygous missense mutations in the SAMD9 gene (610456.0002-610456.0004) in 4 of the patients. Sequencing of SAMD9 in another 18 Japanese patients identified 7 additional patients with SAMD9 missense variants. The mutations were shown to have arisen de novo in all families for which parental DNA was available, except for 1 family with 2 affected sibs, where parental germline mosaicism was suspected. None of the mutations were found in 400 in-house Japanese control samples or in public variant databases. Genetic analysis in 2 patients with monosomy 7 who developed myelodysplastic syndrome (see 252270) showed loss of the signal derived from the mutant allele, suggesting that there was an expansion of the cells that lost chromosome 7 carrying the mutation. Because functional analysis demonstrated potent growth-restricting activity with the SAMD9 mutants, Narumi et al. (2016) suggested that the loss of chromosome 7 occurred as an adaptation to the growth-restricting conditions. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Weight \- Low weight Other \- Intrauterine growth restriction HEAD & NECK Neck \- Hypoplastic or absent thymus CARDIOVASCULAR Vascular \- Patent ductus arteriosus RESPIRATORY Lung \- Aspiration pneumonia, recurrent ABDOMEN Spleen \- Hypoplastic spleen (rare) Gastrointestinal \- Chronic diarrhea \- Dilation of colon \- Gastroesophageal reflux \- Esophageal stricture (rare) \- Achalasia (rare) \- Multiple constrictions of colon (rare) \- Upper gastrointestinal bleeding (rare) \- Lower gastrointestinal bleeding (rare) GENITOURINARY \- Urinary tract infections, recurrent External Genitalia (Male) \- Microphallus \- Hypospadias \- Bifid shawl scrotum Internal Genitalia (Male) \- Cryptorchidism \- Small testes Internal Genitalia (Female) \- Primary ovarian failure \- Hypoplastic ovaries \- Dysgenetic ovaries \- Few primordial follicles of ovaries Kidneys \- Bacterial nephritis (rare) SKELETAL Spine \- Scoliosis, congenital Hands \- Overlapping fingers \- Radial club hand Feet \- Club feet \- Rocker-bottom feet SKIN, NAILS, & HAIR Skin \- Generalized skin pigmentation \- Petechiae NEUROLOGIC Central Nervous System \- Developmental delay \- Limited or no speech (in some patients) \- Motor delay \- Bacterial meningitis (in some patients) \- Intracranial hemorrhage (rare) \- Seizures (rare) \- Paraplegia (rare) \- Hydrocephalus (rare) \- Severe cystic periventricular leukomalacia (rare) \- Marked reduction in volume of myelinated white matter (rare) \- Hypoplastic fenestrated falx cerebri with interdigitation of gyri (rare) ENDOCRINE FEATURES \- Adrenal insufficiency \- Adrenal gland hypoplasia/aplasia \- Elevated plasma corticotropin \- Low serum cortisol \- Elevated plasma renin activity \- Low serum aldosterone \- Primary hypogonadism \- Low serum antimullerian hormone \- Mildly elevated serum luteinizing hormone \- Mildly elevated serum follicle-stimulating hormone \- Highly disorganized adrenal cortex \- Adrenal medulla only partially surrounded by cortex \- Foamy, dysgenetic cortical cells \- Absent 3-layer structure of adrenal cortex HEMATOLOGY \- Thrombocytopenia, transient or persistent (in early infancy) \- Anemia, transient or persistent (in early infancy) \- Mild lymphopenia \- Leukopenia (in some patients) \- Low granulocyte count (in some patients) \- Low T-cell percentage (in some patients) \- High B-cell percentage (in some patients) \- Myelodysplastic syndrome (rare) IMMUNOLOGY \- Bacterial infections, recurrent \- Fungal infections, recurrent \- Viral infections, recurrent \- Sepsis \- Mild decrease in natural killer cell activity \- Low CD4-to-CD8 ratio \- Mild decrease in neutrophil phagocytic activity PRENATAL MANIFESTATIONS Delivery \- Preterm delivery due to suspected fetal distress LABORATORY ABNORMALITIES \- Hypoglycemia \- Hyponatremia \- Hyperkalemia \- Elevated C-reactive protein, persistent \- Markedly elevated serum ferritin (rare) MISCELLANEOUS \- One 46,XY individual exhibited female external genitalia at birth and was designated female \- Mosaic monosomy 7 was observed in 2 patients, who both developed myelodysplastic syndrome and died from the complication MOLECULAR BASIS \- Caused by mutation in the sterile alpha motif domain-containing protein-9 gene (SAMD9, 610456.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	MIRAGE SYNDROME	c4284088	5,686	omim	https://www.omim.org/entry/617053	2019-09-22T15:47:06	{"omim": ["617053"], "orphanet": ["494433"], "synonyms": ["Alternative titles", "Myelodysplasia-infection-restriction of growth-adrenal hypoplasia-genital anomalies-enteropathy syndrome", "Myelodysplasia-infection-restriction of growth-adrenal hypoplasia-genital phenotypes-enteropathy syndrome", "MYELODYSPLASIA, INFECTION, RESTRICTION OF GROWTH, ADRENAL HYPOPLASIA, GENITAL PHENOTYPES, AND ENTEROPATHY"]}
Colobomatous microphthalmia-obesity-hypogenitalism-intellectual disability syndrome is a rare, genetic, syndromic microphthalmia disorder characterized by bilateral, usually asymmetrical, microphthalmia associated typically with a unilateral coloboma, truncal obesity, borderline to mild intellectual disability, hypogenitalism and, more variably, nystagmus, cataracts and developmental delay. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Colobomatous microphthalmia-obesity-hypogenitalism-intellectual disability syndrome	c1866256	5,687	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363741	2021-01-23T17:20:38	{"mesh": ["C566623"], "omim": ["601794"], "umls": ["C1866256"], "icd-10": ["Q87.8"]}
Swollen lymph node in the neck due to tick attached behind ear Cervical lymphadenopathy refers to lymphadenopathy of the cervical lymph nodes (the glands in the neck). The term lymphadenopathy strictly speaking refers to disease of the lymph nodes,[1] though it is often used to describe the enlargement of the lymph nodes. Similarly, the term lymphadenitis refers to inflammation of a lymph node, but often it is used as a synonym of lymphadenopathy. Cervical lymphadenopathy is a sign or a symptom, not a diagnosis. The causes are varied, and may be inflammatory, degenerative, or neoplastic.[2] In adults, healthy lymph nodes can be palpable (able to be felt), in the axilla, neck and groin.[3] In children up to the age of 12 cervical nodes up to 1 cm in size may be palpable and this may not signify any disease.[4] If nodes heal by resolution or scarring after being inflamed, they may remain palpable thereafter.[1] In children, most palpable cervical lymphadenopathy is reactive or infective. In individuals over the age of 50, metastatic enlargement from cancers (most commonly squamous cell carcinomas) of the aerodigestive tract should be considered.[1] ## Contents * 1 Classification * 2 Causes * 2.1 Infection * 2.2 Malignancy * 2.3 Other causes * 3 Diagnosis * 4 References ## Classification[edit] Cervical lymphadenopathy in an individual with infectious mononucleosis Lymph nodes in the neck Cervical lymphadenopathy can be thought of as local where only the cervical lymph nodes are affected, or general where all the lymph nodes of the body are affected. ## Causes[edit] ### Infection[edit] * Pericoronitis[5] * Staphylococcal lymphadenitis[1] * Mycobacterial lymphadenitis[1] * Rubella * Cat scratch fever[1] * Infectious mononucleosis[6] * Streptococcal pharyngitis * Viral respiratory infection * Toxoplasmosis[7] * Tuberculosis[7] * Brucellosis[8] * Primary herpes simplex infection (primary herpetic gingivostomatitis)[1] * Syphilis (secondary)[1] * Cytomegalovirus[1] * Human immunodeficiency virus[1] * Histoplasmosis[5] * Chicken pox[5] ### Malignancy[edit] Lymph nodes may become enlarged in malignant disease. This cervical lymphadenopathy may be reactive or metastatic.[1] Alternatively, enlarged lymph nodes may represent a primary malignancy of the lymphatic system itself, such as lymphoma (both Hodgkin's and non-Hodgkin's),[6] lymphocytic leukemia,[1] Lymphadenopathy that lasts less than two weeks or more than one year with no progressive size increase has a very low likelihood of being neoplastic.[9] Metastatic lymph nodes are enlarged because tumor cells have detached from the primary tumor and started growing in the lymph node ("seeded"). Since cancer generally occurs more frequently in older people, this kind of lymphadenopathy is more common in older persons.[7] Metastatic lymph nodes tend to feel hard and may be fixed to underlying tissues and may or may not be tender.[7] Usually the lymph nodes that directly drain the area of the cancer are affected by the spread (e.g. Sometimes metastatic cervical lymph node is detected before the main cancer). In such cases, this discovery leads to a search for the primary malignancy, firstly in the nearby area with endoscopy, "blind" biopsies, and tonsillectomy on the side of the lymphadenopathy. If no tumor is found, then the rest of the body is examined, looking for lung cancer or other possible sites. If still no primary tumor is detected, the term "occult primary" is used.[8] In lymphoma, usually there are multiple enlarged nodes which feel rubbery to palpation.[8] * Rhabdomyosarcoma * Neuroblastoma ### Other causes[edit] * Surgical trauma, e.g. following a biopsy in the mouth[4] * Kawasaki disease,[5] * Kikuchi-Fujimoto disease * Rosai-Dorfman disease * Castleman disease * sarcoidosis[1] * Lupus erythematosus[7] * Cyclic neutropenia[5] * Orofacial granulomatosis[10] ## Diagnosis[edit] In possible malignancy, it is routine to perform a throat examination including mirror and/or endoscopy.[11] On ultrasound, B-mode imaging depicts lymph node morphology, whilst power Doppler can assess the vascular pattern.[12] B-mode imaging features that can distinguish metastasis and lymphoma include size, shape, calcification, loss of hilar architecture, as well as intranodal necrosis.[12] Soft tissue edema and nodal matting on B-mode imaging suggests tuberculous cervical lymphadenitis or previous radiation therapy.[12] Serial monitoring of nodal size and vascularity are useful in assessing treatment response.[12] Fine needle aspiration cytology (FNAC) has a sensitivity and specificity percentages of 81% and 100%, respectively, in the histopathology of malignant cervical lymphadenopathy.[11] PET-CT has proven to be helpful in identifying occult primary carcinomas of the head and neck, especially when applied as a guiding tool prior to panendoscopy, and may induce treatment related clinical decisions in up to 60% of cases.[11] ## References[edit] 1. ^ a b c d e f g h i j k l m Kerawala C, Newlands C, eds. (2010). Oral and maxillofacial surgery. Oxford: Oxford University Press. pp. 68, 377, 392–94. ISBN 9780199204830. 2. ^ Terézhalmy GT, Huber MA, Jones AC (2009). Physical evaluation in dental practice. Ames, Iowa: Wiley-Blackwell. pp. 120–23, 160, 172. ISBN 978-0-8138-2131-3. 3. ^ Ferrer, Robert (1998-10-15). "Lymphadenopathy: Differential Diagnosis and Evaluation". American Family Physician. 58 (6): 1313–20. PMID 9803196. 4. ^ a b Hupp JR, Ellis E, Tucker MR (2008). Contemporary oral and maxillofacial surgery (5th ed.). St. Louis, Mo.: Mosby Elsevier. pp. 428–30. ISBN 9780323049030. 5. ^ a b c d e Scully, Crispian (2008). Oral and maxillofacial medicine : the basis of diagnosis and treatment (2nd ed.). Edinburgh: Churchill Livingstone. pp. 14, 69–73, 101. ISBN 9780443068188. 6. ^ a b Treister NS, Bruch JM (2010). Clinical oral medicine and pathology. New York: Humana Press. pp. 99, 149. ISBN 978-1-60327-519-4. 7. ^ a b c d e Kalantzis A, Scully C (2005). Oxford handbook of dental patient care, the essential guide to hospital dentistry (2nd ed.). New York: Oxford University Press. pp. 47, 343. ISBN 9780198566236. 8. ^ a b c Odell EW, ed. (2010). Clinical problem solving in dentistry (3rd ed.). Edinburgh: Churchill Livingstone. pp. 91–94. ISBN 9780443067846. 9. ^ Abba, Abdullah A.; Khalil, Mohamed Z. (2012-01-01). "Clinical approach to Lymphadenopathy". Annals of Nigerian Medicine. 6 (1): 11. doi:10.4103/0331-3131.100201. ISSN 0331-3131. 10. ^ Leão, JC; Hodgson, T; Scully, C; Porter, S (Nov 15, 2004). "Review article: orofacial granulomatosis". Alimentary Pharmacology & Therapeutics. 20 (10): 1019–27. doi:10.1111/j.1365-2036.2004.02205.x. PMID 15569103. S2CID 33359041. 11. ^ a b c Balm, A. J. M.; van Velthuysen, M. L. F.; Hoebers, F. J. P.; Vogel, W. V.; van den Brekel, M. W. M. (2010). "Diagnosis and Treatment of a Neck Node Swelling Suspicious for a Malignancy: An Algorithmic Approach". International Journal of Surgical Oncology. 2010: 1–8. doi:10.1155/2010/581540. ISSN 2090-1402. PMC 3265261. PMID 22312490. 12. ^ a b c d Ahuja, A.T. (2008). "Ultrasound of malignant cervical lymph nodes". Cancer Imaging. 8 (1): 48–56. doi:10.1102/1470-7330.2008.0006. ISSN 1470-7330. PMC 2324368. PMID 18390388. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Cervical lymphadenopathy	c0235592	5,688	wikipedia	https://en.wikipedia.org/wiki/Cervical_lymphadenopathy	2021-01-18T18:48:00	{"umls": ["C0235592"], "wikidata": ["Q5065339"]}
Low-grade neuroendocrine tumor of the corpus uteri is an extremely rare uterine cancer typically characterized by a well demarcated, solid, frequently pedunculated tumor originating from neuroendocrine cells scattered within the endometrium, often associated with ectopic hormone production. Patients usually present with vaginal bleeding or discharge and a pelvic mass with a polypoid tumor sometimes protruding through the cervical canal. Symptoms related to ectopic hormone production (flushing, sweating, diarrhea, bronchospasm) may also develop. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others)	Low-grade neuroendocrine tumor of the corpus uteri	None	5,689	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=213736	2021-01-23T17:31:08	{"icd-10": ["C54.0", "C54.1", "C54.2", "C54.3", "C54.8"], "synonyms": ["Low-grade neuroendocrine tumor of the uterine corpus", "Well-differentiated neuroendocrine neoplasm of the endometrium", "Well-differentiated neuroendocrine tumor of the corpus uteri", "Well-differentiated neuroendocrine tumor of the endometrium"]}
The word neuroleptic originates from the Greek word lepsis ("seizure").[1] Antipsychotics (a.k.a. neuroleptics or tranquilizers) were investigated by the anesthesiologists De Castro and Mundeleer who coined the term neuroleptanalgesia, an anesthetic process that involves combining a major neuroleptic tranquilizer/antipsychotic with a potent opioid analgesic to produce a detached, pain-free state. This technique was widely used from the 1960s onwards, initially using a combination of phenoperidine and haloperidol, which was subsequently replaced in the early 1980s by a combination of fentanyl and droperidol. Efforts were also made to develop compounds which combined both types of activity in a single molecule.[2] Neuroleptanalgesia results in amnesia among some patients, but not all. The technique has become less popular with the advent of more modern procedural sedation drug combinations, though it is still rarely used today as a combination of 2.5 mg droperidol and 50 μg (micrograms) of fentanyl in a ratio of 50:1. This combination is characterized by immobility, analgesia, and variable amnesia.[3]:644[4] ## See also[edit] * Anesthetics * Sedation * Twilight sleep ## References[edit] 1. ^ Moby's Medical Dictionary. Elsevier. 2. ^ Iorio, M. A.; Paszkowska Reymer, T.; Frigeni, V. (1987). "Combined analgesic/neuroleptic activity in N-butyrophenone prodine-like compounds". Journal of Medicinal Chemistry. 30 (10): 1906–1910. doi:10.1021/jm00393a037. PMID 2888899. 3. ^ Edmond I Eger II, Lawrence Saidman, Rod Westhorpe. The Wondrous Story of Anesthesia. Springer Science & Business Media, 2013 ISBN 9781461484417 4. ^ Livingstone, Churchill. "Neuroleptanalgesia-Anesthesia". Retrieved 24 February 2014. This analgesic-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Neuroleptanalgesic	None	5,690	wikipedia	https://en.wikipedia.org/wiki/Neuroleptanalgesic	2021-01-18T18:30:27	{"mesh": ["D009458"], "wikidata": ["Q16947814"]}
Northern epilepsy is a rare condition that affects the nervous system. Signs and symptoms of the condition generally develop between ages 5 and 10 years and may include recurrent seizures, mild intellectual disability, and motor abnormalities (i.e. problems with coordination and balance). Some affected people may also experience decreased visual acuity. Northern epilepsy is caused by changes (mutations) in the CLN8 gene and is inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Northern epilepsy	c1864923	5,691	gard	https://rarediseases.info.nih.gov/diseases/4010/northern-epilepsy	2021-01-18T17:58:39	{"mesh": ["C537952"], "omim": ["600143"], "orphanet": ["1947"], "synonyms": ["CLN8", "Neuronal ceroid lipofuscinosis 8", "Ceroid lipofuscinosis neuronal 8", "CLN8 disease, late infantile (subtype)", "CLN8 disease, EPMR (subtype)", "CLN8 disease, Northern epilepsy variant", "NCL, Northern epilepsy variant", "Neuronal ceroid lipofuscinosis, Northern epilepsy variant", "Progressive epilepsy - intellectual disability, Finnish type", "Progressive epilepsy-intellectual disability syndrome, Finnish type"]}
Human disease caused by amoeba protists Amoebiasis Other namesAmoebic dysentery, amebiasis, entamoebiasis[1][2] The life-cycle of various intestinal Entamoeba species SpecialtyInfectious disease SymptomsBloody diarrhea, abdominal pain[3] ComplicationsSevere colitis, colonic perforation, anemia[3] CausesAmoebas of the Entamoeba group[3] Diagnostic methodStool examination, antibodies in the blood[3] Differential diagnosisBacterial colitis[3] PreventionImproved sanitation[3] TreatmentTissue disease: metronidazole, tinidazole, nitazoxanide, dehydroemetine, chloroquine, Intestinal infection: diloxanide furoate, iodoquinoline[3] Frequency~480 million[3] Amoebiasis, also known amoebic dysentery, is an infection caused by any of the amoebae of the Entamoeba group.[3] Symptoms are most common during infection by Entamoeba histolytica.[3] Amoebiasis can be present with no, mild, or severe symptoms.[3] Symptoms may include abdominal pain, diarrhea, or bloody diarrhea.[3] Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis.[3] People affected may develop anemia due to loss of blood.[3] Cysts of Entamoeba can survive for up to a month in soil or for up to 45 minutes under fingernails.[3] Invasion of the intestinal lining results in bloody diarrhea.[3] If the parasite reaches the bloodstream it can spread through the body, most frequently ending up in the liver where it can cause amoebic liver abscesses.[3] Liver abscesses can occur without previous diarrhea.[3] Diagnosis is typical by stool examination using a microscope, but may not reliably exclude infection or separate between specific types.[3] An increased white blood cell count may be present in severe cases.[3] The most accurate test is finding specific antibodies in the blood, but it may remain positive following treatment.[3] Bacterial colitis can result in similar symptoms.[3] Prevention of amoebiasis is by improved sanitation, including separating food and water from faeces.[3] There is no vaccine.[3] There are two treatment options depending on the location of the infection.[3] Amoebiasis in tissues is treated with either metronidazole, tinidazole, nitazoxanide, dehydroemetine or chloroquine, while luminal infection is treated with diloxanide furoate or iodoquinoline.[3] Effective treatment against all stages of the disease may require a combination of medications.[3] Infections without symptoms do not require treatment but infected individuals can spread the parasite to others and treatment can be considered.[3] Treatment of other Entamoeba infections apart from E. histolytica is not needed.[3] Amoebiasis is present all over the world,[4] though most cases occur in the developing world.[5] About 480 million people are currently infected with about 40 million new cases per year with significant symptoms.[3][6] This results in the death of between 40,000–110,000 people a year.[3] Most infections are now believed due to E. dispar.[3] E. dispar is more common in certain areas and symptomatic cases may be less common than previously reported.[3] The first case of amoebiasis was documented in 1875 and in 1891 the disease was described in detail, resulting in the terms amoebic dysentery and amoebic liver abscess.[3] Further evidence from the Philippines in 1913 found that upon swallowing cysts of E. histolytica volunteers developed the disease.[3] ## Contents * 1 Trivia * 2 Signs and symptoms * 3 Cause * 3.1 Transmission * 4 Pathogenesis * 5 Diagnosis * 6 Prevention * 7 Treatment * 8 Prognosis * 9 Epidemiology * 10 History * 11 References * 12 External links ## Trivia[edit] An outbreak of amoebic dysentery is described in Diana Gabaldon's novel A Breath of Snow and Ashes.[7] ## Signs and symptoms[edit] Most infected people, about 90%, are asymptomatic,[8] but this disease has the potential to become serious. It is estimated that about 40,000 to 100,000 people worldwide die annually due to amoebiasis.[9] Infections can sometimes last for years if there is no treatment. Symptoms take from a few days to a few weeks to develop and manifest themselves, but usually it is about two to four weeks. Symptoms can range from mild diarrhea to dysentery with blood, coupled with intense abdominal pains. Extra-intestinal complications might also arise as a result of invasive infection which includes colitis, liver, lung, or brain abscesses.[8] The blood comes from bleeding lesions created by the amoebae invading the lining of the colon. In about 10% of invasive cases the amoebae enter the bloodstream and may travel to other organs in the body. Most commonly this means the liver,[10] as this is where blood from the intestine reaches first, but they can end up almost anywhere in the body. Onset time is highly variable and the average asymptomatic infection persists for over a year. It is theorized that the absence of symptoms or their intensity may vary with such factors as strain of amoeba, immune response of the host, and perhaps associated bacteria and viruses. In asymptomatic infections, the amoeba lives by eating and digesting bacteria and food particles in the gut, a part of the gastrointestinal tract.[8] It does not usually come in contact with the intestine itself due to the protective layer of mucus that lines the gut. Disease occurs when amoeba comes in contact with the cells lining the intestine. It then secretes the same substances it uses to digest bacteria, which include enzymes that destroy cell membranes and proteins. This process can lead to penetration and digestion of human tissues, resulting first in flask-shaped ulcerations in the intestine. Entamoeba histolytica ingests the destroyed cells by phagocytosis and is often seen with red blood cells (a process known as erythrophagocytosis) inside when viewed in stool samples. Especially in Latin America,[citation needed] a granulomatous mass (known as an amoeboma) may form in the wall of the ascending colon or rectum due to long-lasting immunological cellular response, and is sometimes confused with cancer.[11] The ingestion of one viable cyst may cause an infection.[12] Steroid therapy can lead to severe amoebic colitis in persons with asymptomatic or symptomatic E. histolytica infection.[13] Severe amoebic colitis is associated with high mortality, and on average more than 50% with severe colitis die.[13] ## Cause[edit] Amoebiasis is an infection caused by the amoeba Entamoeba histolytica. Likewise amoebiasis is sometimes incorrectly used to refer to infection with other amoebae, but strictly speaking it should be reserved for Entamoeba histolytica infection.[citation needed] Other amoebae infecting humans include:[14] * Parasites * Dientamoeba fragilis, which causes Dientamoebiasis * Entamoeba dispar * Entamoeba hartmanni * Entamoeba coli * Entamoeba polecki * Entamoeba bangladeshi * Entamoeba moshkovskii * Endolimax nana and * Iodamoeba butschlii. Except for Dientamoeba, the parasites above are not thought to cause disease. * Free living amoebas.[15][16] These species are often described as "opportunistic free-living amoebas" as human infection is not an obligate part of their life cycle. * Naegleria fowleri, which causes primary amoebic meningoencephalitis * Acanthamoeba, which causes cutaneous amoebiasis[17] and Acanthamoeba keratitis and sometimes migrates to the brain. * Balamuthia mandrillaris,[18] which causes both skin and brain infections. * Sappinia diploidea ### Transmission[edit] Life-cycle of the Entamoeba histolytica Amoebiasis is usually transmitted by the fecal-oral route,[8] but it can also be transmitted indirectly through contact with dirty hands or objects as well as by anal-oral contact. Infection is spread through ingestion of the cyst form of the parasite, a semi-dormant and hardy structure found in feces. Any non-encysted amoebae, or trophozoites, die quickly after leaving the body but may also be present in stool: these are rarely the source of new infections.[8] Since amoebiasis is transmitted through contaminated food and water, it is often endemic in regions of the world with limited modern sanitation systems, including México, Central America, western South America, South Asia, and western and southern Africa.[19] Amoebic dysentery is one form of traveler's diarrhea,[20] although most traveler's diarrhea is bacterial or viral in origin. ## Pathogenesis[edit] Tissue damage caused by E. histolytica is a result of three main events, host cell death, inflammation, and parasite invasion. Abbreviations: EhMIF, E. histolytica macrophage migration inhibitory factor; MMP, matrix metalloproteinases. Amoebiasis results from tissue destruction induced by the E. histolytica parasite. E. histolytica causes tissue damage by three main events: direct host cell killing, inflammation, and parasite invasion.[21] ## Diagnosis[edit] With colonoscopy it is possible to detect small ulcers of between 3–5mm, but diagnosis may be difficult as the mucous membrane between these areas can look either healthy or inflamed.[3] Trophozoites may be identified at the ulcer edge or within the tissue, using immunohistochemical staining with specific anti-E. histolytica antibodies.[5] Asymptomatic human infections are usually diagnosed by finding cysts shed in the stool. Various flotation or sedimentation procedures have been developed to recover the cysts from fecal matter and stains help to visualize the isolated cysts for microscopic examination. Since cysts are not shed constantly, a minimum of three stools are examined. In symptomatic infections, the motile form (the trophozoite) is often seen in fresh feces. Serological tests exist, and most infected individuals (with symptoms or not) test positive for the presence of antibodies. The levels of antibody are much higher in individuals with liver abscesses. Serology only becomes positive about two weeks after infection. More recent developments include a kit that detects the presence of amoeba proteins in the feces, and another that detects ameba DNA in feces. These tests are not in widespread use due to their expense. Microscopy is still by far the most widespread method of diagnosis around the world. However it is not as sensitive or accurate in diagnosis as the other tests available. It is important to distinguish the E. histolytica cyst from the cysts of nonpathogenic intestinal protozoa such as Entamoeba coli by its appearance. E. histolytica cysts have a maximum of four nuclei, while the commensal Entamoeba coli cyst has up to 8 nuclei. Additionally, in E. histolytica, the endosome is centrally located in the nucleus, while it is usually off-center in Entamoeba coli. Finally, chromatoidal bodies in E. histolytica cysts are rounded, while they are jagged in Entamoeba coli. However, other species, Entamoeba dispar and E. moshkovskii, are also commensals and cannot be distinguished from E. histolytica under the microscope. As E. dispar is much more common than E. histolytica in most parts of the world this means that there is a lot of incorrect diagnosis of E. histolytica infection taking place. The WHO recommends that infections diagnosed by microscopy alone should not be treated if they are asymptomatic and there is no other reason to suspect that the infection is actually E. histolytica. Detection of cysts or trophozoites stools under microscope may require examination of several samples over several days to determine if they are present, because cysts are shed intermittently and may not show up in every sample. Typically, the organism can no longer be found in the feces once the disease goes extra-intestinal.[citation needed] Serological tests are useful in detecting infection by E. histolytica if the organism goes extra-intestinal and in excluding the organism from the diagnosis of other disorders. An Ova & Parasite (O&P) test or an E. histolytica fecal antigen assay is the proper assay for intestinal infections. Since antibodies may persist for years after clinical cure, a positive serological result may not necessarily indicate an active infection. A negative serological result, however, can be equally important in excluding suspected tissue invasion by E. histolytica.[citation needed] Stool antigen detection tests have helped to overcome some of the limitations of stool microscopy. Antigen detection tests are easy to use, but they have variable sensitivity and specificity, especially in low-endemic areas.[5] Polymerase chain reaction (PCR) is considered the gold standard for diagnosis but remains underutilized.[5][22] * Immature E. histolytica/E. dispar cyst in a concentrated wet mount stained with iodine. This early cyst has only one nucleus and a glycogen mass is visible (brown stain). * Amoebae in a colon biopsy from a case of amoebic dysentery. * Immunohistochemical staining of trophozoites (brown) using specific anti–Entamoeba histolytica macrophage migration inhibitory factor antibodies in a patient with amebic colitis. ## Prevention[edit] Specimen of the human intestine that was damaged by amebic ulcer. To help prevent the spread of amoebiasis around the home : * Wash hands thoroughly with soap and hot running water for at least 10 seconds after using the toilet or changing a baby's diaper, and before handling food. * Clean bathrooms and toilets often; pay particular attention to toilet seats and taps. * Avoid sharing towels or face washers. To help prevent infection: * Avoid raw vegetables when in endemic areas, as they may have been fertilized using human feces. * Boil water or treat with iodine tablets. * Avoid eating street foods especially in public places where others are sharing sauces in one container Good sanitary practice, as well as responsible sewage disposal or treatment, are necessary for the prevention of E. histolytica infection on an endemic level. E.histolytica cysts are usually resistant to chlorination, therefore sedimentation and filtration of water supplies are necessary to reduce the incidence of infection.[8] E. histolytica cysts may be recovered from contaminated food by methods similar to those used for recovering Giardia lamblia cysts from feces. Filtration is probably the most practical method for recovery from drinking water and liquid foods. E. histolytica cysts must be distinguished from cysts of other parasitic (but nonpathogenic) protozoa and from cysts of free-living protozoa as discussed above. Recovery procedures are not very accurate; cysts are easily lost or damaged beyond recognition, which leads to many falsely negative results in recovery tests.[23] ## Treatment[edit] Main article: Amoebicide E. histolytica infections occur in both the intestine and (in people with symptoms) in tissue of the intestine and/or liver.[19] Those with symptoms require treatment with two medications, an amoebicidal tissue-active agent and a luminal cysticidal agent.[8] Individuals that are asymptomatic only need a luminal cysticidal agent.[5] ## Prognosis[edit] Significance of Amebiasis In the majority of cases, amoebas remain in the gastrointestinal tract of the hosts. Severe ulceration of the gastrointestinal mucosal surfaces occurs in less than 16% of cases. In fewer cases, the parasite invades the soft tissues, most commonly the liver.[10] Only rarely are masses formed (amoebomas) that lead to intestinal obstruction.(Mistaken for Ca caecum and appendicular mass) Other local complications include bloody diarrhea, pericolic and pericaecal abscess. Complications of hepatic amoebiasis includes subdiaphragmatic abscess, perforation of diaphragm to pericardium and pleural cavity, perforation to abdominal cavital (amoebic peritonitis) and perforation of skin (amoebiasis cutis). Pulmonary amoebiasis can occur from liver lesions by spread through the blood or by perforation of pleural cavity and lung. It can cause lung abscess, pulmono pleural fistula, empyema lung and broncho pleural fistula. It can also reach the brain through blood vessels and cause amoebic brain abscess and amoebic meningoencephalitis. Cutaneous amoebiasis can also occur in skin around sites of colostomy wound, perianal region, region overlying visceral lesion and at the site of drainage of liver abscess. Urogenital tract amoebiasis derived from intestinal lesion can cause amoebic vulvovaginitis (May's disease), rectovesicle fistula and rectovaginal fistula. Entamoeba histolytica infection is associated with malnutrition and stunting of growth.[24] ## Epidemiology[edit] Amoebiasis caused about 55,000 deaths worldwide in 2010, down from 68,000 in 1990.[25][26] In older textbooks it is often stated that 10% of the world's population is infected with Entamoeba histolytica.[citation needed] It is now known that at least 90% of these infections are due to E. dispar.[citation needed] Nevertheless, this means that there are up to 50 million true E. histolytica infections and approximately seventy thousand die each year, mostly from liver abscesses or other complications. Although usually considered a tropical parasite, the first case reported (in 1875) was actually in St Petersburg in Russia, near the Arctic Circle.[27] Infection is more common in warmer areas, but this is because of both poorer hygiene and the parasitic cysts surviving longer in warm moist conditions.[19] ## History[edit] Amoebiasis was first described by Fedor A. Lösch in 1875, in northern Russia.[3][8] The most dramatic incident in the US was the Chicago World's Fair outbreak in 1933, caused by contaminated drinking water. There were more than a thousand cases, with 98 deaths.[28][29] It has been known since 1897 that at least one non-disease-causing species of Entamoeba existed (Entamoeba coli), but it was first formally recognized by the WHO in 1997 that E. histolytica was two species, despite this having first been proposed in 1925.[3] In addition to the now-recognized E. dispar, evidence shows there are at least two other species of Entamoeba that look the same in humans: E. moshkovskii and Entamoeba bangladeshi.[3] The reason these species haven't been differentiated until recently is because of the reliance on appearance.[3] Joel Connolly of the Chicago Bureau of Sanitary Engineering brought the outbreak to an end when he found that defective plumbing permitted sewage to contaminate drinking water. In 1998 there was an outbreak of amoebiasis in the Republic of Georgia.[30] Between 26 May and 3 September 1998, 177 cases were reported, including 71 cases of intestinal amoebiasis and 106 probable cases of liver abscess. The Nicobarese people have attested to the medicinal properties found in Glochidion calocarpum, a plant common to India, saying that its bark and seed are most effective in curing abdominal disorders associated with amoebiasis.[31] ## References[edit] 1. ^ "Entamoebiasis - MeSH - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2016-05-15. Retrieved 2015-07-21. 2. ^ "Entamoebiasis". mesh.kib.ki.se. Archived from the original on 2015-07-22. Retrieved 2015-07-21. 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 ad ae af ag ah ai aj ak al am an Farrar, Jeremy; Hotez, Peter; Junghanss, Thomas; Kang, Gagandeep; Lalloo, David; White, Nicholas J. (2013-10-26). Manson's Tropical Diseases. Elsevier Health Sciences. pp. 664–671. ISBN 9780702053061. 4. ^ Beeching, Nick; Gill, Geoff (2014-04-17). "19". Lecture Notes: Tropical Medicine. John Wiley & Sons. pp. 177–182. ISBN 9781118734568. 5. ^ a b c d e Shirley DT, Farr L, Watanabe K, Moonah S (July 2018). "A Review of the Global Burden, New Diagnostics, and Current Therapeutics for Amebiasis". Open Forum Infectious Diseases. 5 (7): ofy161. doi:10.1093/ofid/ofy161. PMC 6055529. PMID 30046644. 6. ^ Podolsky, Daniel K.; Camilleri, Michael; Fitz, J. Gregory; Kalloo, Anthony N.; Shanahan, Fergus; Wang, Timothy C. (2015). Yamada's Textbook of Gastroenterology. John Wiley & Sons. p. 2323. ISBN 978-1-118-51215-9. 7. ^ "Outlandish Observations". Retrieved 2020-11-24. 8. ^ a b c d e f g h Rawat, Aadish; Singh, Parikshit; Jyoti, Anupam; Kaushik, Sanket; Srivastava, Vijay Kumar (2020-04-30). "Averting transmission: A pivotal target to manage amoebiasis". Chemical Biology & Drug Design. 96 (2): 731–744. doi:10.1111/cbdd.13699. ISSN 1747-0285. PMID 32356312. 9. ^ Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall., 2012, Blackwell Publishing Ltd. 10. ^ a b Nespola B, Betz V, Brunet J, Gagnard JC, Krummel Y, Hansmann Y, et al. (2015). "First case of amebic liver abscess 22 years after the first occurrence". Parasite. 22: 20. doi:10.1051/parasite/2015020. PMC 4472968. PMID 26088504. Archived from the original on 2015-09-24. 11. ^ Day, David W.; Basil C. Morson; Jeremy R. Jass; Geraint Williams; Ashley B. Price (2003). Morson and Dawson's Gastrointestinal Pathology. John Wiley & Sons, Inc. ISBN 978-0-632-04204-3. 12. ^ "Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Entamoeba histolytica". Bad Bug Book. United States Food and Drug Administration: Center for Food Safety & Applied Nutrition. 2007-12-28. Archived from the original on 9 July 2009. Retrieved 2009-07-13. 13. ^ a b Shirley DA, Moonah S (July 2016). "Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review". PLOS Neglected Tropical Diseases. 10 (7): e0004879. doi:10.1371/journal.pntd.0004879. PMC 4965027. PMID 27467600. 14. ^ Berger SA, Marr JS. Human Parasitic Diseases Sourcebook. Jones and Bartlett Publishers: Sudbury, Massachusetts, 2006. 15. ^ Visvesvara GS, Moura H, Schuster FL (June 2007). "Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea". FEMS Immunology and Medical Microbiology. 50 (1): 1–26. doi:10.1111/j.1574-695X.2007.00232.x. PMID 17428307. 16. ^ "Orphanet: Amoebiasis due to free living amoebae". Archived from the original on 2008-11-18. Retrieved 2009-01-17. at Orphanet 17. ^ "EyeRounds.org:Acanthamoeba Keratitis: 39-year-old contact lens wearer with persisting keratitis & pain". Archived from the original on 5 December 2008. Retrieved 2009-01-17. 18. ^ Recavarren-Arce S, Velarde C, Gotuzzo E, Cabrera J (March 1999). "Amoeba angeitic lesions of the central nervous system in Balamuthia mandrilaris amoebiasis". Human Pathology. 30 (3): 269–73. doi:10.1016/S0046-8177(99)90004-7. PMID 10088544. 19. ^ a b c Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 733–8. ISBN 978-0-8385-8529-0. 20. ^ "safewateronline.com: Travelers' Diarrhea". Archived from the original on 6 June 2008. Retrieved 2020-06-28. 21. ^ Ghosh S, Padalia J, Moonah S (21 January 2019). "Cell Death, Inflammation, Invasion, and the Gut Microbiome". Current Clinical Microbiology Reports. 6 (1): 51–57. doi:10.1007/s40588-019-0113-6. PMC 6449278. PMID 31008019. 22. ^ Madden, Gregory R.; Shirley, Debbie-Ann; Townsend, Gregory; Moonah, Shannon (28 October 2019). "Lower Gastrointestinal Bleeding due to Entamoeba histolytica Detected Early by Multiplex PCR: Case Report and Review of the Laboratory Diagnosis of Amebiasis". The American Journal of Tropical Medicine and Hygiene. 101 (6): 1380–1383. doi:10.4269/ajtmh.19-0237. PMC 6896859. PMID 31674299. 23. ^ "FDA Bacteriological Analytical Manual". Archived from the original on 2008-04-06. Retrieved 2008-03-26. 24. ^ Mondal D, Petri WA, Sack RB, Kirkpatrick BD, Haque R, et al. (November 2006). "Entamoeba histolytica-associated diarrheal illness is negatively associated with the growth of preschool children: evidence from a prospective study". Transactions of the Royal Society of Tropical Medicine and Hygiene. 100 (11): 1032–8. doi:10.1016/j.trstmh.2005.12.012. PMID 16730764. 25. ^ Shirley, DT; Watanabe, K; Moonah, S (November 2019). "Significance of amebiasis: 10 reasons why neglecting amebiasis might come back to bite us in the gut". PLOS Neglected Tropical Diseases. 13 (11): e0007744. doi:10.1371/journal.pntd.0007744. PMC 6855409. PMID 31725715. 26. ^ Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. hdl:10536/DRO/DU:30050819. PMID 23245604. S2CID 1541253. 27. ^ Lösch, F. (1875) Massenhafte Entwickelung von Amöben im Dickdarm. Virchow's Archiv 65: 196-211. 28. ^ Markell EK (June 1986). "The 1933 Chicago outbreak of amebiasis". The Western Journal of Medicine. 144 (6): 750. PMC 1306777. PMID 3524005. 29. ^ "Water and Waste Systems". Archived from the original on 2017-01-19. Retrieved 2017-01-19. 30. ^ Kreidl P, Imnadze P, Baidoshvili L, Greco D (October 1999). "Investigation of an outbreak of amoebiasis in Georgia". Euro Surveillance. 4 (10): 103–104. doi:10.2807/esm.04.10.00040-en. PMID 12631887. 31. ^ See p. 412 in: Hammer, K (1990). "Barilla (Salsola soda, Chenopodiaceae)". Economic Botany. 44 (3): 410–412. doi:10.1007/bf03183925. JSTOR 4255259. S2CID 32113455. ## External links[edit] Classification D * ICD-10: A06 * ICD-9-CM: 006 * MeSH: D000562 * DiseasesDB: 4304 External resources * MedlinePlus: 000298 * eMedicine: article/212029 article/996092 * Patient UK: Amoebiasis * Amoebiasis \- Centers for Disease Control and Prevention * v * t * e Amoebozoal diseases Lobosea (free-living) Centramoebida * Acanthamoeba * Acanthamoeba keratitis * Cutaneous acanthamoebiasis * Granulomatous amoebic encephalitis * Acanthamoeba infection * Balamuthia mandrillaris * Balamuthia amoebic encephalitis * Balamuthia infection Flabellinia * Sappinia diploidea/Sappinia pedata * Sappinia amoebic encephalitis Conosa/Archamoebae * Entamoeba histolytica * Amoebiasis * Amoebic dysentery * Amoebic liver abscess * Cutaneous amoebiasis * Amoebic brain abscess * Amebiasis cutis * Entamoeba gingivalis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Amoebiasis	c0002438	5,692	wikipedia	https://en.wikipedia.org/wiki/Amoebiasis	2021-01-18T18:52:23	{"gard": ["652"], "mesh": ["D000562"], "umls": ["C0002438"], "wikidata": ["Q949694"]}
A number sign (#) is used with this entry because of evidence that familial persistent stuttering-1 (STUT1) is caused by heterozygous mutation in the AP4E1 gene (607244) on chromosome 15q21. Description Stuttering is a disorder of the flow of speech characterized by involuntary repetitions or prolongations of sounds or syllables, and by interruptions of speech known as blocks (summary by Raza et al., 2010). Stuttering typically arises in young children, where it affects at least 15% of those in age range 4 to 6 years (Bloodstein, 1995). Stuttering usually resolves spontaneously before adolescence, leading to a population prevalence of 1 to 2% among adults. Stuttering beyond childhood is characterized by a significant bias towards males, with males outnumbering females by a ratio of 3:1 to 5:1 (Yairi et al., 1996). ### Genetic Heterogeneity of Familial Persistent Stuttering Also see STUT2 (609261), mapped to chromosome 12q24; STUT3 (614655), mapped to chromosome 3q; and STUT4 (614668) mapped to chromosome 16q. Clinical Features Raza et al. (2013, 2015) reported a large family from Cameroon in which multiple members had persistent stuttering with onset around ages 2 to 5 years. Most reported that the stuttering was exacerbated under stress and that some improvement in fluency occurred with age. None of the affected individuals had any additional clinical signs or symptoms of other neurologic disease, particularly intellectual disability or spasticity. Inheritance The transmission pattern of STUT1 in the family reported by Raza et al. (2015) was consistent with autosomal dominant inheritance. Inherited factors contributing to stuttering were demonstrated in studies by Howie (1981), Yairi et al. (1996), and Felsenfeld and Plomin (1997). Chakravartti et al. (1979) studied an Indian kindred with 12 stammerers in 5 generations. Autosomal dominant inheritance was espoused. Stuttering is said to be unusually frequent in Japanese, low in Polynesians, and almost completely absent in American Indians. Canhetti-Oliveira and Richieri-Costa (2006) presented 14 stuttering pedigrees. Five of the pedigrees had observed stutterers or recovered stutterers in 3 generations. A predominance of affected males was noted with an M:F ratio of 3.2. As part of a linkage study to identify predisposing loci for stuttering, Drayna et al. (1999) assembled more than 100 small- to medium-sized unrelated families with multiple cases of persistent stuttering, chosen to represent the typical presentation of familial stuttering in the adult population. In these families, they observed a male-to-female ratio among the affected individuals that was strikingly different from the generally accepted ratio in the overall adult stuttering population. They found a male-to-female ratio of 1.57 as compared to 7.07 and 4.8 in 2 other studies. Mapping Raza et al. (2015) mapped the STUT1 locus to chromosome 15q21 based on their identification of mutations in the AP4E1 gene (607244) in affected members of a family from Cameroon, West Africa, previously reported by Raza et al. (2013). Raza et al. (2013) reported a large pedigree from the Republic of Cameroon in which at least 33 individuals had persistent stuttering. The large pedigree was divided into 5 subpedigrees, and these were subjected to genomewide linkage analysis individually or in groups. Evidence for linkage was found for several loci, including 2p, 3q, 3p, 14q, and 2 regions on 15q. On 2p, a peak lod score of 3.86 was found using markers rs11127193, D2S405, and rs7560152. On 3q, a peak lod score of 3.47 was found between rs711995 and D3S1311. On 3p, a peak lod score of 3.18 was found between markers rs304838 and D3S2432. On 14q, a peak lod score of 3.45 was found using rs975232, D14S588, rs8688, and rs987579. Results for 15q were not as strong, but these loci performed well in 2-locus analysis. A lod score of 3.42 was found by analyzing the data for the 2 loci on chromosome 15q, and lod scores ranging from 4.69 to 6.57 were obtained with a combined 2p/15q analysis. Raza et al. (2013) concluded that stuttering in this family is likely due to multiple alleles at different loci, which may have resulted from assortative mating. There was no evidence for a founder effect. ### Heterogeneity Shugart et al. (2004) performed a linkage study of stuttering using 392 markers distributed across the genome in 266 members of 68 families, including 188 affected individuals, in North America and Europe. The single largest pedigree in their sample gave an NPL score of 4.72 at D18S976. Other evidence for linkage was found at D18S78, with an NPL score of 5.143 and Z(lr) score of 2.63 (p = 0.0043). A second region of positive linkage scores was observed on proximal 18q, surrounding marker D18S847 (Z(lr) score, 2.47; p = 0.0068). Shugart et al. (2004) suggested that chromosome 18 may harbor a predisposing locus for stuttering, and that additional susceptibility loci for this disorder may exist. Molecular Genetics In affected members of a large family of Cameroon descent (CAMST01) with STUT1, originally reported by Raza et al. (2013), Raza et al. (2015) identified heterozygosity for 2 missense variants in the AP4E1 gene that occurred in cis (V517I and E801K; 607244.0004). The mutations were found by whole-exome sequencing and segregated with the disorder in the family. The same mutations on the same haplotype were subsequently found in 2 of 96 additional individuals from Cameroon with stuttering. In vitro functional expression studies in HEK293 cells showed that the mutations resulted in slightly decreased assembly of the AP4 complex (about 80% of wildtype). Sequencing of the AP4E1 gene in unrelated affected individuals, including 93 from Cameroon, 132 from Pakistan, and 711 from North America, revealed 23 other rare variants in this gene, including small (1- to 3-bp) deletions, insertions, duplications, frameshifts, and stop codons; no truncating mutations were found in 558 ethnically matched control individuals. Investigation of large population databases, including the 1000 Genomes Project and Exome Sequencing Project, which are not phenotyped for speech fluency, found 3 loss-of-function AP4E1 variants among about 19,000 chromosomes, as well as several rare missense variants; all of these occurred at a significantly lower frequency compared to the variants observed in stuttering individuals. Studies in a yeast 2-hybrid system supported a direct interaction between the AP4 complex and NAGPA (607985), variations in which have also been implicated in stuttering (STUT2; 609261). The findings suggested that defects in intracellular trafficking play a role in persistent stuttering. INHERITANCE \- Autosomal dominant VOICE \- Stuttering, persistent MISCELLANEOUS \- Onset between ages 2 and 5 years \- Exacerbated by stress \- Improvement with age MOLECULAR BASIS \- Caused by mutation in the adaptor-related protein complex 4, epsilon-1 subunit gene (AP4E1, 607244.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	STUTTERING, FAMILIAL PERSISTENT, 1	c3489627	5,693	omim	https://www.omim.org/entry/184450	2019-09-22T16:34:19	{"mesh": ["D013342"], "omim": ["184450"], "synonyms": ["Alternative titles", "STAMMERING"]}
Fukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the muscles, brain, and eyes. Congenital muscular dystrophies are a group of genetic conditions that cause muscle weakness and wasting (atrophy) beginning very early in life. Fukuyama congenital muscular dystrophy affects the skeletal muscles, which are muscles the body uses for movement. The first signs of the disorder appear in early infancy and include a weak cry, poor feeding, and weak muscle tone (hypotonia). Weakness of the facial muscles often leads to a distinctive facial appearance including droopy eyelids (ptosis) and an open mouth. In childhood, muscle weakness and joint deformities (contractures) restrict movement and interfere with the development of motor skills such as sitting, standing, and walking. Fukuyama congenital muscular dystrophy also impairs brain development. People with this condition have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain develops a bumpy, irregular appearance (like that of cobblestones). These changes in the structure of the brain lead to significantly delayed development of speech and motor skills and moderate to severe intellectual disability. Social skills are less severely impaired. Most children with Fukuyama congenital muscular dystrophy are never able to stand or walk, although some can sit without support and slide across the floor in a seated position. More than half of all affected children also experience seizures. Other signs and symptoms of Fukuyama congenital muscular dystrophy include impaired vision, other eye abnormalities, and slowly progressive heart problems after age 10. As the disease progresses, affected people may develop swallowing difficulties that can lead to a bacterial lung infection called aspiration pneumonia. Because of the serious medical problems associated with Fukuyama congenital muscular dystrophy, most people with the disorder live only into late childhood or adolescence. ## Frequency Fukuyama congenital muscular dystrophy is seen almost exclusively in Japan, where it is the second most common form of childhood muscular dystrophy (after Duchenne muscular dystrophy). Fukuyama congenital muscular dystrophy has an estimated incidence of 2 to 4 per 100,000 Japanese infants. ## Causes Fukuyama congenital muscular dystrophy is caused by mutations in the FKTN gene. This gene provides instructions for making a protein called fukutin. Although the exact function of fukutin is unclear, researchers predict that it may chemically modify a protein called alpha (α)-dystroglycan. This protein anchors cells to the lattice of proteins and other molecules (the extracellular matrix) that surrounds them. In skeletal muscles, α-dystroglycan helps stabilize and protect muscle fibers. In the brain, this protein helps direct the movement (migration) of nerve cells (neurons) during early development. The most common mutation in the FKTN gene reduces the amount of fukutin produced within cells. A shortage of fukutin likely prevents the normal modification of α-dystroglycan, which disrupts that protein's normal function. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to progressive weakness and atrophy of the skeletal muscles. Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes cobblestone lissencephaly in children with Fukuyama congenital muscular dystrophy. Less is known about the effects of FKTN mutations in other parts of the body. Because Fukuyama congenital muscular dystrophy involves a malfunction of α-dystroglycan, this condition is described as a dystroglycanopathy. ### Learn more about the gene associated with Fukuyama congenital muscular dystrophy * FKTN ## 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	Fukuyama congenital muscular dystrophy	c0410174	5,694	medlineplus	https://medlineplus.gov/genetics/condition/fukuyama-congenital-muscular-dystrophy/	2021-01-27T08:24:56	{"gard": ["6475"], "mesh": ["D058494"], "omim": ["253800"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that stapes ankylosis with broad thumbs and toes is caused by heterozygous mutation in the NOG gene (602991) on chromosome 17q22. Mutations in the NOG gene can also cause symphalangism and synostosis syndromes. Clinical Features Teunissen and Cremers (1990) reported a family with 5 males in 3 generations who were affected with what appeared to be a 'new' autosomal dominant syndrome. There were several instances of male-to-male transmission. All 5 patients had ankylosis of stapes, hyperopia, broad thumbs, broad first toes, and syndactyly. In most, stapedial ankylosis was bilateral, leading to a 40 to 60 dB conductive hearing loss. There was bilateral syndactyly of the second and third toe in at least 1. Fused cervical vertebrae were seen in 2 of the 5 patients. Carpal and tarsal fusion and symphalangism were not found. Milunsky et al. (1999) described a family with a syndrome that the authors considered to be the same as the autosomal dominant syndrome described by Teunissen and Cremers (1990). A mother and daughter had stapes ankylosis, hyperopia, and short broad thumbs; hyperopia and short broad thumbs were present in the mother's generation and in the mother's brother and their mother. Their paternal grandfather had short broad thumbs. Neither the mother nor the daughter had symphalangism, however, possibly distinguishing this syndrome from the proximal symphalangism syndrome (SYM1; 185800) and from the facioaudiosymphalangism syndrome described by Hilhorst-Hofstee et al. (1997). The mother and daughter did have cylindrical noses and hypoplasia of the alae nasi. Hirshoren et al. (2008) reported a 22-year-old woman of Jewish Ashkenazi origin with bilateral stapes ankylosis, hyperopia, broad thumbs, symphalangism of the second, fourth, and fifth fingers, cutaneous syndactyly of the second and third fingers, hypoplastic nails of the second, fourth, and fifth fingers, and shortened second and fifth fingers; she could not reach her ears to use a hearing aid due to limited elbow pronation/supination and flexion, and mobility of her hips and knees was limited as well. The proband also had bilateral small 'feathery' opacities of the lens, primarily in the cortical regions. Her father had a more severe phenotype, with hypoplastic nails and brachytelephalangia of multiple fingers and toes. Pedigree analysis revealed 7 family members with hearing loss and skeletal anomalies segregating in an autosomal dominant fashion. Hirshoren et al. (2008) stated that the constellation of findings in the proband best fitted a diagnosis of Teunissen-Cremers syndrome, although she had brachydactyly type B (see BDB2, 611377) and symphalangism (see SYNS1, 186500). Molecular Genetics Brown et al. (2002) identified heterozygous mutations in the NOG gene (602991.0001-602991.0002) in 2 families with autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies but without symphalangism. The first family, of Italian descent, had conductive hearing loss that was inherited as an autosomal dominant with complete penetrance. Each affected individual was thought to have had nonsyndromic otosclerosis. The second family was that reported by Milunsky et al. (1999). In a 22-year-old woman of Jewish Ashkenazi origin diagnosed with Teunissen-Cremers syndrome, Hirshoren et al. (2008) identified a missense mutation in the NOG gene (602991.0012) that had previously been found in patients with proximal symphalangism (185800) and brachydactyly, type B2 (611377). The authors noted that although the proband's lens opacities had not previously been reported in Teunissen-Cremers syndrome, the noggin/BMP pathway had been shown to play an important role in the chick and mouse ocular development (see Trousse et al. (2001) and Furuta and Hogan (1998), respectively). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Conductive hearing loss \- Congenital stapes ankylosis \- Hyperopia Mouth \- Hemicylindrical nose \- Hypoplastic alae nasi \- Prominent columella Neck \- Limited neck range of motion SKELETAL Spine \- Fused cervical vertebrae Hands \- Broad thumbs \- Short distal phalanges \- Syndactyly \- Proximal 5th finger symphalangism Feet \- Broad halluces \- Syndactyly MISCELLANEOUS \- Allelic to proximal symphalangism ( 185800 ), multiple synostoses syndrome ( 186500 ), and tarsal-carpal coalition syndrome ( 186570 ) MOLECULAR BASIS \- Caused by mutations in the homolog of the mouse Noggin gene (NOG, 602991.0013 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	STAPES ANKYLOSIS WITH BROAD THUMBS AND TOES	c1866656	5,695	omim	https://www.omim.org/entry/184460	2019-09-22T16:34:20	{"mesh": ["C536943"], "omim": ["184460"], "orphanet": ["140917"], "synonyms": ["Alternative titles", "ANKYLOSIS OF STAPES, HYPEROPIA, BROAD THUMBS, BROAD FIRST TOES, AND SYNDACTYLY", "TEUNISSEN-CREMERS SYNDROME", "STAPES ANKYLOSIS SYNDROME WITHOUT SYMPHALANGISM"]}
A number sign (#) is used with this entry because autosomal recessive nonsyndromic mental retardation-12 (MRT12) can be caused by homozygous mutation in the ST3GAL3 gene (606494) on chromosome 1p34. Clinical Features Najmabadi et al. (2007) and Hu et al. (2011) reported 2 unrelated consanguineous Iranian families with nonsyndromic mild to moderate mental retardation. Mapping Najmabadi et al. (2007) reported a large consanguineous Iranian family in which 8 individuals had nonsyndromic mild mental retardation. Linkage analysis identified a candidate locus on chromosome 1p34-p33 with a maximum lod score of 7.2. Haplotype analysis delineated a 9.4-Mb candidate region between rs514262 and rs953070. Molecular Genetics In affected members of 2 unrelated consanguineous Iranian families with autosomal recessive nonsyndromic mental retardation, including the one reported by Najmabadi et al. (2007), Hu et al. (2011) used linkage analysis, chromosome sorting, and next-generation sequencing and identified 2 different homozygous mutations in the ST3GAL3 gene (A13D, 606494.0001 and D370Y, 606494.0002, respectively). Neither mutation affected the highly conserved sialyl motifs, but rather affected the N-terminal transmembrane domain and C-terminal catalytic domain, respectively. In vitro functional expression studies showed that the mutant proteins were mislocalized to the endoplasmic reticulum and that 1 (D370Y) had loss of catalytic activity. The findings demonstrated a link between the glycoprotein complex, sialyltransferase activity, and higher cognitive functioning. Nomenclature Although Najmabadi et al. (2007) referred to this locus as 'MRT4,' that designation had already been used by Uyguner et al. (2007) to refer to a locus on chromosome 1p21.1-p13.3 (MRT4; 611107). Thus, the locus described here is referred to as MRT12. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Mental retardation (IQ between 25-55) MISCELLANEOUS \- Two families with limited clinical details have been reported (last curated September 2016) MOLECULAR BASIS \- Caused by mutation in the ST3 beta-galactoside alpha-2,3-sialyltransferase 3 gene (ST3GAL3, 606494.0001 ) ▲ 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	MENTAL RETARDATION, AUTOSOMAL RECESSIVE 12	c1970200	5,696	omim	https://www.omim.org/entry/611090	2019-09-22T16:03:40	{"doid": ["0060308"], "mesh": ["C567019"], "omim": ["611090"], "orphanet": ["88616"], "synonyms": ["AR-NSID", "NS-ARID"]}
A number sign (#) is used with this entry because of evidence that erythrokeratodermia variabilis et progressiva-3 (EKVP3) is caused by heterozygous mutation in the gene encoding connexin-43 (GJA1; 121014) on chromosome 6q22. Description Erythrokeratodermia variabilis et progressiva is a rare skin disease. Patients with EKVP3 have normal skin at birth but develop hyperpigmentation and scaling at sites of friction in childhood, with progression to near-confluent corrugated hyperkeratosis, palmoplantar keratoderma, and transient figurate erythema (summary by Boyden et al., 2015). For a discussion of genetic heterogeneity of EKVP, see EKVP1 (133200). Clinical Features Boyden et al. (2015) reported 3 unrelated patients with erythrokeratodermia variabilis. The first was a 2.5-year-old boy who at 5 months of age developed thick, brown-gray scales on frictional surfaces, as well as progressive darkening of his dorsal hands, arms, legs, and face. The palmoplantar surfaces and digits became pink and then markedly hyperkeratotic, and migrating areas of transient figurate erythema overlay the generalized scaling. The second patient was a 6-year-old girl, adopted from Guatemala, who at 8 months of age developed darkening and scaling of frictional surfaces and dorsal hands as well as progressive thickening of palms and soles. At 13 months of age, she had hyperpigmented, hyperkeratotic plaques of the axillae, elbows, and inner thighs, which became confluent by 2 years of age, with sparing of the cheeks and upper chest. She had intermittent annular red patches that faded within hours of onset. The third patient was a 30-year-old woman in whom darkening of the inner thighs was noted at 6 months of age, followed by development of thick scales on the knees, elbows, hands and feet, which progressively spread up the legs and arms. At 10 years of age, she developed pink to deep-red transient erythematous patches, associated with a burning sensation. In all 3 patients, erythema was induced by stress and warm conditions. In addition, all 3 exhibited enlarged porcelain-white lunulae, which extended from the cuticle to the free edge of the nail in 2 of the patients, as well as darkening of the periorificial areas. Histology of the most severely affected skin in each case showed papillomatosis, acanthosis, hypergranulosis, and compact orthohyperkeratosis with retained nuclei. Less severely affected skin showed acanthosis, papillomatosis, orthohyperkeratosis, and follicular plugging. Molecular Genetics By exome sequencing in 3 unrelated patients with erythrokeratodermia variabilis et progressiva, Boyden et al. (2015) identified heterozygosity for 2 de novo missense mutations in the GJA1 (CX43) gene, E227D (121014.0024) and A44V (121014.0025). The mutations were not present in any of the unaffected parents available (1 patient was adopted), in approximately 2,500 control exomes, or in public databases of human genetic variation. Immunostaining of patient skin and transfected HeLa cells showed that, in contrast to wildtype CX43, mutant CX43 did not localize to the membrane but appeared to be retained in the Golgi apparatus. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Hyperpigmentation and scaling at frictional surfaces \- Hyperkeratosis \- Palmoplantar keratoderma \- Erythema (migrating transient figurate erythema--erythema gyratum repens) \- Stinging sensation of erythematous skin \- Progressive skin darkening \- Hyperkeratosis around eyes and mouth \- Darkening of skin around eyes and mouth Skin Histology \- Follicular plugging \- Papillomatosis \- Acanthosis \- Hypergranulosis \- Compact orthohyperkeratosis with retained nuclei Nails \- Enlarged porcelain-white lunulae MISCELLANEOUS \- Normal skin at birth \- Onset of skin lesions within the first year of life \- Erythema induced by heat or stress \- Hyperpigmentation may progress to near-confluent hyperkeratosis \- Based on report of 3 unrelated patients (last curated June 2017) MOLECULAR BASIS \- Caused by mutation in the alpha-1 gap junction protein (GJA1, 121014.0024 ) ▲ 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	ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA 3	c0265961	5,697	omim	https://www.omim.org/entry/617525	2019-09-22T15:45:38	{"doid": ["0080249"], "mesh": ["D056266"], "omim": ["617525"], "orphanet": ["317"]}
Acquired von Willebrand syndrome (AVWS) is a bleeding disorder that can occur due to a variety of conditions, but is not caused by a VWF gene mutation. It is most often seen in persons over age 40 years with no prior bleeding history. This condition may result from lymphoproliferative disorders, autoimmune disorders (including systemic lupus erythrematosus, scleroderma, and antiphospholipid antibody syndrome), heart conditions such as aortic valvular stenosis, increased blood platelet count such as essential thrombocythemia, and certain drugs. About 300 cases of this condition have been reported in the medical literature thus far. Treatment depends on the underlying cause 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	Acquired Von Willebrand syndrome	c0272362	5,698	gard	https://rarediseases.info.nih.gov/diseases/5573/acquired-von-willebrand-syndrome	2021-01-18T18:02:21	{"orphanet": ["99147"], "synonyms": ["Willebrand disease, acquired", "Acquired Von Willebrand disease"]}
Cooks syndrome Other namesAnonychia-onychodystrophy with hypoplasia or absence of distal phalanges syndrome Autosomal dominant is the manner of inheritance of this condition Cooks syndrome is a hereditary disorder which is characterized in the hands by bilateral nail hypoplasia on the thumb, index finger, and middle finger, absence of fingernails (anonychia) on the ring finger and little finger, lengthening of the thumbs, and bulbousness of the fingers. In the feet, it is characterized by absence of toenails and absence/hypoplasia of the distal phalanges.[1] In the second study of this disorder, it was found that the intermediate phalanges, proximal phalanges, and metacarpals were unaffected.[1] The disorder was first described by Cooks et al. in 1985 after being discovered in two generations of one family. It was proposed that the inheritance of the disorder is autosomal dominant.[2] A second family, this with three affected generations, confirmed that the inheritance of the disorder is autosomal dominant. Although several genetic disorders exist which can cause anonychia and onychodystrophy, such disorders often cause other anomalies such as deafness, mental retardation, and defects of the hair, eyes, and teeth. Cooks syndrome is not known to cause any such anomalies.[1] In 1999, a pair of siblings was found with brachydactyly type B. Because the disorder primarily affected the nails and distal phalanges, the research group concluded that brachydactyly type B and Cooks syndrome are the same disorder.[3] However, in 2007, a 2-year-old girl was found with symptoms consistent with both brachydactyly type B and Cooks syndrome. It was found that the two syndromes were distinct clinically, radiologically, and genetically.[4] ## Notes[edit] 1. ^ a b c Nevin NC, Thomas PS, Eedy DJ, Shepherd C (August 1995). "Anonychia and absence/hypoplasia of distal phalanges (Cooks syndrome): report of a second family". J. Med. Genet. 32 (8): 638–41. doi:10.1136/jmg.32.8.638. PMC 1051641. PMID 7473658. 2. ^ Cooks, R. G.; Hertz, M.; Katznelson M. B.; Goodman R. M. (January 1985). "A new nail dysplasia syndrome with onychonychia and absence and/or hypoplasia of distal phalanges". Clinical Genetics. 27 (1): 85–91. doi:10.1111/j.1399-0004.1985.tb00189.x. PMID 3978841. 3. ^ de Ravel, T. J.; Berkowitz, D.E.; Wagner, J.M.; Jenkins, T. (January 1999). "Brachydactyly type B with its distinct facies and 'Cooks syndrome' are the same entity". Clinical Dysmorphology. 8 (1): 41–5. doi:10.1097/00019605-199901000-00008. PMID 10327250. 4. ^ Castori, M.; Brancati, F.; Mingarelli, R.; Mundlos, S.; Dallapiccola, B. (2007-01-15). "A novel patient with Cooks syndrome supports splitting from "classic" brachydactyly type B". American Journal of Medical Genetics. 143 (2): 195–9. doi:10.1002/ajmg.a.31433. PMID 17163524. ## External links[edit] Classification D * ICD-10: Q84.6 * OMIM: 106995 * MeSH: C537766 External resources * Orphanet: 1487 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Cooks syndrome	c1862841	5,699	wikipedia	https://en.wikipedia.org/wiki/Cooks_syndrome	2021-01-18T18:54:58	{"gard": ["4083"], "mesh": ["C537766"], "umls": ["C1862841"], "orphanet": ["1487"], "wikidata": ["Q5167190"]}

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