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An idea that preoccupies an individual and that he is unwilling to give up despite evidence to the contrary This article is about the preoccupation of mind. For other uses, see Idée fixe. This article contains too many or overly lengthy quotations for an encyclopedic entry. Please help improve the article by presenting facts as a neutrally worded summary with appropriate citations. Consider transferring direct quotations to Wikiquote. (September 2010) Part of a series on Psychology * Outline * History * Subfields Basic types * Abnormal * Behavioral genetics * Biological * Cognitive/Cognitivism * Comparative * Cross-cultural * Cultural * Differential * Developmental * Evolutionary * Experimental * Mathematical * Neuropsychology * Personality * Positive * Quantitative * Social Applied psychology * Applied behavior analysis * Clinical * Community * Consumer * Counseling * Critical * Educational * Environmental * Ergonomics * Forensic * Health * Humanistic * Industrial and organizational * Legal * Medical * Military * Music * Occupational health * Political * Religion * School * Sport * Traffic Lists * Disciplines * Organizations * Psychologists * Psychotherapies * Publications * Research methods * Theories * Timeline * Topics * Psychology portal * v * t * e An idée fixe is a preoccupation of mind believed to be firmly resistant to any attempt to modify it, a fixation. The name originates from the French idée [i.de], "idea" and fixe [fiks], "fixed." ## Contents * 1 Background * 2 Legal implications * 3 The development of the notion * 4 In literature * 5 Today's usage * 6 See also * 7 References * 8 External links ## Background[edit] The initial introduction of the term idée fixe, according to intellectual historian Jan E. Goldstein, was as a medical term around 1812 in connection with monomania.[1] As originally employed in the nineteenth and early twentieth centuries,[2][3] idée fixe was "a single pathology of the intellect", distinct from monomania, a broader term that included idée fixe, but also a wider range of pathologies that did not stem from "a single compelling idea or from an emotional excess".[4] A second difference is that the victim of idée fixe was understood to be unaware of the unreality of their frame of mind,[5] while the victim of monomania might be aware. At that time, idée fixe was discussed as a form of neurosis or monomania.[6] > The meaning of monomania in the technical medical sense in which it was first used, was very close to the popular meaning it would soon acquire. It denoted an idée fixe, a single pathological preoccupation in an otherwise sound mind.[7] > > — Jan E. Goldstein, Console and Classify, p. 155 The idea of monomania was developed by Jean-Étienne Dominique Esquirol as a diagnostic category in his work Des Malades Mentales (1839) and related to the idée fixe by Wilhelm Griesinger (1845) who viewed "every single idée fixe [as] the expression of a deeply deranged psychic individuality and probably an indicator of an incipient form of mania".[3] The "pathologicalization" of political convictions was used to discredit political anarchists.[2] The further historical evolution of idée fixe was much entangled with the introduction of psychologists into legal matters such as the insanity defense, and is found in a number of texts.[8][7][9] ## Legal implications[edit] Possibly the best example of the role of idée fixe in an insanity defense today is its use in identifying the paranoid personality disorder. > A frequent manifestation of ... paranoid personality is the presence of an overvalued idea ... a fixed idea (idée fixe) ... which might seem reasonable both to the patient and to other people. However, it comes to dominate completely the person's thinking and life. ... It is quite distinct phenomenologically from both delusion and obsessional idea.[10] > > — Femi Oyebode, The expression of disordered personality ## The development of the notion[edit] The concept of idées fixes has been expanded and refined by Emil Kraepelin (1904), Carl Wernicke (1906), and Karl Jaspers (1963), evolving into a concept of overvalued ideas.[11] An overvalued idea is a false or exaggerated and sustained belief that is maintained with much less than delusional intensity (i.e., the individual is able to acknowledge the possibility that the ideas may not be true).[12] ## In literature[edit] An example of an idée fixe is in Cervantes's Don Quixote:[13] > Don Quixote reveals his kinship to the most commonly encountered of Cervantes's character types: the head-in-clouds fantasist, obsessed by his idée fixe.[14] > > — Anthony J Close, Miguel de Cervantes, Don Quixote Molière also used the idée fixe repeatedly: > Molière's more celebrated comic characters, Arnolphe, Orgon, Alceste, Harpagon, Monsieur Jourdain, Argan: each of them displays to the very end the obsession or idée fixe which colors his outlook on life. It is a characteristic of Molière's heroes that they are never ‘converted’: in every case the dénouement, far from curing them of their folly, merely confirms them in it.[15] > > — William Driver Howarth, Molière, a playwright and his audience' Although Melville's Captain Ahab may come to mind as another famous example of idée fixe, and it is sometimes referred to this way,[16] more often Ahab's obsession is referred to as monomania (the more inclusive term), and Melville himself does that. It would seem from the description of Ahab's possession that idée fixe applies quite accurately, as the following description suggests: > "Not one jot of his great natural intellect had perished." ... "Yielding up all his thoughts and fancies to his one supreme purpose", Ahab has let his mind's guiding and directing power be usurped by the "sheer inveteracy" of a will driven by "one unachieved revengeful desire"[17] > > — Quotes from Moby-Dick, pp. 990, 1007, Thomas Cooley, The ivory leg in the ebony cabinet: madness, race, and gender in Victorian America However, what makes monomania the better term is that "Captain Ahab ... has an inkling of his true state of mind: 'my means are sane, my motive and my object mad.'"[17] The words idée fixe also occur explicitly: for example, in Arthur Conan Doyle's Sherlock Holmes: > There is the condition which the modern French psychologists have called the 'idée fixe', which may be trifling in character, and accompanied by complete sanity in every other way. A man might form such an idée fixe... and under its influence be capable of any fantastic outrage.[18] > > — Arthur Conan Doyle, The return of Sherlock Holmes and in Abraham B. Yehoshua's novel about the Mani family through six generations: > ...I had begun to despair of his accursed idée fixe which devoured every other idée that it encountered...[19] > > — Abraham B. Yehoshua, Mr. Mani and in the account of the war on terror by George Bush's counter-terrorism chief Richard A. Clarke: > Iraq was portrayed as the most dangerous thing in national security. It was an idée fixe, a rigid belief, received wisdom, a decision already made and one that no fact or event could derail.[20] > > — Richard A Clarke, Against All Enemies: Inside America's War on Terror ## Today's usage[edit] See also: Monomania As an everyday term, idée fixe may indicate a mindset akin to prejudice or stereotyping:[21] However, idée fixe has also a pathological dimension, denoting serious psychological issues, as in this account of Japanese culture for a popular audience: > Although her husband did not reproach her, she became like a woman possessed, continually begging for his forgiveness. This he readily gave, but her guilt—and his imagined umbrage—had become for her an idée fixe. Unable to stomach food, she went into a decline and died soon thereafter.[22] > > — Jack Seward, The Japanese[non-primary source needed] The pathology is what is denoted in psychology and in the law, as in this technical article about anorexia nervosa: > The idée fixe—staying thin—becomes at its furthest extreme so powerful as to render any other ideas or life projects meaningless. ... "I felt all inner development was ceasing, that all becoming and growing were being choked, because a single idea was filling my entire soul"[23] > > — Susan Bordo, Toward a new psychology of gender[non-primary source needed] Idée fixe began as a parent category of obsession,[24] and as a preoccupation of mind the idée fixe resembles today's obsessive-compulsive disorder: although the afflicted person can think, reason and act like other people, they are unable to stop a particular train of thought or action.[8] However, in obsessive-compulsive disorder, the victim recognizes the absurdity of the obsession or compulsion, not necessarily the case with an idée fixe, which normally is a delusion.[25] Today, the term idée fixe does not denote a specific disorder in psychology, and does not appear as a technical designation in the Diagnostic and statistical manual of mental disorders.[26] Nonetheless, idée fixe is used still as a descriptive term,[10] and appears in dictionaries of psychology.[27] ## See also[edit] * Affect heuristic * Belief perseverance – Maintaining a belief despite new information that firmly contradicts it * Cognitive bias – Systematic pattern of deviation from norm or rationality in judgment * Confirmation bias – Tendency of people to favor information that confirms their beliefs or values * Delusional disorder – Mental illness featuring beliefs with inadequate grounding * Fixation (psychology) * Moral insanity * Obsessive–compulsive disorder – Disorder that involves repeated thoughts (obsessions) that make a person feel driven to do something (compulsions) * Personality disorder – Maladaptive patterns of behavior * Psychosis – Condition of the mind that involves a loss of contact with reality * Thought disorder – Disorder of thought form, content or stream * Weak central coherence theory ## References[edit] 1. ^ Quoting from Jan Ellen Goldstein (2002). Console and Classify: The French Psychiatric Profession in the Nineteenth Century. University of Chicago Press. p. 155. ISBN 0-226-30161-3. "Idée fixe was also originally a medical term, probably coined by the phrenologists Gall and Spurzheim in connection with Esquirol's delineation of monomania; see their Anatomie et physiologie du système nerveux en général et du cerveau en particulier, Vol. 2 (Paris: F. Schoell, 1812), p. 192. It also was transferred to nonmedical culture, most notably by the composer Hector Berlioz..." The term leitmotif refers to the same musical device as idée fixe. 2. ^ a b Michael Clark, Catherine Crawford (1994). Legal medicine in history. Cambridge University Press. pp. 214 ff. ISBN 0-521-39514-3. 3. ^ a b Alan Felthous, Henning Sass (2008). International Handbook on Psychopathic Disorders and the Law. John Wiley & Sons. p. 11. ISBN 978-0-470-06638-6. 4. ^ Ann-Louise Shapiro (1996). Breaking the Codes: Female Criminality in Fin-de-Siècle Paris. Stanford University Press. p. 100. ISBN 0-8047-2693-0. 5. ^ Daniel Hack Tuke (1892). A Dictionary of Psychological Medicine: Giving the Definition, Etymology and Synonyms of the Terms Used in Medical Psychology with the Symptoms, Treatment, and Pathology of Insanity and the Law of Lunacy in Great Britain and Ireland, Volume 2. J. & A. Churchill. p. 678. "Some of the French alienists extend the use of the term [imperative idea] to actual delusion (idée fixe ), as for instance, ideas of persecution. but it is to be hoped that [imperative idea] will be carefully restricted to that intellectual tyranny which the individual deplores and is not deluded by." 6. ^ "Névroses et Idées Fixes". Mind, Volume 9. Oxford University Press. 1900. pp. 94ff. 7. ^ a b Jan E. Goldstein (2002). Console and Classify: The French Psychiatric Profession in the Nineteenth Century. University of Chicago Press. p. 155. ISBN 0-226-30161-3. 8. ^ a b Lennard J. Davis (2008). Obsession: a history. University of Chicago Press. p. 69 ff. ISBN 978-0-226-13782-7. 9. ^ Dorothea E. von Mücke (2003). The Seduction of the Occult and the Rise of the Fantastic Tale. Stanford University Press. pp. 114 ff. ISBN 0-8047-3860-2. 10. ^ a b Femi Oyebode (2008). "Chapter 21: The expression of disordered personality". Sims' Symptoms in the Mind: An Introduction to Descriptive Psychopathology (Updated 4th ed.). Saunders Ltd. p. 404. ISBN 978-0-7020-2885-4. 11. ^ McKenna, P. J. (1984). "Disorders with overvalued ideas". British Journal of Psychiatry. 145 (6): 579–585. doi:10.1192/bjp.145.6.579. ISSN 0007-1250. PMID 6391600. 12. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Publishing. pp. 826. doi:10.1176/appi.books.9780890425596. ISBN 978-0-89042-554-1. 13. ^ John Farrell (2006). Paranoia and Modernity: Cervantes to Rousseau. Cornell University Press. p. 48. ISBN 0-8014-4410-1. 14. ^ Anthony J. Close (1990). Miguel de Cervantes, Don Quixote. Cambridge University Press. p. 106. ISBN 0-521-31345-7. 15. ^ William Driver Howarth (1982). Molière, a Playwright and His Audience. Cambridge University Press. p. 99. ISBN 0-521-28679-4. 16. ^ Marina Van Zuylen (2005). Monomania: The Flight from Everyday Life in Literature and Art. Cornell University Press. pp. 10, 38, 64, 68. ISBN 0801442982. 17. ^ a b Thomas Cooley (2001). The ivory leg in the ebony cabinet: madness, race, and gender in Victorian America. University of Massachusetts Press. p. 42. ISBN 1-55849-284-4. Page numbers refer to Herman Melville (1983). G Thomas Tanselle (ed.). Moby-Dick, or the Whale (Reprint of the 1851 Northwestern-Newberry ed.). Library of America. ISBN 0-940450-09-7. 18. ^ Sir Arthur Conan Doyle (2003). "The return of Sherlock Holmes". In Kyle Freeman (ed.). The Complete Sherlock Holmes, Volume 1 Barnes & Noble Classics. Spark Educational Publishing. p. 128. ISBN 1-59308-040-9. 19. ^ Abraham B. Yehoshua (1993). Mr. Mani (Hillel Halkin translation ed.). Houghton Mifflin Harcourt. p. 338. ISBN 0-15-662769-8. 20. ^ Richard A Clarke (2004). Against All Enemies: Inside America's War on Terror. Free Press. p. 265. ISBN 0-7432-6045-7. 21. ^ Glen Fisher (1997). Mindsets: The Role of Culture and Perception in International Relations (2nd ed.). Intercultural Press. p. 22. ISBN 1-877864-54-4. 22. ^ Jack Seward (1992). The Japanese: The Often Misunderstood, Sometimes Surprising, and Always Fascinating Culture and Lifestyles of Japan. McGraw-Hill Professional. p. 226. ISBN 0-8442-8393-2. 23. ^ Susan Bordo (1996). "Anorexia nervosa: psychopathology as the crystallization of culture". In Mary M. Gergen, Sara N. Davis (ed.). Toward a New Psychology of Gender. Routledge. p. 441. ISBN 0-415-91308-X. 24. ^ G. E. Berrios (1996). "Note 63; page 153". The history of mental symptoms: descriptive psychopathology since the nineteenth century. Cambridge University Press. ISBN 0-521-43736-9. 25. ^ Ian Jakes (1996). "The distinction between obsessional and psychotic thinking". Theoretical Approaches to Obsessive-Compulsive Disorder. Cambridge University Press. p. 6. ISBN 0-521-46058-1. 26. ^ Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR (4th ed.). American Psychiatric Society. 2000. ISBN 0-89042-025-4. 27. ^ For example, Raymond J. Corsini (2002). The dictionary of psychology. Psychology Press. p. 467. ISBN 1-58391-328-9. ## External links[edit] * The dictionary definition of idée fixe at Wiktionary [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Idée fixe (psychology)	None	26,200	wikipedia	https://en.wikipedia.org/wiki/Id%C3%A9e_fixe_(psychology)	2021-01-18T18:38:02	{"wikidata": ["Q1421961"]}
A number sign (#) is used with this entry because of evidence that adrenoleukodystrophy and adrenomyeloneuropathy are caused by mutation in the ABCD1 gene (300371) on chromosome Xq21. Description Adrenoleukodystrophy is an X-linked disorder which is secondary to a mutation in the ABCD1 gene and results in the apparent defect in peroxisomal beta oxidation and the accumulation of the saturated very long chain fatty acids (VLCFA) in all tissues of the body. The manifestations of the disorder occur primarily in the adrenal cortex, the myelin of the central nervous system, and the Leydig cells of the testes. ABCD1 is an ATPase binding cassette protein in the same category of transporter proteins such as the CFTR and MDR proteins. Identification of X-ALD as a lipid-storage disease, as a defect in the capacity to degrade VLCFAs, and its characterization as a peroxisomal disorder was reviewed by Moser (1997). Moser et al. (2005) provided a clinical review of ALD. Clinical Features Adrenoleukodystrophy can present at a variety of ages and with different manifestations depending on the presence and type of neurologic findings. Moser et al. (2000) stated that there are 7 phenotypes, which include the childhood cerebral form, adrenomyeloneuropathy (AMN), adult cerebral, adolescent, adrenal insufficiency without neurologic disease, asymptomatic, and heterozygotes. The clinical presentation can vary within the same family. One male may have the childhood form of the disorder and his brother may have the adult form. It is apparent that neither the genetic mutation nor the level of biochemical abnormality predicts the phenotypic presentation. Davis et al. (1979) observed a family with 4 cases of adrenoleukodystrophy and 1 of adrenomyeloneuropathy, suggesting the fundamental identity of the 2 disorders. The patient with adrenomyeloneuropathy was well until age 21 years when he developed spastic paraparesis. He subsequently fathered 2 daughters and a stillborn child. He was 41 years old at the time of study and showed no clinical manifestations of adrenal insufficiency. A brother of his developed paraparesis at age 13 and progressed to death at age 19. A nephew became ill at age 4 and died at age 7. Autopsy showed atrophic adrenals although no clinical signs of adrenal insufficiency were observed. O'Neill et al. (1982) studied a kindred in which 14 members were affected with a variable combination of neurologic and adrenal manifestations. Abnormality was identified by increased content of C(26:0) fatty acid (hexacosanoic acid) in cultured skin fibroblasts and abnormal C26/C22 fatty acid ratios. The latter ratios were not proportional to severity of disease, duration, or character of the neurologic syndrome. In the family reported by O'Neill et al. (1980, 1982), clinically apparent Addison disease without neurologic involvement was the expression of adrenoleukodystrophy in males, and spastic paraplegia and sphincter disturbances occurred in female carriers. Berg et al. (1989) described phenotypic features of a 362-member kindred spanning 6 generations. They observed clustering of phenotypes within individual sibships of the pedigree. Willems et al. (1990) showed that patients with ALD and AMN in the same pedigree had identical haplotypes, demonstrating that they are not caused by different allelic mutations. Holmberg et al. (1991) described a remarkable family in Sweden in which there was Addison disease in a 13-year-old boy, adrenomyeloneuropathy in a 58-year-old man, and spastic paraparesis and peripheral neuropathy in at least 3 heterozygous females, including the 85-year-old mother of the man with AMN. Sobue et al. (1994) described considerable phenotypic heterogeneity between 2 proven monozygotic twins, both of whom had myeloneuropathy. Extensive demyelination in the brain was only prominent in the older twin, while adrenal insufficiency was prominent in the younger twin. They suggested that nongenetic factors were important determinants of the phenotypic variation of the adrenoleukodystrophy gene. Korenke et al. (1996) and Di Rocco et al. (2001) also reported pairs of identical male twins with different clinical expressions of ALD. Wilichowski et al. (1998) found no difference in mitochondrial DNA in the twins reported by Korenke et al. (1996). Di Rocco et al. (2001) stated that the discordant adrenoleukodystrophy phenotypes in 3 pairs of monozygotic twins indicated that modifier genes were not involved in determining the occurrence of CNS degeneration. They suggested that identifying environmental factors could be important for effectively preventing CNS degeneration in this disorder. By neuropsychologic testing, Cox et al. (2006) found normal cognitive function in 48 of 52 neurologically asymptomatic boys with ALD (mean age, 6.7 years). All of the patients had normal brain MRI studies. However, there was a negative correlation between age and visual perception as well as age and visuomotor skills. Cox et al. (2006) concluded that a subset of patients with the childhood form of ALD have normal neurodevelopment despite an inherent defect in the ABCD1 gene. ### Childhood Cerebral Adrenoleukodystrophy The classic presentation of childhood cerebral ALD has been analyzed in several large series (Schaumburg et al., 1975; Aubourg et al., 1982). This is the form of the illness that was originally described by Siemerling and Creutzfeldt (1923) and, until it was possible to make the biochemical diagnosis, it was the only form of the disease recognized as adrenoleukodystrophy. It is a rapidly progressive demyelinating condition affecting the cerebral white matter. It is by definition confined to boys who develop cerebral involvement before the age of 10 years. The boys are normal at birth and have unremarkable development. The mean age of onset is approximately 7 years. The disease usually manifests itself early with behavioral manifestations including inattention, hyperactivity, and emotional lability. It often becomes apparent through school difficulties. It progresses into visual symptoms, auditory processing difficulties, and motor incoordination. Once the neurologic manifestations appear, progression of the illness is tragically rapid and the child is often in a vegetative state within 1 to 2 years. Magnetic resonance imaging is often the first diagnostic study and shows a characteristic pattern of symmetric involvement of the posterior parietooccipital white matter in 85% of patients, frontal involvement in 10%, and an asymmetric pattern in the rest. ### Adult/Adrenomyeloneuropathy Budka et al. (1976) reported a case they interpreted as an adult variant of adrenoleukodystrophy. At the time, a geneticist could raise the possibility of this form being the consequence of an allelic mutation, but phenotypic variability within families has subsequently been demonstrated. The neurologic picture was dominated by spastic paraplegia. Both clinically and pathologically, absence of diffuse cerebral involvement was noteworthy. The endocrinologic disorder was the particularly striking feature. Griffin et al. (1977) and Schaumburg et al. (1977) described a variant that they called adrenomyeloneuropathy. Hypogonadism was present in all cases appropriately studied. Adrenal insufficiency began in childhood and progressive spastic paraparesis in the third decade. Neurologic features included peripheral neuropathy, impotence, and sphincter disturbances. O'Neill et al. (1985) found biochemical characteristics of ALD in 2 brothers with spastic paraplegia of onset at age 40 and 50 years. Further study in the family revealed 2 nephews who were also affected as well as asymptomatic carriers in a typical X-linked pedigree pattern. None had symptoms of adrenal insufficiency. Cotrufo et al. (1987) reported the remarkable cases of an uncle and nephew who were completely asymptomatic at ages 25 and 10, respectively, but who showed levels of very long chain fatty acids in plasma consistent with the ALD hemizygote state. Both were found to have adrenocortical insufficiency as evidenced by compensatory high ACTH release. Uyama et al. (1993) described a man who had presenile onset (at age 51 years) of the cerebral form of ALD. The first manifestation was difficulty in recalling where he had placed things. Shortly thereafter, he had problems operating farm machinery and gradually developed difficulty seeing clearly and writing at normal speeds. He could dress himself but often put garments on backward or inside out. He later developed Balint syndrome and dementia. (Balint syndrome is an acquired visuospatial disorder characterized by psychic paralysis of visual fixation, optic ataxia, and disturbance of visual attention with relatively intact vision (Hecaen and De Ajuriaguerra, 1954).) MRI demonstrated demyelinating lesions in the bilateral posterior parietooccipital white matter involving the splenium of the corpus callosum. The patient could not move his eyes on command or follow a moving object. He had difficulty in maintaining central fixation. Optic ataxia was also shown by frequent errors when he attempted to grasp an object at which he was looking. The patient was bedridden by age 54 and died at age 55. Tests of adrenal function yielded normal results. Ratios of C26:0 to C22:0 in plasma and in erythrocyte membranes established the diagnosis of ALD in the proband and demonstrated that his mother was a heterozygote. Van Geel et al. (2001) studied the evolution of the disease in adults. They studied 129 men retrospectively, with a mean follow-up period of 10.1 +/- 5.0 years. Among 32 neurologically asymptomatic patients, 16 (50%) developed some neurologic involvement. Among 68 men with AMN without cerebral involvement, 13 (19%) developed clinically apparent cerebral demyelination. There was a high risk for adult neurologically asymptomatic patients to develop neurologic deficits and for AMN patients to develop cerebral demyelination. This had implications for the phenotype classification, search for modifying factors, and the development and evaluation of new therapies. Eichler et al. (2007) reviewed serial brain MRI scans of 56 adult patients with ALD and white matter abnormalities. Forty-two (75%) of these patients had corticospinal tract involvement, and 21 (50%) of the 42 showed lesion progression over a 3 to 5-year period. Disease progression was slower in adults compared to that previously observed in affected children. Only 3 adult patients showed isolated lesions in the genu or the splenium, all of which developed in childhood or adolescence. The findings suggested that progressive inflammatory demyelination can occur along with the known axonopathy of adulthood. Eichler et al. (2007) suggested that the vulnerability of specific fiber tracts in ALD changes with age. ### Adrenal Insufficiency Addison disease in young males should prompt consideration of ALD as the underlying abnormality. See also Sadeghi-Nejad and Senior (1990). Laureti et al. (1996) performed biochemical analysis of very long chain fatty acids in 14 male patients (age ranging from 12-45 years at diagnosis) previously diagnosed as having primary idiopathic adrenocortical insufficiency. In 5 of the 14 patients, elevated levels of very long chain fatty acids (VLCFA) were found in plasma; none had adrenocortical antibodies. By electrophysiologic tests and magnetic resonance imaging, it was determined that 2 had cerebral ALD, 1 had adrenomyeloneuropathy with cerebral involvement, and 2 had preclinical AMN. Since the adrenal insufficiency may long precede neurologic manifestations and perhaps may occur alone, caution must be exercised in the interpretation of isolated X-linked Addison disease as a separate entity. Of course, autopsy-confirmed adrenal hypoplasia (300200) is a well-established entity. The achalasia-Addisonian syndrome (231550), which appears to be autosomal recessive, is another example of combined adrenal and neurologic (autonomic) involvement. The postperfusion syndrome is an uncommon event following open-heart surgery with extracorporeal circulation. It is associated with a young age at surgery (less than 1 year) and bypass lasting longer than 60 minutes. Luciani et al. (1997) observed the syndrome in an 18-year-old man who underwent transpulmonary patch repair of a ventricular septal defect with cardiopulmonary bypass for 50 minutes. Preoperatively, the patient exhibited a slight gait disorder and unremarkable EEG and laboratory findings. Twelve hours after surgery he developed hypotension and circulatory collapse. This was treated successfully, but 10 days after discharge the patient was admitted with findings suggesting Addison disease. He showed a worsening disturbance of gait, with ataxia and EEG abnormalities. The diagnosis of adrenoleukodystrophy was supported by MRI of the head and confirmed by increased plasma levels of very long chain saturated fatty acids. Thus, Luciani et al. (1997) concluded that this was a case of Addisonian crisis precipitated by surgery in a patient with previously unrecognized ALD. ### Heterozygote Women who are carriers for the condition may develop spastic paraparesis with bowel and bladder difficulties. This appears to be partially a function of age. Heffungs et al. (1980) observed cerebral sclerosis and Addison disease in a previously healthy 14-year-old sister of an affected boy. They suggested that this was the first documented example of adrenoleukodystrophy in a heterozygote. Several other unusual examples have been published. Also see O'Neill et al. (1982). The patient reported by Noetzel et al. (1987) illustrates further the occurrence of a chronic nonprogressive spinal cord syndrome in women heterozygous for ALD. Hershkovitz et al. (2002) reported an 8.5-year-old girl who presented with declining school performance and diffuse frontal white matter demyelination. She was known to be at risk for heterozygosity because 2 maternal uncles had ALD. Levels of very long chain fatty acids were elevated. DNA analysis of the patient and her mother showed a cytosine insertion in codon 515 (515insC) of the ABCD1 gene, resulting in a frameshift after amino acid 171 (tyrosine). Immunocytochemical studies showed that ALDP reactivity was lacking in 99% of the fibroblasts analyzed. Cytogenetic analysis showed a deletion at Xq27.2-qter. Both parents were normal. She underwent bone marrow transplantation from a normal sister and at 18 months was stable. Hershkovitz et al. (2002) recommended that cytogenetic studies be performed in the 1% of heterozygotes who show evidence of cerebral involvement. Jung et al. (2007) reported 2 unrelated women with heterozygous mutations in the ABCD1 gene. The first patient was diagnosed at age 8 years with manic-hebephrenic disorder and subsequent psychotic episodes. She had spastic paraparesis at age 25 and developed cognitive deficits, cerebellar signs, and more severe spastic paraparesis at age 45. She died of pneumonia at age 52. Her brother had Addison disease at age 47, and later developed spastic paraparesis and polyneuropathy. The second patient developed inability to run at age 35 years, 1 year after her son died of ALD. She was wheelchair-bound by age 48. Later features included bilateral visual loss and mild polyneuropathy. She was cognitively intact. ### Other--Spinocerebellar Kobayashi et al. (1986) described 2 adult male first cousins with spinocerebellar degeneration manifested by progressive limb and truncal ataxia, slurred speech, and spasticity of the limbs. Brain CT scans showed atrophy of the pons and cerebellum. Very long chain fatty acids were elevated in the plasma and red cell membranes of the affected patients and were increased to intermediate levels in the female carriers. Biochemical Features An important observation was that of Igarashi et al. (1976). They found that cholesterol esters in the brain and adrenals of these patients had an unusually high proportion of fatty acids with a chain length of 24-30 carbon atoms, rather than the usual length of less than 20. This might interfere with myelin formation in the CNS and steroidogenesis in the adrenal. Biochemical studies of cerebral white matter showed increased amounts of long chain saturated fatty acids in cholesterol esters. ALD is characterized by the accumulation of unbranched saturated fatty acids with a chain length of 24 to 30 carbons, particularly hexacosanoate (C26), in the cholesterol esters of brain white matter and in adrenal cortex and in certain sphingolipids of brain. Accumulation also occurs in plasma-cultured skin fibroblasts and this fact can be used for diagnosis (including prenatal diagnosis) and for the study of the disease's basic mechanisms (Moser et al., 1980). It appears that the defect is in the catabolism of the very long chain fatty acids (see 603314) themselves. A parallel to Refsum disease (266500) in which a fatty acid of dietary origin accumulates because of deficiency of an enzyme for its catabolism is suggested by the finding that the accumulating long chain fatty acids are, at least in part, of exogenous origin (Moser, 1980). This finding and analogy suggest that dietary modification may be beneficial in ALD. Moser et al. (1981) investigated a possible defect in a peroxisomal beta-oxidation system. The work of Hashmi et al. (1986) and of Singh et al. (1988) suggested that the basic defect in X-linked ALD is deficient activity of lignoceroyl-CoA ligase. Singh et al. (1988) and Lazo et al. (1988) presented data demonstrating that the accumulation of very long chain fatty acids in ALD is the result of deficient peroxisomal lignoceroyl-CoA ligase activity. It had previously been thought that the same ligase was responsible for the activation of C16:0 (palmitic acid) and C24:0 (lignoceric acid). Later data indicated that they are separate enzymes. Wanders et al. (1987, 1988) had interpreted their results as indicating that the basic defect in X-linked ALD resides in peroxisomal very long chain fatty acyl-CoA synthetase. This enzyme is present not only in peroxisomes but also in microsomes. The identification of the genetic defect and protein abnormality in ALD has resulted, however, in different conclusions. The defect is not in an enzyme, but in a protein, ABCD1, that has a role in peroxisomal beta-oxidation. It has been suggested that the protein has a role in transport. Beta-oxidation of fatty acids occurs through a carnitine-dependent pathway in the mitochondria and a carnitine-independent pathway in the peroxisomes. In cell cultures and mouse tissue, McGuinness et al. (2003) showed that the ALDP protein transporter may facilitate an interaction between peroxisomes and mitochondria, which is disturbed in X-linked ALD. Stradomska and Tylki-Szymanska (2001) described the results of measuring serum very long chain fatty acid concentrations in 59 females of various ages with heightened risk of carrier status for ALD. In female carriers aged 22 to 50 years, they found serum VLCFA concentrations in a range characteristic of heterozygotes; VLCFA levels were normal in female carriers aged 55 to 64 years. In women aged 37 to 50 years in whom repeat studies of VLCFA concentrations were performed after 5 years, a reduction in VLCFA was observed. Stradomska and Tylki-Szymanska (2001) suggested that the results point to a reduction of serum VLCFA concentrations as X-ALD heterozygotes age. Inheritance Fanconi et al. (1963) suggested X-linked recessive inheritance of a syndrome of Addison disease and cerebral sclerosis. All cases had been male, and in many instances a brother and/or a maternal uncle of the proband has been similarly affected. Using content of C26 fatty acids in cultured fibroblasts, Migeon et al. (1981) demonstrated two types of clones in heterozygotes, thus corroborating X-linkage and demonstrating lyonization of the ALD locus. The presence of more mutant than wildtype clones in cultures from most heterozygotes suggested a proliferative advantage of the mutant cells. This advantage appears to exist in vivo also because most heterozygotes showed increased levels of fatty acids in plasma and, in 1 family, women heterozygous for both ALD and G6PD showed an excess of G6PD blood cells of the A (rather than B) type, which was in coupling with the mutant gene. (In Lesch-Nyhan syndrome (308000), it is the wildtype red cell precursors that enjoy a selective advantage so that in heterozygotes the levels of HPRT in red cells are normal.) Using the probe M27-beta, Watkiss et al. (1993) found no evidence for skewed X-inactivation in 12 female carriers of ALD. The probe M27-beta detects locus DXS225, which contains a highly polymorphic VNTR sequence. In addition, the locus contains MspI sites that are methylated on the active X chromosome but unmethylated on the inactive X chromosome. Because such sites are vulnerable to digestion by the isoschizomer HpaII only when they are unmethylated, i.e., when they lie on the inactive X chromosome, M27-beta can be used to differentiate between the active and inactive X chromosomes. In the 5 families, they observed 3 manifesting heterozygotes who had presented to a neurologist independently of the illness in affected males in the family. Only 1 of the 3 manifesting carriers showed skewing, but 2 of 9 nonmanifesting carriers did also. Maestri and Beaty (1992) examined the implications of a 2-locus model to explain heterogeneity in ALD, i.e., the occurrence of severe childhood form (ALD) and the milder adult-onset form (AMN) in the same family, or even the same sibship. They considered 2 models. Under a dominant epistatic model, a single M allele at an autosomal modifier locus ameliorates the most severe effects of the disease allele, thus leading to the milder AMN phenotype; only males with genotype mm would have ALD. Under a recessive epistatic model, 2 copies of the M allele would be necessary to have the milder AMN phenotype. Maestri and Beaty (1992) showed that the recurrence risk for a second affected male depended on the frequency of the protective allele at this modifier locus. They suggested sampling discordant affected sib pairs as a strategy for detecting linkage between a polymorphic DNA marker and a possible modifier gene. Mapping Close linkage of ALD and G6PD was indicated by the absence of recombination in 18 opportunities. This means that the ALD locus is in the terminal segment of the long arm of the X, i.e., Xq28. That the locus is not closely linked to Xg had been shown by Spira et al. (1971). Close linkage to DXS52 (maximum lod score = 4.17 at theta = 0.0) was found by van Oost et al. (1987). Close linkage of ALD to the cluster of colorblindness genes is indicated by the increased frequency of colorblindness in affected males and by the demonstration of deletion of cone pigment genes with the use of DNA probes (Aubourg et al., 1988). Aubourg et al. (1988) studied the red and green visual pigment genes in 8 kindreds with ALD and demonstrated frequent structural changes, including deletions and intragenic recombinations. Sack et al. (1989) found increased frequency of abnormal color vision in men with adrenomyeloneuropathy and pointed to these findings as supporting very close linkage of the ALD and the colorblindness loci, thus giving the opportunity for contiguous gene defects. Aubourg et al. (1990) reported studies on a large number of patients with ALD. No deletions were found with probes that lie 3-prime of the green pigment genes. One of the 8 previously reported ALD patients had a long deletion 5-prime of the red pigment gene, a deletion causing blue cone monochromacy. This finding and the previous finding of a 45% frequency of phenotypic color vision defects in patients with AMN suggested to Aubourg et al. (1990) that the ALD/AMN gene may lie 5-prime to the red pigment gene and that the frequent phenotypic color vision anomalies owe their origin to deleted DNA that includes regulatory genes for color vision. In studies of an ALD patient who also had blue cone monochromacy, Feil et al. (1991) characterized a complex chromosomal rearrangement in band Xq28. Two CpG islands were mapped, at 46 and 115 kb upstream from the visual pigment genes, one or the other of which might mark the location of the ALD gene. Sack et al. (1993) gave a molecular analysis of the chromosomal rearrangement in kindred 'O' reported by Aubourg et al. (1988). Alpern et al. (1993) characterized the physiologic defect in color vision. The DNA in a hemizygous male showed altered restriction fragment sizes compatible with a deletion extending from the 5-prime end of the color pigment gene cluster. The DNA change had removed the red pigment gene and juxtaposed a 15-kb DNA sequence to the remaining pigment gene. Sack et al. (1993) demonstrated linkage with the ALD gene, located centromeric to the color pigment gene cluster; maximum lod = 3.19 at theta = 0.0. On physiologic testing, Alpern et al. (1993) found color matching they interpreted as indicating the presence of an abnormal rudimentary visual pigment. They suggested that this may reflect the presence of a recombinant visual pigment protein or altered regulation of residual pigment genes due to the DNA change: deletion of the long-wave pigment gene and reorganized sequences 5-prime to the pigment gene cluster. In several large families with ALD, van Oost et al. (1991) extended the linkage of ALD to DXS52 and arrived at a maximal lod score of 22.5 at 1 cM. They also found tight linkage of ALD to F8C and showed that both ALD and F8C are distal to DXS52. No major structural rearrangement in Xqter was observed; in particular, there were no abnormalities in the color vision genes. The occurrence of several cases in which both ALD and Emery-Dreifuss muscular dystrophy (310300) were thought to be present suggested that these loci are closely situated (Moser, 1987); however, the diagnosis of ALD was not confirmed in these patients, and in testing of additional patients with EMD, none was found to have ALD (Moser, 1989). Using probe St14 (DXS52), Boue et al. (1985) and Aubourg et al. (1987) found a total lod score in their combined families of 13.766 at theta = 0. In an analysis of 59 ALD kindreds, Sack and Morrell (1993) found normal hybridization using a probe situated 30 kb centromeric to the color pigment genes. However, using a probe located 100 kb further centromeric, they found 2 overlapping deletions in 2 patients. Additional study indicated that the telomeric ends of the 2 deletions were 8 kb apart. Thus, the location of the ALD gene appeared to have been defined as approximately 150 kb centromeric of the color pigment genes. Mosser et al. (1993) identified the ALD gene by positional cloning. Sarde et al. (1994) determined that the ALD gene is 720 kb proximal to the R/GCP genes and other genes lie between the two. Thus the occurrence of color vision abnormalities in ALD is not secondary to localization. Pathogenesis Hoefnagel et al. (1962) described the histologic findings in endocrine glands, especially the pituitary and adrenal. Ropers et al. (1977) described typical morphologic changes in cultured fibroblasts on light microscopy. The changes, seen only 4 or 5 days after subculture, consisted of expansion of the cells, which appeared abnormally large. Lyonization was demonstrated in cultured fibroblasts of the mother. Ho et al. (1995) predicted that disruptive effects of the accumulation of very long chain saturated fatty acids on cell membrane structure and function may explain the neurologic manifestations of ALD patients. Especially the 26-carbon acid, hexacosanoic acid, is involved. They studied the interaction of radiolabelled hexacosanoic acid with model membranes and bovine serum albumin by NMR spectroscopy to compare properties of the hexacosanoic acid with those of typical dietary fatty acids. Desorption of hexacosanoic acid from membranes was orders of magnitude slower than that of shorter-chain fatty acids and binding to serum albumin was ineffective. Federico et al. (1988) added to the evidence for autoimmune factors in the pathogenesis of ALD by the description of a 53-year-old man with CNS white matter demyelination and evidence of a multisystem immunologic disorder including autoimmune thyroiditis, antigastric mucosa antibodies, and antismooth muscle antibodies. The cerebrospinal fluid showed a marked increase in IgG index and several oligoclonal bands with an alkaline isoelectric point. In a review of brain autopsy material from 9 cases of ALD, Eichler et al. (2008) observed marked demyelinative lesions in the white matter with sparing of the subcortical white matter. One additional case of pure adrenomyeloneuropathy did not show white matter demyelination. The lesion edges were regions of active demyelination with macrophages containing granules consisting of lipid inclusions consistent with myelin debris. Dense perivascular aggregates of macrophages and lymphocytes were closer to the lesion, but macrophages were less prominent within the cores of lesions. These findings suggested that macrophages played a phagocytic role but not a role in active myelin destruction. Further studies showed that white matter areas beyond the actively demyelinating edge were essentially devoid of microglia due to apoptosis, whereas microglia density was normal in remote normal brain tissue. Injection of lysophosphatidylcholine in mouse brains induced microglial apoptosis. Eichler et al. (2008) concluded that microglial apoptosis resulting from accumulation of very-long chain fatty acids may be an early change in the pathogenesis of ALD that occurs before demyelination, and that the loss of microglia prevents them from protecting oligodendrocytes and axons. Hein et al. (2008) found that rat oligodendrocytes and astrocytes exposed to VLCFA in culture died within 24 hours, with the greatest effect on myelin-producing oligodendrocytes. VLCFA caused increased intracellular calcium in oligodendrocytes, astrocytes, and neurons. VLCFA also induced depolarization of mitochondria and promoted permeability of the inner mitochondrial membrane. Hein et al. (2008) concluded that VLCFAs are potently cytotoxic due to mitochondrial dysfunction and calcium deregulation. Fourcade et al. (2008) found that XLD fibroblasts showed decreased mitochondrial potential and increased sensitivity to oxidative stress. In vitro, the alpha-tocopherol analog Trolox was able to reverse these oxidative defects, as measured by decreased levels of lipoxidative protein damage. Diagnosis Moser et al. (1981) developed a plasma method for the detection of very long chain fatty acids providing for the diagnosis of affected individuals and assisting in carrier identification. Moser et al. (1999) reported the results of testing with this assay, the most widely used procedure for the diagnosis of X-linked ALD and other peroxisomal disorders, in 3,000 patients and 29,000 controls. VLCFA levels are elevated at birth, and the assay is highly accurate in hemizygotes. Eighty-five percent of obligate heterozygotes will have an elevated level, but a normal result did not exclude carrier status. A variety of other peroxisomal disorders, including Zellweger syndrome and other single enzyme defects in peroxisomal beta oxidation, also share an elevation of VLCFA levels, but can readily be discerned from ALD by the clinical situation. Moser and Moser (1999) provided an authoritative discussion of the prenatal diagnosis of X-linked ALD. They concluded that measurement of VLCFA levels in cultured amniocytes and chorionic villus cells (the most frequently used procedure) is reliable provided that care is taken to minimize the risk of false-negative results by performance of subcultures in appropriate media. The procedure can be complemented by assays of VLCFA oxidation, and under certain circumstances, immunocytochemical assays for the expression of ALDP. Mutation analysis is the most reliable diagnostic procedure when the nature of the mutation in the at-risk family is known. Inoue et al. (1996) found abnormal lignoceric acid oxidation in 19 of 19 ALD patients and in 3 of 3 obligate heterozygous carrier women. Among 10 women at risk of being a carrier, 3 with normal levels of VLCFA had abnormal lignoceric acid oxidation. Inoue et al. (1996) suggested that this combined biochemical procedure could improve the accuracy of carrier detection in ALD. Various techniques have been developed to identify ALD carriers more accurately. Boehm et al. (1999) developed and validated a robust DNA diagnostic test involving nonnested genomic amplification of the ALD gene, followed by fluorescent dye-primer sequencing and analysis. Lachtermacher et al. (2000) noted that a very small percentage (0.1%) of affected males had plasma C26:0 levels that are borderline normal, and 15% of obligate female carriers have normal results. Effective mutation detection in these families is therefore fundamental to unambiguous determination of genetic status. Of particular concern are female members of kindreds segregating X-ALD mutations, because normal VLCFA levels do not guarantee lack of carrier status. Lachtermacher et al. (2000) described a fast method for detection of X-ALD mutations. The method was based on SSCP analysis of nested PCR fragments followed by sequence-determination reactions. Using this method, they found X-ALD mutations in 30 kindreds, including 15 not previously reported. Using records from the Kennedy Krieger Institute between 1981 and 1998 and the Mayo Clinic Rochester from 1996 to 1998, Bezman et al. (2001) estimated that the minimum frequency of X-linked ALD hemizygotes in the US is 1:42,000, and that of hemizygotes plus heterozygotes is 1:16,800. Five percent of male probands were estimated to have new mutations. Extended family testing identified asymptomatic hemizygotes, who could benefit from therapy, and heterozygotes, who could benefit from genetic counseling. Clinical Management Kolodny (1987) concluded that asymptomatic individuals with the adrenomyeloneuropathy gene, as well as patients with this disorder and heterozygotes, may benefit from a combined oleic acid, VLCFA-restricted diet. Moser (1993) reviewed the film 'Lorenzo's Oil,' a fictionalized account of a family's search for a treatment of ALD, afflicting, in this case, a boy named Lorenzo Odone. Moser (1993) concluded that it overstated the success that can be achieved with the oil, invented conflicts between the parents and the medical establishment, and presented an inaccurate and malicious portrayal of the United Leukodystrophy Foundation. 'Dr. Nicolai,' played in the film by Peter Ustinov, copied Moser's 'appearance and speech with remarkable accuracy.' In an open trial in 14 men with adrenomyeloneuropathy, 5 symptomatic heterozygous women, and 5 boys (mean age, 13 years) with preclinical adrenomyeloneuropathy, Aubourg et al. (1993) could find no evidence of a clinically relevant benefit from dietary treatment with oleic and erucic acids (glyceryl trierucate and trioleate oil; 'Lorenzo's oil'). Asymptomatic thrombocytopenia was noted in 6 patients. Poulos et al. (1994) examined the fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient who had received Lorenzo's oil for 9 months. There was improvement in the fatty acid composition of the plasma and liver but not in the brain. This indicated that very little erucic acid crossed the blood-brain barrier. These findings suggested to the authors that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy. Treatment with Lorenzo's oil normalizes the level of VLCFA in plasma within 4 weeks. In spite of this promising biochemical effect, clinical results have been disappointing when the oils were fed to symptomatic patients (Aubourg et al., 1993). Moser et al. (1994) reported a positive result in patients in whom therapy was begun before neurologic symptoms were present, suggesting that fatty acid abnormality is of pathogenic significance. However, a 3-year follow-up with somatosensory-evoked potentials and motor-evoked potentials of 8 patients by Restuccia et al. (1999) showed no evidence of any benefit of dietary treatment, even when initiated early in the disease before the appearance of inflammatory lesions. Moser et al. (2005) identified asymptomatic boys with X-linked adrenoleukodystrophy who had a normal MRI and assessed the effect of Lorenzo's oil (4:1 glyceryl trioleate-glyceryl trierucate) on disease progression. By a plasma very long chain fatty acids assay used to screen at-risk boys, 89 affecteds were identified, and all were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 +/- 2.7 years. Of the 89 boys, 24% developed MRI abnormalities and 11% developed neurologic and MRI abnormalities. Moser et al. (2005) concluded that reduction of hexacosanoic acid by Lorenzo's oil was associated with reduced risk of developing MRI abnormalities. They recommended therapy with Lorenzo's oil in asymptomatic boys with X-linked adrenoleukodystrophy who had normal brain MRI results. Their experience with other ALD patients and that of Rizzo et al. (1989) indicated that total fat intake in excess of 30 to 35% of total calories may counteract or nullify the C26:0-reducing effect of Lorenzo's oil. Those patients who developed progressive MRI abnormalities should be considered for hematopoietic stem cell transplantation (HSCT) as recommended by Peters et al. (2004). Adrenal function must be monitored since 80% asymptomatic patients with ALD develop evidence of adrenal insufficiency (Dubey et al., 2005) and adrenal hormone replacement therapy should be provided when indicated by laboratory findings. Thus, a 3-prong therapeutic approach is recommended. Aubourg et al. (1990) achieved reversal of early neurologic and neuroradiologic features in an 8-year-old boy who received bone marrow transplantation (BMT) from his fraternal twin brother. Malm et al. (1997) described experience with bone marrow transplantation in 3 children with ALD. They concluded that BMT must be considered very early, even in a child without symptoms but with signs of demyelination on MRI, if a suitable donor is available. Shapiro et al. (2000) discussed the experience of BMT in 12 patients over an extended period of time and came to the conclusion that it did result in improved outcome if performed early in the course of symptomatic disease. Kruse et al. (1994) systematically studied 25 patients with adrenoleukodystrophy. Using multislice proton magnetic resonance spectroscopy, they demonstrated a reduction in N-acetyl aspartate, an increase in choline, and occasionally an increase in lactate. They concluded that magnetic resonance spectroscopic imaging is a more sensitive indicator of early neurologic involvement than is magnetic resonance imaging and therefore a more useful gauge of demyelination by which therapeutic approaches could be judged. Because of the circumstantial evidence that immunologic factors contribute to the pathogenesis of the CNS lesions in ALD, Naidu et al. (1988) administered cyclophosphamide for 5 to 11 days to 4 patients with childhood ALD and to 1 patient with the adult cerebral form. The rate of neurologic progression in the 4 patients with childhood disease did not differ from that in 167 untreated patients with childhood disease surveyed previously. Cappa et al. (1994) gave intravenous high-dose immunoglobulins to 6 patients with adrenoleukodystrophy who were already on a restricted very long chain fatty acid diet supplemented with glycerol trioleate/erucic acid. The MRI and symptoms deteriorated in this group at the same rate as they did in 6 control patients on the same restricted/supplemented diet who did not receive immunoglobulins. El-Deiry et al. (1997) studied the prevalence of adrenal dysfunction in 71 females who were obligate carriers of the X-linked trait by pedigree analysis and whose plasma very long chain fatty acid levels were consistent with a heterozygote status. The authors concluded that, in ALD heterozygotes, adrenal cortical insufficiency rarely develops, although isolated mineralocorticoid insufficiency may occur in these individuals. Furthermore, they inferred that ALD heterozygotes may be predisposed to hypoaldosteronism related to the use of nonsteroidal antiinflammatory agents. A subclinical decrease in glucocorticoid reserve, as measured by synthetic ovine corticotropin releasing hormone testing, may be present in a majority of these women. The authors suggested that aldosterone levels be included in ACTH stimulation testing done to detect adrenal insufficiency in affected women. Nonsteroidal antiinflammatory agents should be considered a risk factor for the development of hypoaldosteronism in women heterozygous for ALD. Peters et al. (2004) reviewed results in 126 boys with X-ALD who received hematopoietic cell transplantation from 1982 to 1999. Complete data were available and analyzed for 94 boys with cerebral X-ALD. The estimated 5- and 8-year survival was 56%. The leading cause of death was disease progression. Donor-derived engraftment occurred in 86% of patients. Demyelination involved parietal-occipital lobes in 90%, leading to visual and auditory processing deficits in many boys. Peters et al. (2004) concluded that boys with early-stage disease benefit from hematopoietic cell transplantation, whereas boys with advanced disease may be candidates for experimental therapies. Schonberger et al. (2007) reported a boy with childhood ALD who underwent hematopoietic stem cell transplantation but died from transplant-related complications 76 days later. Postmortem examination showed mixed chimerism of the mutant and wildtype alleles in 23 tissue samples examined, including 12 CNS samples. Normal ALD protein was localized to peroxisomes within multiple cell types, including neurons. Schonberger et al. (2007) noted that detection of ALD protein so soon after transplant may indicate that healthy donor cells assisted affected recipient cells in metabolic function. Peripheral blood samples from an affected male cousin who had successful HSCT showed the wildtype ALD allele exclusively. There was no clinical disease progression after transplant. The findings in both patients indicated that HSCT can result in restoration and widespread presence of intact donor ALD protein in various recipient tissues. Cartier et al. (2009) initiated a gene therapy trial in 2 ALD patients for whom there were no matched donors for hematopoietic stem cell transplantation. Autologous CD34(+) cells were removed from the patients, genetically corrected ex vivo with a lentiviral vector encoding wildtype ABCD1, and then reinfused into the patients after they had received myeloablative treatment. Over a span of 24 to 30 months of follow-up, Cartier et al. (2009) detected polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein. Cartier et al. (2009) concluded that their results strongly suggested that hematopoietic stem cells were transduced in the patients. Beginning from 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the 2 patients stopped, a clinical outcome comparable to that achieved by allogeneic hematopoietic stem cell transplant. Thus, Cartier et al. (2009) concluded that lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD. Engelen et al. (2010) reported the results of a randomized control trial of 40 mg daily lovastatin in 14 patients with ALD. Treatment with lovastatin resulted in a small decrease of plasma C24:0 and C26:0, likely due to a decrease in LDL cholesterol. Levels of C18:1 were also slightly reduced. However, there was no effect on C26:0 in erythrocytes or lymphocytes or on VLCFAs in the LDL lipoprotein fraction. These data indicated lovastatin should not be prescribed as a therapy to lower levels of VLCFAs in patients with ALD. No adverse events were observed. Fourcade et al. (2010) demonstrated that valproic acid (VPA), a widely used antiepileptic drug with histone deacetylase inhibitor properties, induced the expression of the ABCD2 peroxisomal transporter (601081). VPA corrected the oxidative damage in ALD human fibroblasts and decreased the levels of monounsaturated VLCFA (C26:1 n-9), but not saturated VLCFA. Overexpression of ABCD2 alone prevented oxidative lesions to proteins in a mouse model of ALD. A 6-month pilot trial of VPA in ALD patients resulted in reversion of the oxidative damage to proteins in peripheral blood mononuclear cells. Molecular Genetics See the MOLECULAR GENETICS section in 300371. Population Genetics Moser et al. (1991) reported that their laboratory had identified more than 900 hemizygotes and 1,000 heterozygotes. Approximately 50% of the hemizygotes had a rapidly progressive childhood or adolescent form of the disease. In 25% of males, a slowly progressive paraparesis was the clinical picture. The illness occasionally presented as Addison disease without apparent neurologic involvement. Approximately 15% of heterozygotes developed moderately severe spastic paraparesis. In studies of 30 Dutch kindreds, van Geel et al. (1994) phenotyped 77 affected males and found that 35 (46%) had adrenomyeloneuropathy and 24 (31%) had the childhood or adolescent cerebral ALD. These percentages differed significantly from previous reports in which 25 to 28% of the patients developed AMN and 53 to 57% developed childhood or adolescent cerebral ALD. In studies in Australasia and Spain, Kirk et al. (1998) and Ruiz et al. (1998), respectively, provided new information about the epidemiology of ALD and the relative frequency of ALD phenotypes. The first study originated from the unit that had served as the ALD Referral Center in Australasia for the previous 15 years. Based on the number of ALD cases identified during this period and the number of live births, they arrived at a minimum incidence of 1.6 per 100,000 live births, slightly higher than the 1.1 per 100,000 based on similar analyses in the United States (Moser et al., 1995) and considerably higher than the estimated 1 per 200,000 males in the Netherlands (van Geel et al., 1994). Of the 95 affected males studied by Kirk et al. (1998), 51 had cerebral adrenoleukodystrophy, 24 had adrenomyeloneuropathy, 15 had Addison disease only, and 5 remained asymptomatic when last examined. Of the 60 patients belonging to 48 kindreds studied by Ruiz et al. (1998), 33% had childhood cerebral ALD plus adolescent cerebral ALD, 16% had adult cerebral ALD, 27% had adrenomyeloneuropathy, 12% had Addison disease only, and 12% had presymptomatic ALD. Bezman and Moser (1998) reviewed the relative frequency of phenotypes in 388 patients from 253 sibships from the United States and Canada in whom the genotype and phenotype of every male was known. This determination of every male eliminated the ascertainment bias introduced by other series in which ALD status was not known. When the proband was excluded, the phenotypic breakdown was 33% with childhood cerebral ALD, 26% with adrenomyeloneuropathy, 14% Addison only, 13% asymptomatic, 4% adolescent, and 2% adult cerebral. These numbers were very similar to the series from the Netherlands in which there was an attempt to identify everyone in the country with ALD. Bezman et al. (2001) determined the minimum frequency of hemizygotes in the United States to be 1:42,000 and that of hemizygotes and heterozygotes to be 1:16,800. In a retrospective hospital- and clinic-based study involving 122 children with an inherited leukodystrophy, Bonkowsky et al. (2010) found that the most common diagnoses were metachromatic leukodystrophy (250100) (8.2%), Pelizaeus-Merzbacher disease (312080) (7.4%), mitochondrial diseases (4.9%), and adrenoleukodystrophy (4.1%). No final diagnosis was reported in 51% of patients. The disorder was severe: epilepsy was found in 49%, mortality was 34%, and the average age at death was 8.2 years. The population incidence of leukodystrophy in general was found to be 1 in 7,663 live births. Animal Model Forss-Petter et al. (1997) and Lu et al. (1997) generated mice deficient in ALDP by targeted disruption. Motor functions in Aldp-deficient mice developed on schedule, and unexpectedly, adult animals appeared unaffected by neurologic symptoms up to 6 months of age. Biochemical analyses demonstrated impaired beta-oxidation in mutant fibroblasts and abnormal accumulation of very long chain fatty acids in the CNS and kidney. In 6-month-old mutants, adrenal cortex cells displayed a ballooned morphology and needle-like lipid inclusions, also found in testis and ovaries. However, lipid inclusions and demyelinating lesions of the CNS were not a feature. Contrary to the original suggestion that there was no phenotype associated with these mice, Pujol et al. (2002) determined that older mice have changes resembling AMN. Older Aldp-deficient mice exhibited an abnormal neurologic and behavioral phenotype, starting at around 15 months. This was correlated with slower nerve conduction and with myelin and axonal anomalies detectable in the spinal cord and sciatic nerve, but not in brain. The Drosophila recessive mutant 'bubblegum' (bgm) exhibits adult neurodegeneration, with marked dilation of photoreceptor axons. This mutant shows elevated levels of VLCFAs, as seen in ALD. Min and Benzer (1999) found that feeding the fly mutant one of the components of 'Lorenzo's oil,' glyceryl trioleate oil, blocked the accumulation of excess VLCFAs as well as development of the pathology. In Abcd1-knockout mice, Pujol et al. (2004) demonstrated that axonal damage was the first pathologic event in this model, followed by myelin degeneration. The phenotype could be modulated through expression levels of Abcd2 (601081). Overexpression of Abcd2 in Abcd1-knockout mice prevented both VLCFA accumulation and neurodegenerative features, whereas Abcd1/Abcd2 double mutants exhibited an earlier onset and more severe disease. Oezen et al. (2005) reported normal VLCFA levels in mitochondria of Abcd1-deficient mice. Polarographic analysis of the respiratory chain as well as enzymatic assays of isolated muscle mitochondria revealed no differences between Abcd1-deficient and control mice. Ultrastructural analysis revealed normal size, structure, and localization of mitochondria in muscle of both groups. Mitochondrial enzyme activity in brain homogenates of Abcd1-deficient and wildtype animals also did not differ, and studies on mitochondrial oxidative phosphorylation in permeabilized human skin fibroblasts of ALD patients and controls revealed no abnormalities. Oezen et al. (2005) concluded that accumulation of VLCFA per se does not cause mitochondrial abnormalities, and vice versa mitochondrial abnormalities are not responsible for the accumulation of VLCFA in Abcd1-deficient mice. Fourcade et al. (2008) found evidence of lipoxidative protein damage in the spinal cord of Abcd1-null mice as early as 3.5 months of age before the onset of neurologic symptoms. At 12 months, Abcd1-null mice had accumulated additional proteins affected by oxidative damage. Abcd1-null mice, spinal cord slices from these mice, and human ALD fibroblasts all showed a defective antioxidant response to VLCFA. In early symptomatic Abcd1/Abcd2 double-knockout mice, Mastroeni et al. (2009) demonstrated that intracisternal injection of an adeno-associated viral vector engineered to express human IGF1 (147440) and NTF3 (162660), 2 potent inducers of myelin formation and oligodendrocyte survival, resulted in protective effects against the demyelination process and amelioration of disease progression. Studies of CSF showed persistent expression of the genes after 20 weeks, suggesting effective transduction of leptomeningeal cells and a long-lasting effect. History Moser (1997) suggested that the first patient with X-ALD was described by Haberfeld and Spieler (1910). A previously normal boy developed disturbances in eye movement and vision at the age of 6 years, became apathetic, and showed deterioration of school work. Four months later his gait became spastic, and this progressed to an inability to walk. He was hospitalized at 7 years of age. Dark skin was noted. He died 8 months later. An older brother had died of a similar illness at 8.5 years. The postmortem brain was studied by Schilder (1913) and reported as the second of 3 cases that he referred to as 'encephalitis periaxialis diffusa,' characterized by diffuse involvement of the cerebral hemispheres in children with severe loss of myelin, which resembled multiple sclerosis because of the relative preservation of axons and the accumulation of lymphocytes, fat-laden phagocytes, and glial cells. The findings in the adrenal gland were not reported. Involvement of the adrenal gland was reported by Siemerling and Creutzfeldt (1923). Blaw (1970) coined the name 'adrenoleukodystrophy.' Gumbinas et al. (1976) suggested that progressive spastic paraparesis with adrenal insufficiency is 'a distinct disease, differing importantly from adrenoleukodystrophy.' INHERITANCE \- X-linked recessive HEAD & NECK Ears \- Hearing loss Eyes \- Loss of vision ABDOMEN Gastrointestinal \- Fecal incontinence GENITOURINARY External Genitalia (Male) \- Impotence Bladder \- Urinary incontinence NEUROLOGIC Central Nervous System \- Neurodegeneration, progressive \- Cognitive decline \- Loss of speech \- Dementia \- Bulbar palsy \- Seizures \- Paraparesis \- Spasticity \- Incoordination \- Ataxia \- White matter abnormalities \- Cerebral demyelination and inflammation Peripheral Nervous System \- Sensory loss \- Distal axonopathy (adrenomyeloneuropathy) Behavioral Psychiatric Manifestations \- Behavioral changes \- Attention deficit-hyperactivity disorder \- Autistic features \- Psychosis ENDOCRINE FEATURES \- Adrenal insufficiency (Addison disease) LABORATORY ABNORMALITIES \- Systemic accumulation of very long chain fatty acids (VLCFA) MISCELLANEOUS \- Highly variable phenotype, ranging from asymptomatic to death by age 3 years \- Onset ranges from childhood (severe phenotype) to adulthood (limited phenotype) \- Progressive disorder \- Heterozygous female carriers may manifest symptoms \- Estimated incidence of 1 in 17,000 MOLECULAR BASIS \- Caused by mutation in the ATP-binding cassette, subfamily D, member 1 gene (ABCD1, 300371.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	ADRENOLEUKODYSTROPHY	c0162309	26,201	omim	https://www.omim.org/entry/300100	2019-09-22T16:20:53	{"doid": ["10588"], "mesh": ["D000326"], "omim": ["300100"], "icd-10": ["E71.52", "E71.522", "E71.529"], "orphanet": ["43", "139396", "139399"], "synonyms": ["Alternative titles", "ADDISON DISEASE AND CEREBRAL SCLEROSIS", "SIEMERLING-CREUTZFELDT DISEASE", "BRONZE SCHILDER DISEASE", "MELANODERMIC LEUKODYSTROPHY"], "genereviews": ["NBK1315"]}
Spinal muscular atrophy-progressive myoclonic epilepsy syndrome is characterized by hereditary myoclonus and progressive distal muscular atrophy. Less than 10 cases have been reported. Treatment with clonazepam results in complete and lasting improvement of the myoclonus. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Spinal muscular atrophy-progressive myoclonic epilepsy syndrome	c1834569	26,202	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2590	2021-01-23T18:34:17	{"gard": ["3044", "3875"], "mesh": ["C537563"], "omim": ["159950"], "umls": ["C1834569"], "icd-10": ["G25.3"], "synonyms": ["Hereditary myoclonus-progressive distal muscular atrophy syndrome", "Jankovic-Rivera syndrome", "SMA-PME"]}
Inflammation of the middle ear Otitis media Other namesOtitis media with effusion: serous otitis media, secretory otitis media A bulging tympanic membrane which is typical in a case of acute otitis media SpecialtyOtorhinolaryngology SymptomsEar pain, fever, hearing loss[1][2] TypesAcute otitis media, otitis media with effusion, chronic suppurative otitis media[3][4] CausesViral, bacterial[4] Risk factorsSmoke exposure, daycare[4] PreventionVaccination, breastfeeding[1] MedicationParacetamol (acetaminophen), ibuprofen, benzocaine ear drops[1] Frequency471 million (2015)[5] Deaths3,200 (2015)[6] Otitis media is a group of inflammatory diseases of the middle ear.[2] One of the two main types is acute otitis media (AOM),[3] an infection of rapid onset that usually presents with ear pain.[1] In young children this may result in pulling at the ear, increased crying, and poor sleep.[1] Decreased eating and a fever may also be present.[1] The other main type is otitis media with effusion (OME), typically not associated with symptoms,[1] although occasionally a feeling of fullness is described;[4] it is defined as the presence of non-infectious fluid in the middle ear for more than three months.[4] Chronic suppurative otitis media (CSOM) is middle ear inflammation that results in discharge from the ear for more than three months.[7] It may be a complication of acute otitis media.[4] Pain is rarely present.[4] All three types of otitis media may be associated with hearing loss.[2][3] The hearing loss in OME, due to its chronic nature, may affect a child's ability to learn.[4] The cause of AOM is related to childhood anatomy and immune function.[4] Either bacteria or viruses may be involved.[4] Risk factors include exposure to smoke, use of pacifiers, and attending daycare.[4] It occurs more commonly among indigenous peoples and those who have cleft lip and palate or Down syndrome.[4][8] OME frequently occurs following AOM and may be related to viral upper respiratory infections, irritants such as smoke, or allergies.[3][4] Looking at the eardrum is important for making the correct diagnosis.[9] Signs of AOM include bulging or a lack of movement of the tympanic membrane from a puff of air.[1][10] New discharge not related to otitis externa also indicates the diagnosis.[1] A number of measures decrease the risk of otitis media including pneumococcal and influenza vaccination, breastfeeding, and avoiding tobacco smoke.[1] The use of pain medications for AOM is important.[1] This may include paracetamol (acetaminophen), ibuprofen, benzocaine ear drops, or opioids.[1] In AOM, antibiotics may speed recovery but may result in side effects.[11] Antibiotics are often recommended in those with severe disease or under two years old.[10] In those with less severe disease they may only be recommended in those who do not improve after two or three days.[10] The initial antibiotic of choice is typically amoxicillin.[1] In those with frequent infections tympanostomy tubes may decrease recurrence.[1] In children with otitis media with effusion antibiotics may increase resolution of symptoms, but may cause diarrhoea, vomiting and skin rash.[12] Worldwide AOM affects about 11% of people a year (about 325 to 710 million cases).[13][14] Half the cases involve children less than five years of age and it is more common among males.[4][13] Of those affected about 4.8% or 31 million develop chronic suppurative otitis media.[13] The total number of people with CSOM is estimated at 65–330 million people.[15] Before the age of ten OME affects about 80% of children at some point.[4] Otitis media resulted in 3,200 deaths in 2015 – down from 4,900 deaths in 1990.[6][16] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Acute otitis media * 3.2 Otitis media with effusion * 3.3 Chronic suppurative otitis media * 3.4 Adhesive otitis media * 4 Prevention * 5 Management * 5.1 Antibiotics * 5.2 Tympanostomy tube * 5.3 Otitis media with effusion * 5.4 Chronic suppurative otitis media * 5.5 Alternative medicine * 6 Outcomes * 6.1 Membrane rupture * 6.2 Hearing loss * 7 Epidemiology * 8 Etymology * 9 References * 10 External links ## Signs and symptoms[edit] Otitis media. The primary symptom of acute otitis media is ear pain; other possible symptoms include fever, reduced hearing during periods of illness, tenderness on touch of the skin above the ear, purulent discharge from the ears, irritability, and diarrhea (in infants). Since an episode of otitis media is usually precipitated by an upper respiratory tract infection (URTI), there are often accompanying symptoms like a cough and nasal discharge.[1] One might also experience a feeling of fullness in the ear. Discharge from the ear can be caused by acute otitis media with perforation of the eardrum, chronic suppurative otitis media, tympanostomy tube otorrhea, or acute otitis externa. Trauma, such as a basilar skull fracture, can also lead to cerebrospinal fluid otorrhea (discharge of CSF from the ear) due to cerebral spinal drainage from the brain and its covering (meninges).[citation needed] ## Causes[edit] The common cause of all forms of otitis media is dysfunction of the Eustachian tube.[17] This is usually due to inflammation of the mucous membranes in the nasopharynx, which can be caused by a viral upper respiratory tract infection (URTI), strep throat, or possibly by allergies.[18] By reflux or aspiration of unwanted secretions from the nasopharynx into the normally sterile middle-ear space, the fluid may then become infected — usually with bacteria. The virus that caused the initial upper respiratory infection can itself be identified as the pathogen causing the infection.[18] ## Diagnosis[edit] Perforation of the right tympanic membrane resulting from a previous severe acute otitis media As its typical symptoms overlap with other conditions, such as acute external otitis, symptoms alone are not sufficient to predict whether acute otitis media is present; it has to be complemented by visualization of the tympanic membrane.[19][20] Examiners may use a pneumatic otoscope with a rubber bulb attached to assess the mobility of the tympanic membrane. Other methods to diagnose otitis media is with a tympanometry, reflectometry or hearing test. In more severe cases, such as those with associated hearing loss or high fever, audiometry, tympanogram, temporal bone CT and MRI can be used to assess for associated complications, such as mastoid effusion, subperiosteal abscess formation, bony destruction, venous thrombosis or meningitis.[21] Acute otitis media in children with moderate to severe bulging of the tympanic membrane or new onset of otorrhea (drainage) is not due to external otitis. Also, the diagnosis may be made in children who have mild bulging of the ear drum and recent onset of ear pain (less than 48 hours) or intense erythema (redness) of the ear drum. To confirm the diagnosis, middle-ear effusion and inflammation of the eardrum have to be identified; signs of these are fullness, bulging, cloudiness and redness of the eardrum.[1] It is important to attempt to differentiate between acute otitis media and otitis media with effusion (OME), as antibiotics are not recommended for OME.[1] It has been suggested that bulging of the tympanic membrane is the best sign to differentiate AOM from OME, with a bulging of the membrane suggesting AOM rather than OME.[22] Viral otitis may result in blisters on the external side of the tympanic membrane, which is called bullous myringitis (myringa being Latin for "eardrum").[23] However, sometimes even examination of the eardrum may not be able to confirm the diagnosis, especially if the canal is small. If wax in the ear canal obscures a clear view of the eardrum it should be removed using a blunt cerumen curette or a wire loop. Also, an upset young child's crying can cause the eardrum to look inflamed due to distension of the small blood vessels on it, mimicking the redness associated with otitis media. ### Acute otitis media[edit] The most common bacteria isolated from the middle ear in AOM are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis,[1] and Staphylococcus aureus.[24] ### Otitis media with effusion[edit] Otitis media with effusion (OME), also known as serous otitis media (SOM) or secretory otitis media (SOM), and colloquially referred to as 'glue ear,'[25] is fluid accumulation that can occur in the middle ear and mastoid air cells due to negative pressure produced by dysfunction of the Eustachian tube. This can be associated with a viral upper respiratory infection (URI) or bacterial infection such as otitis media.[26] An effusion can cause conductive hearing loss if it interferes with the transmission of vibrations of middle ear bones to the vestibulocochlear nerve complex that are created by sound waves.[27] Early-onset OME is associated with feeding of infants while lying down, early entry into group child care, parental smoking, lack, or too short a period of breastfeeding and greater amounts of time spent in group child care, particularly those with a large number of children. These risk factors increase the incidence and duration of OME during the first two years of life.[28] ### Chronic suppurative otitis media[edit] Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear and mastoid cavity that is characterised by discharge from the middle ear through a perforated tympanic membrane for at least 6 weeks. CSOM occurs following an upper respiratory tract infection that has led to acute otitis media. This progresses to a prolonged inflammatory response causing mucosal (middle ear) oedema, ulceration and perforation. The middle ear attempts to resolve this ulceration by production of granulation tissue and polyp formation. This can lead to increased discharge and failure to arrest the inflammation, and to development of CSOM, which is also often associated with cholesteatoma. There may be enough pus that it drains to the outside of the ear (otorrhea), or the pus may be minimal enough to be seen only on examination with an otoscope or binocular microscope. Hearing impairment often accompanies this disease.People are at increased risk of developing CSOM when they have poor eustachian tube function, a history of multiple episodes of acute otitis media, live in crowded conditions, and attend paediatric day care facilities. Those with craniofacial malformations such as cleft lip and palate, Down syndrome, and microcephaly are at higher risk.[citation needed] Worldwide approximately 11% of the human population is affected by AOM every year, or 709 million cases.[13][14] About 4.4% of the population develop CSOM.[14] According to the World Health Organization, CSOM is a primary cause of hearing loss in children.[29] Adults with recurrent episodes of CSOM have a higher risk of developing permanent conductive and sensorineural hearing loss. In Britain, 0.9% of children and 0.5% of adults have CSOM, with no difference between the sexes.[29] The incidence of CSOM across the world varies dramatically where high income countries have a relatively low prevalence while in low income countries the prevalence may be up to three times as great.[13] Each year 21,000 people worldwide die due to complications of CSOM.[29] ### Adhesive otitis media[edit] Adhesive otitis media occurs when a thin retracted ear drum becomes sucked into the middle-ear space and stuck (i.e., adherent) to the ossicles and other bones of the middle ear. * Acute otitis media * Acute otitis media, myringitis bullosa * Myringitis bullosa in influenza * Chronic otitis media (otitis media chronica mesotympanalis) * Otitis media chronica mesotympanalis * Otitis media chronica mesotympanalis * Otitis media chronica mesotympanalis ## Prevention[edit] AOM is far less common in breastfed infants than in formula-fed infants,[30] and the greatest protection is associated with exclusive breastfeeding (no formula use) for the first six months of life.[1] A longer duration of breastfeeding is correlated with a longer protective effect.[30] Pneumococcal conjugate vaccines (PCV) in early infancy decrease the risk of acute otitis media in healthy infants.[31] PCV is recommended for all children, and, if implemented broadly, PCV would have a significant public health benefit.[1] Influenza vaccination in children appears to reduce rates of AOM by 4% and the use of antibiotics by 11% over 6 months.[32] However, the vaccine resulted in increased adverse-effects such as fever and runny nose.[32] The small reduction in AOM may not justify the side effects and inconvenience of influenza vaccination every year for this purpose alone.[32] PCV does not appear to decrease the risk of otitis media when given to high-risk infants or for older children who have previously experienced otitis media.[31] Risk factors such as season, allergy predisposition and presence of older siblings are known to be determinants of recurrent otitis media and persistent middle-ear effusions (MEE).[33] History of recurrence, environmental exposure to tobacco smoke, use of daycare, and lack of breastfeeding have all been associated with increased risk of development, recurrence, and persistent MEE.[34][35] Pacifier use has been associated with more frequent episodes of AOM.[36] Long-term antibiotics, while they decrease rates of infection during treatment, have an unknown effect on long-term outcomes such as hearing loss.[37] This method of prevention has been associated with emergence of antibiotic-resistant otitic bacteria. They are thus not recommended.[1] There is moderate evidence that the sugar substitute xylitol may reduce infection rates in those who go to daycare.[38] Evidence does not support zinc supplementation as an effort to reduce otitis rates except maybe in those with severe malnutrition such as marasmus.[39] Probiotics do not show evidence of preventing acute otitis media in children.[40] ## Management[edit] Oral and topical pain killers are effective to treat the pain caused by otitis media. Oral agents include ibuprofen, paracetamol (acetaminophen), and opiates. Evidence for the combination over single agents is lacking.[41] Topical agents shown to be effective include antipyrine and benzocaine ear drops.[42] Decongestants and antihistamines, either nasal or oral, are not recommended due to the lack of benefit and concerns regarding side effects.[43] Half of cases of ear pain in children resolve without treatment in three days and 90% resolve in seven or eight days.[44] The use of steroids is not supported by the evidence for acute otitis media.[45][46] ### Antibiotics[edit] It is important to weigh the benefits and harms before using antibiotics for acute otitis media. As over 82% of acute episodes settle without treatment, about 20 children must be treated to prevent one case of ear pain, 33 children to prevent one perforation, and 11 children to prevent one opposite-side ear infection. For every 14 children treated with antibiotics, one child has an episode of either vomiting, diarrhea or a rash.[11] If pain is present, pain medications may be used. For people requiring surgery to treat otitis media with effusion, preventative antibiotics may not help reduce the risk of post-surgical complications.[47] For bilateral acute otitis media in infants younger than 24 months of age, there is evidence that the benefits of antibiotics outweigh the harms.[11] A 2015 Cochrane review concluded that watchful waiting is the preferred approach for children over six months with non severe acute otitis media.[48] Summary[48] Outcome Findings in words Findings in numbers Quality of evidence Pain Pain at 24 hours Antibiotics causes little or no reduction to the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on high quality evidence. RR 0.89 (0.78 to 1.01) High Pain at 2 to 3 days Antibiotics slightly reduces the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on high quality evidence. RR 0.70 (0.57 to 0.86) High Pain at 4 to 7 days Antibiotics slightly reduces the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on high quality evidence. RR 0.76 (0.63 to 0.91) High Pain at 10 to 12 days Antibiotics probably reduces the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on moderate quality evidence. RR 0.33 (0.17 to 0.66) Moderate Abnormal tympanometry 2 to 4 weeks Antibiotics slightly reduces the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on high quality evidence. RR 0.82 (0.74 to 0.90) High 3 months Antibiotics causes little or no reduction to the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on high quality evidence. RR 0.97 (0.76 to 1.24) High Vomiting Diarrhoea or rash Antibiotics slightly increases the chance of experiencing the outcome when compared with placebo for acute otitis media in children. Data are based on high quality evidence. RR 1.38 (1.19 to 1.59) High Most children older than 6 months of age who have acute otitis media do not benefit from treatment with antibiotics. If antibiotics are used, a narrow-spectrum antibiotic like amoxicillin is generally recommended, as broad-spectrum antibiotics may be associated with more adverse events.[1][49] If there is resistance or use of amoxicillin in the last 30 days then amoxicillin-clavulanate or another penicillin derivative plus beta lactamase inhibitor is recommended.[1] Taking amoxicillin once a day may be as effective as twice[50] or three times a day. While less than 7 days of antibiotics have fewer side effects, more than seven days appear to be more effective.[51] If there is no improvement after 2–3 days of treatment a change in therapy may be considered.[1] Azithromycin appears to have less side effects than either high dose amoxicillin or amoxicillin/clavulanate.[52] ### Tympanostomy tube[edit] Tympanostomy tubes (also called "grommets") are recommended with three or more episodes of acute otitis media in 6 months or four or more in a year, with at least one episode or more attacks in the preceding 6 months.[1] There is tentative evidence that children with recurrent acute otitis media (AOM) who receive tubes have a modest improvement in the number of further AOM episodes (around one fewer episode at six months and less of an improvement at 12 months following the tubes being inserted).[53][54] Evidence does not support an effect on long-term hearing or language development.[54][55] A common complication of having a tympanostomy tube is otorrhea, which is a discharge from the ear.[56] The risk of persistent tympanic membrane perforation after children have grommets inserted may be low.[53] It is still uncertain whether or not grommets are more effective than a course of antibiotics.[53] Oral antibiotics should not be used to treat uncomplicated acute tympanostomy tube otorrhea.[56] They are not sufficient for the bacteria that cause this condition and have side effects including increased risk of opportunistic infection.[56] In contrast, topical antibiotic eardrops are useful.[56] ### Otitis media with effusion[edit] The decision to treat is usually made after a combination of physical exam and laboratory diagnosis, with additional testing including audiometry, tympanogram, temporal bone CT and MRI.[57][58][59] Decongestants,[60] glucocorticoids,[61] and topical antibiotics are generally not effective as treatment for non-infectious, or serous, causes of mastoid effusion.[57] Moreover, it is recommended against using antihistamines and decongestants in children with OME.[60] In less severe cases or those without significant hearing impairment, the effusion can resolve spontaneously or with more conservative measures such as autoinflation.[62][63] In more severe cases, tympanostomy tubes can be inserted,[55] possibly with adjuvant adenoidectomy[57] as it shows a significant benefit as far as the resolution of middle ear effusion in children with OME is concerned.[64] ### Chronic suppurative otitis media[edit] Topical antibiotics are of uncertain benefit as of 2020.[65] Some evidence suggests that topical antibiotics may be useful either alone or with antibiotics by mouth.[65] Antiseptics are of unclear effect.[66] Topical antibiotics (quinolones) are probably better at resolving ear discharge than antiseptics.[67] ### Alternative medicine[edit] Complementary and alternative medicine is not recommended for otitis media with effusion because there is no evidence of benefit.[26] Homeopathic treatments have not been proven to be effective for acute otitis media in a study with children.[68] An osteopathic manipulation technique called the Galbreath technique[69] was evaluated in one randomized controlled clinical trial; one reviewer concluded that it was promising, but a 2010 evidence report found the evidence inconclusive.[70] ## Outcomes[edit] Disability-adjusted life year for otitis media per 100,000 inhabitants in 2004. no data < 10 10–14 14–18 18–22 22–26 26–30 30–34 34–38 38–42 42–46 46–50 > 50 Deaths from otitis media per million persons in 2012 0 1 2–4 Complications of acute otitis media consists of perforation of the ear drum, infection of the mastoid space behind the ear (mastoiditis), and more rarely intracranial complications can occur, such as bacterial meningitis, brain abscess, or dural sinus thrombosis.[71] It is estimated that each year 21,000 people die due to complications of otitis media.[13] ### Membrane rupture[edit] In severe or untreated cases, the tympanic membrane may perforate, allowing the pus in the middle-ear space to drain into the ear canal. If there is enough, this drainage may be obvious. Even though the perforation of the tympanic membrane suggests a highly painful and traumatic process, it is almost always associated with a dramatic relief of pressure and pain. In a simple case of acute otitis media in an otherwise healthy person, the body's defenses are likely to resolve the infection and the ear drum nearly always heals. An option for severe acute otitis media in which analgesics are not controlling ear pain is to perform a tympanocentesis, i.e., needle aspiration through the tympanic membrane to relieve the ear pain and to identify the causative organism(s). ### Hearing loss[edit] Children with recurrent episodes of acute otitis media and those with otitis media with effusion or chronic suppurative otitis media have higher risks of developing conductive and sensorineural hearing loss. Globally approximately 141 million people have mild hearing loss due to otitis media (2.1% of the population).[72] This is more common in males (2.3%) than females (1.8%).[72] This hearing loss is mainly due to fluid in the middle ear or rupture of the tympanic membrane. Prolonged duration of otitis media is associated with ossicular complications and, together with persistent tympanic membrane perforation, contributes to the severity of the disease and hearing loss. When a cholesteatoma or granulation tissue is present in the middle ear, the degree of hearing loss and ossicular destruction is even greater.[73] Periods of conductive hearing loss from otitis media may have a detrimental effect on speech development in children.[74][75][76] Some studies have linked otitis media to learning problems, attention disorders, and problems with social adaptation.[77] Furthermore, it has been demonstrated that patients with otitis media have more depression/anxiety-related disorders compared to individuals with normal hearing.[78] Once the infections resolve and hearing thresholds return to normal, childhood otitis media may still cause minor and irreversible damage to the middle ear and cochlea.[79] More research on the importance of screening all children under 4 years old for otitis media with effusion needs to be performed.[75] ## Epidemiology[edit] Acute otitis media is very common in childhood. It is the most common condition for which medical care is provided in children under five years of age in the US.[18] Acute otitis media affects 11% of people each year (709 million cases) with half occurring in those below five years.[13] Chronic suppurative otitis media affects about 5% or 31 million of these cases with 22.6% of cases occurring annually under the age of five years.[13] Otitis media resulted in 2,400 deaths in 2013—down from 4,900 deaths in 1990.[16] ## Etymology[edit] The term otitis media is composed of otitis, Ancient Greek for "inflammation of the ear", and media, Latin for "middle". ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, et al. (March 2013). "The diagnosis and management of acute otitis media". Pediatrics. 131 (3): e964-99. doi:10.1542/peds.2012-3488. PMID 23439909. 2. ^ a b c Qureishi A, Lee Y, Belfield K, Birchall JP, Daniel M (January 2014). 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The Cochrane Database of Systematic Reviews. 1: CD013051. doi:10.1002/14651858.CD013051.pub2. PMC 6956124. PMID 31896168. 66. ^ Head K, Chong LY, Bhutta MF, Morris PS, Vijayasekaran S, Burton MJ, et al. (January 2020). Cochrane ENT Group (ed.). "Topical antiseptics for chronic suppurative otitis media". The Cochrane Database of Systematic Reviews. 1: CD013055. doi:10.1002/14651858.CD013055.pub2. PMC 6956662. PMID 31902140. 67. ^ Head K, Chong LY, Bhutta MF, Morris PS, Vijayasekaran S, Burton MJ, et al. (Cochrane ENT Group) (January 2020). "Antibiotics versus topical antiseptics for chronic suppurative otitis media". The Cochrane Database of Systematic Reviews. 1: CD013056. doi:10.1002/14651858.CD013056.pub2. PMC 6956626. PMID 31902139. 68. ^ Jacobs J, Springer DA, Crothers D (February 2001). "Homeopathic treatment of acute otitis media in children: a preliminary randomized placebo-controlled trial". The Pediatric Infectious Disease Journal. 20 (2): 177–83. doi:10.1097/00006454-200102000-00012. PMID 11224838. 69. ^ Pratt-Harrington D (October 2000). "Galbreath technique: a manipulative treatment for otitis media revisited". The Journal of the American Osteopathic Association. 100 (10): 635–9. PMID 11105452. 70. ^ Bronfort G, Haas M, Evans R, Leininger B, Triano J (February 2010). "Effectiveness of manual therapies: the UK evidence report". Chiropractic & Osteopathy. 18 (1): 3. doi:10.1186/1746-1340-18-3. PMC 2841070. PMID 20184717. 71. ^ Jung TT, Alper CM, Hellstrom SO, Hunter LL, Casselbrant ML, Groth A, et al. (April 2013). "Panel 8: Complications and sequelae". Otolaryngology–Head and Neck Surgery. 148 (4 Suppl): E122-43. doi:10.1177/0194599812467425. PMID 23536529. S2CID 206466859. 72. ^ a b Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. (December 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607. 73. ^ da Costa SS, Rosito LP, Dornelles C (February 2009). "Sensorineural hearing loss in patients with chronic otitis media". European Archives of Oto-Rhino-Laryngology. 266 (2): 221–4. doi:10.1007/s00405-008-0739-0. hdl:10183/125807. PMID 18629531. S2CID 2932807. 74. ^ Roberts K (June 1997). "A preliminary account of the effect of otitis media on 15-month-olds' categorization and some implications for early language learning". Journal of Speech, Language, and Hearing Research. 40 (3): 508–18. doi:10.1044/jslhr.4003.508. PMID 9210110. 75. ^ a b Simpson SA, Thomas CL, van der Linden MK, Macmillan H, van der Wouden JC, Butler C (January 2007). "Identification of children in the first four years of life for early treatment for otitis media with effusion". The Cochrane Database of Systematic Reviews (1): CD004163. doi:10.1002/14651858.CD004163.pub2. PMID 17253499. 76. ^ Macfadyen, C. A.; Acuin, J. M.; Gamble, C. (2005-10-19). "Topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations". The Cochrane Database of Systematic Reviews (4): CD004618. doi:10.1002/14651858.CD004618.pub2. ISSN 1469-493X. PMC 6669264. PMID 16235370. 77. ^ Bidadi S, Nejadkazem M, Naderpour M (November 2008). "The relationship between chronic otitis media-induced hearing loss and the acquisition of social skills". Otolaryngology–Head and Neck Surgery. 139 (5): 665–70. doi:10.1016/j.otohns.2008.08.004. PMID 18984261. S2CID 37667672. 78. ^ Gouma P, Mallis A, Daniilidis V, Gouveris H, Armenakis N, Naxakis S (January 2011). "Behavioral trends in young children with conductive hearing loss: a case-control study". European Archives of Oto-Rhino-Laryngology. 268 (1): 63–6. doi:10.1007/s00405-010-1346-4. PMID 20665042. S2CID 24611204. 79. ^ Yilmaz S, Karasalihoglu AR, Tas A, Yagiz R, Tas M (February 2006). "Otoacoustic emissions in young adults with a history of otitis media". The Journal of Laryngology and Otology. 120 (2): 103–7. doi:10.1017/S0022215105004871. PMID 16359151. ## External links[edit] * Neff MJ (June 2004). "AAP, AAFP, AAO-HNS release guideline on diagnosis and management of otitis media with effusion". American Family Physician. 69 (12): 2929–31. PMID 15222658. * Secretory otitis media (Ear disorder) at the Encyclopædia Britannica * Otitis media (Pathology) at the Encyclopædia Britannica Classification D * ICD-10: H65-H67 * ICD-9-CM: 017.40, 055.2, 381.0, 381.1, 381.2, 381.3, 381.4, 382 * MeSH: D010033 * DiseasesDB: 29620 External resources * MedlinePlus: 000638 * eMedicine: emerg/351 ent/426 complications, ent/209 with effusion, ent/212 Medical treat., ent/211 Surgical treat. ped/1689 Wikimedia Commons has media related to Otitis media. * v * t * e Diseases of the outer and middle ear Outer ear * Otitis externa * Otomycosis Middle ear and mastoid * Otitis media * Mastoiditis * Bezold's abscess * Gradenigo's syndrome * Tympanosclerosis * Cholesteatoma * Perforated eardrum Symptoms * Ear pain * Hearing loss Tests * Otoscope * pneumatic * tympanometry * v * t * e Common cold Viruses * Adenovirus * Coronavirus * Enterovirus * Rhinovirus Symptoms * Cough * Fatigue * Fever * Headache * Loss of appetite * Malaise * Muscle aches * Nasal congestion * Rhinorrhea * Sneezing * Sore throat * Weakness Complications * Acute bronchitis * Bronchiolitis * Croup * Otitis media * Pharyngitis * Pneumonia * Sinusitis * Strep throat Drugs * Antiviral drugs * Pleconaril (experimental) Authority control * NDL: 00573957 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Otitis media	c0029882	26,203	wikipedia	https://en.wikipedia.org/wiki/Otitis_media	2021-01-18T19:01:14	{"mesh": ["D010033"], "umls": ["C0029882"], "wikidata": ["Q223254"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Familial atrial fibrillation" – news · newspapers · books · scholar · JSTOR (September 2019) Familial atrial fibrillation Familial atrial fibrillation has an autosomal dominant pattern of inheritance. SpecialtyMedical genetics, cardiology Familial atrial fibrillation is an autosomal dominant heart condition that causes disruptions in the heart's normal rhythm.[1][2] This condition is characterized by uncoordinated electrical activity in the heart's upper chambers (the atria), which causes the heartbeat to become fast and irregular. ## Contents * 1 Cause * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Cause[edit] It is associated with multiple genes: Type OMIM Gene Locus ATFB1 608583 ? 10q22-q24 ATFB2 608988 ? 6q ATFB3 607554 KCNQ1 11 ATFB4 611493 KCNE2 21 ATFB5 611494 ? 4q25 ATFB6 612201 NPPA 1p36-p35 ATFB7 612240 KCNA5 12p13 ATFB8 613055 ? 16q22 Mutations in the KCNQ1 gene cause familial atrial fibrillation. The KCNE2 and KCNJ2 genes are associated with familial atrial fibrillation. A small percentage of all cases of familial atrial fibrillation are associated with changes in the KCNE2, KCNJ2, and KCNQ1 genes. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged potassium ions into and out of cells. In heart muscle, the ion channels produced from the KCNE2, KCNJ2, and KCNQ1 genes play critical roles in maintaining the heart's normal rhythm. Mutations in these genes have been identified in only a few families worldwide. These mutations increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, increasing the risk of syncope, stroke, and sudden death.[citation needed] Most cases of atrial fibrillation are not caused by mutations in a single gene. This condition is often related to structural abnormalities of the heart or underlying heart disease. Additional risk factors for atrial fibrillation include high blood pressure (hypertension), diabetes mellitus, a previous stroke, or an accumulation of fatty deposits and scar-like tissue in the lining of the arteries (atherosclerosis). Although most cases of atrial fibrillation are not known to run in families, studies suggest that they may arise partly from genetic risk factors. Researchers are working to determine which genetic changes may influence the risk of atrial fibrillation.[citation needed] Familial atrial fibrillation appears to be inherited in an autosomal dominant pattern, which means the defective gene is located on an autosome, and only one copy of the defective gene - inherited from one parent - is sufficient to cause the disorder. ## Diagnosis[edit] If untreated, this abnormal heart rhythm can lead to dizziness, chest pain, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, or fainting (syncope). Atrial fibrillation also increases the risk of stroke. Complications of familial atrial fibrillation can occur at any age, although some people with this heart condition never experience any health problems associated with the disorder.Atrial fibrillation is the most common type of sustained abnormal heart rhythm (arrhythmia), affecting more than 3 million people in the United States. The risk of developing this irregular heart rhythm increases with age. The incidence of the familial form of atrial fibrillation is unknown; however, recent studies suggest that up to 30 percent of all people with atrial fibrillation may have a history of the condition in their family.[citation needed] ## Treatment[edit] This section is empty. You can help by adding to it. (December 2017) ## References[edit] 1. ^ Reference, Genetics Home. "Familial atrial fibrillation". Genetics Home Reference. Retrieved 29 September 2019. 2. ^ "Familial atrial fibrillation \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 29 September 2019. ## External links[edit] Classification D * OMIM: 608583 * MeSH: C563817 * DiseasesDB: 34356 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever * v * 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) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Familial atrial fibrillation	c1837014	26,204	wikipedia	https://en.wikipedia.org/wiki/Familial_atrial_fibrillation	2021-01-18T19:07:27	{"gard": ["9740"], "mesh": ["C563817"], "umls": ["C1837014"], "orphanet": ["334"], "wikidata": ["Q5432932"]}
Ewing sarcoma is a type of cancerous tumor that mainly affects children and young adults. Ewing sarcoma usually occurs in the long bones of the arms and legs, pelvis, or chest. Symptoms may include swelling over the location of the tumor, and pain which gets worse over time. Other symptoms may depend on the size and location of the tumor. Ewing sarcoma can spread to other parts of the body (metastasize), and other symptoms may develop such as fever, night sweats, and tiredness. The cause of Ewing sarcoma is unknown. Diagnosis is based on a clinical examination, health history, imaging studies, and blood tests. A biopsy to examine a small piece of the tumor under a microscope is also often done. Treatment depends upon the size, location, and whether the tumor has spread. It usually includes chemotherapy, radiation and/or surgery. Many people with Ewing sarcoma experience side effects from treatment which can include decreased numbers of white blood cells, infections, fever, and an increased risk for a second cancer. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Ewing sarcoma	c0553580	26,205	gard	https://rarediseases.info.nih.gov/diseases/6390/ewing-sarcoma	2021-01-18T18:00:39	{"mesh": ["D012512"], "omim": ["612219"], "umls": ["C0553580"], "orphanet": ["319"], "synonyms": ["Ewing's tumor", "Sarcoma, Ewing's", "Ewing tumor", "Ewing's sarcoma"]}
Hirschsprung disease-type D brachydactyly syndrome is characterized by Hirschsprung disease and absence or hypoplasia of the nails and distal phalanges of the thumbs and great toes (type D brachydactyly). It has been described in four males from one family (two brothers and two maternal uncles). Transmission appears to be X-linked recessive but autosomal dominant inheritance with incomplete penetrance in females can not be ruled out. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Hirschsprung disease-type D brachydactyly syndrome	c1844017	26,206	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2150	2021-01-23T17:36:40	{"gard": ["2700"], "mesh": ["C538319"], "omim": ["306980"], "umls": ["C1844017"], "icd-10": ["Q43.1"]}
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(March 2018) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Occult fracture SpecialtyOrthopaedic An occult fracture is a fracture that is not readily visible, generally in regard to projectional radiography ("X-ray"). Radiographically, occult and subtle fractures are a diagnostic challenge. They may be divided into (1) "high energy trauma fracture," (2) "fatigue fracture" from cyclical and sustained mechanical stress, and (3) "insufficiency fracture" occurring in weakened bone (e.g., in osteoporosis and postradiotherapy). Independently of the cause, the initial radiographic examination can be negative either because the findings seem normal or are too subtle. Advanced imaging tools such as computed tomography, magnetic resonance imaging, and scintigraphy are highly valuable in the early detection of these fractures.[1] Fractures represent up to 80% of the missed diagnoses in the emergency department. Failure to recognize the subtle signs of osseous injury is one of the reasons behind this major diagnostic challenge. While occult fractures present no radiographic findings, radiographically subtle fractures are easily overlooked on initial radiographs. In both cases, a negative radiographic diagnosis with prominent clinical suspicion of osseous injury will prompt advanced imaging examination such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine to confirm or exclude the clinically suspected diagnosis. The burden entailed in missing these fractures includes prolonged pain with a loss of function, and disability. Early detection, on the other hand, enables more effective treatment, a shorter hospitalization period if necessary, and decreased medical costs in the long run. It will also prevent inherent complications such as nonunion, malunion, premature osteoarthritis, and avascular osteonecrosis (as in scaphoid fracture). Occult and subtle fractures may be divided into: (1) fractures associated with high energy trauma; fatigue fracture secondary to repetitive and unusual stress being applied to bone with normal elastic resistance; and insufficiency fracture resulting from normal or minimal stress on a bone with decreased elastic resistance. The term "stress fracture" is more general and encompasses both of the latter two entities.[1] Radiographically occult and subtle fractures are often a challenging diagnostic problem in daily clinical practice. Radiologists should be aware of the different situations and mechanisms of these injuries as well as the subtle radiographic signs that can be encountered in each situation. The knowledge of normal images and the consideration of the clinical context are of great value in improving the detection of these fractures either on conventional radiographs or with more advanced imaging tools.[1] ## Contents * 1 Imaging tools * 1.1 Projectional radiography * 1.2 Computed Tomography * 1.3 Magnetic resonance imaging * 1.4 Nuclear medicine * 1.5 Ultrasonography * 2 High-energy trauma fractures * 3 Fatigue fractures * 4 Insufficiency fractures * 5 References ## Imaging tools[edit] Thanks to rapid technological advancement, new and more efficient imaging hardware is constantly released for all imaging modalities including CT, MRI, nuclear medicine, and ultrasound. Nonetheless, not every department can afford all new technologies, and radiologists sometimes have to face the challenge of providing the highest diagnostic performance with basic imaging tools. This can only be achieved by ensuring high quality of examination with the available imaging tools.[1] ### Projectional radiography[edit] Radiography is the first step for detection of fractures. The detection of subtle signs of fracture requires a high standard for the acquisition technique and a thorough and systematic interpretation of radiographic images. Correct diagnosis primarily relies on the reader's experience. Awareness of normal anatomic features is crucial for the interpreter to be able to detect subtle signs of fracture. Fat pads should be carefully examined for convexity, which implies joint effusion (e.g., in the hip and elbow). However, the radiographic technique (positioning in particular) must be optimal for this evaluation to be valid. Osseous lines should be checked for integrity (e.g., acetabular rim in the hip). Trabecular angulation, impaction lines, and sclerotic bands also suggest fracture in osseous structures with a significant proportion of cancellous bone such as proximal femur.[1] The general rule is to perform two orthogonal views, but more specific views should be added if there is any suspicion of fracture. Moreover, one should be aware of the commonly encountered lesions and their locations. In wrist trauma, for instance, the interpreter should pay close attention to the scaphoid and triquetrum, which are the two most commonly injured carpal bones. The mechanism of trauma may also be helpful to locate the potential fracture. A fall on an outstretched hand suggests scaphoid fracture. Although the classical presentation consists of a radiolucent line and cortical disruption, the radiographic signs will depend upon the time elapsed between the first clinical symptoms and the time of radiographic examination, the location of the fracture within the bone, and the ratio of cortical to cancellous bone. Particular attention should be paid when analysing the subchondral plate, which may be disrupted or deformed. In metaphyseal areas, delayed signs of fracture include a band of sclerosis perpendicular to the trabeculae, while diaphyseal fractures may present as periosteal thickening.[1] Digital radiography known as tomosynthesis has been shown to be superior to conventional radiographs in the detection of occult fracture of the scaphoid. Tomosynthesis has the ability to demonstrate cortical, as well as moderately displaced trabecular fractures. Thus, the performance of tomosynthesis in detecting radiographically occult fractures is considered as comparable to CT.[1] ### Computed Tomography[edit] Multidetector computed tomography (MDCT) is a highly valuable imaging tool for the diagnosis of occult fractures. CT has several advantages including short acquisition time (compared to MRI), the ability to acquire volumetric and isotropic image data sets, the opportunity to reconstruct multiplanar reformations in any arbitrary plane, and excellent spatial resolution. Moreover, the image quality for multiplanar reconstruction may be increased by reducing slice thickness and acquisition pitch. In general, bony structures are best demonstrated by using a small focal spot and using a "bone" algorithm. CT contributes much to the diagnosis of occult fractures by depicting subtle fracture lines, depressed, or distracted articular surfaces and by assessing bone loss It also detects late bony changes such as increased medullary density, endosteal sclerosis, sclerotic lines in trabecular bone, and periosteal thickening. Moreover, CT aids in excluding other differential diagnoses, especially in case of isolated bone marrow edema, by confirming the normal appearance of the remaining trabeculae and excluding space-occupying lesions such as malignancy and osteomyelitis.[1] Newest generation of CT, such as dedicated cone-beam CT (CBCT) system for musculoskeletal extremities, may be beneficial in various conditions, such as arthritis and occult fractures. Although dedicated CBCT for musculoskeletal extremities is still a matter of research, it has been shown to be of potential benefit as an adjunct for CT and MRI. It offers the possibility of volumetric imaging, which may be helpful in case of suspected occult fractures. It also provides higher spatial resolution and a potentially reduced dose compared to CT.[1] ### Magnetic resonance imaging[edit] The diagnostic performance of MRI in the detection of occult fractures has been shown to be comparable, or better than MDCT. Indeed, while the specificity of both CT and MRI for the diagnosis of fracture can be as high as 100%, the sensitivity was reported to be higher for MRI. The superiority of MRI over any other imaging modality including MDCT for the detection of occult hip fractures is now recognised. For instance, an occult intertrochanteric extension of a greater trochanter fracture can be most effectively appreciated on MRI Moreover, MRI is extremely helpful in detecting associated soft tissue abnormalities, especially ligamentous lesions. MRI is now considered as the standard in this context. However, because of its relative unavailability in emergency settings and high costs, MRI may only be performed in "high risk patients" with negative X-rays. For example, when a hip occult fracture is suspected, patients with reduced baseline mobility and pain on axial compression are considered at risk and, therefore, should be examined by MRI. MRI signs of occult fractures are evident several weeks before radiographic signs appear. In the hip, a limited and cost-effective MR protocol, with only T1 weighted () coronal images, may enable a reliable diagnosis or exclusion of occult fracture in very little time, for example, 7 minutes. Typically, a linear hypointensity is observed on T1 W images. MRI is also highly sensitive to marrow abnormalities surrounding the fracture line, which appear as hypointensity on T1 W images and hyperintensity on fluid-sensitive sequences. Such signal changes are thought to be a combination of bone marrow edema, intraosseous haemorrhage, and/or granulation tissue and help to identify even undisplaced fractures. However, in the absence of a history of trauma and linear hypointensities on T1 W images, isolated bone marrow edema may represent other pathologies such as osteoid osteoma and sclerosing osteomyelitis.[1] Although 1.5 T and 3 T MR is considered as the current gold standard for the detection of radiographically occult fractures, ultra-high field MR provide higher signal-to-noise ratio and, therefore, is expected to be superior to 1.5 T and 3 T. Ultra-high field MR seems to be promising in the diagnosis of a variety of musculoskeletal conditions including trauma, but it is not used in daily routine yet.[1] ### Nuclear medicine[edit] The most traditional method is bone scintigraphy. Although scintigraphy is highly sensitive for the detection of occult fracture, its lack of specificity limits its diagnostic utility. However, when MRI is not available, scintigraphy may be of value, especially in the absence of trauma history, for example, for detection of insufficiency and fatigue fractures. While radiography may show only late signs of bone reaction (such as periosteal thickening and band of sclerosis), scintigraphic examination allows for earlier detection of bony changes. Regarding Fluorine-18 2-deoxy-D-glucose (FDG) positron emission tomography (PET), it is critical to be aware that occult fractures may be responsible of marked metabolic uptake, and, thus, represent a potential false positive of metastatic disease. Integrated hybrid single-photon emission computerized tomography (SPECT)/CT combines the detection of abnormal bone metabolism with SPECT, to the precise anatomical detail provided by high resolution CT. For instance, SPECT/CT may be interesting in the detection of radiographic occult fractures of the wrist and other sport-related injuries.[1] ### Ultrasonography[edit] High frequency ultrasound has been shown to be of value, particularly in the pediatric population. In this case, and in an emergency setting, ultrasonography can be more accessible and less time-consuming than radiographs and has high specificity and sensitivity in the evaluation of suspected long bone fractures. The utility of ultrasonography has also been shown for adults with suspicion of wrist trauma or fatigue/stress fracture. Recently, it has been suggested that therapeutic ultrasound may be beneficial as a primary evaluation of bone stress injury; however, its benefit seems to be more evident in selected high-risk patients rather than general population.[1] ## High-energy trauma fractures[edit] Occult osseous injuries may result from a direct blow to the bone by compressive forces of adjacent bones against one another or by traction forces during an avulsion injury. Lesions in the tibial plateau, hip, ankle, and wrist are often missed. In a tibial plateau fracture, any disruption of the posterior and anterior cortical rims of the plateau should be sought. Impaction of subchondral bone will appear as an increased sclerosis of the subchondral bone (Figure 1). In the hip, posterior acetabular fractures also present subtle radiographic findings. The acetabular lines should then be carefully examined keeping in mind that the posterior rim, which is harder to see on X-rays, is more frequently fractured than the anterior rim (Figure 2). In the wrist, detection of carpal bone fractures is often challenging, with up to 18% of scaphoid fractures radiographically occult. Carpal fractures, especially the scaphoid, are associated with the risk of avascular necrosis. In apparently normal wrist radiographs from symptomatic patients, if there is history of a fall on an outstretched hand with pain in the anatomic snuffbox, suggesting scaphoid injury, the initial examination with posteroanterior, lateral, and pronation oblique views must be complemented by other specific views such as supination oblique and the "scaphoid" view A careful examination of cortices for evidence of discontinuity or offset and cancellous bone for lucency is necessary (Figure 3).[1] * a * b * c Figure 1: A 56-year-old woman presenting with left knee pain after a fall. (a) Initial anteroposterior radiograph was considered normal, however, subtle cortical disruption of the anterior rim of the medial tibial plateau, medial to the tibial spine, is noted (arrow). (b) Coronal T1-weighted MRI confirms the cortical disruption (arrow) and shows extensive fracture through the proximal tibia. (c) Coronal proton density-weighted image with fat saturation shows extensive edema in the subchondral bone. Note also hypersignal adjacent to the medial collateral ligament corresponding to a grade I sprain (arrowheads).[1] Figure 2: Posterior acetabular fracture in a 49-year-old woman presenting with hip pain after a fall. (a) Anteroposterior radiograph of the left hip shows a radiolucent line through the posterior acetabular wall (arrows). (b) Axial CT confirms the acetabular fracture (arrow).[1] * a * b * c Figure 3: A 26-year-old man presenting with wrist pain after being assaulted. (a) Initial anteroposterior radiograph shows a subtle linear lucency within the scaphoid extending to the scaphocapitate articular surface that was overlooked (arrow). (b) Initial "scaphoid" view was negative. (c) Followup anteroposterior radiographs, 12 days later, shows obvious scaphoid fracture (arrows).[1] Triquetral fracture usually occurs on the dorsal aspect by impingement from the ulnar styloid or avulsion of strong ligamentous attachment. The dorsal avulsion fracture or "chip fracture" appears as a small bony fragment on the dorsal aspect of the triquetrum and is best detected on the lateral view(Figure 4). When radiography is negative in patients with high suspicion of a fracture, both MRI and MDCT will be of value. However, it has been shown that MRI is superior for detecting trabecular fractures in carpal bones. * a * b Figure 4: Dorsal triquetral fracture of the left wrist in a 30-year-old man after a trauma. (a) Anteroposterior radiograph shows a normal appearance. (b) Lateral radiograph of the same wrist demonstrates a chip fracture off the dorsal aspect of the triquetrum (arrow).[1] The greater tuberosity of the humerus is also an illustrative location of occult fractures. The osseous injury may follow seizures, glenohumeral dislocation, forced abduction, or direct impaction. They are commonly discovered on MRI in symptomatic patients with suspicion of rotator cuff tear. Coronal images are best suited for detection. They appear as crescentic oblique lines surrounded by a bone marrow edema pattern (Figure 5). The rotator cuff must be inspected since associated ligamentous lesions are common. In the ankle, malleoli and tarsal bones should be checked carefully for any cortical disruptions and radiolucent lines that may reveal a fracture. Awareness of the exact location of the pain will help direct the attention of the interpreter when searching for very subtle signs of fracture (Figure 6).[1] Figure 5: Traumatic fracture of the greater tuberosity in a 51-year-old man presenting with left shoulder pain after a fall on ice. Initial radiographs were normal. Coronal inversion recovery MRI shows a fracture line (arrow) through the greater tuberosity surrounded by a bone marrow edema pattern.[1] * a * b Figure 6: Subtle anterior talar fracture in a 39-year-old man presenting with ankle pain after a fall. (a) Anteroposterior radiograph shows a subtle oblique radiolucent line through the talus (white arrows). (b) Sagittal CT reformation confirms the presence of an anterior talar fracture with cortical offset (black arrow). Avulsion fractures, which consist of a detached bone fragment resulting from a ligament or tendon pulling away from the bone, may also present with subtle radiographic signs. Tiny osseous fragments near the presumed attachment site of a ligament suggest this diagnosis. Common sites are the lateral tibial plateau (the Segond fracture), the spinal tuberosity of the tibia resulting from anterior cruciate ligament avulsion, and the ischial tuberosity.[1] ## Fatigue fractures[edit] Fatigue fractures occur when healthy bone is exposed to repeated stress. The bone is a living tissue, with the capacity to repair itself; fatigue fractures occur when repetitive injuries exceed the repair capacity of the bone. This type of fracture does not occur as a single event but rather incrementally as a sequence of cellular events that begin with increased osteoclastic activity. Microfractures occur later and are accompanied by bone marrow edema, which can be detected on MRI. This stage appears on MRI as an isolated bone marrow edema pattern without a fracture line and is called stress reaction. Then, periosteal new bone forms and may be visible on radiography. Full cortical fractures occur if the repetitive stress continues. Only timely detection and appropriate management can interrupt this sequence.[1] Fatigue fractures are more frequent in women which may be due to the relatively smaller bones of women. Moreover, pregnancy is a well-recognized risk factor for femoral neck fatigue fracture. While fibular and metatarsal fractures have a low risk of complications, other sites including the femoral neck, midanterior tibia, navicular, talar, and other intraarticular fractures are prone to complications such as delayed union, nonunion, and displacement. The site of the insufficiency fracture may be specific to the activity: for example, rugby and basketball players are more prone to navicular fractures, while gymnasts have a higher risk for talar fractures (Figure 7). Long distance runners are at increased risk for pelvic, tibial (Figures 8 and 9), and fibular fractures. In the military, calcaneus (Figure 10) and metatarsals are the most commonly cited injuries, especially in new recruits. Billiard players are at risk for upper limb fractures (Figure 11).[1] * a * b Figure 7: Fatigue fracture of the talus in a 25-year-old male basketball player with right hind foot and ankle pain, without history of trauma, and a normal initial radiograph (not shown). (a) One-month followup lateral radiograph shows normal appearance. (b) Sagittal T1-weighted MRI shows an irregular fracture line (arrow) within an ill-defined area of hypointensity corresponding to bone marrow edema.[1] * a * b * c Figure 8: Proximal diaphyseal fatigue fracture of the tibia in a 20-year-old man with a history of regular jogging. (a) Lateral radiograph shows no obvious fracture lines but a subtle localized medial tibial cortex periosteal reaction (arrows). (b) Sagittal reformatted CT image acquired 1-month after the radiograph shows a linear hypoattenuation in the tibial cortex (arrowhead), as well as obvious periosteal thickening (arrows). (c) Sagittal T2-weighted fat-saturated image acquired the same day shows an area of hyperintensity spreading over the proximal tibia (arrows), which is consistent with the presence of proximal tibial fracture.[1] * a * b Figure 9: Proximal metaphyseal fatigue fracture of the tibia in a 27-year-old recent male military recruit. (a) Anteroposterior radiograph is within normal limits. (b) Coronal T1-weighted MR image shows a marked linear hypoattenuation along the medial tibial metaphysis (arrow) surrounded by diffuse hypointensity in keeping with posttraumatic edema.[1] * a * b Figure 10: Calcaneal fatigue fracture in a 30-year-old male runner. Radiographs were normal (not shown). (a) Sagittal T1-weighted and (b) short tau inversion recovery images show a linear hypointensity (arrows) of calcaneal tuberosity within diffuse bone marrow edema, which appears as an ill-defined area of hyperintensity on a fluid sensitive pulse sequence (arrowheads).[1] * a * b * c Figure 11: Stress fracture of the right radius in a 40-year-old man, a semiprofessional billiard player, with no history of trauma and complaining of pain of the right forearm for one month. (a) Anteroposterior radiograph shows medial radial cortex periosteal reaction (arrow) but no fracture line is seen. (b) Coronal reformatted CT depicts monocortical fracture line through the periosteal thickening (arrowheads). (c) Coronal T2-weighted fat-suppressed MRI shows intramedullary hyperintensity within the bone marrow (arrow) corresponding to bone marrow edema.[1] Radiographic examination usually shows delayed signs of fracture up to 2 to 3 months after initial injury. In a bony region with a high proportion of cancellous bone (e.g., femoral neck), a fatigue fracture appears as an ill-defined transverse sclerotic band (in contact or close to the medial cortex), with a periosteal thickening appearing at a later stage. In case of continued stress, a fracture line through the thickened cortex and a region of sclerosis may be observed. MRI is of great value for early diagnosis and displaying bone marrow edema, while scintigraphy is useful for showing increased metabolic activity within the bone. However, MRI is preferred since scintigraphy lacks specificity. In case of isolated bone marrow edema in MRI without a fracture line, the diagnosis of fatigue fracture may be more complicated, and other conditions such as transient edema and osteoid osteoma need to be excluded. Additional imaging by CT is warranted in such cases.[1] ## Insufficiency fractures[edit] Insufficiency fractures occur in weakened bones. Although osteoporosis is a classic cause, other conditions resulting in bone demineralization are well-recognized risk factors. These include previous radiation therapy and chemotherapy, especially in a context of gynaecologic malignancy, chronic renal failure, chronic rheumatological diseases, and corticosteroid therapy. In long bones, chronic joint diseases such as rheumatoid arthritis are associated with angular deformity and flexion contraction, increasing the stress on the bone around the joints and, therefore, the risk of insufficiency fracture. Pelvic, sacral, and proximal femoral fractures are of increasing significance especially with the aging of the population.[1] Figure 12: Right sacral alar insufficiency fracture in a 29-year-old woman with a 9-year history of corticosteroid therapy for systemic lupus erythematous. Conventional radiographs showed normal appearance (not shown). Coronal inversion recovery MRI shows an area of hyperintensity in the right sacral ala (white arrows), centered on a linear hypointensity corresponding to the fracture line (black arrowhead).[1] The sacrum is usually masked by overlapping bowel gas in conventional radiographs, and the subtle radiographic findings are usually nondiagnostic and even misleading. The characteristic "H" pattern has been correlated with biomechanical models of patient activities. The vertical parasagittal planes correspond to the region of maximal stress during walking, while the horizontal fracture develops later, secondary to the loss of lateral support by parasagittal fractures. MRI is the primary imaging technique in this case, with the most common MRI pattern showing bone marrow edema and a fracture line (Figure 12). Coronal views are quite contributive in sacral fractures, allowing the detection of the horizontal component, especially with fluid-sensitive sequences. Although the sacrum is the most commonly involved, pelvic insufficiency fractures are often multiple, and other typical locations should be mentioned.[1] Proximal femoral fractures usually occur in osteoporotic patients, and their signs include subtle neck angulation, trabecular angulation, and subcapital impaction line. A frog-leg lateral view may be helpful if the greater trochanter is short enough. However, positioning can be difficult because of hip pain. In patients with strong suspicion of proximal femoral fracture and negative radiographs, MRI limited to coronal T1 W images and scintigraphy can be highly valuable (Figures 13 and 14). Such an option, with limited examination time, is cost-effective and allows reliable exclusion or confirmation of the diagnosis, preventing an unnecessary stay at the hospital or delayed treatment. Moreover, MRI helps to detect soft tissue abnormalities which are more frequently seen in femoral, acetabular, and pubic injuries than sacral lesions. Concomitant fractures are also frequently seen in typical pelvic sites.[1] * a * b Figure 13: Partial osseous avulsion of the gluteal muscles at the greater trochanter in a 59-year-old man who presented with the right hip pain without a history of trauma. Lauenstein view and anteroposterior and radiographs (not shown) did not show an obvious fracture line or disruption of bony contours in the acetabulum or the right femoral neck. (a) Coronal T1-weighted MRI displays an incomplete fracture line extending partially from the greater trochanter (arrow). (b) Coronal short tau inversion recovery MRI shows heterogeneous hyperintensity in the same region (arrow) as well as hyperintensity within the gluteus medius and minimus muscles (arrowheads) consistent with tissue edema and hematoma.[1] * a * b Figure 14: Subcapital insufficiency fracture in a 55-year-old man with a left hip pain without a history of trauma. Anteroposterior and Lauenstein view radiographs centered on the left hip do not show an obvious fracture line, but mild acetabular osteophytosis was noted consistent with hip osteoarthritis (not shown). (a) Coronal T1-weighted MRI shows a linear low-signal band through the femoral neck corresponding to a fracture line (arrowheads). (b) Bone scintigraphy shows focal uptake (arrow) corresponding to the fracture.[1] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai Jarraya, Mohamed; Hayashi, Daichi; Roemer, Frank W.; Crema, Michel D.; Diaz, Luis; Conlin, Jane; Marra, Monica D.; Jomaah, Nabil; Guermazi, Ali (2013). "Radiographically Occult and Subtle Fractures: A Pictorial Review". Radiology Research and Practice. 2013: 1–10. doi:10.1155/2013/370169. ISSN 2090-1941. PMC 3613077. PMID 23577253. CC-BY 3.0 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Occult fracture	c0524598	26,207	wikipedia	https://en.wikipedia.org/wiki/Occult_fracture	2021-01-18T18:58:52	{"mesh": ["D005596"], "umls": ["C0524598"], "wikidata": ["Q1543994"]}
A number sign (#) is used with this entry because of evidence that slow-channel congenital myasthenic syndrome-2A (CMS2A) is caused by heterozygous mutation in the CHRNB1 gene (100710) on chromosome 17p13. Mutation in the CHRNB1 gene can also cause congenital myasthenic syndrome-2C associated with acetylcholine receptor (AChR) deficiency (CMS2C; 616314). Description Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; cholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Engel et al. (1996) reported a 19-year-old girl who had myasthenic symptoms since birth involving ocular and other cranial and limb muscles. Electrophysiologic studies showed prolonged endplate currents and prolonged AChR channel-opening episodes, and ultrastructural studies of muscle biopsies showed an endplate myopathy with loss of AChR from degenerating junctional folds. Gomez et al. (1996) reported a 32-year-old man with SCCMS. He had presented with poor head control and a weak suck after a normal birth. He sat at 30 months and walked at 5 years of age. Ophthalmoparesis was noted at 8 years, and he developed fatigability at age 10 years. By age 13, he had knee and hip contractures and was wheelchair-bound. Edrophonium test was positive. Prednisone produced subjective improvement at age 14. From age 15 to 16 he was treated with pyridostigmine, guanidine, and thymectomy without improvement. The patient was a thin male with short stature, a long, thin face, high-arched palate, and high-pitched voice. He had nearly complete ophthalmoparesis, fatigable ptosis, and severe atrophy and weakness of all limb muscles. Electrophysiologic studies showed a repetitive compound muscle action potential (CMAP) response to single nerve stimulus and a decremental response to repetitive stimulation. The duration of the endplate potential was increased and prolonged, and miniature endplate potential (MEPP) amplitudes were decreased, consistent with impaired kinetics. Muscle biopsy showed a severe endplate myopathy with degeneration of the junctional folds and extensive remodeling of the postsynaptic membrane. Molecular Genetics In a 19-year-old girl with CMS2A, Engel et al. (1996) identified a heterozygous missense mutation in the CHRNB1 gene (V266M; 100710.0001), In a 32-year-old male with CMS2A, Gomez et al. (1996) identified a heterozygous missense mutation in the CHRNB1 gene (L263M; 100710.0002). Functional expression studies showed that the L263M mutation interrupted the leucine ring of the AChR channel gate, causing an 8-fold increase in channel open time and resulting in severe endplate myopathy as well as extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function and the muscle fiber damage and weakness resulting from a single point mutation were a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity. INHERITANCE \- Autosomal dominant GROWTH Other \- Small body habitus HEAD & NECK Face \- Long face \- Thin face \- Facial muscle weakness Eyes \- Ophthalmoplegia \- Ptosis Mouth \- High-arched palate SKELETAL \- Joint contractures (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia, neonatal \- Generalized muscle weakness, particularly affecting the limbs \- Muscle atrophy \- Easy fatigability \- Repetitive response to single nerve stimulus \- Decremental response to repetitive nerve stimulation \- Prolonged endplate currents \- Prolonged AChR channel opening episodes \- Endplate myopathy \- Degenerating junctional folds \- Loss of AChR NEUROLOGIC Central Nervous System \- Delayed motor development due to muscle weakness MISCELLANEOUS \- Onset at birth \- Two unrelated patients have been reported (last curated April 2015) MOLECULAR BASIS \- Caused by mutation in the cholinergic receptor, nicotinic, beta polypeptide 1 gene (CHRNB1, 100710.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	MYASTHENIC SYNDROME, CONGENITAL, 2A, SLOW-CHANNEL	c0751882	26,208	omim	https://www.omim.org/entry/616313	2019-09-22T15:49:14	{"doid": ["0110681"], "mesh": ["D020294"], "omim": ["616313"], "orphanet": ["98913", "590"], "synonyms": [], "genereviews": ["NBK1168"]}
Bier spots are a benign vascular anomaly characterized by white spots on the skin surrounded by a pale halo of erythema (redness). They are more common on the arms, the legs and the trunk. They are better observed when a tourniquet is placed around the affected arm or leg, and become less obvious when raising it. The spots are thought to be due to raised pressure constricting small veins (venous hypertension) and in most cases no cause is found (idiopathic). Bier spots usually affect healthy people, and may appear during pregnancy. But sometimes, they are part of a systemic disease such as cryoglobulinaemia, polycythaemia, scleroderma, aortic hypoplasia and coarctation, alopecia areata, Peutz-Jeghers syndrome, lichen planus, rapid heartbeat (tachycardia), lymphedema and excessive sweating of the hands (palmar hyperhidrosis). They are usually, self-limiting and except for counseling, require no treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Bier spots	c0406529	26,209	gard	https://rarediseases.info.nih.gov/diseases/13027/bier-spots	2021-01-18T18:01:47	{"synonyms": ["Physiologic anaemic macules", "Angiospastic macules", "Exaggerated physiologic speckled mottling of skin"]}
Littoral cell angioma of the spleen (LCA) is a very rare, vascular tumor of the spleen. Most reported cases have been non-cancerous (benign), but an LCA can become cancerous (malignant). In many cases, LCA does not cause any symptoms. It may be discovered due to abdominal pain or by accident (incidentally) when having a physical exam or during tests performed for other reasons. Besides abdominal pain, LCA may cause an enlarged spleen (splenomegaly), anemia, or thrombocytopenia. Case reports have associated LCA with various other conditions including portal hypertension, Crohn's disease, Gaucher disease, lymphoma, aplastic anemia, colon cancer, pancreatic cancer, lung cancer, and myelodysplastic syndrome. LCA affects men and women equally and can occur at any age, but it mostly occurs in middle-aged adults and occasionally in children. LCA is difficult to diagnose with imaging studies because of its similar appearance to other types of benign splenic tumors as well as malignant tumors such as lymphoma and Kaposi sarcoma. For this reason, the specific tumor type often cannot be confirmed until it is biopsied or removed, and then tested. Currently, the main treatment for LCA is open splenectomy (spleen removal) or hand-assisted laparoscopic total splenectomy, a less-invasive technique. Some authors have suggested only continued surveillance of the tumor may be appropriate if no symptoms are present, because the chance for malignancy in an asymptomatic person is thought to be low, and splenectomy leads to impairment of immune function. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Littoral cell angioma of the spleen	c1627365	26,210	gard	https://rarediseases.info.nih.gov/diseases/9714/littoral-cell-angioma-of-the-spleen	2021-01-18T17:59:20	{"mesh": ["C537031"], "umls": ["C1627365"], "synonyms": ["Littoral cell angioma"]}
Helicobacter cellulitis SpecialtyDermatology Helicobacter cellulitis is a cutaneous condition caused by Helicobacter cinaedi.[1]:280 H. cinaedi can cause cellulitis and bacteremia in immunocompromised people.[2] ## See also[edit] * Cellulitis * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ Kiehlbauch JA, Tauxe RV, Baker CN, Wachsmuth IK (1994). "Helicobacter cinaedi-associated bacteremia and cellulitis in immunocompromised patients". Annals of Internal Medicine. 121 (2): 90–93. doi:10.7326/0003-4819-121-2-199407150-00002. PMID 8017741. * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports *[transl.]: translation	Helicobacter cellulitis	None	26,211	wikipedia	https://en.wikipedia.org/wiki/Helicobacter_cellulitis	2021-01-18T18:30:42	{"wikidata": ["Q5705021"]}
This article is about the sleeping disorder. For other uses, see Insomnia (disambiguation). "Trouble sleeping" redirects here. For other uses, see Trouble sleeping (disambiguation). Inability to fall or stay asleep Insomnia Other namesSleeplessness, trouble sleeping A drawing of someone with insomnia from the 14th century Pronunciation * /ɪnˈsɒmniə/[1] SpecialtyPsychiatry, sleep medicine SymptomsTrouble sleeping, daytime sleepiness, low energy, irritability, depressed mood[1] ComplicationsMotor vehicle collisions[1] CausesUnknown, psychological stress, chronic pain, heart failure, hyperthyroidism, heartburn, restless leg syndrome, others[2] Diagnostic methodBased on symptoms, sleep study[3] Differential diagnosisDelayed sleep phase disorder, restless leg syndrome, sleep apnea, psychiatric disorder[4] TreatmentSleep hygiene, cognitive behavioral therapy, sleeping pills[5][6][7] Frequency~20%[8][9][10] Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping.[1] They may have difficulty falling asleep, or staying asleep as long as desired.[9][11] Insomnia is typically followed by daytime sleepiness, low energy, irritability, and a depressed mood.[1] It may result in an increased risk of motor vehicle collisions, as well as problems focusing and learning.[1] Insomnia can be short term, lasting for days or weeks, or long term, lasting more than a month.[1] Insomnia can occur independently or as a result of another problem.[2] Conditions that can result in insomnia include psychological stress, chronic pain, heart failure, hyperthyroidism, heartburn, restless leg syndrome, menopause, certain medications, and drugs such as caffeine, nicotine, and alcohol.[2][8] Other risk factors include working night shifts and sleep apnea.[9] Diagnosis is based on sleep habits and an examination to look for underlying causes.[3] A sleep study may be done to look for underlying sleep disorders.[3] Screening may be done with two questions: "do you experience difficulty sleeping?" and "do you have difficulty falling or staying asleep?"[9] Sleep hygiene and lifestyle changes are typically the first treatment for insomnia.[5][7] Sleep hygiene includes a consistent bedtime, exposure to sunlight, a quiet and dark room, and regular exercise.[7] Cognitive behavioral therapy may be added to this.[6][12] While sleeping pills may help, they are associated with injuries, dementia, and addiction.[5][6] These medications are not recommended for more than four or five weeks.[6] The effectiveness and safety of alternative medicine is unclear.[5][6] Between 10% and 30% of adults have insomnia at any given point in time and up to half of people have insomnia in a given year.[8][9][10] About 6% of people have insomnia that is not due to another problem and lasts for more than a month.[9] People over the age of 65 are affected more often than younger people.[7] Females are more often affected than males.[8] Descriptions of insomnia occur at least as far back as ancient Greece.[13] ## Contents * 1 Signs and symptoms * 1.1 Poor sleep quality * 1.2 Subjectivity * 2 Causes * 2.1 Genetics * 2.2 Substance-induced * 2.2.1 Alcohol-induced * 2.2.2 Benzodiazepine-induced * 2.2.3 Opioid-induced * 2.3 Risk factors * 3 Mechanism * 4 Diagnosis * 4.1 DSM-5 criteria * 4.2 Types * 5 Prevention * 6 Management * 6.1 Non-medication based * 6.1.1 Sleep hygiene * 6.1.2 Cognitive behavioral therapy * 6.1.3 Internet interventions * 6.2 Medications * 6.2.1 Antihistamines * 6.2.2 Melatonin * 6.2.3 Antidepressants * 6.2.4 Benzodiazepines * 6.2.5 Other sedatives * 6.2.6 Antipsychotics * 6.3 Alternative medicine * 7 Prognosis * 8 Epidemiology * 9 Society and culture * 10 References * 11 External links ## Signs and symptoms[edit] Potential complications of insomnia.[14] Symptoms of insomnia:[15] * Difficulty falling asleep, including difficulty finding a comfortable sleeping position * Waking during the night, being unable to return to sleep and waking up early * Not able to focus on daily tasks, difficulty in remembering * Daytime sleepiness, irritability, depression or anxiety * Feeling tired or having low energy during the day[16] * Trouble concentrating * Being irritable, acting aggressive or impulsive Sleep onset insomnia is difficulty falling asleep at the beginning of the night, often a symptom of anxiety disorders. Delayed sleep phase disorder can be misdiagnosed as insomnia, as sleep onset is delayed to much later than normal while awakening spills over into daylight hours.[17] It is common for patients who have difficulty falling asleep to also have nocturnal awakenings with difficulty returning to sleep. Two-thirds of these patients wake up in the middle of the night, with more than half having trouble falling back to sleep after a middle-of-the-night awakening.[18] Early morning awakening is an awakening occurring earlier (more than 30 minutes) than desired with an inability to go back to sleep, and before total sleep time reaches 6.5 hours. Early morning awakening is often a characteristic of depression.[19] Anxiety symptoms may well lead to insomnia. Some of these symptoms include tension, compulsive worrying about the future, feeling overstimulated, and overanalyzing past events.[20] ### Poor sleep quality[edit] Poor sleep quality can occur as a result of, for example, restless legs, sleep apnea or major depression. Poor sleep quality is defined as the individual not reaching stage 3 or delta sleep which has restorative properties.[21] Major depression leads to alterations in the function of the hypothalamic-pituitary-adrenal axis, causing excessive release of cortisol which can lead to poor sleep quality. Nocturnal polyuria, excessive nighttime urination, can be very disturbing to sleep.[22] ### Subjectivity[edit] Main article: Sleep state misperception Some cases of insomnia are not really insomnia in the traditional sense, because people experiencing sleep state misperception often sleep for a normal amount of time.[23] The problem is that, despite sleeping for multiple hours each night and typically not experiencing significant daytime sleepiness or other symptoms of sleep loss, they do not feel like they have slept very much, if at all.[23] Because their perception of their sleep is incomplete, they incorrectly believe it takes them an abnormally long time to fall asleep, and they underestimate how long they remain asleep.[23] ## Causes[edit] Symptoms of insomnia can be caused by or be associated with: * Sleep breathing disorders, such as sleep apnea or upper airway resistance syndrome[24] * Use of psychoactive drugs (such as stimulants), including certain medications, herbs, caffeine, nicotine, cocaine, amphetamines, methylphenidate, aripiprazole, MDMA, modafinil, or excessive alcohol intake[25] * Use of or withdrawal from alcohol and other sedatives, such as anti-anxiety and sleep drugs like benzodiazepines[25] * Use of or withdrawal from pain-relievers such as opioids[25] * Heart disease[26] * Restless legs syndrome, which can cause sleep onset insomnia due to the discomforting sensations felt and the need to move the legs or other body parts to relieve these sensations[27] * Periodic limb movement disorder (PLMD), which occurs during sleep and can cause arousals of which the sleeper is unaware[28] * Pain:[29] an injury or condition that causes pain can preclude an individual from finding a comfortable position in which to fall asleep, and can also cause awakening. * Hormone shifts such as those that precede menstruation and those during menopause[30] * Life events such as fear, stress, anxiety, emotional or mental tension, work problems, financial stress, birth of a child, and bereavement[27] * Gastrointestinal issues such as heartburn or constipation[31] * Mental disorders such as bipolar disorder, clinical depression, generalized anxiety disorder, post traumatic stress disorder, schizophrenia, obsessive compulsive disorder, dementia,[32]:326 and ADHD[33] * Disturbances of the circadian rhythm, such as shift work and jet lag, can cause an inability to sleep at some times of the day and excessive sleepiness at other times of the day. Chronic circadian rhythm disorders are characterized by similar symptoms.[25] * Certain neurological disorders, brain lesions, or a history of traumatic brain injury[34] * Medical conditions such as hyperthyroidism[2] * Abuse of over-the counter or prescription sleep aids (sedative or depressant drugs) can produce rebound insomnia.[25] * Poor sleep hygiene, e.g., noise or over-consumption of caffeine[25] * A rare genetic condition can cause a prion-based, permanent and eventually fatal form of insomnia called fatal familial insomnia.[35] * Physical exercise: exercise-induced insomnia is common in athletes in the form of prolonged sleep onset latency.[36] * Increased exposure to the blue light from artificial sources, such as phones or computers[37] * Chronic pain[38] * Lower back pain[38] * Asthma[38] Sleep studies using polysomnography have suggested that people who have sleep disruption have elevated nighttime levels of circulating cortisol and adrenocorticotropic hormone. They also have an elevated metabolic rate, which does not occur in people who do not have insomnia but whose sleep is intentionally disrupted during a sleep study. Studies of brain metabolism using positron emission tomography (PET) scans indicate that people with insomnia have higher metabolic rates by night and by day. The question remains whether these changes are the causes or consequences of long-term insomnia.[39] ### Genetics[edit] Heritability estimates of insomnia vary between 38% in males to 59% in females.[40] A genome-wide association study (GWAS) identified 3 genomic loci and 7 genes that influence the risk of insomnia, and showed that insomnia is highly polygenic.[41] In particular, a strong positive association was observed for the MEIS1 gene in both males and females. This study showed that the genetic architecture of insomnia strongly overlaps with psychiatric disorders and metabolic traits. It has been hypothesised that the epigenetics might also influence insomnia through a controlling process of both sleep regulation and brain-stress response having an impact as well on the brain plasticity.[42] ### Substance-induced[edit] #### Alcohol-induced[edit] Main article: Alcohol use and sleep Alcohol is often used as a form of self-treatment of insomnia to induce sleep. However, alcohol use to induce sleep can be a cause of insomnia. Long-term use of alcohol is associated with a decrease in NREM stage 3 and 4 sleep as well as suppression of REM sleep and REM sleep fragmentation. Frequent moving between sleep stages occurs, with awakenings due to headaches, the need to urinate, dehydration, and excessive sweating. Glutamine rebound also plays a role as when someone is drinking; alcohol inhibits glutamine, one of the body's natural stimulants. When the person stops drinking, the body tries to make up for lost time by producing more glutamine than it needs. The increase in glutamine levels stimulates the brain while the drinker is trying to sleep, keeping him/her from reaching the deepest levels of sleep.[43] Stopping chronic alcohol use can also lead to severe insomnia with vivid dreams. During withdrawal REM sleep is typically exaggerated as part of a rebound effect.[44] #### Benzodiazepine-induced[edit] Like alcohol, benzodiazepines, such as alprazolam, clonazepam, lorazepam, and diazepam, are commonly used to treat insomnia in the short-term (both prescribed and self-medicated), but worsen sleep in the long-term. While benzodiazepines can put people to sleep (i.e., inhibit NREM stage 1 and 2 sleep), while asleep, the drugs disrupt sleep architecture: decreasing sleep time, delaying time to REM sleep, and decreasing deep slow-wave sleep (the most restorative part of sleep for both energy and mood).[45][46][47] #### Opioid-induced[edit] Opioid medications such as hydrocodone, oxycodone, and morphine are used for insomnia that is associated with pain due to their analgesic properties and hypnotic effects. Opioids can fragment sleep and decrease REM and stage 2 sleep. By producing analgesia and sedation, opioids may be appropriate in carefully selected patients with pain-associated insomnia.[29] However, dependence on opioids can lead to long-term sleep disturbances.[48] ### Risk factors[edit] Insomnia affects people of all age groups but people in the following groups have a higher chance of acquiring insomnia.[49] * Individuals older than 60 * History of mental health disorder including depression, etc. * Emotional stress * Working late night shifts * Traveling through different time zones[11] * Having chronic diseases such as diabetes, kidney disease, lung disease, Alzheimer's, or heart disease[50] * Alcohol or drug use disorders * Gastrointestinal reflux disease * Heavy smoking * Work stress[51] ## Mechanism[edit] Two main models exists as to the mechanism of insomnia, (1) cognitive and (2) physiological. The cognitive model suggests rumination and hyperarousal contribute to preventing a person from falling asleep and might lead to an episode of insomnia. The physiological model is based upon three major findings in people with insomnia; firstly, increased urinary cortisol and catecholamines have been found suggesting increased activity of the HPA axis and arousal; second increased global cerebral glucose utilization during wakefulness and NREM sleep in people with insomnia; and lastly increased full body metabolism and heart rate in those with insomnia. All these findings taken together suggest a dysregulation of the arousal system, cognitive system, and HPA axis all contributing to insomnia.[9][52] However, it is unknown if the hyperarousal is a result of, or cause of insomnia. Altered levels of the inhibitory neurotransmitter GABA have been found, but the results have been inconsistent, and the implications of altered levels of such a ubiquitous neurotransmitter are unknown. Studies on whether insomnia is driven by circadian control over sleep or a wake dependent process have shown inconsistent results, but some literature suggests a dysregulation of the circadian rhythm based on core temperature.[53] Increased beta activity and decreased delta wave activity has been observed on electroencephalograms; however, the implication of this is unknown.[54] Around half of post-menopausal women experience sleep disturbances, and generally sleep disturbance is about twice as common in women as men; this appears to be due in part, but not completely, to changes in hormone levels, especially in and post-menopause.[30][55] Changes in sex hormones in both men and women as they age may account in part for increased prevalence of sleep disorders in older people.[56] ## Diagnosis[edit] In medicine, insomnia is widely measured using the Athens insomnia scale.[57] It is measured using eight different parameters related to sleep, finally represented as an overall scale which assesses an individual's sleep pattern. A qualified sleep specialist should be consulted for the diagnosis of any sleep disorder so the appropriate measures can be taken. Past medical history and a physical examination need to be done to eliminate other conditions that could be the cause of insomnia. After all other conditions are ruled out a comprehensive sleep history should be taken. The sleep history should include sleep habits, medications (prescription and non-prescription), alcohol consumption, nicotine and caffeine intake, co-morbid illnesses, and sleep environment.[58] A sleep diary can be used to keep track of the individual's sleep patterns. The diary should include time to bed, total sleep time, time to sleep onset, number of awakenings, use of medications, time of awakening, and subjective feelings in the morning.[58] The sleep diary can be replaced or validated by the use of out-patient actigraphy for a week or more, using a non-invasive device that measures movement.[59] Workers who complain of insomnia should not routinely have polysomnography to screen for sleep disorders.[60] This test may be indicated for patients with symptoms in addition to insomnia, including sleep apnea, obesity, a thick neck diameter, or high-risk fullness of the flesh in the oropharynx.[60] Usually, the test is not needed to make a diagnosis, and insomnia especially for working people can often be treated by changing a job schedule to make time for sufficient sleep and by improving sleep hygiene.[60] Some patients may need to do an overnight sleep study to determine if insomnia is present. Such a study will commonly involve assessment tools including a polysomnogram and the multiple sleep latency test. Specialists in sleep medicine are qualified to diagnose disorders within the, according to the ICSD, 81 major sleep disorder diagnostic categories.[61] Patients with some disorders, including delayed sleep phase disorder, are often mis-diagnosed with primary insomnia; when a person has trouble getting to sleep and awakening at desired times, but has a normal sleep pattern once asleep, a circadian rhythm disorder is a likely cause. In many cases, insomnia is co-morbid with another disease, side-effects from medications, or a psychological problem. Approximately half of all diagnosed insomnia is related to psychiatric disorders.[62] In depression in many cases "insomnia should be regarded as a co-morbid condition, rather than as a secondary one;" insomnia typically predates psychiatric symptoms.[62] "In fact, it is possible that insomnia represents a significant risk for the development of a subsequent psychiatric disorder."[9] Insomnia occurs in between 60% and 80% of people with depression.[63] This may partly be due to treatment used for depression.[63] Determination of causation is not necessary for a diagnosis.[62] ### DSM-5 criteria[edit] The DSM-5 criteria for insomnia include the following:[64] Predominant complaint of dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms: * Difficulty initiating sleep. (In children, this may manifest as difficulty initiating sleep without caregiver intervention.) * Difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings. (In children, this may manifest as difficulty returning to sleep without caregiver intervention.) * Early-morning awakening with inability to return to sleep. In addition, * The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning. * The sleep difficulty occurs at least 3 nights per week. * The sleep difficulty is present for at least 3 months. * The sleep difficulty occurs despite adequate opportunity for sleep. * The insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder (e.g., narcolepsy, a breathing-related sleep disorder, a circadian rhythm sleep-wake disorder, a parasomnia). * The insomnia is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication). * Coexisting mental disorders and medical conditions do not adequately explain the predominant complaint of insomnia. ### Types[edit] Insomnia can be classified as transient, acute, or chronic. 1. Transient insomnia lasts for less than a week. It can be caused by another disorder, by changes in the sleep environment, by the timing of sleep, severe depression, or by stress. Its consequences – sleepiness and impaired psychomotor performance – are similar to those of sleep deprivation.[65] 2. Acute insomnia is the inability to consistently sleep well for a period of less than a month. Insomnia is present when there is difficulty initiating or maintaining sleep or when the sleep that is obtained is non-refreshing or of poor quality. These problems occur despite adequate opportunity and circumstances for sleep and they must result in problems with daytime function.[66] Acute insomnia is also known as short term insomnia or stress related insomnia.[67] 3. Chronic insomnia lasts for longer than a month. It can be caused by another disorder, or it can be a primary disorder. People with high levels of stress hormones or shifts in the levels of cytokines are more likely than others to have chronic insomnia.[68] Its effects can vary according to its causes. They might include muscular weariness, hallucinations, and/or mental fatigue.[65] ## Prevention[edit] Prevention and treatment of insomnia may require a combination of cognitive behavioral therapy,[12] medications,[69] and lifestyle changes.[70] Among lifestyle practices, going to sleep and waking up at the same time each day can create a steady pattern which may help to prevent insomnia.[11] Avoidance of vigorous exercise and caffeinated drinks a few hours before going to sleep is recommended, while exercise earlier in the day may be beneficial.[70] Other practices to improve sleep hygiene may include:[70][71] * Avoiding or limiting naps * Treating pain at bedtime * Avoiding large meals, beverages, alcohol, and nicotine before bedtime * Finding soothing ways to relax into sleep, including use of white noise * Making the bedroom suitable for sleep by keeping it dark, cool, and free of devices, such as clocks, a cell phone, or television * Maintain regular exercise * Try relaxing activities before sleeping * Use your bed only for sleep or sex * Stop checking the time ## Management[edit] It is recommended to rule out medical and psychological causes before deciding on the treatment for insomnia.[72] Cognitive behavioral therapy is generally the first line treatment once this has been done.[73] It has been found to be effective for chronic insomnia.[12] The beneficial effects, in contrast to those produced by medications, may last well beyond the stopping of therapy.[74] Medications have been used mainly to reduce symptoms in insomnia of short duration; their role in the management of chronic insomnia remains unclear.[8] Several different types of medications may be used.[75][76][69] Many doctors do not recommend relying on prescription sleeping pills for long-term use.[70] It is also important to identify and treat other medical conditions that may be contributing to insomnia, such as depression, breathing problems, and chronic pain.[70][77] Many people with insomnia remain insufficiently treated as of 2003.[78] ### Non-medication based[edit] Non-medication based strategies have comparable efficacy to hypnotic medication for insomnia and they may have longer lasting effects. Hypnotic medication is only recommended for short-term use because dependence with rebound withdrawal effects upon discontinuation or tolerance can develop.[79] Non medication based strategies provide long lasting improvements to insomnia and are recommended as a first line and long-term strategy of management. Behavioral sleep medicine (BSM) tries to address insomnia with non-pharmacological treatments. The BSM strategies used to address chronic insomnia include attention to sleep hygiene, stimulus control, behavioral interventions, sleep-restriction therapy, paradoxical intention, patient education, and relaxation therapy.[80] Some examples are keeping a journal, restricting the time spent awake in bed, practicing relaxation techniques, and maintaining a regular sleep schedule and a wake-up time.[77] Behavioral therapy can assist a patient in developing new sleep behaviors to improve sleep quality and consolidation. Behavioral therapy may include, learning healthy sleep habits to promote sleep relaxation, undergoing light therapy to help with worry-reduction strategies and regulating the circadian clock.[77] Music may improve insomnia in adults (see music and sleep).[81] EEG biofeedback has demonstrated effectiveness in the treatment of insomnia with improvements in duration as well as quality of sleep.[82] Self-help therapy (defined as a psychological therapy that can be worked through on one's own) may improve sleep quality for adults with insomnia to a small or moderate degree.[83] Stimulus control therapy is a treatment for patients who have conditioned themselves to associate the bed, or sleep in general, with a negative response. As stimulus control therapy involves taking steps to control the sleep environment, it is sometimes referred interchangeably with the concept of sleep hygiene. Examples of such environmental modifications include using the bed for sleep or sex only, not for activities such as reading or watching television; waking up at the same time every morning, including on weekends; going to bed only when sleepy and when there is a high likelihood that sleep will occur; leaving the bed and beginning an activity in another location if sleep does not result in a reasonably brief period of time after getting into bed (commonly ~20 min); reducing the subjective effort and energy expended trying to fall asleep; avoiding exposure to bright light during nighttime hours, and eliminating daytime naps.[84] A component of stimulus control therapy is sleep restriction, a technique that aims to match the time spent in bed with actual time spent asleep. This technique involves maintaining a strict sleep-wake schedule, sleeping only at certain times of the day and for specific amounts of time to induce mild sleep deprivation. Complete treatment usually lasts up to 3 weeks and involves making oneself sleep for only a minimum amount of time that they are actually capable of on average, and then, if capable (i.e. when sleep efficiency improves), slowly increasing this amount (~15 min) by going to bed earlier as the body attempts to reset its internal sleep clock. Bright light therapy may be effective for insomnia.[85] Paradoxical intention is a cognitive reframing technique where the insomniac, instead of attempting to fall asleep at night, makes every effort to stay awake (i.e. essentially stops trying to fall asleep). One theory that may explain the effectiveness of this method is that by not voluntarily making oneself go to sleep, it relieves the performance anxiety that arises from the need or requirement to fall asleep, which is meant to be a passive act. This technique has been shown to reduce sleep effort and performance anxiety and also lower subjective assessment of sleep-onset latency and overestimation of the sleep deficit (a quality found in many insomniacs).[86] #### Sleep hygiene[edit] Sleep hygiene is a common term for all of the behaviors which relate to the promotion of good sleep. They include habits which provide a good foundation for sleep and help to prevent insomnia. However, sleep hygiene alone may not be adequate to address chronic insomnia.[59] Sleep hygiene recommendations are typically included as one component of cognitive behavioral therapy for insomnia (CBT-I).[59][6] Recommendations include reducing caffeine, nicotine, and alcohol consumption, maximizing the regularity and efficiency of sleep episodes, minimizing medication usage and daytime napping, the promotion of regular exercise, and the facilitation of a positive sleep environment.[87] Exercise can be helpful when establishing a routine for sleep but should not be done close to the time that you are planning on going to sleep. The creation of a positive sleep environment may also be helpful in reducing the symptoms of insomnia. In order to create a positive sleep environment one should remove objects that can cause worry or distressful thoughts from view.[citation needed] #### Cognitive behavioral therapy[edit] Main article: Cognitive behavioral therapy for insomnia There is some evidence that cognitive behavioral therapy for insomnia (CBT-I) is superior in the long-term to benzodiazepines and the nonbenzodiazepines in the treatment and management of insomnia.[88] In this therapy, patients are taught improved sleep habits and relieved of counter-productive assumptions about sleep. Common misconceptions and expectations that can be modified include 1. unrealistic sleep expectations (e.g., I need to have 8 hours of sleep each night) 2. misconceptions about insomnia causes (e.g., I have a chemical imbalance causing my insomnia) 3. amplifying the consequences of insomnia (e.g., I cannot do anything after a bad night's sleep) and 4. performance anxiety after trying for so long to have a good night's sleep by controlling the sleep process. Numerous studies have reported positive outcomes of combining cognitive behavioral therapy for insomnia treatment with treatments such as stimulus control and the relaxation therapies. Hypnotic medications are equally effective in the short-term treatment of insomnia, but their effects wear off over time due to tolerance. The effects of CBT-I have sustained and lasting effects on treating insomnia long after therapy has been discontinued.[89][90] The addition of hypnotic medications with CBT-I adds no benefit in insomnia. The long lasting benefits of a course of CBT-I shows superiority over pharmacological hypnotic drugs. Even in the short term when compared to short-term hypnotic medication such as zolpidem, CBT-I still shows significant superiority. Thus CBT-I is recommended as a first line treatment for insomnia.[91] CBT is the well-accepted form of therapy for insomnia since it has no known adverse effects, whereas taking medications to alleviate insomnia symptoms have been shown to have adverse side effects.[92] Nevertheless, the downside of CBT is that it may take a lot of time and motivation.[93] Metacognition is a recent trend in approach to behaviour therapy of insomnia.[94] #### Internet interventions[edit] Despite the therapeutic effectiveness and proven success of CBT, treatment availability is significantly limited by a lack of trained clinicians, poor geographical distribution of knowledgeable professionals, and expense.[95] One way to potentially overcome these barriers is to use the Internet to deliver treatment, making this effective intervention more accessible and less costly. The Internet has already become a critical source of health-care and medical information.[96] Although the vast majority of health websites provide general information,[96][97] there is growing research literature on the development and evaluation of Internet interventions.[98][99] These online programs are typically behaviorally-based treatments that have been operationalized and transformed for delivery via the Internet. They are usually highly structured; automated or human supported; based on effective face-to-face treatment; personalized to the user; interactive; enhanced by graphics, animations, audio, and possibly video; and tailored to provide follow-up and feedback.[99] There is good evidence for the use of computer based CBT for insomnia.[100] ### Medications[edit] Many people with insomnia use sleeping tablets and other sedatives. In some places medications are prescribed in over 95% of cases.[101] They, however, are a second line treatment.[102] In 2019, the US Food and Drug Administration stated it is going to require warnings for eszopiclone, zaleplon, and zolpidem, due to concerns about serious injuries resulting from abnormal sleep behaviors, including sleepwalking or driving a vehicle while asleep.[103] The percentage of adults using a prescription sleep aid increases with age. During 2005–2010, about 4% of U.S. adults aged 20 and over reported that they took prescription sleep aids in the past 30 days. Rates of use were lowest among the youngest age group (those aged 20–39) at about 2%, increased to 6% among those aged 50–59, and reached 7% among those aged 80 and over. More adult women (5%) reported using prescription sleep aids than adult men (3%). Non-Hispanic white adults reported higher use of sleep aids (5%) than non-Hispanic black (3%) and Mexican-American (2%) adults. No difference was shown between non-Hispanic black adults and Mexican-American adults in use of prescription sleep aids.[104] #### Antihistamines[edit] As an alternative to taking prescription drugs, some evidence shows that an average person seeking short-term help may find relief by taking over-the-counter antihistamines such as diphenhydramine or doxylamine.[105] Diphenhydramine and doxylamine are widely used in nonprescription sleep aids. They are the most effective over-the-counter sedatives currently available, at least in much of Europe, Canada, Australia, and the United States, and are more sedating than some prescription hypnotics.[106] Antihistamine effectiveness for sleep may decrease over time, and anticholinergic side-effects (such as dry mouth) may also be a drawback with these particular drugs. While addiction does not seem to be an issue with this class of drugs, they can induce dependence and rebound effects upon abrupt cessation of use.[citation needed] However, people whose insomnia is caused by restless legs syndrome may have worsened symptoms with antihistamines.[107] #### Melatonin[edit] The evidence for melatonin in treating insomnia is generally poor.[108] There is low quality evidence that it may speed the onset of sleep by 6 minutes.[108] Ramelteon, a melatonin receptor agonist, does not appear to speed the onset of sleep or the amount of sleep a person gets.[108] Most melatonin drugs have not been tested for longitudinal side effects.[109] Prolonged-release melatonin may improve quality of sleep in older people with minimal side effects.[110][111] Studies have also shown that children who are on the Autism spectrum or have learning disabilities, Attention-Deficit Hyperactivity Disorder (ADHD) or related neurological diseases can benefit from the use of melatonin. This is because they often have trouble sleeping due to their disorders. For example, children with ADHD tend to have trouble falling asleep because of their hyperactivity and, as a result, tend to be tired during most of the day. Another cause of insomnia in children with ADHD is the use of stimulants used to treat their disorder. Children who have ADHD then, as well as the other disorders mentioned, may be given melatonin before bedtime in order to help them sleep.[112] #### Antidepressants[edit] While insomnia is a common symptom of depression, antidepressants are effective for treating sleep problems whether or not they are associated with depression. While all antidepressants help regulate sleep, some antidepressants such as amitriptyline, doxepin, mirtazapine, and trazodone can have an immediate sedative effect, and are prescribed to treat insomnia.[113] Amitriptyline and doxepin both have antihistaminergic, anticholinergic, and antiadrenergic properties, which contribute to both their therapeutic effects and side effect profiles, while mirtazapine's side effects are primarily antihistaminergic, and trazodone's side-effects are primarily antiadrenergic. Mirtazapine is known to decrease sleep latency (i.e., the time it takes to fall asleep), promoting sleep efficiency and increasing the total amount of sleeping time in people with both depression and insomnia.[114][115] Agomelatine, a melatonergic antidepressant with sleep-improving qualities that does not cause daytime drowsiness,[116] is licensed for marketing in the European Union[117] and TGA Australia.[118] After trials in the United States its development for use there was discontinued in October 2011[119] by Novartis, who had bought the rights to market it there from the European pharmaceutical company Servier.[120] A 2018 Cochrane review found the safety of taking antidepressants for insomnia to be uncertain with no evidence supporting long term use.[121] #### Benzodiazepines[edit] Normison (temazepam) is a benzodiazepine commonly prescribed for insomnia and other sleep disorders.[122] The most commonly used class of hypnotics for insomnia are the benzodiazepines.[32]:363 Benzodiazepines are not significantly better for insomnia than antidepressants.[123] Chronic users of hypnotic medications for insomnia do not have better sleep than chronic insomniacs not taking medications. In fact, chronic users of hypnotic medications have more regular nighttime awakenings than insomniacs not taking hypnotic medications.[124] Many have concluded that these drugs cause an unjustifiable risk to the individual and to public health and lack evidence of long-term effectiveness. It is preferred that hypnotics be prescribed for only a few days at the lowest effective dose and avoided altogether wherever possible, especially in the elderly.[125] Between 1993 and 2010, the prescribing of benzodiazepines to individuals with sleep disorders has decreased from 24% to 11% in the US, coinciding with the first release of nonbenzodiazepines.[126] The benzodiazepine and nonbenzodiazepine hypnotic medications also have a number of side-effects such as day time fatigue, motor vehicle crashes and other accidents, cognitive impairments, and falls and fractures. Elderly people are more sensitive to these side-effects.[127] Some benzodiazepines have demonstrated effectiveness in sleep maintenance in the short term but in the longer term benzodiazepines can lead to tolerance, physical dependence, benzodiazepine withdrawal syndrome upon discontinuation, and long-term worsening of sleep, especially after consistent usage over long periods of time. Benzodiazepines, while inducing unconsciousness, actually worsen sleep as – like alcohol – they promote light sleep while decreasing time spent in deep sleep.[128] A further problem is, with regular use of short-acting sleep aids for insomnia, daytime rebound anxiety can emerge.[129] Although there is little evidence for benefit of benzodiazepines in insomnia compared to other treatments and evidence of major harm, prescriptions have continued to increase.[130] This is likely due to their addictive nature, both due to misuse and because – through their rapid action, tolerance and withdrawal they can "trick" insomniacs into thinking they are helping with sleep. There is a general awareness that long-term use of benzodiazepines for insomnia in most people is inappropriate and that a gradual withdrawal is usually beneficial due to the adverse effects associated with the long-term use of benzodiazepines and is recommended whenever possible.[131][132] Benzodiazepines all bind unselectively to the GABAA receptor.[123] Some theorize that certain benzodiazepines (hypnotic benzodiazepines) have significantly higher activity at the α1 subunit of the GABAA receptor compared to other benzodiazepines (for example, triazolam and temazepam have significantly higher activity at the α1 subunit compared to alprazolam and diazepam, making them superior sedative-hypnotics – alprazolam and diazepam, in turn, have higher activity at the α2 subunit compared to triazolam and temazepam, making them superior anxiolytic agents). Modulation of the α1 subunit is associated with sedation, motor impairment, respiratory depression, amnesia, ataxia, and reinforcing behavior (drug-seeking behavior). Modulation of the α2 subunit is associated with anxiolytic activity and disinhibition. For this reason, certain benzodiazepines may be better suited to treat insomnia than others.[citation needed] #### Other sedatives[edit] Drugs that may prove more effective and safer than benzodiazepines for insomnia is an area of active research.[133] Nonbenzodiazepine sedative-hypnotic drugs, such as zolpidem, zaleplon, zopiclone, and eszopiclone, are a class of hypnotic medications that are similar to benzodiazepines in their mechanism of action, and indicated for mild to moderate insomnia. Their effectiveness at improving time to sleeping is slight, and they have similar – though potentially less severe – side effect profiles compared to benzodiazepines.[134] Suvorexant is FDA approved for insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.[135] Prescribing of nonbenzodiazepines has seen a general increase since their initial release on the US market in 1992, from 2.3% in 1993 among individuals with sleep disorders to 13.7% in 2010.[126] Barbiturates, while once used, are no longer recommended for insomnia due to the risk of addiction and other side affects.[136] #### Antipsychotics[edit] The use of antipsychotics for insomnia, while common, is not recommended as the evidence does not demonstrate a benefit and the risk of adverse effects is significant.[137][138] Concerns regarding side effects is greater in the elderly.[139] ### Alternative medicine[edit] Herbs such as valerian, chamomile, lavender, or cannabis, may be used,[140] but there is no clinical evidence that they are effective. It is unclear if acupuncture is useful.[141] ## Prognosis[edit] Disability-adjusted life year for insomnia per 100,000 inhabitants in 2004. more than 80 less than 25 no data 25–30.25 30.25–36 36–41.5 41.5–47 47–52.5 52.5–58 58–63.5 63.5–69 69–74.5 74.5–80 A survey of 1.1 million residents in the United States found that those that reported sleeping about 7 hours per night had the lowest rates of mortality, whereas those that slept for fewer than 6 hours or more than 8 hours had higher mortality rates. Getting 8.5 or more hours of sleep per night was associated with a 15% higher mortality rate. Severe insomnia – sleeping less than 3.5 hours in women and 4.5 hours in men – is associated with a 15% increase in mortality.[142] With this technique, it is difficult to distinguish lack of sleep caused by a disorder which is also a cause of premature death, versus a disorder which causes a lack of sleep, and the lack of sleep causing premature death. Most of the increase in mortality from severe insomnia was discounted after controlling for associated disorders. After controlling for sleep duration and insomnia, use of sleeping pills was also found to be associated with an increased mortality rate.[142] The lowest mortality was seen in individuals who slept between six and a half and seven and a half hours per night. Even sleeping only 4.5 hours per night is associated with very little increase in mortality. Thus, mild to moderate insomnia for most people is associated with increased longevity and severe insomnia is associated only with a very small effect on mortality.[142] It is unclear why sleeping longer than 7.5 hours is associated with excess mortality.[142] ## Epidemiology[edit] Between 10% and 30% of adults have insomnia at any given point in time and up to half of people have insomnia in a given year.[9][8][10] About 6% of people have insomnia that is not due to another problem and lasts for more than a month.[9] People over the age of 65 are affected more often than younger people.[7] Females are more often affected than males.[8] Insomnia is 40% more common in women than in men.[143] There are higher rates of insomnia reported among university students compared to the general population.[144] ## Society and culture[edit] The word insomnia is from Latin: in \+ somnus "without sleep" and -ia as nominalizing suffix. The popular press have published stories about people who supposedly never sleep, such as that of Thái Ngọc, and Al Herpin[145] Horne writes "everybody sleeps and needs to do so;" and generally this appears true. However, he also relates from contemporary accounts the case of Paul Kern, who was shot in wartime and then "never slept again" until his death in 1943.[146] Kern appears to be a completely isolated, unique case. ## References[edit] 1. ^ a b c d e f g "What Is Insomnia?". NHLBI. December 13, 2011. Archived from the original on 28 July 2016. Retrieved 9 August 2016. 2. ^ a b c d "What Causes Insomnia?". NHLBI. December 13, 2011. Archived from the original on 28 July 2016. Retrieved 9 August 2016. 3. ^ a b c "How Is Insomnia Diagnosed?". NHLBI. December 13, 2011. Archived from the original on 11 August 2016. Retrieved 9 August 2016. 4. ^ Watson NF, Vaughn BV (2006). Clinician's Guide to Sleep Disorders. CRC Press. p. 10. 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ISBN 978-3-319-30572-1. ## External links[edit] Classification D * ICD-10: F51.0, G47.0 * ICD-9-CM: 307.42, 307.41, 327.0, 780.51, 780.52 * MeSH: D007319 * DiseasesDB: 26877 * SNOMED CT: 193462001 External resources * MedlinePlus: 000805 * eMedicine: med/2698 * Patient UK: Insomnia * v * t * e Sleep and sleep disorders Stages of sleep cycles * Rapid eye movement (REM) * Non-rapid eye movement * Slow-wave Brain waves * Alpha wave * Beta wave * Delta wave * Gamma wave * K-complex * Mu rhythm * PGO waves * Sensorimotor rhythm * Sleep spindle * Theta wave Sleep disorders Dyssomnia * Excessive daytime sleepiness * Hypersomnia * Insomnia * Kleine–Levin syndrome * Narcolepsy * Night eating syndrome * Nocturia * Sleep apnea * Catathrenia * Central hypoventilation syndrome * Obesity hypoventilation syndrome * Obstructive sleep apnea * Periodic breathing * Sleep state misperception Circadian rhythm disorders * Advanced sleep phase disorder * Cyclic alternating pattern * Delayed sleep phase disorder * Irregular sleep–wake rhythm * Jet lag * Non-24-hour sleep–wake disorder * Shift work sleep disorder Parasomnia * Bruxism * Nightmare disorder * Night terror * Periodic limb movement disorder * Rapid eye movement sleep behavior disorder * Sleepwalking * Somniloquy Benign phenomena * Dreams * Exploding head syndrome * Hypnic jerk * Hypnagogia / Sleep onset * Hypnopompic state * Sleep paralysis * Sleep inertia * Somnolence * Nocturnal clitoral tumescence * Nocturnal penile tumescence * Nocturnal emission Treatment * Sleep diary * Sleep hygiene * Sleep induction * Hypnosis * Lullaby * Somnology * Polysomnography Other * Sleep medicine * Behavioral sleep medicine * Sleep study Daily life * Bed * Bunk bed * Daybed * Four-poster bed * Futon * Hammock * Mattress * Sleeping bag * Bed bug * Bedding * Bedroom * Bedtime * Bedtime story * Bedtime toy * Biphasic and polyphasic sleep * Chronotype * Dream diary * Microsleep * Mouth breathing * Nap * Nightwear * Power nap * Second wind * Siesta * Sleep and creativity * Sleep and learning * Sleep deprivation / Sleep debt * Sleeping while on duty * Sleepover * Snoring * v * t * e Hypnotics/sedatives (N05C) GABAA Alcohols * 2M2B * Chloralodol * Ethanol (alcohol) * Diethylpropanediol * Ethchlorvynol * Methylpentynol * Trichloroethanol Barbiturates * Allobarbital * Amobarbital * Aprobarbital * Barbital * Butabarbital * Butobarbital * Cyclobarbital * Ethallobarbital * Heptabarb * Hexobarbital * Mephobarbital * Methohexital * Narcobarbital * Pentobarbital * Phenallymal * Phenobarbital * Propylbarbital * Proxibarbal * Reposal * Secobarbital * Talbutal * Thiamylal * Thiopental * Thiotetrabarbital * Vinbarbital * Vinylbital Benzodiazepines * Brotizolam * Cinolazepam * Climazolam * Doxefazepam * Estazolam * Flunitrazepam * Flurazepam * Flutoprazepam * Lorazepam * Loprazolam * Lormetazepam * Midazolam * Nimetazepam * Nitrazepam * Phenazepam * Quazepam * Temazepam * Triazolam Carbamates * Carisoprodol * Emylcamate * Ethinamate * Hexapropymate * Meprobamate * Methocarbamol * Phenprobamate * Procymate * Tybamate Imidazoles * Etomidate * Metomidate * Propoxate Monoureides * Acecarbromal * Apronal (apronalide) * Bromisoval * Capuride * Carbromal * Ectylurea Neuroactive steroids * Acebrochol * Allopregnanolone * Alphadolone * Alphaxolone * Eltanolone * Hydroxydione * Minaxolone * Progesterone Nonbenzodiazepines * Eszopiclone * Indiplon * Lirequinil * Necopidem * Pazinaclone * Saripidem * Suproclone * Suriclone * Zaleplon * Zolpidem * Zopiclone Phenols * Propofol Piperidinediones * Glutethimide * Methyprylon * Pyrithyldione * Piperidione Quinazolinones * Afloqualone * Cloroqualone * Diproqualone * Etaqualone * Mebroqualone * Mecloqualone * Methaqualone * Methylmethaqualone * Nitromethaqualone * SL-164 Others * Acetophenone * Acetylglycinamide chloral hydrate * Bromide compounds * Lithium bromide * Potassium bromide * Sodium bromide * Centalun * Chloral betaine * Chloral hydrate * Chloralose * Clomethiazole * Dichloralphenazone * Gaboxadol * Kavalactones * Loreclezole * Paraldehyde * Petrichloral * Sulfonylalkanes * Sulfonmethane (sulfonal) * Tetronal * Trional * Triclofos * Sesquiterpene * Isovaleramide * Isovaleric acid * Valerenic acid GABAB * 1,4-Butanediol * 4-Fluorophenibut * Aceburic acid * Baclofen * GABOB * GHB (sodium oxybate) * GBL * GVL * Phenibut * Tolibut H1 Antihistamines * Captodiame * Cyproheptadine * Diphenhydramine * Doxylamine * Hydroxyzine * Methapyrilene * Perlapine * Pheniramine * Promethazine * Propiomazine Antidepressants * Serotonin antagonists and reuptake inhibitors * Etoperidone * Nefazodone * Trazodone * Tricyclic antidepressants * Amitriptyline * Doxepin * Trimipramine, etc. * Tetracyclic antidepressants * Mianserin * Mirtazapine, etc. Antipsychotics * Typical antipsychotics * Chlorpromazine * Thioridazine, etc. * Atypical antipsychotics * Olanzapine * Quetiapine * Risperidone, etc. α2-Adrenergic * Clonidine * Detomidine * Dexmedetomidine * Lofexidine * Medetomidine * Romifidine * Tizanidine * Xylazine 5-HT2A Antidepressants * Trazodone * Tricyclic antidepressants * Amitriptyline * Doxepin * Trimipramine, etc. * Tetracyclic antidepressants * Mianserin * Mirtazapine, etc. Antipsychotics * Typical antipsychotics * Chlorpromazine * Thioridazine, etc. * Atypical antipsychotics * Olanzapine * Quetiapine * Risperidone, etc. Others * Niaprazine Melatonin * Agomelatine * Melatonin * Ramelteon * Tasimelteon Orexin * Almorexant * Filorexant * Lemborexant * Suvorexant α2δ VDCC * Gabapentin * Gabapentin enacarbil * Mirogabalin * Phenibut * Pregabalin Others * Cannabidiol * Cannabis * Chlorophenylalkyldiols * Fenpentadiol * Metaglycodol * Phenaglycodol * Diethylpropanediol * Evoxine * Fenadiazole * Guaifenesin-related muscle relaxants * Chlorphenesin * Mephenesin * Mephenoxalone * Metaxalone * Methocarbamol * Midaflur * Opioids (e.g., morphine) * Passion flower * Scopolamine * Trazodone * UMB68 * Valnoctamide * v * t * e Insomnia pharmacotherapies GABAAR PAMs * Benzodiazepines: Brotizolam * Cinolazepam * Climazolam * Clorazepate * Doxefazepam * Estazolam * Etizolam * Flunitrazepam * Flurazepam * Flutoprazepam * Haloxazolam * Loprazolam * Lormetazepam * Midazolam * Nimetazepam * Nitrazepam * Quazepam * Temazepam * Triazolam; Nonbenzodiazepines/Z-drugs: Eszopiclone * Zaleplon * Zolpidem * Zopiclone; Others: Alcohols (e.g., ethchlorvynol, amylene hydrate, ethanol) * Barbiturates (e.g., amobarbital, pentobarbital, phenobarbital, secobarbital) * Bromides (e.g., potassium bromide, sodium bromide) * Carbamates (e.g., meprobamate) * Chloral hydrate * Clomethiazole * Kava * Paraldehyde * Piperidinediones (e.g., glutethimide) * Quinazolinones (e.g., methaqualone) * Sulfonmethane * Valerian Antihistamines (H1R inverse agonists) * Alimemazine * Captodiame * Dimenhydrinate * Diphenhydramine * Doxylamine * Etodroxizine * Hydroxyzine * Meclizine * Methapyrilene * Pheniramine * Phenyltoloxamine * Pimethixene * Promethazine * Propiomazine * Pyrilamine * TCAs (e.g., amitriptyline, doxepin, trimipramine) * TeCAs (e.g., mirtazapine) * Triprolidine OXR antagonists * Almorexant§ * Filorexant§ * Lemborexant§ * Suvorexant MTR agonists * Agomelatine * Melatonin * Ramelteon * Tasimelteon Miscellaneous * Antipsychotics (e.g., quetiapine, olanzapine, chlorpromazine) * Ashwagandha * Benzoctamine * Cannabinoids (e.g., cannabis, dronabinol (THC), nabilone) * Chamomile * Fenadiazole * Gabapentinoids (e.g., gabapentin, pregabalin, phenibut) * Hops * Lavender * Menthyl isovalerate * Niaprazine * Opioids (e.g., hydrocodone, oxycodone, morphine) * Passion flower * Scopolamine * Serotonin precursors (tryptophan, 5-HTP) * Sodium oxybate (GHB) * Sympatholytics (e.g., clonidine, guanfacine) * TCAs (e.g., amitriptyline, doxepin, trimipramine) * TeCAs (e.g., mirtazapine) * Theanine * Trazodone * Valnoctamide Authority control * BNE: XX527001 * BNF: cb119320824 (data) * GND: 4052584-3 * LCCN: sh85066717 * NDL: 00563661 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Insomnia	c0917801	26,212	wikipedia	https://en.wikipedia.org/wiki/Insomnia	2021-01-18T19:00:11	{"mesh": ["D007319"], "umls": ["C0917801", "C3279991", "C0393770"], "icd-9": ["780.52", "307.42", "780.51", "327.0", "307.41"], "icd-10": ["G47.0", "F51.0"], "wikidata": ["Q1869874"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive distal spinal muscular atrophy-5 (DSMA5) is caused by homozygous mutation in the DNAJB2 gene (604139) on chromosome 2q35. Description DSMA5 is an autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired (summary by Blumen et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of distal SMA, see HMN1 (182960). Clinical Features Blumen et al. (2012) reported 3 adult sibs, born of Moroccan Jewish Israeli parents, with distal muscle weakness. The parents' consanguinity was probable, but not certain. The proband presented at age 18 years with difficulty walking due to distal lower limb weakness and foot drop. Her older sibs had onset of a similar disorder at ages 23 and 20 years. All sibs had slowly progressive weakness, hypotonia, and muscle atrophy of the lower limbs, more pronounced distally. Knee and ankle jerks were absent; 1 patient had pes cavus. The 2 older sibs used a wheelchair and the proband used a walker. The upper limbs were relatively spared, although both triceps and biceps reflexes were absent in all patients. One patient had mild dysphonic speech, but none had cognitive, sensory, cerebellar, or autonomic symptoms. Nerve conduction studies showed decreased motor amplitudes in the peroneal and tibial regions. Electromyography showed severe denervation of distal, and later, proximal muscles of the lower limbs with mild denervation of some intrinsic hand muscles. Gess et al. (2014) reported 2 sisters, born of consanguineous Turkish parents, with onset of a pure motor neuropathy at ages 16 and 19 years, respectively. Initial symptoms included frequent stumbling due to weakness of the distal lower limbs. Physical examination showed mild atrophy of the peroneal muscles, mild paresis of the foot and toe dorsiflexors, and weakness of knee flexion. Neither patient had sensory involvement. Nerve conduction studies showed a pure motor axonal neuropathy. ### Clinical Variability Gess et al. (2014) reported 2 sisters of Austrian descent with onset of a distal sensory neuropathy, which they authors designated axonal Charcot-Marie-Tooth disease (CMT2), at 30 and 23 years of age. Initial symptoms included unstable gait and dys/paresthesias in the distal lower limbs. Physical examination showed incomplete paresis of foot and toe dorsiflexion, high steppage gait, peroneal muscle atrophy, and reduced sensation to the middle of the calf. Deep tendon reflexes were absent in the lower limbs and absent or decreased in the upper limbs. Both patients also had mildly reduced force of hip and knee flexors. Nerve conduction studies showed a length-dependent axonal motor and sensory neuropathy. Electromyographic studies in 1 patient showed mild fibrillations in the tibial muscle. Whole-exome sequencing identified a homozygous missense variant in the DNAJB2 gene (Y5C; 604139.0003) that segregated with the disorder in the family. Functional studies were not performed. The proband was 1 of 90 patients with autosomal recessive inherited neuropathies who underwent genetic studies. The Y5C mutation had previously been found in this family by Schabhuttl et al. (2014), who reported the family as family HMNS-R1. The findings expanded the phenotype associated with DNAJB2 mutations to include sensory impairment. Inheritance The transmission pattern of DSMA5 in the family reported by Blumen et al. (2012) was consistent with autosomal recessive inheritance. Mapping By homozygosity mapping of a Moroccan Jewish Israeli family with autosomal recessive distal spinal muscular atrophy, Blumen et al. (2012) found linkage to a 7.6-Mb region on chromosome 2q34-q36.1 between D2S128 and D2S339 (maximum lod score of 3.091 at D2S2248). Molecular Genetics In 3 sibs with DSMA5, Blumen et al. (2012) identified a homozygous splice site mutation in the DNAJB2 gene (604139.0001). The mutation was found by homozygosity mapping followed by candidate gene analysis. Mutations in the DNAJB2 gene were not found in 40 additional patients with distal spinal muscular atrophy. In 2 sisters, born of consanguineous Turkish parents, with DSMA5, Gess et al. (2014) identified a homozygous splice site mutation in the DNAJB2 gene (604139.0002). The mutation was demonstrated to result in a loss of protein expression. The proband was from a larger cohort of 90 patients with autosomal recessive hereditary neuropathies who underwent genetic studies. INHERITANCE \- Autosomal recessive SKELETAL Feet \- Pes cavus (1 patient) MUSCLE, SOFT TISSUES \- Distal muscle atrophy, lower limbs more severely affected than upper limbs \- Distal muscle weakness, lower limbs more severely affected than upper limbs \- Toe and foot dorsiflexor weakness \- Proximal muscle weakness, lower limbs, mild NEUROLOGIC Central Nervous System \- Impaired gait \- Foot drop Peripheral Nervous System \- Areflexia of the upper and lower limbs \- Decreased amplitudes of motor nerves in the lower limbs seen on nerve conduction studies \- Distal sensory impairment (1 family) \- Axonal sensorimotor neuropathy (1 family) VOICE \- Dysphonia, mild (1 patient) MISCELLANEOUS \- Onset in young adulthood (range 18 to 23 years) \- Slowly progressive \- Three unrelated families have been reported (last curated July 2016) \- Two of 3 patients became wheelchair-bound MOLECULAR BASIS \- Caused by mutation in the DNAJ/HSP40 homolog, subfamily B, member 2 gene (DNAJB2, 604139.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL RECESSIVE, 5	c3553989	26,213	omim	https://www.omim.org/entry/614881	2019-09-22T15:53:50	{"doid": ["0111214"], "omim": ["614881"], "orphanet": ["443950", "314485"], "synonyms": ["Young adult-onset dHMN", "Autosomal recessive distal spinal muscular atrophy type 5", "dSMA5", "DNAJB2-related CMT2"]}
Mucormycosis Other namesZygomycosis[1] This patient presented with a case of a periorbital fungal infection known as mucormycosis, or phycomycosis. SpecialtyInfectious disease CausesWeakened immune system Risk factorsHIV/AIDS, diabetes mellitus, diabetic ketoacidosis, lymphoma, organ transplant, long-term steroid use Treatmentamphotericin B, surgical debridement PrognosisPoor Mucormycosis is any fungal infection caused by fungi in the order Mucorales.[2]:328 Generally, species in the Mucor, Rhizopus, Absidia, and Cunninghamella genera are most often implicated.[3][4] The disease is often characterized by hyphae growing in and around blood vessels and can be potentially life-threatening in diabetic or severely immunocompromised individuals. "Mucormycosis" and "zygomycosis" are sometimes used interchangeably.[5] However, zygomycota has been identified as polyphyletic, and is not included in modern fungal classification systems. Also, while zygomycosis includes Entomophthorales, mucormycosis excludes this group. ## Contents * 1 Signs and symptoms * 2 Risk factors * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 6.1 Outbreaks * 7 References * 8 External links ## Signs and symptoms[edit] A 47-year-old man with mucormycosis and electron micrograph of his skin showing sporangia of Mucorales fungi.[6] Mucormycosis frequently infects the sinuses, brain, or lungs. While infection of the oral cavity or brain are the most common forms of mucormycosis, the fungus can also infect other areas of the body such as the gastrointestinal tract, skin, and other organ systems.[7] In rare cases, the maxilla may be affected by mucormycosis.[8] The rich blood vessel supply of maxillofacial areas usually prevents fungal infections, although more virulent fungi, such as those responsible for mucormycosis, can often overcome this difficulty.[8] There are several key signs which point towards mucormycosis. One such sign is fungal invasion into the blood vessels which results in the formation of blood clots and surrounding tissue death due to a loss of blood supply.[9] If the disease involves the brain, then symptoms may include a one-sided headache behind the eyes, facial pain, fevers, nasal congestion that progresses to black discharge, and acute sinusitis along with eye swelling.[10] Affected skin may appear relatively normal during the earliest stages of infection. This skin quickly becomes reddened and may be swollen before eventually turning black due to tissue death.[9] Other forms of mucormycosis may involve the lungs, skin, or be widespread throughout the body; symptoms may also include difficulty breathing, and persistent cough. In cases of tissue death, symptoms include nausea and vomiting, coughing up blood, and abdominal pain.[7][10] ## Risk factors[edit] Predisposing factors for mucormycosis include HIV/AIDS, uncontrolled diabetes mellitus, cancers such as lymphomas, kidney failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis energy malnutrition,[7][8] and deferoxamine therapy.[medical citation needed] Despite this, however, there have been cases of mucormycosis reported with no apparent predisposing factors present.[11] ## Diagnosis[edit] As swabs of tissue or discharge are generally unreliable, the diagnosis of mucormycosis tends to be established with a biopsy specimen of the involved tissue.[citation needed] ## Treatment[edit] If mucormycosis is suspected, amphotericin B therapy should be immediately administered due to the rapid spread and high mortality rate of the disease. Amphotericin B is usually administered for an additional 4–6 weeks after initial therapy begins to ensure eradication of the infection. Isavuconazole was recently FDA approved to treat invasive aspergillosis and invasive mucormycosis.[12] After administration of either amphotericin B or posaconazole, surgical removal of the "fungus ball" is indicated. The disease must be monitored carefully for any signs of reemergence.[7][13] Surgical therapy can be very drastic, and in some cases of disease involving the nasal cavity and the brain, removal of infected brain tissue may be required. In some cases surgery may be disfiguring because it may involve removal of the palate, nasal cavity, or eye structures.[10] Surgery may be extended to more than one operation.[7] It has been hypothesized that hyperbaric oxygen may be beneficial as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the organism.[9] Treatment approach may be different particularly when the Conidiobolus do not respond to antifungal agents in antiretroviral therapy resistant AIDS patients.[14] ## Prognosis[edit] In most cases, the prognosis of mucormycosis is poor and has varied mortality rates depending on its form and severity. In the rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient, with a mortality rate of up to 90%.[9] Patients with AIDS have a mortality rate of almost 100%.[13] Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.[10] ## Epidemiology[edit] Mucormycosis is a very rare infection, and as such, it is hard to note histories of patients and incidence of the infection.[7] However, one American oncology center revealed that mucormycosis was found in 0.7% of autopsies and roughly 20 patients per every 100,000 admissions to that center.[13] In the United States, mucormycosis was most commonly found in rhinocerebral form, almost always with hyperglycemia and metabolic acidosis (e.g. DKA).[11] In most cases the patient is immunocompromised, although rare cases have occurred in which the subject was not; these are usually due to a traumatic inoculation of fungal spores. Internationally, mucormycosis was found in 1% of patients with acute leukemia in an Italian review.[7] ### Outbreaks[edit] Not every hospital in the USA is required to publicize details of infectious outbreaks which occur within their facilities. In 2014, details of a lethal mucormycosis outbreak[15] which occurred in 2008 emerged after television and newspaper reports responded to an article in a pediatric medical journal.[16] Contaminated hospital linen was found to be spreading the infection. A 2018 study found many freshly laundered hospital linens delivered to U.S. transplant hospitals were contaminated with Mucorales.[17] A cluster of infections occurred in the wake of the 2011 Joplin tornado. As of July 19, a total of 18 suspected cases of cutaneous mucormycosis had been identified, of which 13 were confirmed. A confirmed case was defined as 1) necrotizing soft-tissue infection requiring antifungal treatment or surgical debridement in a person injured in the tornado, 2) with illness onset on or after May 22 and 3) positive fungal culture or histopathology and genetic sequencing consistent with a Mucormycete. No additional cases related to that outbreak have been reported since June 17. Ten patients required admission to an intensive-care unit, and five died.[18][19] Cutaneous mucormycosis has been reported after previous natural disasters; however, this is the first known cluster occurring after a tornado. None of the infections were found in persons cleaning up debris; instead it is believed transmission occurred through penetrating injuries inflicted by contaminated objects (e.g. splinters from a woodpile).[20] Following COVID-19 pandemic, a number of cases linked to immunosuppressive treatment for COVID-19 were reported in India. In Ahmedabad, 44 cases including nine deaths were reported by mid-December 2020. Cases were also reported in Mumbai and Delhi.[21] ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Zygomycosis". www.orpha.net. Retrieved June 28, 2019. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ Rinaldi M.G. (1989). "Zygomycosis". Infect Dis Clin North Am. 3 (1): 19–41. PMID 2647832. 4. ^ Lee F.Y.; Mossad S.B.; Adal K.A. (1999). "Pulmonary mucormycosis: the last 30 years". Arch Intern Med. 159 (12): 1301–9. doi:10.1001/archinte.159.12.1301. PMID 10386506. 5. ^ Staff Springfield News-Leader (June 10, 2011) "Aggressive fungus strikes Joplin tornado victims" Seattle PI, Hearst Communications Inc. 6. ^ Ran Yuping (2016). "Observation of Fungi, Bacteria, and Parasites in Clinical Skin Samples Using Scanning Electron Microscopy". In Janecek, Milos; Kral, Robert (eds.). Modern Electron Microscopy in Physical and Life Sciences. InTech. doi:10.5772/61850. ISBN 978-953-51-2252-4. 7. ^ a b c d e f g Nancy F Crum-Cianflone; MD MPH. "Mucormycosis". eMedicine. Retrieved May 19, 2008. 8. ^ a b c Auluck A (2007). "Maxillary necrosis by mucormycosis. a case report and literature review" (PDF). Med Oral Patol Oral Cir Bucal. 12 (5): E360–4. PMID 17767099. Retrieved May 19, 2008. 9. ^ a b c d Spellberg B, Edwards J, Ibrahim A (2005). "Novel perspectives on mucormycosis: pathophysiology, presentation, and management". Clin. Microbiol. Rev. 18 (3): 556–69. doi:10.1128/CMR.18.3.556-569.2005. PMC 1195964. PMID 16020690. 10. ^ a b c d "MedlinePlus Medical Encyclopedia: Mucormycosis". Retrieved May 19, 2008. 11. ^ a b Roden MM, Zaoutis TE, Buchanan WL, et al. (September 2005). "Epidemiology and outcome of Mucormycosis: a review of 929 reported cases". Clin. Infect. Dis. 41 (5): 634–53. doi:10.1086/432579. PMID 16080086. 12. ^ Lyndsay Mayer. "Mucormycosis". Food and Drug Administration. Retrieved April 5, 2017. 13. ^ a b c Rebecca J. Frey. "Mucormycosis". Health A to Z. Archived from the original on May 18, 2008. Retrieved May 19, 2008. 14. ^ Dhurat, Rachita; Kothavade, Rajendra J.; Kumar, Anand (January 2018). "A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis". Indian Journal of Medical Microbiology. 36 (1): 136–139. doi:10.4103/ijmm.IJMM_16_330. ISSN 1998-3646. PMID 29735845. 15. ^ Catalanello, Rebecca (April 16, 2014). "Mother believes her newborn was the first to die from fungus at Children's Hospital in 2008". NOLA.com. 16. ^ "5 Children's Hospital patients died in 2008, 2009 after contact with deadly fungus". "We acknowledge that Children's Hospital is Hospital A in an upcoming article in The Pediatric Infectious Disease Journal. The safety and well-being of our patients are our top priorities, so as soon as a problem was suspected, the State Health Department and CDC were notified and invited to assist in the investigation. The hospital was extremely aggressive in trying to isolate and then eliminate the source of the fungus." 17. ^ Sundermann, Alexander; et al. (2018). "How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery Study of Large United States Transplant and Cancer Centers". Clinical Infectious Diseases. 68 (5): 850–853. doi:10.1093/cid/ciy669. PMC 6765054. PMID 30299481. 18. ^ Williams, Timothy (June 10, 2011) Rare Infection Strikes Victims of a Tornado in Missouri. New York Times. 19. ^ Neblett Fanfair, Robyn; Benedict, Kaitlin; Bos, John; Bennett, Sarah D.; Lo, Yi-Chun; Adebanjo, Tolu; Etienne, Kizee; Deak, Eszter; Derado, Gordana; Shieh, Wun-Ju; Drew, Clifton; Zaki, Sherif; Sugerman, David; Gade, Lalitha; Thompson, Elizabeth H.; Sutton, Deanna A.; Engelthaler, David M.; Schupp, James M.; Brandt, Mary E.; Harris, Julie R.; Lockhart, Shawn R.; Turabelidze, George; Park, Benjamin J. (2012). "Necrotizing Cutaneous Mucormycosis after a Tornado in Joplin, Missouri, in 2011". New England Journal of Medicine. 367 (23): 2214–25. doi:10.1056/NEJMoa1204781. PMID 23215557. 20. ^ Fanfair, Robyn Neblett; et al. (July 29, 2011). "Notes from the Field: Fatal Fungal Soft-Tissue Infections After a Tornado – Joplin, Missouri, 2011". MMWR Weekly. 60 (29): 992. 21. ^ "'Black' Fungal Disease that Causes Blindness, Death Strikes Guj after Covid-19; Kills 9 in Ahmedabad". News18. December 18, 2020. Retrieved December 18, 2020. ## External links[edit] Classification D * ICD-10: B46.0-B46.5 * ICD-9-CM: 117.7 * MeSH: D009091 * DiseasesDB: 31759 * SNOMED CT: 76627001 External resources * MedlinePlus: 000649 * Patient UK: Mucormycosis * Orphanet: 73263 * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mucormycosis	c0026718	26,214	wikipedia	https://en.wikipedia.org/wiki/Mucormycosis	2021-01-18T18:44:37	{"mesh": ["D009091"], "icd-9": ["117.7"], "icd-10": ["B46.5", "B46.0"], "orphanet": ["73263"], "wikidata": ["Q6931254"]}
A number sign (#) is used with this entry because of evidence that infantile parkinsonism-dystonia-2 (PKDYS2) is caused by homozygous mutation in the SLC18A2 gene (193001) on chromosome 10q25. One such family has been reported. Description PKDYS2 is an autosomal recessive complex infantile-onset neurologic disorder characterized by abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. Some patients have variable degrees of developmental delay. Features of the disorder are consistent with decreased levels of monoamine neurotransmitters, although levels of these in the spinal fluid are normal. Preliminary findings indicate that treatment with a dopamine receptor agonist results in dramatic and sustained clinical improvement (summary by Rilstone et al., 2013). For a discussion of genetic heterogeneity of PKDYS, see 613135. Clinical Features Rilstone et al. (2013) reported a highly consanguineous large Saudi Arabian family in which multiple members had a complex neurologic disorder apparent since infancy. The proband was a 16-year-old girl with global developmental delay and abnormal movements. She first presented at age 4 months with hypotonia, loss of acquired head control, and paroxysmal stereotyped episodes of eye deviation and crying lasting hours, consistent with oculogyric crises. Seizures were ruled out. She sat at 30 months, crawled at 4 years, and walked at 13 years. At age 16, she had had fatigue, excessive diaphoresis, nasal and oropharyngeal secretions, noisy breathing, hypernasal speech, poor distal perfusion, cold hands and feet, and disrupted sleep, suggesting autonomic dysfunction. She also had ataxia, axial hypotonia, appendicular hypertonia with mild hyperreflexia, ptosis, hypomimia, facial dyskinesia, dysarthria, and limited upward gaze. Coordination testing revealed a fine tremor, dysdiadochokinesia, and poor fine motor skills. Her gait was parkinsonian, with shuffling, stooped posture, and dystonia. Brain imaging and CSF neurotransmitter levels were normal, but urinary analysis showed increased levels of neurotransmitter metabolites, including homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), as well as decreased levels of norepinephrine and dopamine. There was no improvement with administration of vitamin B6 or folinic acid, and treatment with L-dopa resulted in severe exacerbation of the symptoms. Her 3 younger sibs and several cousins were similarly affected. Her younger sibs were less severely affected, likely because treatment started earlier (see CLINICAL MANAGEMENT). The patients had variable cognitive deficits, ranging from inability to read or write and poor or absent language development to normal language development and ability to learn to read. The clinical features were consistent with monoamine deficiency, despite normal levels of brain monoamines. Heterozygous carriers of the mutation had a very high rate of depression. Clinical Management In affected members of a family with PKDYS2, Rilstone et al. (2013) found that treatment with L-dopa resulted in severe exacerbation of the symptoms. In contrast, treatment with a dopamine receptor agonist (pramipexole) resulted in dramatic and sustained disappearance of parkinsonism and dystonic episodes as well as improvement in other symptoms. The younger the affected child at onset of treatment, the more substantial the recovery. Inheritance The transmission pattern of PKDYS2 in the family reported by Rilstone et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of a highly consanguineous Saudi Arabian family with PKYS2, Rilstone et al. (2013) identified a homozygous missense mutation in the SLC18A2 gene (P387L; 193001.0001). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies in COS-7 cells showed that the mutation resulted in a severe, although not complete, loss of transport function for serotonin, consistent with a loss of function. The findings suggested that the disorder resulted from defective monoamine loading into synaptic vesicles, causing impaired synaptic neurotransmission and symptoms consistent with depletion of monoamines. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial hypomimia \- Facial dyskinesia Eyes \- Oculogyric crises \- Limited upward gaze \- Ptosis Nose \- Nasal secretions Mouth \- Oral secretions RESPIRATORY \- Noisy breathing SKELETAL Hands \- Cold hands \- Poor distal perfusion Feet \- Cold feet \- Poor distal perfusion SKIN, NAILS, & HAIR Skin \- Increased sweating MUSCLE, SOFT TISSUES \- Axial hypotonia \- Appendicular hypertonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Cognitive deficits, variable \- Poor fine motor skills \- Incoordination \- Delayed walking \- Ataxic gait \- Shuffling gait \- Stooped posture \- Oculogyric crisis \- Parkinsonism \- Tremor \- Dystonia \- Autonomic dysfunction \- Disrupted sleep \- Hyperreflexia \- Dysarthria Behavioral Psychiatric Manifestations \- Depression (in heterozygous carriers) VOICE \- Hypernasal speech METABOLIC FEATURES \- Temperature instability LABORATORY ABNORMALITIES \- Normal levels of CSF neurotransmitters \- Increased urinary homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) \- Decreased urinary norepinephrine and dopamine MISCELLANEOUS \- Onset in infancy \- Favorable clinical response to dopamine receptor agonist \- Poor response to L-dopa \- One consanguineous Saudi Arabian family has been reported (last curated July 2018) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 18 (vesicular monoamine), member 2 gene (SLC18A2, 193001.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PARKINSONISM-DYSTONIA, INFANTILE, 2	None	26,215	omim	https://www.omim.org/entry/618049	2019-09-22T15:43:52	{"omim": ["618049"], "orphanet": ["352649"], "synonyms": []}
There is a relatively low prevalence of HIV/AIDS in New Zealand, with an estimated 2,900 people out a population of 4.51 million living with HIV/AIDS as of 2014. The rate of newly diagnosed HIV infections was stable at around 100 annually through the late 1980s and the 1990s but rose sharply from 2000 to 2005. It has since stabilised at roughly 200 new cases annually. Male-to-male sexual contact has been the largest contributor to new HIV cases in New Zealand since record began in 1985. Heterosexual contact is the second largest contributor to new cases, but unlike male-to-male contact, they are mostly acquired outside New Zealand.[1] In 2018 the New Zealand Government reported a “major reduction” in the number of people diagnosed with HIV.[2] The first recorded death in New Zealand due to AIDS was in New Plymouth in 1983.[3] In 1985 Eve van Grafhorst was ostracised in Australia since she had contracted HIV/AIDS caused by a transfusion of infected blood. The family moved to New Zealand where she died at the age of 11. By the time of her death, her plight had significantly raised the level of AIDS awareness in New Zealand. World AIDS Day is observed in New Zealand. ## Contents * 1 Organisations * 2 Antiretroviral medications * 3 See also * 4 References * 5 External links ## Organisations[edit] The Ministry of Health is the government department which deals with health issues, including HIV/AIDS. The New Zealand AIDS Foundation is a registered charitable trust which focuses on prevention of AIDS in the most at-risk group, namely men who have sex with men. Other organisations that assist with people living with HIV are as follows: Body Positive provides rapid HIV tests and support for people who are positive. Positive Women. This service looks after women who are HIV positive. There are many other places that offer similar services including the Burnett Center, INA Foundation, New Zealand Prostitutes Collective, Family Planning and Sexual Health Clinics. ## Antiretroviral medications[edit] The Pharmaceutical Management Agency (Pharmac) manages the national schedule of subsidised medications. As of 2014, twenty-one different antiretroviral medications were subsidised for people with confirmed HIV/AIDS or for post-exposure prophylaxis.[1] In March 2018, New Zealand became one of the first countries in the world to publicly fund pre-exposure prophylaxis medication for those at a high risk of contracting HIV.[4] ## See also[edit] * LGBT New Zealand * AIDS pandemic * GayNZ.com, an online LGBT community forum ## References[edit] 1. ^ a b "UNGASS Country Progress Report New Zealand: Reporting Period: January 2014 – December 2014" (PDF). April 2015. Retrieved 6 February 2017. 2. ^ "Major reduction in numbers of people diagnosed with HIV". The Beehive. Retrieved 2020-03-21. 3. ^ UNAIDS factsheet 4. ^ "NZ ahead of the pack in funding revolutionary HIV-prevention drug PrEP". 7 February 2018. Retrieved 18 November 2018. ## External links[edit] * HIV and AIDS Information, Ministry of Health * New Zealand AIDS Foundation * Bodypositive.org.nz * www.positivewomen.org.nz * Queer Resources Aotearoa New Zealand \- a history of HIV/AIDS in New Zealand * Streaming audio interviews on HIV/AIDS in New Zealand * The New Zealand AIDS Memorial Quilt * Ending HIV NZ * v * t * e HIV/AIDS in Oceania Sovereign states * Australia * Federated States of Micronesia * Fiji * Kiribati * Marshall Islands * Nauru * New Zealand * Palau * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu Associated states of New Zealand * Cook Islands * Niue Dependencies and other territories * American Samoa * Christmas Island * Cocos (Keeling) Islands * Easter Island * French Polynesia * Guam * Hawaii * New Caledonia * Norfolk Island * Northern Mariana Islands * Pitcairn Islands * Tokelau * Wallis and Futuna * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by region [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HIV/AIDS in New Zealand	None	26,216	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_New_Zealand	2021-01-18T18:51:39	{"wikidata": ["Q5629867"]}
A number sign (#) is used with this entry because of evidence that lymphoproliferative syndrome-1 (LPFS1) is caused by homozygous mutation in the ITK gene (186973) on chromosome 5q33. Description Lymphoproliferative syndrome-1 is an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia. Autoimmune disorders, such as autoimmune hemolytic anemia or renal disease, may also occur. Patients show a high EBV viral load and decreased invariant natural killer T cells. It is unknown whether patients with ITK mutations are intrinsically susceptible to development of lymphoma or dysgammaglobulinemia in the absence of EBV infection (summary by Stepensky et al., 2011; Linka et al., 2012). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240). Clinical Features Huck et al. (2009) reported 2 sisters, born of consanguineous Turkish parents, who died in childhood after developing severe immune dysregulation and therapy-resistant Epstein-Barr virus (EBV)-positive B-cell proliferation following EBV infection. The older girl presented at age 5 years with aphthous stomatitis and subsequent candida stomatitis. From the age of 6 years, she successively developed recurrent episodes of fever and elevated C-reactive protein (CRP; 123260), nodular interstitial pulmonary infiltrates, generalized lymphadenopathy, hepatosplenomegaly with impaired liver function, pleural and pericardial effusion, anemia, thrombocytopenia, and hypogammaglobulinemia. Laboratory studies were consistent with chronic active EBV infection. Lymph node biopsy showed polymorphic B-cell proliferation. At age 8 years, she developed an EBV-associated Hodgkin lymphoma of the nasal concha. Bone marrow aspirate was normal, with no evidence of lymphoma infiltration, histiocytosis, or hemophagocytosis. Despite treatment, she died of bacterial pneumonia at age 10 years. Her younger sister developed recurrent episodes of fever unresponsive to antibiotic treatment at age 5 years. Within 4 months, the symptoms progressed to a life-threatening condition with profound pancytopenia, retroperitoneal and abdominal lymphadenopathy, hepatosplenomegaly, severely impaired liver function, ascites, and pleural effusion. She had active EBV infection and B-cell lymphoproliferation. She died from complications of a peripheral blood stem cell transplantation. One of the patients examined had decreased numbers of natural killer (NK) T cells. Huck et al. (2009) noted the phenotypic similarities to the X-linked lymphoproliferative syndromes observed in boys. Stepensky et al. (2011) reported a consanguineous Arab family in which 3 patients presented between ages 3 and 5 years with fever, lymphadenopathy, and Hodgkin lymphoma associated with EBV infection. One patient was treated with successfully with chemotherapy but later developed fatal hemophagocytic lymphohistiocytosis; the second patient was treated successfully with chemotherapy but later developed autoimmune renal disease and was treated successfully with antiviral therapy; and the third patient underwent successful bone marrow transplant from a donor sib who was heterozygous for the mutation. Linka et al. (2012) reported a patient, born of consanguineous Moroccan parents, who was diagnosed at age 11 years with an EBV-associated B-cell lymphoproliferative disorder. He also had autoimmune hemolytic anemia, thrombocytopenia, and progressive lymphopenia. He died at age 26 years. Inheritance The transmission pattern of LPFS1 in the families reported by Linka et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics By linkage analysis, followed by candidate gene sequencing, Huck et al. (2009) identified a homozygous mutation in the ITK gene (R335W; 186973.0001) in 2 Turkish sisters with fatal EBV-associated lymphoproliferative syndrome. In 3 members of a consanguineous Arab family with lymphoproliferative syndrome-1, Stepensky et al. (2011) identified a homozygous truncating mutation in the ITK gene (Y588X; 186973.0002). The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder in the family. In a patient, born of consanguineous Moroccan parents, with lymphoproliferative syndrome-1, Linka et al. (2012) identified a homozygous missense mutation in the ITK gene (R29H; 186973.0003). Linka et al. (2012) performed functional studies on cells from the patients reported by Huck et al. (2009), Stepensky et al. (2011), and Linka et al. (2012), and found that all had a reduced calcium signaling response after TCR stimulation and were unable to enhance calcium response in Itk-null mouse cells, consistent with a loss of function. In vitro studies showed that all mutant proteins had reduced half-lives; the R29H mutation impeded membrane targeting of ITK. INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Hepatomegaly \- Impaired liver function Spleen \- Splenomegaly HEMATOLOGY \- Anemia \- Thrombocytopenia \- Pancytopenia IMMUNOLOGY \- Lymphadenopathy \- Recurrent infections \- Mononucleosis \- Hypogammaglobulinemia \- Evidence of EBV infection \- Polymorphic B cell lymphoproliferation \- Decreased ITK protein in lymphoid tissue \- Decreased natural killer T cells \- Depleted CD4+ T cells \- Lymphohistiocytosis \- Autoimmune disorders NEOPLASIA \- Increased risk for lymphoma Hodgkin disease LABORATORY ABNORMALITIES \- Increased C-reactive protein \- Elevated erythrocyte sedimentation rate (ESR) \- High EBV viral load MISCELLANEOUS \- Onset in childhood \- Fatal without bone marrow transplantation MOLECULAR BASIS \- Caused by mutation in the IL2-inducible T-cell kinase gene (ITK, 186973.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LYMPHOPROLIFERATIVE SYNDROME 1	c3552634	26,217	omim	https://www.omim.org/entry/613011	2019-09-22T15:59:59	{"doid": ["0060707"], "omim": ["613011"], "orphanet": ["538963"], "synonyms": ["Autosomal recessive lymphoproliferative disease due to ITK deficiency", "ITK deficiency"]}
Mixed affective state Other namesMixed affective state,mixed episode, mixed-manic episode, dysphoric mania "Melancholy passing into mania",illustration portraying the "inbetween" like state that many people in a mixed episode might feel SpecialtyPsychiatry SymptomsDepressed mood, racing thoughts, agitation, anxiety, irritability/aggression, emotional lability, suicide ideation[1] A mixed affective state, formerly known as a mixed-manic or mixed episode, has been defined as a state wherein features unique to both depression and mania—such as episodes of despair, doubt, anguish, rage or homicidal ideation, suicidal ideation, splitting, racing thoughts, sensory overload, pressure of activity, and heightened irritability—occur either simultaneously or in very short succession. Previously, the diagnostic criteria for both a manic and depressive episode had to be met in a consistent and sustained fashion, with symptoms enduring for at least a week (or any duration if psychiatric hospitalization was required), thereby restricting the official acknowledgement of mixed affective states to only a minority of patients with bipolar I disorder. In current DSM-5 nomenclature, however, a "mixed episode" no longer stands as an episode of illness unto itself; rather, the symptomology specifier "with mixed features" can be applied to any major affective episode (manic, hypomanic, or depressive), meaning that they are now officially recognized in patients with, in addition to bipolar I disorder, bipolar II disorder and, by convention, major depressive disorder. A depressive mixed state in a patient, however, even in the absence of discrete periods of mania or hypomania, effectively rules out unipolar depression. ## Contents * 1 Diagnostic criteria * 2 Treatment * 3 See also * 4 References * 5 External links ## Diagnostic criteria[edit] As affirmed by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the symptomology specifier "with mixed features" can be applied to manic episodes of bipolar I disorder, hypomanic episodes of either bipolar I disorder or bipolar II disorder and depressive episodes of either bipolar disorder or major depressive disorder, with at least three concurrent features of the opposite polarity being present. As a result, the presence of "mixed features" are now recognized in patients with bipolar II disorder and major depression; as earlier noted, however, although it is customary to withhold a diagnosis of a bipolar disorder until a manic or hypomanic episode appears, the presence of such features in a depressed patient even with no history of discrete mania or hypomania is strongly suggestive of the disorder. Two features of both mania or hypomania and depression may superficially overlap and even resemble each other, namely "an increase in goal-directed activity" (psychomotor acceleration) vs. psychomotor agitation and "flight of ideas" and "racing thoughts" vs. depressive rumination. Attending to the patient's experiences is very important. In the psychomotor agitation commonly seen in depression, the "nervous energy" is always overshadowed by a strong sense of exhaustion and manifests as purposeless movements (e.g., pacing, hand-wringing); in psychomotor acceleration, however, the excess in movement stems from an abundance of energy and is often channelled and purposeful. Likewise, in depressive rumination, the patient experiences the repetitive thoughts as heavy, leaden, and plodding; in psychic acceleration, however, (as seen in mania or hypomania) the thoughts move in a rapid progression, with many themes, rather than a singular one, being touched upon. Even when such experiences are accounted for on the basis of depression, the possibility does still exist, however, that the depressive episode may be complicated by other manic or hypomanic symptoms, in which case it is often prudent to attend to the patient's personal and family history (e.g., family history of bipolar disorder, early age of onset) to determine whether or not the patient has bipolar disorder.[2] ## Treatment[edit] Treatment of mixed states is typically based upon administration of mood stabilizing medication, which may include anticonvulsants such as valproic acid; atypical antipsychotics such as quetiapine, olanzapine, aripiprazole, and ziprasidone; or first-generation antipsychotics such as haloperidol. There is question of lithium's efficacy for treatment of mixed states due to conflicting conclusions drawn from various trials and research.[3][4] Mood stabilizers work to reduce the manic symptoms associated with the mixed state, but they are not considered particularly effective for improving concurrent depressive symptoms.[5] ## See also[edit] * Dopamine * Mania * Hyperthymic temperament * Cyclothymia * Narcissistic personality disorder * Borderline personality disorder ## References[edit] 1. ^ https://psycheducation.org/diagnosis/mixed-states/ 2. ^ Swann AC (2013). "Activated depression: mixed bipolar disorder or agitated unipolar depression?". Curr Psychiatry Rep. 15 (8): 376. doi:10.1007/s11920-013-0376-1. PMID 23881708. 3. ^ Krüger S, Young T, Bräunig P. "[Pharmacotherapy of manic-depressive mixed States]". Psychiatr Prax. 33 Suppl 1: S32-9. doi:10.1055/s-2005-867019. PMID 16511729. 4. ^ Muzina D. J. (2009). "Pharmacologic treatment of rapid cycling and mixed states in bipolar disorder: an argument for the use of lithium". Bipolar Disorders. 11: 84–91. doi:10.1111/j.1399-5618.2009.00713.x. 5. ^ Thase ME, Sachs GS (Sep 2000). "Bipolar depression: pharmacotherapy and related therapeutic strategies". Biol Psychiatry. 48 (6): 558–572. doi:10.1016/s0006-3223(00)00980-x. ## External links[edit] Classification D * ICD-10: F38.0 * ICD-9-CM: 296.6 * v * t * e Mood disorder History * Emil Kraepelin * Karl Leonhard * John Cade * Mogens Schou * Frederick K. Goodwin * Kay Redfield Jamison Symptoms * Hallucination * Delusion * Emotional dysregulation * Anhedonia * Dysphoria * Suicidal ideation * Mood swing * Sleep disorder * Hypersomnia * Insomnia * Psychosis * Racing thoughts * Reduced affect display * Depression (differential diagnoses) Spectrum * Bipolar disorder * Bipolar I * Bipolar II * Cyclothymia * Bipolar NOS * Depression * Major depressive disorder * Dysthymia * Seasonal affective disorder * Atypical depression * Melancholic depression * Schizoaffective disorder * Mania * Mixed affective state * Hypomania * Major depressive episode * Rapid cycling Treatment Anticonvulsants * Carbamazepine * Lamotrigine * Oxcarbazepine * Valproate * Sodium valproate * Valproate semisodium Sympathomimetics, SSRIs and similar * Dextroamphetamine * Methylphenidate * Bupropion * Sertraline * Fluoxetine * Escitalopram Other mood stabilizers * Antipsychotics * Lithium * Lithium carbonate * Lithium citrate * Lithium sulfate * Lithium toxicity * Atypical antipsychotics Non-pharmaceutical * Clinical psychology * Electroconvulsive therapy * Involuntary commitment * Light therapy * Psychotherapy * Transcranial magnetic stimulation * Cognitive behavioral therapy * Dialectical behavior 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mixed affective state	None	26,218	wikipedia	https://en.wikipedia.org/wiki/Mixed_affective_state	2021-01-18T18:57:12	{"icd-9": ["296.6"], "icd-10": ["F38.0"], "wikidata": ["Q6884016"]}
A number sign (#) is used with this entry because of evidence that rhizomelic short stature with microcephaly, micrognathia, and developmental delay (SRMMD) is caused by heterozygous mutation in the ARCN1 gene (600820) on chromosome 11q23. Clinical Features Izumi et al. (2016) studied 4 individuals from 3 unrelated families who exhibited rhizomelic short stature as well as microcephaly, micrognathia, laxity of the small joints, and developmental delay. Other variable features included posterior cataract, cleft palate, ventricular septal defect, cryptorchidism, seizures, and autism. Two of the patients were a father and daughter; the father had previously been described by Verloes et al. (1997). Molecular Genetics By whole-exome sequencing in 4 patients who had rhizomelic short stature with microcephaly, micrognathia, and developmental delay, Izumi et al. (2016) identified heterozygosity for truncating mutations in the ARCN1 gene (600820.0001-600820.0003). One of the probands (see 600820.0003) was also heterozygous for a missense mutation in the SYT1 gene (D233N; see 185605), which Izumi et al. (2016) suggested might have contributed to the additional feature of seizures in that patient; however, given that all 4 patients with ARCN1 mutations exhibited comparable degrees of developmental delay and intellectual disability, the authors concluded that the ARCN1 mutations likely play a major role in the neurologic features observed in this syndrome, and that ARCN1 is probably required for normal brain growth and cognitive development. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Weight \- Low weight Other \- Intrauterine growth retardation \- Failure to thrive HEAD & NECK Head \- Microcephaly \- Scaphocephaly Face \- Micrognathia \- Retrognathia Eyes \- Hypotelorism \- Divergent squint \- Astigmatism \- Myopia \- Posterior cataract, bilateral (in 1 patient) Mouth \- High-arched palate (in 1 patient) \- Cleft palate (in 1 patient) CARDIOVASCULAR Heart \- Ventricular septal defect (in 1 patient) RESPIRATORY \- Respiratory distress due to severe micrognathia (in some patients) Nasopharynx \- Obstructive sleep apnea (in 1 patient) CHEST Ribs Sternum Clavicles & Scapulae \- Moderate sternal depression (in 1 patient) Breasts \- Widely spaced nipples (in 1 patient) ABDOMEN Gastrointestinal \- Feeding difficulties (in some patients) \- Severe gastroesophageal reflux (in 1 patient) GENITOURINARY External Genitalia (Male) \- Hypospadias (in 1 patient) \- Micropenis (in 1 patient) \- Hypoplastic scrotum (in 1 patient) SKELETAL \- Advanced bone age Skull \- Microcephaly Pelvis \- Coxa valga (in 1 patient) Limbs \- Rhizomelic shortening \- Wide femoral neck (in some patients) \- Metaphyseal widening (in 1 patient) \- Limited extension of elbows (in 1 patient) \- Short bowed legs (in 1 patient) Hands \- Laxity of small joints (in some patients) Feet \- Cutaneous syndactyly of second and third toes (in 1 patient) MUSCLE, SOFT TISSUES \- Hypertrophic muscular appearance (in one family) NEUROLOGIC Central Nervous System \- Mental retardation \- Motor delay \- Seizures (in 1 patient) \- Ataxic gait (in 1 patient) \- Delayed white matter myelination in T2-weighted images (in 1 patient) \- Mild cerebellar atrophy (in 1 patient) Behavioral Psychiatric Manifestations \- Mild autism (in 1 patient) MISCELLANEOUS \- Based on report of 4 patients from 3 families (last curated October 2017) \- Variable features present MOLECULAR BASIS \- Caused by mutation in the archain-1 gene (ARCN1, 600820.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SHORT STATURE, RHIZOMELIC, WITH MICROCEPHALY, MICROGNATHIA, AND DEVELOPMENTAL DELAY	c4310686	26,219	omim	https://www.omim.org/entry/617164	2019-09-22T15:46:39	{"omim": ["617164"]}
A number sign (#) is used with this entry because fumarase deficiency (FMRD) is caused by homozygous or compound heterozygous mutation in the fumarate hydratase gene (FH; 136850) on chromosome 1q43. Heterozygous mutation in the FH gene can cause hereditary leiomyomatosis and renal cell cancer (HLRCC; 150800). Description Fumarase deficiency is a severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy (summary by Kerrigan et al., 2000 and Mroch et al., 2012). Clinical Features Zinn et al. (1986) reported the case of a male infant with mitochondrial encephalopathy who presented at 1 month of age with failure to thrive, developmental delay, hypotonia, cerebral atrophy, lactic and pyruvic acidemia, and fumaric aciduria. The patient died at 8 months of age. Mitochondria isolated from skeletal muscle showed selective defects in the oxidation of glutamate and succinate, whereas isolated liver mitochondria oxidized these normally. Fumarase activity was virtually absent in mitochondria of both sources. Homogenates of liver and muscle also showed very much reduced fumarase activity, indicating that the cytosolic form of the enzyme was also deficient. Organ differences in intramitochondrial accumulation of fumarase were thought to account for the selective oxidative defects observed in skeletal muscle and not in liver mitochondria. Whelan et al. (1983) reported isolated fumaric aciduria in 2 adult sibs with mental retardation and speech impairment. The authors attributed the increased urinary excretion to a defect in renal clearance; fumarase activity was not assessed. Petrova-Benedict et al. (1987) reported a case of fumarase deficiency in a mentally retarded child who presented at 6 months of age with hypotonia, microcephaly, and delayed development. Fumarase was deficient in both the mitochondrial and the cytosolic compartments, but the cytosolic enzyme appeared to be more severely affected. Snodgrass (1987) commented on the occurrence of mild hyperammonemia in fumarase deficiency. Gellera et al. (1990) described the clinical features of fumarase deficiency. A 7-month old boy died in a demented state after a clinical course characterized by generalized seizures, psychomotor deterioration, and fumaric aciduria. Marked deficiency of both mitochondrial and cytosolic fumarases was found in skeletal muscle, brain, cerebellum, heart, kidney, liver, and cultured fibroblasts. Anti-fumarase crossreacting material was present in negligible amounts in these tissues. Kerrigan et al. (2000) reported the clinical features of 8 affected members of a large consanguineous family with fumarase deficiency living in an isolated community in the southwestern United States. The ages of the patients ranged from 20 months to 12 years. All patients were profoundly developmentally retarded and had no language development. Only 1 child had achieved independent walking; all the others were unable to sit. All patients had relative macrocephaly and ventricular enlargement. Other common features included hypotonia, seizures, and status epilepticus. Dysmorphic features included frontal bossing, hypertelorism, depressed nasal bridge, anteverted nares, and high-arched palate. Five of 8 had polycythemia at birth. Neuroimaging showed striking abnormalities of the brain, including polymicrogyria, angulation of the frontal horns, decreased periventricular white matter, and small brainstem. Four patients had optic nerve hypoplasia or pallor. Mroch et al. (2012) reported 2 brothers, born of unrelated parents, with genetically confirmed FH deficiency resulting in death in infancy. The first boy was born prematurely from a pregnancy complicated by polyhydramnios, and showed hypotonia and respiratory insufficiency after birth. An ultrasound at 20 weeks' gestation had shown agenesis of the corpus callosum, ventriculomegaly, bilateral renal pyelectasis, and a ventriculoseptal defect. Postmortem imaging showed lissencephaly. He developed severe metabolic acidosis, necrotizing enterocolitis, liver failure associated with coagulopathy and hyperbilirubinemia, and encephalopathy, resulting in death at age 22 days. Biochemical studies showed increased urinary tyrosine metabolites, citric cycle intermediates, citrulline, fumaric, malic, and succinic acids, and skin biopsy showed fumarase deficiency. Postmortem examination showed a distended abdomen, and the liver showed intrahepatic bile stasis. Electron microscopy of the liver revealed multiple swollen mitochondria with flat, plate-like, haphazardly arranged cristae. Genetic analysis identified compound heterozygosity for a point mutation in the FH gene and a deletion of the FH gene (136850.0010 and 136850.0011). Prenatal diagnosis confirming the deficiency was performed on the subsequent pregnancy by genetic testing of amniocytes. Ultrasound at 20 weeks showed ventriculomegaly, dangling choroid plexus, and possible agenesis of the corpus callosum. The parents elected to continue with the pregnancy, but the infant died on day 26. Postmortem examination again showed hepatic involvement, with fibrosis, iron deposition, and bile stasis. Electron microscopy showed abnormal mitochondria similar to that observed in his affected brother. Each unaffected parent was heterozygous for 1 of the mutations, and neither showed cancer or abnormal cutaneous findings suggesting HLRCC. Inheritance In the case reported by Petrova-Benedict et al. (1987), the parents of the affected child were first cousins. In the case reported by Gellera et al. (1990), autosomal recessive inheritance was supported by the finding of fumarase activities 30 to 50% of normal in both mitochondria and cytosol from cultured fibroblasts of the parents. Molecular Genetics Coughlin et al. (1993) identified a homozygous mutation in the FH gene (136850.0001) in a patient with fumarase deficiency. Bourgeron et al. (1993, 1994) identified a homozygous mutation in the fumarase gene (136850.0002) in 2 patients with progressive encephalopathy associated with fumarase deficiency. In 2 brothers with infantile-lethal fumarase deficiency, Mroch et al. (2012) identified compound heterozygous mutations in the FH gene (136850.0010-136850.0011). Population Genetics There is an unusually high incidence of fumarase deficiency in the southwestern United States among members of the Fundamentalist Church of Jesus Christ of Latter Day Saints (FLDS), a religious community that practices inbreeding and polygamy. The genetic defect was traced to one of the community's founding patriarchs, the late Joseph Smith Jessop, and the first of his plural wives, who had 14 children together (Dougherty, 2005). INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Macrocephaly, relative Face \- Frontal bossing Eyes \- Hypertelorism \- Optic pallor \- Optic atrophy \- Visual impairment Nose \- Depressed nasal bridge \- Anteverted nares Mouth \- High-arched palate ABDOMEN Liver \- Liver failure \- Cholestasis \- Fibrosis \- Iron deposition \- Abnormal swollen mitochondria with flat, haphazardly arranged cristae SKIN, NAILS, & HAIR Skin \- Cutaneous leiomyomata (heterozygote carriers) MUSCLE, SOFT TISSUES \- Hypotonia \- Decreased muscle bulk \- Decreased subcutaneous fat NEUROLOGIC Central Nervous System \- Mental retardation, profound \- Developmental delay \- No language development \- Cerebral atrophy \- Seizures \- Status epilepticus \- Hypotonia \- Most patients do not achieve independent sitting or walking \- Ventricular enlargement \- Polymicrogyria \- Open operculum \- Choroid plexus cysts \- Decreased white matter volume \- Angulation of the frontal horns \- Small brainstem \- Agenesis of the corpus callosum METABOLIC FEATURES \- Metabolic acidosis HEMATOLOGY \- Polycythemia, neonatal \- Coagulopathy in those with liver failure LABORATORY ABNORMALITIES \- Lactic acidemia \- Pyruvic acidemia \- Fumaric aciduria \- Fumarase activity (mitochondrial and cytosolic) is decreased \- Increased urinary citric acid cycle intermediates \- Increased urinary fumaric acid \- Increased urinary malic acid \- Increased urinary succinic acid \- Hyperbilirubinemia in those with liver failure MISCELLANEOUS \- Allelic to hereditary multiple leiomyoma of skin (see 150800 ) and hereditary leiomyomatosis and renal cell cancer ( 150800 ) MOLECULAR BASIS \- Caused by mutation in the fumarate hydratase gene (FH, 136850.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	FUMARASE DEFICIENCY	c0342770	26,220	omim	https://www.omim.org/entry/606812	2019-09-22T16:09:59	{"doid": ["0111261"], "mesh": ["C538191"], "omim": ["606812"], "orphanet": ["24"], "synonyms": ["Alternative titles", "FUMARIC ACIDURIA"], "genereviews": ["NBK1506"]}
Familial clubfoot with or without associated lower limb anomalies is a rare congenital limb malformation syndrome characterized by malalignment of the bones and joints of the foot and ankle, with presence of forefoot and midfoot adductus, hindfoot varus, and ankle equinus, presenting as rigid inward turning of the foot towards the midline, in various members of a single family. Hypoplasia of lower leg muscles is a frequently associated finding. Patients may present with other low-limb malformations, such as patellar hypoplasia, oblique talus, tibial hemimelia, and polydactyly. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Familial clubfoot with or without associated lower limb anomalies	c0009081	26,221	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199315	2021-01-23T18:59:28	{"mesh": ["D003025"], "omim": ["119800", "613618"], "icd-10": ["Q66.8"]}
Paratuberculosis Other namesJohne's disease Pronunciation * Johne's disease: /ˈjoʊnə/ SpecialtyVeterinary medicine Paratuberculosis is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants.[1] It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis. Infections normally affect ruminants (mammals that have four compartments of their stomachs, of which the rumen is one), but have also been seen in a variety of nonruminant species, including rabbits, foxes, and birds. Horses, dogs, and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with some states in Australia (where it is usually called bovine Johne's disease or BJD) being the only areas proven to be free of the disease.[2] At least in Canada, the signs of BJD usually start when cattle are four to seven years of age, and then usually only are diagnosed in one animal at a time.[3] Cattle "with signs of Johne’s disease shed billions of bacteria through their manure and serve as a major source of infection for future calves."[4] Some sources define "paratuberculosis" by the lack of Mycobacterium tuberculosis, rather than the presence of any specific infectious agent,[5] leaving ambiguous the appropriateness of the term to describe Buruli ulcer or Lady Windermere syndrome. ## Contents * 1 Bacterium * 2 Signs and symptoms * 3 Pathophysiology * 4 Morbidity and mortality * 5 Human risks * 6 Action and regulations * 7 References * 8 External links ## Bacterium[edit] The disease, discovered by Heinrich A. Johne, a German bacteriologist and veterinarian, in 1905, is caused by a bacterium named Mycobacterium avium subspecies paratuberculosis, an acid-fast bacillus, often abbreviated MAP. MAP is akin to, but distinct from, Mycobacterium tuberculosis, the main cause of tuberculosis in humans, and Mycobacterium bovis, the main cause of tuberculosis in cattle and occasionally also in humans. MAP is 99% genetically related to Mycobacterium avium, but has different phenotypic characteristics, such as:[citation needed] * slower growth * requires the addition of an iron transport chemical known as mycobactin when grown in vitro * forms a rough colony when grown on a solid agar medium * Infects mammals instead of birds Also, the environmental distribution of MAP is markedly different from that of M. avium, which can produce mycobactin, so can grow and multiply outside the body.[citation needed] ## Signs and symptoms[edit] In cattle, the main signs of paratuberculosis are diarrhea and wasting. Most cases are seen in 2- to 6-year-old animals. The initial signs can be subtle, and may be limited to weight loss, decreased milk production, or roughening of the hair coat. The diarrhea is usually thick, without blood, mucus, or epithelial debris, and may be intermittent. Several weeks after the onset of diarrhea, a soft swelling may occur under the jaw. Known as "bottle jaw" or intermandibular edema, this symptom is due to protein loss from the bloodstream into the digestive tract. Paratuberculosis is progressive; affected animals become increasingly emaciated and usually die as the result of dehydration and severe cachexia.[citation needed] Signs are rarely evident until two or more years after the initial infection, which usually occurs shortly after birth. Animals are most susceptible to the infection in the first year of life. Newborns most often become infected by swallowing small amounts of infected manure from the birthing environment or udder of the mother. In addition, newborns may become infected while in the uterus or by swallowing bacteria passed in milk and colostrum. Animals exposed at an older age, or exposed to a very small dose of bacteria at a young age, are not likely to develop clinical disease until they are much older than two years.[citation needed] The clinical signs are similar in other ruminants. In sheep and goats, the wool or hair is often damaged and easily shed, and diarrhea is uncommon. In deer, paratuberculosis can progress rapidly. Intestinal disease has also been reported in rabbits and nonhuman primates.[citation needed] Unlike cattle and sheep, infections in deer often present with clinical illness in animals under one year of age.[citation needed] ## Pathophysiology[edit] The primary site targeted by Johne's disease is the lower part of the intestine known as the ileum. The wall of the ileum contains a large number of pockets of lymphoid tissue known as Peyer's patches that lie just beneath the interior surface of the intestine. Peyer's patches are clusters of macrophages and lymphocytes organized much like lymph nodes. Covering Peyer's patches are a layer of cells called M cells. These cells function to sample the content of the lumen of the intestines and pass antigens (bacteria) through to the underlying cells of the Peyer's patch to "show" these antigens to the macrophages and lymphocytes. This is a means of "educating" the cells in a young animal about its environment, and is a protective mechanism designed to help the animal become immune to pathogens in its environment.[citation needed] Unfortunately, when M cells bring M. paratuberculosis to the Peyer's patch, the bacteria find an ideal place for growth. Macrophages in Peyer's patches engulf M. paratuberculosis for the purpose of destroying the foreign invader, but for reasons yet unclear, these macrophages fail to do this. Inside a macrophage, M. paratuberculosis multiplies until it eventually kills the cell, spreads, and infects other nearby cells. In time, other parts of the ileum and other regions of the body are teeming with millions of the mycobacteria. How M. paratuberculosis neutralizes or evades the normally efficient bacterial killing mechanisms of the macrophages is unknown, although the unusually resistant cell wall of mycobacteria likely plays an important role.[citation needed] The animal's immune system reacts to the M. paratuberculosis invasion by recruiting more macrophages and lymphocytes to the site of the infection. The lymphocytes release a variety of chemicals signals, called cytokines, in an attempt to increase the bacterial killing power of the macrophages. Macrophages fuse together, forming large cells, called multinucleated giant cells, in an apparent attempt to kill the mycobacteria. Infiltration of infected tissues with millions of lymphocytes and macrophages leads to visible thickening of the intestines. This prevents nutrient absorption, and diarrhea results. Late in the infection, antibody production by the animal occurs to M. paratuberculosis in serum of animals, and is an indicator that clinical signs of disease and death from the infection will soon follow.[citation needed] For goats infected with this disease, the most apparent sign of having it is their bodies wasting away, even with a sufficient diet. If a goat develops Johne's and it has diarrhea, it is most likely going to die. When it has diarrhea, the goat is at the last stages of the disease. Herds should be tested once or twice a year to maintain the health and keep out the disease.[citation needed] ## Morbidity and mortality[edit] In an endemic herd, only a minority of the animals develops clinical signs; most animals either eliminate the infection or become asymptomatic carriers. The mortality rate is about 1%, but up to 50% of the animals in the herd can be asymptomatically infected, resulting in losses in production. Once the symptoms appear, paratuberculosis is progressive and affected animals eventually die. The percentage of asymptomatic carriers that develop overt disease is unknown.[6] ## Human risks[edit] MAP is capable of causing Johne's-like symptoms in humans, though difficulty in testing for MAP infection presents a diagnostic hurdle.[7] As of October 2019, neither the World Health Organization nor any individual nation had declared Johne’s disease to be zoonotic.[1] Clinical similarities are seen between Johne's disease in ruminants and inflammatory bowel disease in humans,[8] and because of this, some researchers contend the organism is a cause of Crohn's disease.[9][10] However, epidemiologic studies have provided variable results; in certain studies, the organism (or an immune response directed against it) has been much more frequently found in patients with Crohn's disease than asymptomatic people. ## Action and regulations[edit] Paratuberculosis is a reportable disease in some states of the US.[11] US Federal regulations prohibit culture positive or DNA test-positive animals from being moved across state lines except for slaughter.[citation needed] Dr Cheryl Waldner obtained in February 2020 a five-year CAD 2.35 million fund to research beef cattle health and productivity, one aspect of which is the control of "production-limiting" diseases such as Johne's disease.[12] ## References[edit] 1. ^ a b Hendrick, Steve; Waldner, Cheryl (2 October 2019). "HOME» RESEARCH » JOHNE'S DISEASE". Beef Cattle Research Council. 2. ^ Collins M. and Manning E. "Johne's Information Center" The University of Wisconsin-School of Veterinary Medicine. 13 March 2003. 3. ^ Furber, Debbie (16 December 2016). "When Johne's hits home". Canadian Cattlemen The Beef Magazine. 4. ^ Hendrick, Steve (19 March 2013). "Johne's Disease And The Ethical Dilemma". Beef Cattle Research Council. 5. ^ "paratuberculosis" at Dorland's Medical Dictionary 6. ^ Paratuberculosis. In the Merck Veterinary Manual, 8th ed. Edited by S. E. Aiello. Whitehouse Station, NJ: Merck and Co. 1998. 7. ^ Richter, E., Wessling, J., Lügering, N., Domschke, W., & Rüsch-Gerdes, S. (2002). Mycobacterium avium subsp. paratuberculosis Infection in a Patient with HIV, Germany. Emerging Infectious Diseases, 8(7), 729–731. http://doi.org/10.3201/eid0807.010388 8. ^ Juste RA, Elguezabal N, Garrido JM, et al. (2008). "On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease". PLoS ONE. 3 (7): e2537. Bibcode:2008PLoSO...3.2537J. doi:10.1371/journal.pone.0002537. PMC 2434204. PMID 18596984. 9. ^ Uzoigwe JC, Khaitsa ML, Gibbs PS (October 2007). "Epidemiological evidence for Mycobacterium avium subspecies paratuberculosis as a cause of Crohn's disease". Epidemiol. Infect. 135 (7): 1057–68. doi:10.1017/S0950268807008448. PMC 2870686. PMID 17445316. 10. ^ Gitlin L, Borody TJ, Chamberlin W, Campbell J. Mycobacterium avium ss paratuberculosis-associated diseases: piecing the Crohn's puzzle together. J Clin Gastroenterol. 2012 Sep;46(8) 649-55. doi:10.1097/MCG.0b013e31825f2bce 11. ^ United States Department of Agriculture, "National Animal Health Reporting System - Reportable Diseases" Archived 2009-08-29 at the Wayback Machine 12. ^ "University of Saskatchewan funded for five years in beef research". North Bay Nugget. Sun Media Community Newspapers part of Postmedia Network. 3 February 2020. ## External links[edit] Classification D * MeSH: D010283 * DiseasesDB: 33739 * USDA Johne's resource page * University of Wisconsin School of Veterinary Medicine Johne's Information Center * Paratuberculosis at Curlie * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Paratuberculosis	c0030524	26,222	wikipedia	https://en.wikipedia.org/wiki/Paratuberculosis	2021-01-18T18:38:34	{"mesh": ["D010283"], "wikidata": ["Q707388"]}
## Clinical Features Ziprkowski and Adam (1964) described a Sephardic Jewish family from Morocco in which 2 children in each of 2 families with consanguineous parents had congenital deafness with total albinism. The 2 sibships were related to each other and shared a pair of great-great-grandparents in common. In 1 sibship, 3 sibs of the 2 doubly affected sibs had only congenital deafness. Fraser (1982) suggested the existence of 2 separate recessive disorders segregating in this highly consanguineous group. Lezirovitz et al. (2006) reported a Brazilian family in which the 16-year-old male proband had complete oculocutaneous albinism (OCA4; 606574) and moderate to severe congenital sensorineural deafness (DFNB1; 220290). A younger sister had oculocutaneous albinism without deafness, and 2 additional sisters had profound and mild sensorineural hearing loss, respectively, without albinism. Molecular Genetics Lezirovitz et al. (2006) identified a homozygous mutation in the GJB2 gene (121011.0005) in 3 members of a Brazilian family with sensorineural hearing loss consistent with DFNB1. Interestingly, 1 of the patients had only mild hearing loss that developed later in childhood. Further molecular analysis of the same family identified a homozygous mutation in the MATP gene (606202.0009) in the 2 sibs with oculocutaneous albinism consistent with OCA4. The proband, who had both disorders, carried both homozygous mutations. Although the parents did not acknowledge consanguinity, haplotype analysis indicated that they shared a common ancestor. Lezirovitz et al. (2006) hypothesized that the patients reported by Ziprkowski and Adam (1964) likely also resulted from the coincident inheritance of 2 separate recessive disorders, as suggested by Fraser (1982). GU \- Hypogonadism Ears \- Congenital hearing loss Neuro \- Mental retardation Inheritance \- Autosomal recessive \- ? two separate loci Skin \- Albinism ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS, CONGENITAL, WITH TOTAL ALBINISM	c1857343	26,223	omim	https://www.omim.org/entry/220900	2019-09-22T16:28:57	{"mesh": ["C565646"], "omim": ["220900"]}
Monosomy 18q is a partial deletion of the long arm of chromosome 18 characterized by highly variable phenotype, most commonly including hypotonia, developmental delay, short stature, growth hormone deficiency, hearing loss and external ear anomalies, intellectual disability, palatal defects, dysmorphic facial features, skeletal anomalies (foot deformities, tapering fingers, scoliosis) and mood disorders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Monosomy 18q	c0432443	26,224	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1600	2021-01-23T19:10:08	{"mesh": ["C536580"], "omim": ["601808"], "umls": ["C0432443", "C2931249"], "icd-10": ["Q93.5"], "synonyms": ["18q deletion syndrome", "18q- syndrome", "Deletion 18q"]}
Lichen planus pigmentosus (LPP) is a rare form of lichen planus. It is characterized by oval or irregularly-shaped brown to gray-brown macules and patches on the skin. Areas that are exposed to sun such as the forehead, temples and neck are most commonly affected. However, the macules and patches may also develop on the trunk or in places where two areas of skin touch or rub together (i.e. the armpit, groin, etc). LPP is a chronic, relapsing condition with periods of worsening symptoms separated by periods of remission (decreasing or disappearing symptoms). The cause of LPP is unknown, but studies suggest it may be triggered by UV light, viral infections, or agents applied to the skin such as mustard oil and amla oil. Treatment for LPP depends on the symptoms in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Lichen planus pigmentosus	c0406366	26,225	gard	https://rarediseases.info.nih.gov/diseases/10816/lichen-planus-pigmentosus	2021-01-18T17:59:25	{"orphanet": ["254463"], "synonyms": ["LP pigmentosus", "Lichen planus pigmentosa", "LP pigmentosa", "Lichen planus pigmentosus inversus"]}
Acrodermatitis SpecialtyDermatology Acrodermatitis /ac·ro·der·ma·ti·tis/[1] is a childhood form of dermatitis selectively affecting the hands and feet and may be accompanied by mild symptoms of fever and malaise. It may also be associated with hepatitis B and other viral infections.[2] The lesions appear as small coppery-red, flat-topped firm papules that appear in crops and sometimes in long linear strings, often symmetric. It is a diffuse chronic skin disease usually confined to the limbs, seen mainly in women in Northern, Central, and Eastern Europe, and characterized initially by an erythematous, oedematous, pruritic phase followed by sclerosis and atrophy. It is caused by infection with Borrelia burgdorferi.[3] ## Types[edit] Types include: * Acrodermatitis enteropathica * Acropustulosis * Acrodermatitis chronica atrophicans * Papular acrodermatitis of childhood * Dermatitis repens ## References[edit] 1. ^ "Acrodermatitis : definition on Dorland's Medical Dictionary for Health Consumers". TheFreeDictionary. Retrieved 17 February 2013. 2. ^ "Acrodermatitis". MedlinePlus. Retrieved 16 February 2013. 3. ^ "Acrodermatitis : definition on Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition". TheFreeDictionary. Retrieved 17 February 2013. ## External links[edit] Classification D * ICD-10: L30.8 * MeSH: D000169 External resources * MedlinePlus: 001446 * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Acrodermatitis	c0001197	26,226	wikipedia	https://en.wikipedia.org/wiki/Acrodermatitis	2021-01-18T19:01:12	{"gard": ["5722"], "mesh": ["D000169"], "umls": ["C0001197"], "icd-10": ["L30.8"], "wikidata": ["Q4675757"]}
Nuclear sclerosis of the lens differs from cortical (see 609026) and subcapsular opacities in that there is no enlargement of intercellular spaces or breakdown of cell membranes. This form of noncongenital cataract is strongly associated with increasing age. Heiba et al. (1993) analyzed the familial distribution of age-related nuclear sclerosis of the lens to detect a possible role of a major gene in sibships in the Beaver Dam Eye Study. Included in the analysis were 1,247 people, aged 43 to 84 years, from 564 sibships with at least 2 affected members in each sibship. There were significant sib correlations for all sibs, and separately for sister-sister, sister-brother, and brother-brother pairs. Segregation analysis excluded the hypothesis of a random environmental major effect. Comparing different models, Heiba et al. (1993) concluded that a single recessive gene can account for 35% of the total variability. Klein et al. (2006) found that 2 serum markers of systemic inflammation and vascular endothelial dysfunction, interleukin-6 (147620) and intracellular adhesion molecule-1 (147840), were significantly associated with age-related nuclear cataract but not with cortical or posterior subcapsular cataract. In the Beaver Dam Eye Study population, Klein et al. (2006) found that statin use appeared to be associated with a lower risk of age-related nuclear cataract. Tan et al. (2007) studied the association of statin use with long-term incident cataract in the Blue Mountains Eye Study cohort. After controlling for age, gender, and other factors, statin use was found to reduce by 50% the risk of cataract development, principally nuclear or cortical cataract subtypes. Eyes \- Nuclear sclerosis of the lens Inheritance \- Autosomal recessive gene accounts for 35% of variability ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CATARACT, AGE-RELATED NUCLEAR	c1832423	26,227	omim	https://www.omim.org/entry/601371	2019-09-22T16:14:56	{"doid": ["83"], "mesh": ["C563333"], "omim": ["601371"], "icd-10": ["H25.1"], "synonyms": ["Alternative titles", "NUCLEAR SCLEROSIS OF THE LENS"]}
A number sign (#) is used with this entry because autosomal dominant Larsen syndrome (LRS) is caused by heterozygous mutation in the gene encoding filamin B (FLNB; 603381) on chromosome 3p14. An autosomal recessive syndrome with overlapping features (multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects; 245600) has been found to be caused by mutation in the B3GAT3 gene (606374) on chromosome 11q12. Description Larsen syndrome is an osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication (summary by Bicknell et al., 2007). Clinical Features Larsen et al. (1950) called attention to a syndrome of multiple congenital dislocations and characteristic facies (prominent forehead, depressed nasal bridge, wide-spaced eyes). Clubfoot, bilateral dislocation of elbows, hips and knees (most characteristically, anterior dislocation of the tibia on the femur), and short metacarpals with cylindrical fingers lacking the usual tapering were the skeletal features of note. Cleft palate, hydrocephalus, and abnormalities of spinal segmentation were found in some patients. Harris and Cullen (1971) described affected mother and daughter. Bilateral dislocation of the knees, pes cavus, cylindrically shaped fingers, and characteristic facies (wide-spaced eyes, flattened nasal bridge and prominent forehead) were present in both. The maternal grandfather was said to have had similar facies. One of the original cases of Larsen et al. (1950), 23 years of age in 1972, had an affected child. Features in addition to knee dislocations included flat face, accessory carpal bones, and short terminal phalanges creating pseudoclubbing. Multiple congenital dislocations with osseous anomalies and unusual facies are characteristic. Anterior dislocation of the tibia on the femur is usual. A juxtacalcaneal accessory ossification center and abnormality of vertebrae are observed. Latta et al. (1971) made a point of a juxtacalcaneal accessory bone which may be specific for this entity. Tsang et al. (1986) reported 'new' oral and craniofacial findings in a patient with Larsen syndrome. Stanley et al. (1988) described mixed hearing loss in a child with Larsen syndrome. On the basis of this and other cases, the authors suggested that there may be involvement of the ossicular joints in this disorder. Le Marec et al. (1994) described a male infant who, in addition to the typical manifestations of Larsen syndrome, had laryngomalacia with apnea and multiple abnormalities of the cervical spine (segmentation defects, kyphosis, atlantoaxial dislocation, and narrowing of subdural space at the apex of the kyphosis). Although abnormalities of the cervical spine were not emphasized in the original description of the syndrome (Larsen et al., 1950), they may be the most serious manifestation. Cervical kyphosis in particular may be life-threatening because of the impingement on the spinal cord at the apex of the kyphosis. Of the 9 affected infants followed by Johnston et al. (1996), 5 were noted to have cervical kyphosis because of marked hypoplasia of 1 or 2 vertebral bodies (usually the fourth or fifth cervical vertebra, or both) at the apex of the kyphosis; the infants were successfully managed by posterior cervical arthrodesis alone. Johnston et al. (1996) suggested that the prevalence of cervical kyphosis in Larsen syndrome has probably been underestimated but may easily be documented because no dynamic studies or cooperation by the patients are necessary. They concluded that early diagnosis followed by operative stabilization should help such patients avoid neurologic deficits. Becker et al. (2000) reported the case of a mildly affected father and a severe form of Larsen syndrome in a fetus detected by sonography. The mother had requested prenatal diagnosis on the grounds of an unknown congenital disorder in her husband. His height was 172 cm. He presented with a flat palate and craniofacial dysmorphism (small teeth, hypertelorism, and a prominent forehead). The fingers and toes had short terminal phalanges creating pseudoclubbing. Congenital bilateral clubfoot had required orthopedic correction. Sonographic examination in the man's pregnant wife showed that both legs of the fetus were fixed in an extended position at the knee joints with overstretching of the joints, consistent with genua recurvata. Irregularities of the knee joints and clubfeet were noted. The elbows were flexed and mobile. The fingers seemed to be thickened and in a constantly flexed position. The facial profile showed dysmorphism including a prominent forehead, flat nose, and micrognathia. The parents opted to terminate the pregnancy. Autopsy of the fetus confirmed the sonographic findings in the female fetus with a normal 46,XX karyotype. The diagnosis of Larsen syndrome in the father had been missed by highly skilled genetic counselors. A similar experience of misdiagnosis was reported by Vujic et al. (1995), who reported that none of 26 family members with Larsen syndrome who had received medical treatment had been diagnosed correctly. Becker et al. (2000) raised the possibility that the mild manifestation of Larsen syndrome in the father was due to mosaicism. Inheritance Dominant inheritance of Larsen syndrome seemed certain from the reports of Latta et al. (1971) and of McFarlane (1947). The mother of the patient reported by Latta et al. (1971) had a saddle nose which developed at age 18 after tennis-ball trauma. McFarlane (1947) reported a woman with saddle nose, congenital dislocation of the knees, and hyperextensibility of the elbows. By each of 3 different mates she produced an affected child with bilateral knee dislocations. Hall (1978) followed up on the 2-generation family reported by Latta et al. (1971); she was convinced that the mother was affected and made the further observation that in her 30s the mother had developed polychondritis of her tracheobronchial cartilage with recurrent pulmonary problems because of airway stenosis. Sugarman (1975) described affected black mother and daughter. The diagnosis in the cases of Henriksson et al. (1977) and of Marques (1980) is doubtful (Gorlin, 1982). Gorlin (1982) observed affected mother and son. Petrella et al. (1993) provided follow-up on 2 sibs with Larsen syndrome reported by Bloch and Peck (1965). This family had been cited as a possible example of the recessive form of Larsen syndrome. Congenital dislocation of the knees with unilateral cataract and unilateral undescended testis was present in a newborn male; a sister was born with bilateral dislocation of the knees and hips and cleft palate. The parents were unaffected. However, reinterpretation as the autosomal dominant form of Larsen syndrome with germline mosaicism was required because the sister gave birth to an affected daughter (Petrella et al., 1993). Frints et al. (2000) and Debeer et al. (2003) described cases of asymmetric Larsen syndrome which they interpreted as examples of unilateral somatic mosaicism. Mapping In a large Swedish kindred with autosomal dominant Larsen syndrome, Vujic et al. (1995) found that the gene, which they symbolized LAR1, is strongly linked to a region of 3p defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to 3p21.1-p14.1. Linkage and recombination analysis using a COL7A1 (120120) PvuII intragenic polymorphism versus Larsen syndrome and chromosome 3 markers indicated that COL7A1 is located close to, but separate from, the LAR1 locus. The kindred contained a total of 49 individuals thought to be carriers of the mutant gene. Altogether, 48 family members, of whom 26 were affected, were included in the DNA study. Molecular Genetics In 4 individuals with sporadically occurring Larsen syndrome and 1 family with a dominantly inherited form of the condition, Krakow et al. (2004) found heterozygosity for de novo missense mutations in the FLNB gene (603381.0004; 603381.0005). Bicknell et al. (2007) identified several different heterozygous mutations in the FLNB gene (see, e.g., 603381.0011; 603381.0012) in 20 unrelated patients with Larsen syndrome. One of the mutations was detected in 6 unrelated probands. History One of the earliest reports of Larsen syndrome may have been that of McFarland (1929). INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (final adult height less than 152cm) Other \- Prenatal growth deficiency HEAD & NECK Face \- Flat face \- Prominent forehead Ears \- Hearing loss, conductive \- Malformations of the auditory ossicles Eyes \- Hypertelorism \- Anterior corneal lens opacities Nose \- Depressed nasal bridge Mouth \- Cleft palate \- Cleft lip Teeth \- Hypodontia CARDIOVASCULAR Heart \- Aortic dilatation \- Atrial septal defect \- Ventricular septal defect RESPIRATORY Airways \- Tracheal stenosis \- Tracheomalacia \- Bronchomalacia CHEST External Features \- Pectus excavatum \- Pectus carinatum GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKELETAL Skull \- Flattened frontal bone \- Small skull base \- Shallow orbits Spine \- Cervical vertebrae hypoplasia \- Subluxation or fusion of the cervical vertebrae \- Cervical kyphosis \- Scoliosis \- Wedged vertebrae \- Spondylolysis \- Spina bifida occulta Pelvis \- Dislocation of the hip Limbs \- Joint laxity \- Dislocations of the elbows \- Dislocations of the wrists \- Dislocations of the knees \- Dysplastic epiphyseal centers Hands \- Cylindric fingers \- Spatulate thumbs \- Short metacarpals \- Supernumerary carpal bones \- Multiple carpal ossification centers Feet \- Talipes equinovalgus \- Talipes equinovarus \- Short metatarsals \- Supernumerary tarsal bones \- Delayed coalescence of calcaneal ossification centers SKIN, NAILS, & HAIR Nails \- Short nails NEUROLOGIC Central Nervous System \- Mental retardation \- Spinal cord compression MISCELLANEOUS \- Intrafamilial variation \- Autosomal recessive inheritance ( 245600 ) has also been suggested \- Joint dislocations become less frequent with age MOLECULAR BASIS \- Caused by mutation in the filamin B gene (FLNB, 603381.0004 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LARSEN SYNDROME	c2931648	26,228	omim	https://www.omim.org/entry/150250	2019-09-22T16:39:07	{"doid": ["14764"], "mesh": ["C537873"], "omim": ["150250"], "orphanet": ["503"], "genereviews": ["NBK2534"]}
Omenn syndrome (OS) is an inflammatory condition characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency (SCID; see this term). ## Epidemiology Prevalence is unknown. ## Clinical description OS presents during the first year of life with features of SCID including chronic diarrhea, pneumonitis and failure to thrive. In addition, patients present with inflammatory symptoms including lymphadenopathy, hepatosplenomegaly and generalized erythroderma, which may often cause alopecia and loss of eyebrows and eyelashes; protein loss may lead to generalized edema and metabolic disturbances. The signs and symptoms of OS can evolve over time and may not appear simultaneously. Some patients present with some but not all of these symptoms and may be described as having atypical Omenn syndrome. OS may also be associated with syndromic disorders including cartilage-hair hypoplasia (CHH), adenosine deaminase (ADA) deficiency, monosomy 22q11, coloboma of the eye, CHARGE syndrome and ligase 4 deficiency (see these terms). ## Etiology OS is not caused by a defined genetic defect. Rather than a distinct form of SCID, it is a distinct inflammatory phenotype that can be associated with genetically diverse SCIDs. The majority of cases reported to date have hypomorphic mutations in RAG1 and RAG2 genes (11p13). The other cases have mutations in the RMRP, ADA, IL2RG, IL7RA, DCLRE1C, CHD7 and LIG4 genes (9p21-p12, 20q13.11, Xq13, 5p13, 10p, 8q12.2 and 13q22-q34). ## Diagnostic methods OS may pose a diagnostic challenge because lymphocyte counts may be normal or high, unlike in typical SCID. Diagnosis is based on inflammation with evidence of abnormal expansion of one or more T-cell clones in peripheral blood and tissue, skin biopsies showing acanthosis and parakeratosis on staining with hematoxylin and eosin, evidence of dysplastic thymus with few remnant lymphoid cells and lymphadenopathy. Typically B cells are absent, as are immunoglobulins apart from IgE which is often raised. Eosinophilia is also observed. ## Differential diagnosis Differential diagnoses include graft-versus-host disease, histiocytosis, Job syndrome, Netherton syndrome, and severe combined immunodeficiencies (see these terms), particularly those associated with maternal T-cell engraftment. ## Antenatal diagnosis OS is not a single genetic disorder, but if the causative gene is identified in the index patient, prenatal diagnosis may be offered, although subsequent individuals are likely to have SCID. ## Genetic counseling Transmission is autosomal recessive. ## Management and treatment Initial treatment is based on immunosuppressive drugs including prednisone and cyclosporin followed by hematopoietic stem cell transplantation, in a centre recognized as treating such disorders ideally using HLA-identical family donors or, if this is not available, other appropriate donors after use of appropriate conditioning regimens. ## Prognosis If untreated, prognosis is poor and the disease is fatal. Skin inflammation worsens with time leading to severe barrier problems that facilitate life-threatening and overwhelming bacterial and fungal infections in already severely immunocompromised patients. Viral infections are most severe and life-threatening. Survival rates with treatment have been reported as greater than 80%. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Omenn syndrome	c2700553	26,229	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=39041	2021-01-23T18:12:56	{"gard": ["8198"], "mesh": ["D016511"], "omim": ["603554"], "umls": ["C2700553"], "icd-10": ["D81.8"], "synonyms": ["Combined immunodeficiency with hypereosinophilia"]}
For the anatomical abnormality observed in 1965, see Fraser syndrome. Frasier syndrome SpecialtyEndocrinology, obstetrics and gynaecology, urology, medical genetics Frasier syndrome is a urogenital anomaly associated with the WT1 (Wilms tumor 1 gene) gene.[1][2][3] It was first characterized in 1964.[4] ## Contents * 1 Presentation * 2 Genetics * 2.1 Inheritance pattern * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Presentation[edit] Frasier syndrome presents at birth with male pseudohermaphroditism (the external genitalia have a female appearance despite an XY genotype), streak gonads and progressive glomerulonephropathy (focal segmental glomerulosclerosis). Patients are also at increased risk of genito-urinary tumors (usually gonadoblastoma). The glomerulonephropathy presents later than in Denys-Drash syndrome, and the tumour risk phenotype is different; whilst Denys-Drash syndrome is associated with Wilms' tumour, Frasier syndrome is associated with gonadoblastoma. Differentiating between the two syndromes can be challenging.[5] ## Genetics[edit] The WT1 gene exists on chromosome 11 (at 11p13), and codes for a four zinc finger transcription factor. Its role as a transcription factor is related to proper kidney and gonadal development.[6][7] The link between kidney and gonadal development and WT1 was highlighted in past studies looking at the related Denys-Drash syndrome. Results of various investigations identified the loss of function of WT1 to be a prerequisite of Wilms' tumour development, and also a key trait of individuals with genital abnormalities.[8] Mutations responsible for Frasier syndrome predominantly occur in intron 9 of the WT1 gene, specifically nucleotide substitutions that influence an intron splice site. Mutations in this region proved for the absence of three amino acids—KTS—between the third and fourth WT1 zinc fingers.[9] Referring to the autosomal dominant expressive nature of this disease, it is only necessary for an individual to have one complement of the mutated intronic sequence to appear affected.[10] Differing from the similar Denys-Drash syndrome, where a mutated form of the WT1 protein exists, Frasier syndrome expression works solely on the existence of a changed ratio of KTS isoforms: normal WT1 proteins including the KTS site (+KTS), and mutated, shortened proteins lacking the KTS site (–KTS).[1] Through alternative splicing, a specific ratio of the two isoforms normally exists, though the mutation in the intron 9 splice site severely lowers levels of the +KTS isoform; this leads to Frasier syndrome.[9] ### Inheritance pattern[edit] Frasier syndrome is inherited in an autosomal dominant fashion, indicating the need for only one mutated allele in a cell to lead to expression of the disease. Mutations predominantly occur de novo, allowing for expression in an individual that has no family history of it. The mutations occur during gamete formation or early in embryogenesis.[10] ## Diagnosis[edit] This section is empty. You can help by adding to it. (March 2018) ## Treatment[edit] Reconstructive surgery. ## References[edit] 1. ^ a b Klamt B, Koziell A, Poulat F, et al. (April 1998). "Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms". Hum. Mol. Genet. 7 (4): 709–14. doi:10.1093/hmg/7.4.709. PMID 9499425. 2. ^ Reference, Genetics Home. "Frasier syndrome". Genetics Home Reference. Retrieved 2018-04-17. 3. ^ "Frasier syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17. 4. ^ Frasier, SD; Bashore, SD; Bashore, RA; Mosier, HD (May 1964). "Gonadoblastoma associated with pure gonadal dysgenesis in monozygous twins". J. Pediatr. 64 (5): 740–5. doi:10.1016/S0022-3476(64)80622-3. PMID 14149008. 5. ^ https://www.ncbi.nlm.nih.gov/omim/136680 6. ^ Dai YL.; Fu JF.; Hong F.; et al. (Jul 2011). "WT1 mutation as a cause of 46 XY DSD and Wilm's tumour: a case report and literature review". Acta Paediatrica. 100 (7): 39–52. doi:10.1111/j.1651-2227.2011.02167.x. PMID 21314844. 7. ^ "WT1". Genetics Home Reference. U.S. National Library of Medicine. Retrieved 10 November 2014. 8. ^ Hastie, Nicholas D. (Aug 1992). "Dominant negative mutations in the Wilms tumour (WT1) gene cause Denys-Drash syndrome--proof that a tumour-suppressor gene plays a crucial role in normal genitourinary development". Hum Mol Genet. 1 (5): 293–5. doi:10.1093/hmg/1.5.293. PMID 1338905. 9. ^ a b Barbaux S.; Niaudet P.; Gubler MC.; et al. (Dec 1997). "Donor splice-site mutations in WT1 are responsible for Frasier syndrome". Nature Genetics. 17 (4): 467–70. doi:10.1038/ng1297-467. PMID 9398852. 10. ^ a b "Frasier syndrome". Genetics Home Reference. U.S. National Library of Medicine. Retrieved 10 November 2014. ## External links[edit] Classification D * OMIM: 136680 * MeSH: D052159 * DiseasesDB: 32455 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Frasier syndrome	c0950122	26,230	wikipedia	https://en.wikipedia.org/wiki/Frasier_syndrome	2021-01-18T18:58:59	{"gard": ["2375"], "mesh": ["D052159"], "umls": ["C0950122"], "orphanet": ["347"], "wikidata": ["Q5493754"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (June 2020) This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Syndromes affecting the heart" – news · newspapers · books · scholar · JSTOR (March 2019) A syndrome is a set of medical signs and symptoms that are correlated with each other. A syndrome can affect one or more of body systems. Different syndromes affect different groups of organs. This is a list of syndromes that may affect the heart. Syndromes affecting primarily the heart are written in bold letters. [1][2] Syndrome Cause cardiac symptoms Other symptoms or organs affected Notes 1q21.1 deletion syndrome genetic (Chromosome 1) Cardiovascular anomalies are present in 30% of the cases (for example anomalous origin of the coronary artery in "Class II-deletion") * TAR syndrome * Neuropsychiatric * Craniofacial abnormalities * Eye * Kidney DiGeorge syndrome genetic (Chromosome 22) commonly interrupted aortic arch, truncus arteriosus and tetralogy of Fallot * Craniofacial * Thymic aplasia * Cleft palate * Hypocalcemia/hypoparathyroidism Acute coronary syndrome Commonly associated with three clinical manifestations: ST elevation myocardial infarction (STEMI, 30%), non ST elevation myocardial infarction (NSTEMI, 25%), or unstable angina (38%) Blockage of a coronary artery Adams–Nance syndrome maybe disturbance in glycine metabolism persistent tachycardia, paroxymal hypertension * Seizure * Eye (Microphthalmia, Cataract) Alagille syndrome genetic (Autosomal dominant inheritance: loss of function mutations in either JAG1 or NOTCH2) Congenital heart problems e.g. pulmonary artery stenosis (common), Tetralogy of Fallot, overriding aorta, ventricular septal defect; and right ventricular hypertrophy. Liver (jaundice, pruritus, hepatosplenomegaly, acholia, xanthoma) Andersen–Tawil syndrome This condition affects the QT interval (in blue) Antley–Bixler syndrome Barth syndrome Brugada syndrome Cantú syndrome genetic (Chromosome 12, autosomal dominant) Cardiac syndrome X Cardiorenal syndrome Kidney Cat eye syndrome CHARGE syndrome Coffin–Lowry syndrome genetic (RPS6KA3 gene mutation, Chromosome X) Costello syndrome Down syndrome genetic (Chromosome 21) Dressler syndrome autoimmune inflammatory reaction secondary to MI. Edwards syndrome genetic (Chromosome 18) Eisenmenger's syndrome Ellis–van Creveld syndrome Emanuel syndrome HEC syndrome Heyde's syndrome Ho–Kaufman–Mcalister syndrome Holt–Oram syndrome ASD, and a first degree heart block. Hypoplastic left heart syndrome Jacobsen syndrome genetic (Chromosome 11q deletion) Jaffe–Campanacci syndrome Jervell and Lange-Nielsen syndrome genetic (autosomal recessive) a type of long QT syndrome Kabuki syndrome Kearns–Sayre syndrome Long QT syndrome Lutembacher's syndrome Malpuech facial clefting syndrome Marden–Walker syndrome Marfan syndrome McKusick–Kaufman syndrome McLeod syndrome Noonan syndrome Noonan syndrome with multiple lentigines Ortner's syndrome Bouveret Hoffmann syndrome another name for "Paroxysmal tachycardia" Patau syndrome genetic (Chromosome 13) Pre-excitation syndrome Romano–Ward syndrome Scimitar syndrome Shone's syndrome Short QT syndrome Sick sinus syndrome Taussig–Bing syndrome double outlet right ventricle (DORV) and subpulmonic VSD. a cyanotic congenital heart defect Timothy syndrome Townes–Brocks syndrome Triploid syndrome Turner syndrome VACTERL syndrome Wellens' syndrome Williams syndrome Wolff–Parkinson–White syndrome A Delta wave often seen in an affected individual Zunich–Kaye syndrome Lown–Ganong–Levine syndrome ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Search by disease name". www.orpha.net. Retrieved 21 March 2019. 2. ^ The British Medical Association illustrated medical dictionary. London: Dorling Kindersley. 2002. pp. 177, 536. ISBN 9780751333831. OCLC 51643555. ## External links[edit] * What Is the Heart? – NIH Wikimedia Commons has media related to Syndromes affecting the heart. * 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 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disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Syndromes affecting the heart	None	26,231	wikipedia	https://en.wikipedia.org/wiki/Syndromes_affecting_the_heart	2021-01-18T18:48:30	{"wikidata": ["Q30672802"]}
A number sign (#) is used with this entry because of evidence that Fuchs endothelial corneal dystrophy-4 (FECD4) is caused by heterozygous mutation in the SLC4A11 gene (610206) on chromosome 20p13. Description Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium. Late-onset FECD is marked by thickening of Descemets membrane and excrescences, called guttae, that typically appear in the fourth or fifth decade. Disease progression results in decreased visual acuity as a result of increasing corneal edema, and end-stage disease is marked by painful epithelial bullae (summary by Riazuddin et al., 2013). For a discussion of genetic heterogeneity of Fuchs endothelial corneal dystrophy, see FECD1 (136800). Molecular Genetics Vithana et al. (2008) analyzed the SLC4A11 gene (610206) in 89 patients with late-onset FECD, 8 of whom had a family history of FECD, and identified 4 heterozygous mutations in 1 familial and 3 sporadic cases (610206.0017-610206.0020), respectively. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CORNEAL DYSTROPHY, FUCHS ENDOTHELIAL, 4	c0016781	26,232	omim	https://www.omim.org/entry/613268	2019-09-22T15:59:07	{"doid": ["11555"], "mesh": ["D005642"], "omim": ["613268"], "orphanet": ["98974"], "synonyms": ["Alternative titles", "CORNEAL DYSTROPHY, FUCHS ENDOTHELIAL, LATE-ONSET"]}
Polycythemia vera is a condition characterized by an increased number of red blood cells in the bloodstream. Affected individuals may also have excess white blood cells and blood clotting cells called platelets. These extra cells and platelets cause the blood to be thicker than normal. As a result, abnormal blood clots are more likely to form and block the flow of blood through arteries and veins. Individuals with polycythemia vera have an increased risk of deep vein thrombosis (DVT), a type of blood clot that occurs in the deep veins of the arms or legs. If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE). Affected individuals also have an increased risk of heart attack and stroke caused by blood clots in the heart and brain. Polycythemia vera typically develops in adulthood, around age 60, although in rare cases it occurs in children and young adults. This condition may not cause any symptoms in its early stages. Some people with polycythemia vera experience headaches, dizziness, ringing in the ears (tinnitus), impaired vision, or itchy skin. Affected individuals frequently have reddened skin because of the extra red blood cells. Other complications of polycythemia vera include an enlarged spleen (splenomegaly), stomach ulcers, gout (a form of arthritis caused by a buildup of uric acid in the joints), heart disease, and cancer of blood-forming cells (leukemia). ## Frequency The prevalence of polycythemia vera varies worldwide. The condition affects an estimated 44 to 57 per 100,000 individuals in the United States. For unknown reasons, men develop polycythemia vera more frequently than women. ## Causes Mutations in the JAK2 and TET2 genes are associated with polycythemia vera. Although it remains unclear exactly what initiates polycythemia vera, researchers believe that it begins when mutations occur in the DNA of a hematopoietic stem cell. These stem cells are located in the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets. JAK2 gene mutations seem to be particularly important for the development of polycythemia vera, as nearly all affected individuals have a mutation in this gene. The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. JAK2 gene mutations result in the production of a JAK2 protein that is constantly turned on (constitutively activated), which increases production of blood cells and prolongs their survival. With so many extra cells in the bloodstream, abnormal blood clots are more likely to form. Thicker blood also flows more slowly throughout the body, which prevents organs from receiving enough oxygen. Many of the signs and symptoms of polycythemia vera are related to a shortage of oxygen in body tissues. The function of the TET2 gene is unknown. Although mutations in the TET2 gene have been found in approximately 16 percent of people with polycythemia vera, it is unclear what role these mutations play in the development of the condition. ### Learn more about the genes associated with Polycythemia vera * JAK2 * TET2 ## Inheritance Pattern Most cases of polycythemia vera are not inherited. This condition is associated with genetic changes that are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. In rare instances, polycythemia vera has been found to run in families. In some of these families, the risk of developing polycythemia vera appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of an altered gene in each cell is sufficient to increase the risk of developing polycythemia vera, although the cause of this condition in familial cases is unknown. In these families, people seem to inherit an increased risk of polycythemia vera, not the disease itself. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Polycythemia vera	c0032463	26,233	medlineplus	https://medlineplus.gov/genetics/condition/polycythemia-vera/	2021-01-27T08:24:52	{"gard": ["7422"], "mesh": ["D011087"], "omim": ["263300"], "synonyms": []}
## Clinical Features In 2 Hutterite sisters, Opitz et al. (1985) reported a disorder characterized by congenital shortness with mild spondylorhizomelic dwarfism; later deceleration of weight gain presumably due to CNS-based severe feeding problems; a CNS defect with normal prenatal brain growth but later deceleration from the 50th to the 2nd centile with severe mental retardation and decorticate disturbance of neurologic function and possible renal involvement with terminal nephrotic syndrome. The older sister died at age 3 years. Because of cultural limitations the affected sibs were incompletely studied. Lowry (1997) reported that 1 of the Hutterite sisters originally reported by Opitz et al. (1985) died at 2 years and the other at 3 years after a clinical course of a severe degenerative cerebral condition. He later saw another patient with the same clinical presentation who was a first cousin once removed of the 2 sisters reported by Opitz et al. (1985). Udler et al. (1997) described an Israeli-Jewish child of Yemenite origin who, they suggested, may be affected with this disorder. Height was below the 3rd centile due to skeletal abnormalities. Intelligence was borderline. There was marked proteinuria and she was in renal failure. Skeletal abnormalities consisted of platyspondyly and delayed ossification of the vertebral bodies. The trunk was short. GU \- Terminal nephrotic syndrome Growth \- Congenital shortness \- Mild spondylorhizomelic dwarfism \- Feeding problems Neuro \- Normal prenatal brain growth \- Later decelerated brain growth \- Severe mental retardation \- Decorticate neurological function 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HUTTERITE CEREBROOSTEONEPHRODYSPLASIA SYNDROME	c1856054	26,234	omim	https://www.omim.org/entry/236450	2019-09-22T16:27:02	{"mesh": ["C536074"], "omim": ["236450"], "synonyms": ["Alternative titles", "COND", "CEREBROOSTEONEPHOSIS SYNDROME"]}
A number sign (#) is used with this entry because of evidence that more than one gene is involved in the causation of noninsulin-dependent diabetes mellitus (NIDDM). See 601283 for description of a form of NIDDM linked to 2q, which may be caused by mutation in the gene encoding calpain-10 (CAPN10; 605286). See 601407 for description of a chromosome 12q locus, NIDDM2, found in a Finnish population. See 603694 for description of a locus on chromosome 20, NIDDM3. See 608036 for description of a locus on chromosome 5q34-q35, NIDDM4. See 616087 for description of NIDDM5, which comprises susceptibility related to a nonsense mutation in the TBC1D4 gene (612465) on chromosome 13q22. A mutation has been observed in hepatocyte nuclear factor-4-alpha (HNF4A; 600281.0004) in a French family with NIDDM of late onset. Mutations in the NEUROD1 gene (601724) on chromosome 2q32 were found to cause type II diabetes mellitus in 2 families. Mutation in the GLUT2 glucose transporter was associated with NIDDM in 1 patient (138160.0001). Mutation in the MAPK8IP1 gene, which encodes the islet-brain-1 protein, was found in a family with type II diabetes in individuals in 4 successive generations (604641.0001). Polymorphism in the KCNJ11 gene (600937.0014) confers susceptibility. In French white families, Vionnet et al. (2000) found evidence for a susceptibility locus for type II diabetes on 3q27-qter. They confirmed the diabetes susceptibility locus on 1q21-q24 reported by Elbein et al. (1999) in whites and by Hanson et al. (1998) in Pima Indians. A mutation in the GPD2 gene (138430.0001) on chromosome 2q24.1, encoding mitochondrial glycerophosphate dehydrogenase, was found in a patient with type II diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type II diabetes. Triggs-Raine et al. (2002) stated that in the Oji-Cree, a gly319-to-ser change in HNF1-alpha (142410.0008) behaves as a susceptibility allele for type II diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type II diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type II diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type II diabetes in 1 family. A (single-nucleotide polymorphism) SNP in the 3-prime untranslated region of the resistin gene (605565.0001) was associated with susceptibility to diabetes and to insulin resistance-related hypertension in Chinese subjects. Susceptibility to insulin resistance has been associated with polymorphism in the TCF1 (142410.0011), PPP1R3A (600917.0001), PTPN1 (176885.0001), ENPP1 (173335.0006), IRS1 (147545.0002), and EPHX2 (132811.0001) genes. The K121Q polymorphism of ENPP1 (173335.0006) is associated with susceptibility to type II diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type II diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type II diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type II diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type II diabetes. Variation in the PPARG gene (601487) has been associated with risk of type 2 diabetes. A promoter polymorphism in the IL6 gene (147620) is associated with susceptibility to NIDDM. Variation in the KCNJ15 gene (602106) has been associated with T2DM in lean Asians. Variation in the SLC30A8 gene (611145) has been associated with susceptibility to T2D. Variation in the HMGA1 gene (600701.0001) is associated with an increased risk of type II diabetes. Mutation in the MTNR1B gene (600804) is associated with susceptibility to type 2 diabetes. Noninsulin-dependent diabetes mellitus is distinct from MODY (606391) in that it is polygenic, characterized by gene-gene and gene-environment interactions with onset in adulthood, usually at age 40 to 60 but occasionally in adolescence if a person is obese. The pedigrees are rarely multigenerational. The penetrance is variable, possibly 10 to 40% (Fajans et al., 2001). Persons with type II diabetes usually have an obese body habitus and manifestations of the so-called metabolic syndrome (see 605552), which is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia. ### Protection Against Type 2 Diabetes Mellitus Protein-truncating variants in the SLC30A8 (611145) have been associated with a reduced risk for T2D. Inheritance In 3 families with MODY and 7 with 'common' type II diabetes mellitus, O'Rahilly et al. (1992) excluded linkage to the INS locus (176730). Exclusive of the mendelian forms of NIDDM represented by MODY, the high incidence of diabetes in certain populations and among first-degree relatives of type II diabetic patients, as well as the high concordance in identical twins, provides strong evidence that genetic factors underlie susceptibility to the common form of NIDDM which affects up to 6% of the United States population. Although defects in both insulin secretion and insulin action may be necessary for disease expression in groups with a high incidence of NIDDM, such as offspring of type II diabetic parents and Pima Indians, insulin resistance and decreased glucose disposal can be shown to precede and predict the onset of diabetes (Martin et al., 1992; Bogardus et al., 1989). In both of these groups, relatives and Pima Indians, there is evidence of familial clustering of insulin sensitivity. Thus, insulin resistance appears to be a central feature of NIDDM and may be an early and inherited marker of the disorder. Martinez-Marignac et al. (2007) analyzed and discussed the use of admixture mapping of type 2 diabetes genetic risk factors in Mexico City. Type 2 diabetes is at least twice as prevalent in Native American populations as in populations of European ancestry. The authors characterized the admixture proportions in a sample of 286 unrelated type 2 diabetes patients and 275 controls from Mexico City. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). The average proportions of Native American, European, and West African admixture were estimated as 65%, 30%, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90% and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4. This association of socioeconomic status with individual admixture proportion showed that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7, from which Martinez-Marignac et al. (2007) could estimate the number of evenly distributed AIMs required to localize genes underlying disease risk between populations of European and Native American ancestry, i.e., about 1,400. Sample sizes of about 2,000 cases would be required to detect any locus that contributed an ancestry risk ratio of at least 1.5. Kong et al. (2009) found 3 SNPs at 11p15 that had association with type 2 diabetes and parental origin specific effects; These were rs2237892, rs231362, and rs2334499. For rs2334499 the allele that confers risk when paternally inherited (T) is protective when maternally inherited. Biochemical Features A subgroup of patients diagnosed with type II diabetes have circulating antibodies to islet cell cytoplasmic antigens, most frequently to glutamic acid decarboxylase (see GAD2; 138275). Among 1,122 type II diabetic patients, Tuomi et al. (1999) found GAD antibody in 9.3%, a significantly higher prevalence than that found in patients with impaired glucose tolerance or in controls. The GADab+ patients had lower fasting C-peptide concentration, lower insulin response to oral glucose, and higher frequency of the high-risk HLA-DQB10201/0302 (see 604305) genotype (though significantly lower than in patients with type I diabetes) when compared with GADab- patients. Tuomi et al. (1999) suggested the designation latent autoimmune diabetes in adults (LADA) to define the subgroup of type II diabetes patients with GADab positivity (greater than 5 relative units) and age at onset greater than 35 years. Both defective insulin secretion and insulin resistance have been reported in relatives of NIDDM subjects. Elbein et al. (1999) tested 120 members of 26 families containing an NIDDM sib pair with a tolbutamide-modified, frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) and acute insulin response to glucose (AIRglucose). Both SI x AIRglucose and SI showed strong negative genetic correlations with diabetes (-85 +/- 3% and -87 +/- 2%, respectively, for all family members), whereas AIRglucose did not correlate with diabetes. The authors concluded that insulin secretion, as measured by SI x AIRglucose, is decreased in nondiabetic members of familial NIDDM kindreds; that SI x AIRglucose in these high-risk families is highly heritable; and that the same polygenes may determine diabetes status and a low SI x AIRglucose. They also suggested that insulin secretion, when expressed as an index normalized for insulin sensitivity, is more familial than either insulin sensitivity or first-phase insulin secretion alone, and may be a very useful trait for identifying genetic predisposition to NIDDM. Genotype/Phenotype Correlations Li et al. (2001) assessed the prevalence of families with both type I and type II diabetes in Finland and studied, in patients with type II diabetes, the association between a family history of type 1 diabetes, GAD antibodies (GADab), and type I diabetes-associated HLA-DQB1 genotypes. Further, in mixed type I/type II diabetes families, they investigated whether sharing an HLA haplotype with a family member with type I diabetes influenced the manifestation of type II diabetes. Among 695 families with more than 1 patient with type II diabetes, 100 (14%) also had members with type I diabetes. Type II diabetic patients from the mixed families more often had GADab (18% vs 8%) and DQB10302/X genotype (25% vs 12%) than patients from families with only type II diabetes; however, they had a lower frequency of DQB102/0302 genotype compared with adult-onset type I patients (4% vs 27%). In the mixed families, the insulin response to oral glucose load was impaired in patients who had HLA class II risk haplotypes, either DR3(17)-DQA10501-DQB102 or DR40401/4-DQA10301-DQB10302, compared with patients without such haplotypes. This finding was independent of the presence of GADab. The authors concluded that type I and type II diabetes cluster in the same families. A shared genetic background with a patient with type I diabetes predisposes type II diabetic patients both to autoantibody positivity and, irrespective of antibody positivity, to impaired insulin secretion. Their findings also supported a possible genetic interaction between type I and type II diabetes mediated by the HLA locus. Clinical Management Fonseca et al. (1998) studied the effects of troglitazone monotherapy on glycemic control in patients with NIDDM in 24 hospital and outpatient clinics in the U.S. and Canada. Troglitazone 100, 200, 400, or 600 mg, or placebo, was administered once daily with breakfast to 402 patients with NIDDM and fasting serum glucose (FSG) greater than 140 mg/dL, glycosylated hemoglobin (HbA1c) greater than 6.5%, and fasting C-peptide greater than 1.5 ng/mL. Patients treated with 400 and 600 mg troglitazone had significant decreases from baseline in mean FSG (-51 and -60 mg/dL, respectively) and HbA1c (-0.7% and -1.1%, respectively) at month 6 compared to placebo-treated patients. In the diet-only subset, 600 mg troglitazone therapy resulted in a significant (P less than 0.05) reduction in HbA1c (-1.35%) and a significant reduction in FSG (-42 mg/dL) compared with placebo. Patients previously treated with sulfonylurea therapy had significant (P less than 0.05) decreases in mean FSG with 200 to 600 mg troglitazone therapy compared with placebo (-48, -61, and -66 mg/dL, respectively). The authors concluded that troglitazone monotherapy significantly improves HbA1c and fasting serum glucose, while lowering insulin and C-peptide in patients with NIDDM. Chung et al. (2000) studied the effect of HMG-CoA reductase inhibitors on bone mineral density (BMD) of type II diabetes mellitus by a retrospective review of medical records. In the control group, BMD of the spine significantly decreased after 14 months. In the treatment group, BMD of the femoral neck significantly increased after 15 months. In male subjects treated with HMG-CoA reductase inhibitors, there was a significant increase in BMD of the femoral neck and femoral trochanter, but in female subjects, only BMD of the femoral neck increased. The authors concluded that HMG-CoA reductase inhibitors may increase BMD of the femur in male patients with type II diabetes mellitus. Aljada et al. (2001) investigated the effect of troglitazone on the proinflammatory transcription factor NF-kappa-B (see 164011) and its inhibitory protein I-kappa-B (see 164008) in mononuclear cells (MNC) in obese patients with type II diabetes. Seven obese patients with type II diabetes were treated with troglitazone (400 mg/day) for 4 weeks, and blood samples were obtained at weekly intervals. NF-kappa-B binding activity in MNC nuclear extracts was significantly inhibited after troglitazone treatment at week 1 and continued to be inhibited up to week 4. On the other hand, I-kappa-B protein levels increased significantly after troglitazone treatment at week 1, and this increase persisted throughout the study. The authors concluded that troglitazone has profound antiinflammatory effects in addition to antioxidant effects in obese type II diabetics, and that these effects may be relevant to the beneficial antiatherosclerotic effects of troglitazone at the vascular level. In a multicenter, double-blind trial, Garber et al. (2003) enrolled patients with type II diabetes who had inadequate glycemic control (glycosylated hemoglobin A1C greater than 7% and less than 12%) with diet and exercise alone to compare the benefits of initial therapy with glyburide/metformin tablets versus metformin or glyburide monotherapy. They randomized 486 patients to receive glyburide/metformin tablets, metformin, or glyburide. Changes in A1C, fasting plasma glucose, fructosamine, serum lipids, body weight, and 2-hour postprandial glucose after a standardized meal were assessed after 16 weeks of treatment. Glyburide/metformin tablets caused a superior mean reduction in A1C from baseline versus metformin and glyburide monotherapy. Glyburide/metformin also significantly reduced fasting plasma glucose and 2-hour postprandial glucose values compared with either monotherapy. The final mean doses of glyburide/metformin were lower than those of metformin and glyburide. The authors concluded that first-line treatment with glyburide/metformin tablets provided superior glycemic control over component monotherapy, allowing more patients to achieve American Diabetes Association treatment goals with lower component doses in drug-naive patients with type II diabetes. The GoDARTs and UKPDS Diabetes Pharmacogenetics Study Group and Wellcome Trust Case Control Consortium 2 (2011) performed a genomewide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in 2 cohorts including 1,783 Scottish individuals and 1,113 individuals in the UK Prospective Diabetes Study. In a combined metaanalysis, the consortia identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 x 10(-9), OR = 1.35, 95% CI 1.22-1.49) at a locus containing the ATM gene (607585). In a rat hepatoma cell line, inhibition of ATM with KU-55933, a selective ATM inhibitor, attenuated the phosphorylation and activation of AMP-activated protein kinase (see 602739) in response to metformin. The consortia concluded that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. Yee et al. (2012) commented on the GoDARTS and UKPDS paper and examined the inhibitory effect of KU-55933 on metformin in H4IIE cells and in HEK293 cells stably expressing OCT1. They demonstrated in both cases that KU-55933 inhibits metformin uptake via inhibition of OCT1 and that the attenuation of metformin-induced AMPK phosphorylation is a result of its inhibition of metformin uptake into the cells. This effect is independent of ATM. Yee et al. (2012) demonstrated that ATM does not have a detectable effect on OCT1 activity. Woods et al. (2012) also found that in hepatocytes lacking AMPK activity (see Woods et al., 2011), metformin still has the ability to reduce hepatic glucose output. Woods et al. (2012) argued that the SNP rs11212617 maps to a locus on chromosome 11q22 that encodes a number of genes and that no direct evidence had been found that ATM acts upstream of AMPK; Woods et al. (2012) concluded that other genes within this locus should be considered as candidates responsible for the reduced therapeutic effect of metformin action. Zhou et al. (2012) concurred with the comments of Yee et al. (2012) and Woods et al. (2012) that all genes surrounding rs11212617 should be examined. In 66 patients with T2D, Ferrannini et al. (2014) studied the effects of the selective SGLT2 (SLC5A2; 182381) inhibitor empagliflozin. Empagliflozin-induced glycosuria improved beta-cell function and insulin sensitivity, thus lowering fasting and postprandial glycemia, after 1 dose, despite a decrease in insulin secretion and tissue glucose disposal and a rise in endogenous glucose production. Chronic dosing shifted substrate utilization from carbohydrate to lipid. Bonner et al. (2015) observed an increase in glucagon secretion in human pancreatic islet cells after siRNA-mediated SLC5A2 knockdown. Treatment of human islets with dapagliflozin, a selective and potent SGLT2 inhibitor, prevented induction of SLC5A2 mRNA at high glucose concentrations and concomitantly increased glucagon mRNA levels. Acute inhibition of active SGLT2 glucose transport using dapagliflozin at glucose concentrations of 6 mM resulted in a marked increase of glucagon secretion without affecting glucagon content or insulin secretion. Commenting on the findings by Ferrannini et al. (2014) and Bonner et al. (2015), Hattersley and Thorens (2015) cautioned that the increased glucagon secretion that results from SGLT2 inhibition means that the glucose level will fall less than would be expected given the degree of urinary glucose loss, which is significant because it is glycosuria that causes most of the symptoms of diabetes, including polyuria, polydipsia, weight loss, and genitourinary infection. Pathogenesis Piatti et al. (2000) compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cGMP in 35 healthy volunteers with, or 27 without, at least 1 sib and 1 parent with type II diabetes. The mean insulin sensitivity index (ISI) was significantly greater in those without a family history as compared with nondiabetic volunteers with a family history of type II diabetes, whether they had normal glucose tolerance or impaired glucose tolerance. In addition, basal NO levels, evaluated by the measurement of its stable end products (i.e., nitrite and nitrate levels, NO2-/NO3-) were significantly higher, and levels of cGMP, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type II diabetes. Furthermore, when the 62 volunteers were analyzed as 1 group, there was a negative correlation between ISI and NO2-/NO3- levels and a positive correlation between ISI and cGMP levels. The authors concluded that alterations of the NO/cGMP pathway seem to be an early event in nondiabetic individuals with a family history of type II diabetes, and that these changes are correlated with the degree of insulin resistance. To investigate how insulin resistance arises, Petersen et al. (2003) studied 16 healthy, lean elderly aged 61 to 84 and 13 young participants aged 18 to 39 matched for lean body mass (BMI less than 25) and fat mass assessed by DEXA (dual energy X-ray absorptiometry) scanning, and activity level. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue, assessed by NMR spectroscopy, and with an approximately 40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo NMR spectroscopy. Petersen et al. (2003) concluded that their data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly. Petersen et al. (2004) performed glucose clamp studies in healthy, young, lean, insulin-resistant offspring of patients with type II diabetes and insulin-sensitive subjects matched for age, height, weight, and physical activity. The insulin-stimulated rate of glucose uptake by muscle was approximately 60% lower in insulin-resistant subjects than in controls (p less than 0.001) and was associated with an increase of approximately 80% in intramyocellular lipid content (p less than 0.005). The authors attributed the latter increase to mitochondrial dysfunction, noting a reduction of approximately 30% in mitochondrial phosphorylation (p = 0.01 compared to controls). Petersen et al. (2004) concluded that insulin resistance in the skeletal muscle of insulin-resistant offspring of patients with type II diabetes is associated with dysregulation of intramyocellular fatty acid metabolism, possibly because of an inherited defect in mitochondrial oxidative phosphorylation. Do et al. (2005) assessed the correlation between persistent diabetic macular edema and hemoglobin A1c. Patients with type II diabetes and persistent clinically significant macular edema had higher HbA1c at the time of their disease than patients with resolved macular edema. Patients with bilateral disease had more elevated HbA1c than those with unilateral disease. Foti et al. (2005) reported 4 patients with insulin resistance and type II diabetes in whom cell-surface insulin receptors were decreased and INSR (147670) gene transcription was impaired, although the INSR genes were normal. In these individuals, expression of HMGA1 (600701) was markedly reduced; restoration of HMGA1 protein expression in their cells enhanced INSR gene transcription and restored cell-surface insulin receptor protein expression and insulin-binding capacity. Foti et al. (2005) concluded that defects in HMGA1 may cause decreased insulin receptor expression and induce insulin resistance. Increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway and promote the O-glycosylation of proteins by O-glycosyl transferase (OGT; 300255). Dentin et al. (2008) showed that OGT triggered hepatic gluconeogenesis through the O-glycosylation of the transducer of regulated cAMP response element-binding protein (CREB) 2 (TORC2 or CRTC2; 608972). CRTC2 was O-glycosylated at sites that normally sequester CRTC2 in the cytoplasm through a phosphorylation-dependent mechanism. Decreasing amounts of O-glycosylated CRTC2 by expression of the deglycosylating enzyme O-GlcNAcase (604039) blocked effects of glucose on gluconeogenesis, demonstrating the importance of the hexosamine biosynthetic pathway in the development of glucose intolerance. Mapping In an autosomal genome screen in 363 nondiabetic Pima Indians at 516 polymorphic microsatellite markers, Pratley et al. (1998) found a suggestion of linkage at several chromosomal regions with particular characteristics known to be predictive of NIDDM: 3q21-q24, linked to fasting plasma insulin concentration and in vivo insulin action; 4p15-q12, linked to fasting plasma insulin concentration; 9q21, linked to 2-hour insulin concentration during oral glucose tolerance testing; and 22q12-q13, linked to fasting plasma glucose concentration. None of the linkages exceeded a lod score of 3.6 (a 5% probability of occurring in a genomewide screen). In 719 Finnish sib pairs with type II diabetes, Ghosh et al. (2000) performed a genome scan at an average resolution of 8 cM. The strongest results were for chromosome 20, where they observed a weighted maximum lod score of 2.15 at map position 69.5 cM from pter, and secondary weighted lod score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. The next largest maximum lod score was for chromosome 11 (maximum lod score = 1.75 at 84.0 cM), followed by chromosomes 2, 10, and 6. When they conditioned on chromosome 2 at 8.5 cM, the maximum lod score for chromosome 20 increased to 5.50 at 69.0 cM. Watanabe et al. (2000) reported results from an autosomal genome scan for type II diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sib pair and analyzed by the variance components-based quantitative-trait locus linkage approach. In diabetic individuals, the strongest results were observed on chromosomes 3 and 13. Integrating genome scan results of Ghosh et al. (2000), they identified several regions that may harbor susceptibility genes for type II diabetes in the Finnish population. In a genomewide scan of 359 Japanese individuals with type II diabetes from 159 families, including 224 affected sib pairs, Mori et al. (2002) found suggestive linkage at chromosome 11p13-p12, with a maximum lod score of 3.08. Analysis of sib pairs who had a BMI of less than 30 revealed suggestive linkage at chromosomes 7p22-p21 and 11p13-p12 (lod scores of 3.51 and 3.00, respectively). Analysis of sib pairs who were diagnosed before the age of 45 revealed suggestive linkage at chromosome 15q13-q21, with a maximum lod score of 3.91. Demenais et al. (2003) applied the genome search metaanalysis (GSMA) method to genomewide scans conducted with 4 European type II diabetes mellitus cohorts comprising a total of 3,947 individuals, 2,843 of whom were affected. The analysis provided evidence for linkage of type II diabetes to 6 regions, with the strongest evidence on chromosome 17p11.2-q22 (p = 0.0016), followed by 2p22.1-p13.2 (p = 0.027), 1p13.1-q22 (p = 0.028), 12q21.1-q24.12 (p = 0.029), 6q21-q24.1 (p = 0.033), and 16p12.3-q11.2 (p = 0.033). Linkage analysis of the pooled raw genotype data generated maximum lod scores in the same regions as identified by GSMA; the maximum lod score for the 17p11.2-q22 region was 1.54. Using nonparametric linkage analyses, Van Tilburg et al. (2003) performed a genomewide scan to find susceptibility loci for type II diabetes mellitus in the Dutch population. They studied 178 families from the Netherlands, who constituted 312 affected sib pairs. Because obesity and type II diabetes mellitus are interrelated, the dataset was stratified for the subphenotype BMI, corrected for age and gender. This resulted in a suggestive maximum multipoint lod score of 2.3 (single-point P value, 9.7 x 10(-4); genomewide P value, 0.028) for the most obese 20% pedigrees of the dataset, between marker loci D18S471 and D18S843. In the lowest 80% obese pedigrees, 2 interesting loci on chromosome 2 and 19 were found, with lod scores of 1.5 and 1.3. Shtir et al. (2007) performed ordered subset analysis on affected individuals from 2 sets of families ascertained on affected sib pairs with type 2 diabetes mellitus and found that 33 families with the lowest average fasting insulin (606035) showed evidence for linkage to a locus on chromosome 6q (maximum lod score of 3.45 at 128 cM near D6S1569, uncorrected p = 0.017) that was coincident with QTL linkage results for fasting and 2-hour insulin levels in family members without type 2 diabetes mellitus. The Wellcome Trust Case Control Consortium (2007) described a joint genomewide association study using the Affymetrix GeneChip 500K Mapping Array Set, undertaken in the British population, which examined approximately 2,000 individuals and a shared set of approximately 3,000 controls for each of 7 major diseases. Case-control comparisons identified 3 significant independent association signals for type 2 diabetes, at rs9465871 on chromosome 6p22, rs4506565 on chromosome 10q25, and rs9939609 on chromosome 16q12. In a genomewide association study of 1,363 French type 2 diabetes cases and controls, Sladek et al. (2007) confirmed the known association with rs7903146 of the TCF7L2 gene (602228.0001) on chromosome 10q25.2 (p = 3.2 x 10(-17)). They also found significant association between T2D and 2 SNPs on chromosome 10q23.33 (rs1111875 and rs7923837), located near the telomeric end of a 270-kb linkage disequilibrium block containing the IDE (146680), HHEX (604420), KIF11 (148760) genes. Sladek et al. (2007) stated that fine mapping of the HHEX locus and biologic studies would be required to identify the causative variant. The Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research (2007) analyzed 386,731 common SNPs in 1,464 patients with type 2 diabetes and 1,467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators Finland-United States Investigation of NIDDM Genetics (FUSION) and Wellcome Trust Case Control Consortium/United Kingdom Type 2 Diabetes Genetics Consortium (WTCCC/UKT2D), this group identified and confirmed 3 loci associated with type 2 diabetes--in a noncoding region near CDKN2A (600160) and CDKN2B (600431), in an intron of IGF2BP2 (608289), and in an intron of CDKAL1 (611259)--and replicated associations near HHEX and SLC30A8 (611145) by recent whole-genome association study. The Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research (2007) identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR; 600842) with serum triglycerides (see 613463). The authors concluded that the discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genomewide association studies to provide potentially important clues to the pathogenesis of common diseases. Onuma et al. (2010) analyzed the GCKR SNP rs780094 in 488 Japanese patients with type 2 diabetes and 398 controls and found association between a reduced risk of T2DM and the A allele (odds ratio, 0.711; p = 4.2 x 10(-4)). A metaanalysis with 2 previous association studies (Sparso et al., 2008 and Horikawa et al., 2008) confirmed the association of rs780094 with T2D susceptibility. In the general Japanese population, individuals with the A/A genotype had lower levels of fasting plasma glucose (see 613463), fasting plasma insulin, and HOMA-IR than those with the G/G genotype (p = 0.008, 0.008, and 0.002, respectively); conversely, those with the A/A genotype had higher triglyceride levels than those with the G/G genotype (p = 0.028). Adopting a genomewide association strategy, Scott et al. (2007) genotyped 1,161 Finnish type 2 diabetes cases and 1,174 Finnish normal glucose tolerant controls with greater than 315,000 SNPs and imputed genotypes for an additional greater than 2 million autosomal SNPs. Scott et al. (2007) carried out association analysis with these SNPs to identify genetic variants that predispose to type 2 diabetes, compared to their type 2 diabetes association results with the results of 2 similar studies, and genotyped 80 SNPs in an additional 1,215 Finnish type 2 diabetes cases and 1,258 Finnish normal glucose tolerant controls. Scott et al. (2007) identified type 2 diabetes-associated variants in an intergenic region of chromosome 11p12, contributed to the identification of type 2 diabetes-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirmed that variants near TCF7L2, SLC30A8, HHEX, FTO (610966), PPARG (601487), and KCNJ11 (600937) are associated with type 2 diabetes risk. Scott et al. (2007) concluded that this brings the number of type 2 diabetes loci now confidently identified to at least 10. Starting from genomewide genotype data for 1,924 diabetic cases and 2,938 population controls generated by the Wellcome Trust Case Control Consortium, Zeggini et al. (2007) set out to detect replicated diabetes association signals through analysis of 3,757 additional cases and 5,346 controls and by integration of their findings with equivalent data from other international consortia. Zeggini et al. (2007) detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed associations at HHEX/IDE and at SLC30A8. Zeggini et al. (2007) concluded that their findings provided insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes. Van Vliet-Ostaptchouk et al. (2008) genotyped 501 unrelated Dutch patients with type 2 diabetes and 920 healthy controls for 2 SNPs in strong linkage disequilibrium near the HHEX gene, rs7923837 and rs1111875, and found that for both SNPs, the risk for T2D was significantly increased in carriers of the major alleles (OR of 1.57 and p = 0.017; OR of 1.68 and p = 0.003, respectively). Assuming a dominant genetic model, the population-attributable risks for diabetes due to the at-risk alleles of rs7923837 and rs1111875 were estimated to be 33% and 36%, respectively. Gudmundsson et al. (2007) found that the A allele of rs4430796 in the HNF1B gene (189907) was associated with a protective effect against type 2 diabetes in a study of 1,380 Icelandic patients and 9,940 controls, and in 7 additional type 2 diabetes case-control groups of European, African, and Asian ancestry (p = 2.7 x 10(-7) and odds ratio of 0.91, for the combined results). This SNP is also associated with prostate cancer risk (see HPC11, 611955). Prokopenko et al. (2008) reviewed advances in identifying common genetic variants that contribute to complex multifactorial phenotypes such as type 2 diabetes (T2D), particularly the ability to perform genomewide association studies in large samples. They noted that the 2 most robust T2D candidate-gene associations previously reported, for common polymorphisms in PPARG and KCNJ11, have only modest effect sizes, with each copy of the susceptibility allele increasing the risk of disease by 15 to 20%. In contrast, microsatellite mapping detected an association with variation in the TCF7L2 gene that has a substantially stronger effect, with the 10% of Europeans who are homozygous for the risk allele having approximately twice the odds of developing T2D compared to those carrying no copies of the risk allele. Prokopenko et al. (2008) stated that about 20 common variants had been robustly implicated in T2D susceptibility to date, but noted that for most of the loci, causal variants had yet to be identified with any certainty. The Wellcome Trust Case Control Consortium (2010) undertook a large direct genomewide study of association between copy number variants (CNVs) and 8 common human diseases involving approximately 19,000 individuals. Association testing and follow-up replication analyses confirmed association of CNV at the TSPAN8 (600769) locus with type 2 diabetes. At the time of the report of Fuchsberger et al. (2016), the variants associated with T2D that had been identified by genomewide association studies, although common, explained only a minority of observed T2D heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from 5 ancestry groups. To increase statistical power, Fuchsberger et al. (2016) expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with T2D after sequencing were overwhelmingly common and most fell within regions previously identified by genomewide association studies. Fuchsberger et al. (2016) concluded that, although comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to T2D. ### Association with Variation in KCNQ1 Yasuda et al. (2008) carried out a multistage genomewide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1 (607542), and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest p value (6.7 x 10(-13), odds ratio = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese, and European ancestry as well as in 2 independent Japanese populations, and metaanalysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a p value of 1.7 x 10(-42) (odds ratio = 1.40; 95% confidence interval = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Unoki et al. (2008) conducted a genomewide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 to be a strong candidate for conferring susceptibility to type 2 diabetes. Unoki et al. (2008) detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model p = 3.1 x 10(-12); odds ratio = 1.26, 95% confidence interval = 1.18-1.34). Several other SNPs in the same linkage disequilibrium block were strongly associated with type 2 diabetes. The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean and Danish populations. Gaulton et al. (2015) performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. They identified 49 distinct association signals at these 39 loci, including 5 mapping in or near KCNQ1 (607542). Gaulton et al. (2015) found 5 SNPs in the region flanking KCNQ1 with modest effect on diabetes risk, with the weakest association at rs458069 (p = 1.0 x 10(-6), OR 1.06, 95% CI 1.04-1.09) and the strongest association at rs74046911 (p = 9.6 x 10(-26), OR 1.29, 95% CI 1.23-1.35). ### Association with Variation in SHBG Ding et al. (2009) analyzed levels of sex hormone-binding globulin (see SHBG; 182205) in 359 women newly diagnosed with type 2 diabetes and 359 female controls and found that higher plasma levels of SHBG were prospectively associated with a lower risk of type 2 diabetes, with multivariable odds ratios ranging from 1.00 for the lowest quartile of plasma levels to 0.09 for the highest quartile; the results were replicated in an independent cohort of men (p less than 0.001 for results in both women and men). Ding et al. (2009) identified an SHBG SNP, rs6259, that was associated with a 10% higher plasma level of SHBG, and another SNP, rs6257, that was associated with a 10% lower plasma level of SHBG; variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated SHBG levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard deviation increase in plasma level of SHBG was 0.28 among women and 0.29 among men. Ding et al. (2009) suggested that variation in the SHBG gene on chromosome 17p13-p12 may have a causal role in the risk of type 2 diabetes. Kong et al. (2009) identified a differentially methylated CTCF binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. The CTCF-binding site is OREG0020670 and its 2-kb region located 17 kb centromeric to the type 2 diabetes marker rs2334499. Perry et al. (2010) genotyped 27,657 type 2 diabetes patients and 58,481 controls from 15 studies at the SHBG promoter SNP rs1799941 that is strongly associated with serum levels of SHBG. The authors used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The rs1799941 variant was associated with type 2 diabetes (OR, 0.94; 95% CI, 0.91-0.97; p = 2 x 10(-5)), with the SHBG-raising A allele associated with reduced risk of type 2 diabetes, the results were very similar in men and women. There was no evidence that rs1799941 was associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. ### Association with Variation in RBP4 Serum levels of RBP4 (180250), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggested that elevated RBP4 levels cause insulin resistance (Yang et al., 2005). Graham et al. (2006) found that serum RBP4 levels correlated with the magnitude of insulin resistance in human subjects with obesity (601665), impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body mass index (BMI), waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein (138190) and serum RBP4 levels were inversely correlated. Graham et al. (2006) concluded that RBP4 is elevated in serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. They suggested that these findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels. Aeberli et al. (2007) studied serum RBP4, serum retinol (SR), the RBP4-to-SR molar ratio, and dietary vitamin A intakes in seventy-nine 6- to 14-year-old normal-weight and overweight children and investigated the relationship of these variables to insulin resistance, subclinical inflammation, and the metabolic syndrome. Only 3% of children had low vitamin A status. Independent of age, vitamin A intakes, and C-reactive protein (see 123260), BMI, body fat percentage, and waist-to-hip ratio were significant predictors of RBP4, serum retinol, and RBP4/SR. Aeberli et al. (2007) concluded that independent of subclinical inflammation and vitamin A intakes, serum RBP4 and the RBP4-to-SR ratio are correlated with obesity, central obesity, and components of the metabolic syndrome in prepubertal and early pubertal children. Molecular Genetics ### Mutation in PPAR-Gamma Altshuler et al. (2000) confirmed an association of the common pro12-to-ala polymorphism in PPAR-gamma (601487.0002) with type II diabetes. They found a modest but significant increase in diabetes risk associated with the more common proline allele (approximately 85% frequency). Because the risk allele occurs at such high frequency, its modest effect translates into a large population-attributable risk--influencing as much as 25% of type II diabetes in the general population. Savage et al. (2002) described a family, which they referred to as a 'Europid pedigree,' in which several members had severe insulin resistance. The grandparents had typical late-onset type II diabetes with no clinical features of severe insulin resistance. Three of their 6 children and 2 of their grandchildren had acanthosis nigricans, elevated fasting plasma insulin levels. Hypertension was also a feature. By mutation screening, Savage et al. (2002) identified a heterozygous frameshift resulting in a premature stop mutation of the PPARG (601487.0011) gene which was present in the grandfather, all 5 relatives with severe insulin resistance, and 1 other relative with normal insulin levels. Further candidate gene studies revealed a heterozygous frameshift/premature stop mutation in PPP1R3A (600917.0003) which was present in the grandmother, in all 5 individuals with severe insulin resistance, and in 1 other relative. Thus, all 5 family members with severe insulin resistance, and no other family members, were double heterozygotes with respect to frameshift mutations. (Although the article by Savage et al. (2002) originally stated that the affected individuals were compound heterozygotes, they were actually double heterozygotes. Compound heterozygosity is heterozygosity at the same locus for each of 2 different mutant alleles; double heterozygosity is heterozygosity at each of 2 separate loci. The use of an incorrect term in the original publication was the result of a 'copy-editing error that was implemented after the authors returned corrected proofs' (Savage et al., 2002).) ### Association with Insulin Receptor Substrate-2 Mammarella et al. (2000) genotyped 193 Italian patients with type II diabetes and 206 control subjects for the insulin receptor substrate-2 G1057D polymorphism (600797.0001). They found evidence for a strong association between type II diabetes and the polymorphism, which appears to be protective against type II diabetes in a codominant fashion. ### Association with Adiponectin For a discussion of an association between variation in the ADIPOQ gene (605441) on chromosome 3q27 and type 2 diabetes, see ADIPQTL1 (612556). ### Association with Mitochondrial DNA Variation A common mtDNA variant (T16189C) in a noncoding region of mtDNA was positively correlated with blood fasting insulin by Poulton et al. (1998). Poulton et al. (2002) demonstrated a significant association between the 16189 variant and type II diabetes in a population-based case-control study in Cambridgeshire, UK (n = 932, odds ratio = 1.61; 1.0-2.7, P = 0.048), which was greatly magnified in individuals with a family history of diabetes from the father's side (odds ratio = infinity; P less than 0.001). Poulton et al. (2002) demonstrated that the 16189 variant had arisen independently many times and on multiple mitochondrial haplotypes. They speculated that the 16189 variant may alter mtDNA bending and hence could influence interactions with regulatory proteins which control replication or transcription. Mohlke et al. (2005) presented data supporting previous evidence for association of 16189T-C with reduced ponderal index at birth and also showed evidence for association with reduced birth weight but not with diabetes status. This study suggested that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population studied. Furthermore, the data did not support a reported maternal inheritance pattern of type II diabetes mellitus but instead showed a strong effect of recall bias. Because mitochondria play pivotal roles in both insulin secretion from the pancreatic beta cells and insulin resistance of skeletal muscles, Fuku et al. (2007) performed a large-scale association study to identify mitochondrial haplogroups that may confer resistance against or susceptibility to type II diabetes mellitus. The study population comprised 2,906 unrelated Japanese individuals, including 1,289 patients with type II diabetes mellitus and 1,617 controls, and 1,365 unrelated Korean individuals, including 732 patients with type II diabetes and 633 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups. Multivariate logistic regression analysis with adjustment for age and sex revealed that the mitochondrial group N9a was significantly associated with resistance against type II diabetes mellitus (P = 0.0002) with an odds ratio of 0.55 (95% confidence interval 0.40-0.75). Even in the modern environment, which is often characterized by satiety and physical inactivity, this haplotype might confer resistance against type II diabetes mellitus. The N9a haplogroup found to be associated with reduced susceptibility to type II diabetes mellitus by Fuku et al. (2007) consisted of a synonymous SNP in ND2 (516001), 5231G-A; a missense change in ND5 (516005), thr8 to ala; and a synonymous change also in ND5, 12372G-A. ### Mutation in PAX4 Shimajiri et al. (2001) scanned the PAX4 gene (167413) in 200 unrelated Japanese probands with type 2 diabetes and identified an arg121-to-tyr mutation (R121W; 167413.0001) in 6 heterozygous patients and 1 homozygous patient (mutant allele frequency 2.0%). The mutation was not found in 161 nondiabetic subjects (p = 0.01). Six of 7 patients had a family history of diabetes or impaired glucose tolerance, and 4 of 7 had transient insulin therapy at the onset. One of them, a homozygous carrier, had relatively early-onset diabetes and slowly fell into an insulin-dependent state without an autoimmune-mediated process. ### Association with TFAP2B Maeda et al. (2005) performed a genomewide, case-control association study using gene-based SNPs in Japanese patients with type II diabetes and controls and identified several variations within the TFAP2B gene (601601) that were significantly associated with type II diabetes: an intron 1 VNTR (p = 0.0009), intron 1 +774G-T (p = 0.0006), and intron 1 +2093A-C (p = 0.0004). The association of TFAP2B with type II diabetes was also observed in a U.K. population. Maeda et al. (2005) suggested that the TFAP2B gene may confer susceptibility to type II diabetes. ### Mutation in ABCC8 Babenko et al. (2006) screened the ABCC8 gene (600509) in 34 patients with permanent neonatal diabetes (606176) or transient neonatal diabetes (see 601410) and identified heterozygosity for 7 missense mutations in 9 patients (see, e.g., 600509.0017-600509.0020). The mutation-positive fathers of 5 of the probands with transient neonatal diabetes developed type II diabetes mellitus in adulthood; Babenko et al. (2006) proposed that mutations of the ABCC8 gene may give rise to a monogenic form of type II diabetes with variable expression and age at onset. ### Association with WFS1 Sandhu et al. (2007) conducted a gene-centric association study for type 2 diabetes in multiple large cohorts and identified 2 SNPs located in the WFS1 gene, rs10010131 (606201.0021) and rs6446482 (602201.0022), that were strongly associated with diabetes risk (P = 1.4 x 10(-7) and P = 3.4 x 10(-7), respectively, in the pooled study set). The risk allele was the major allele for both SNPs, with a frequency of 60% for both. The authors noted that both are intronic, with no obvious evidence for biologic function. ### Association with IL6 Mohlig et al. (2004) investigated the IL6 -174C-G SNP (147620.0001) and development of NIDDM. They found that this SNP modified the correlation between BMI and IL6 by showing a much stronger increase of IL6 at increased BMI for CC genotypes compared with GG genotypes. The -174C-G polymorphism was found to be an effect modifier for the impact of BMI regarding NIDDM. The authors concluded that obese individuals with BMI greater than or equal to 28 kg/m2 carrying the CC genotype showed a more than 5-fold increased risk of developing NIDDM compared with the remaining genotypes and, hence, might profit most from weight reduction. Illig et al. (2004) investigated the association of the IL6 SNPs -174C-G and -598A-G on parameters of type 2 diabetes and the metabolic syndrome in 704 elderly participants of the Kooperative Gesundheitsforschung im Raum Augsburg/Cooperative Research in the Region of Augsburg (KORA) Survey 2000. They found no significant associations, although both SNPs exhibited a positive trend towards association with type 2 diabetes. Illig et al. (2004) also found that circulating IL6 levels were not associated with the IL6 polymorphisms; however, significantly elevated levels of the chemokine monocyte chemoattractant protein-1 (MCP1; 158105)/CC chemokine ligand-2 (CKR2; 601267) in carriers of the protective genotypes suggested an indirect effect of these SNPs on the innate immune system. ### Association with KCNJ15 Okamoto et al. (2010) identified a synonymous SNP (rs3746876, C566T) in exon 4 of the KCNJ15 (602106) that showed significant association with type 2 diabetes mellitus affecting lean individuals in 3 independent Japanese sample sets (p = 2.5 x 10(-7); odds ratio, 2.54) and with unstratified T2DM (p = 6.7 x 10(-6); OR, 1.76). The diabetes risk allele frequency was, however, very low among Europeans and no association between the variant and T2DM could be shown in a Danish case-control study. Functional analysis in HEK293 cells demonstrated that the risk T allele increased KCNJ15 expression via increased mRNA stability, which resulted in higher expression of protein compared to the C allele. ### Mutation in and Association with MTNR1B Bonnefond et al. (2012) performed large-scale exon resequencing of the MTNR1B gene (600804) in 7,632 Europeans, including 2,186 individuals with type 2 diabetes mellitus, and identified 36 very rare variants associated with T2D. Among the very rare variants, partial or total loss-of-function variants but not neutral ones contributed to T2D (odds ratio, 5.67; p = 4.09 x 10(-4)). Genotyping 4 variants with complete loss of melatonin-binding and signaling capabilities (A42P, 600804.0001; L60R, 600804.0002; P95L, 600804.0003; and Y308S, 600804.0004) as a pool in 11,854 additional French individuals, including 5,967 with T2D, demonstrated their association with T2D (odds ratio, 3.88; p = 5.37 x 10(-3)). Bonnefond et al. (2012) concluded that their study established a firm functional link between MTNR1B and T2D risk. Gaulton et al. (2015) performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 (600288) chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. Gaulton et al. (2015) confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells and observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. ### Mutation in SLC16A11 The SIGMA Type 2 Diabetes Consortium (2014) analyzed 9.2 million SNPs in each of 8,214 Mexicans and other Latin Americans, 3,848 with type 2 diabetes and 4,366 nondiabetic controls. In addition to replicating previous findings, the SIGMA Type 2 Diabetes Consortium (2014) identified a novel locus associated with type 2 diabetes at genomewide significance spanning the solute carriers SLC16A11 (615765) and SLC16A13 (p = 3.9 x 10(-13); odds ratio = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (p = 1.1 x 10(-4); odds ratio = 1.20). The risk haplotype carries 4 missense SNPs, all in SLC16A11: V113I (rs117767867), D127G (rs13342692), G40S (rs75418188), and P443T (rs75493593). This haplotype is present at 50% frequency in Native American samples and approximately 10% in East Asian, but is rare in European and African samples. Each haplotype copy is associated with a 20% increased risk of type 2 diabetes. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SIGMA Type 2 Diabetes Consortium (2014) concluded that, despite type 2 diabetes having been well studied by genomewide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism. ### Association with STARD10 Using pancreatic samples from nondiabetic individuals and patients with type 2 diabetes mellitus, Carrat et al. (2017) performed cis-expression quantitative trait locus (eQTL) analysis of islet transcriptomes and observed that carriers of T2DM risk alleles at 11q13 displayed reduced levels of STARD10 (617382) mRNA. In addition, beta cell-selective deletion of Stard10 in mice resulted in impaired glucose-stimulated Ca(2+) dynamics and insulin secretion, and recaptitulated the pattern of improved proinsulin (see 176730) processing observed in human carriers of the risk alleles, whereas overexpresion of Stard10 in the adult beta cell improved glucose tolerance in high-fat-fed mice. Carrat et al. (2017) suggested that T2DM risk associated with variation at this locus is mediated through reduction in STARD10 expression in the beta cell. Other Features Diabetes mellitus is a recognized consequence of hereditary hemochromatosis (HFE; 235200). To test whether common mutations in the HFE gene (613609) that associate with this condition and predispose to increases in serum iron indices are overrepresented in diabetic populations, Halsall et al. (2003) determined the allele frequencies of the C282Y (613609.0001) and H63D (613609.0002) HFE mutations among a cohort of 552 patients with typical type II diabetes mellitus. There was no evidence for overrepresentation of iron-loading HFE alleles in type II diabetes mellitus, suggesting that screening for HFE mutations in this population is of no value. Meigs et al. (2008) genotyped SNPs at 18 loci associated with diabetes in 2,377 participants of the Framingham Offspring Study. They created a genotype score from the number of risk alleles and used logistic regression to generate C statistics indicating the extent to which the genotype score can discriminate the risk of diabetes when used alone and in addition to clinical risk factors. There were 255 new cases of diabetes during 28 years of follow-up. The mean (+/- standard deviation) genotype score was 17.7 +/- 2.7 among subjects in whom diabetes developed and 17.1 +/- 2.6 among those in whom diabetes did not develop (P = less than 0.001). The sex-associated odds ratio for diabetes was 1.12 per risk allele (95% confidence interval, 1.07 to 1.17). The C statistic was 0.534 without the genotype score and 0.581 with the score (P = 0.01). In a model adjusted for age, sex, family history, body mass index, fasting glucose level, systolic blood pressure, high-density lipoprotein cholesterol level, and triglyceride level, the C statistic was 0.900 without the genotype score and 0.901 with the score, not significantly different. The genotype score resulted in the appropriate risk reclassification of, at most, 4% of the subjects. Meigs et al. (2008) concluded that a genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone. Lyssenko et al. (2008) genotyped 16 SNPs and examined clinical factors in 16,061 Swedish and 2,770 Finnish subjects. Type 2 diabetes developed in 2,201 (11.7%) of these subjects during a median follow-up period of 23.5 years. Strong predictors of diabetes were a family history of the disease, increased body mass index, elevated liver enzyme levels, current smoking status, and reduced measures of insulin secretion action. Variants in 11 genes were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic (also known as C statistics) curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P = 1.0 x 10(-4)). Lyssenko et al. (2008) concluded that as compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up. Animal Model The most widely used animal model of nonobese NIDDM is the Goto-Kakizaki (GK) rat. Galli et al. (1996) mapped 3 independent loci involved in the disease. Thus, NIDDM in the rat is polygenic. The 3 NIDDM loci were found to have distinct physiologic effects. One affected postprandial but not fasting hyperglycemia, whereas the other 2 affected both. Gauguier et al. (1996) mapped up to 6 independently segregating loci predisposing to hyperglycemia, glucose intolerance, or altered insulin secretion in the GK rat. Both Galli et al. (1996) and Gauguier et al. (1996) identified a locus implicated in body weight. The close similarity between diabetes-related phenotypes in the GK rat and human NIDDM suggested to the authors that similar patterns of genetic heterogeneity may underlie the disease in humans and that the results in rats may be useful in understanding the human disease. Fakhrai-Rad et al. (2000) mapped the NIDDM1B locus in the GK rat to a 1-cM region by genetic and pathophysiologic characterization of new congenic substrains for the locus. The gene encoding insulin-degrading enzyme (IDE; 146680) was also mapped to this 1-cM region, and 2 amino acid substitutions (H18R and A890V) were identified in the GK allele which reduced insulin-degrading activity by 31% in transfected cells. However, when the H18R and A890V variants were studied separately, no effects were observed, suggesting a synergistic effect of the 2 variants on insulin degradation. No effect on insulin degradation was observed in cell lysates, suggesting that the effect may be coupled to receptor-mediated internalization of insulin. Congenic rats with the IDE GK allele displayed postprandial hyperglycemia, reduced lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake, and reduced insulin degradation in isolated muscle. Analysis of additional rat strains demonstrated that the dysfunctional IDE allele was unique to GK rats. The authors concluded that IDE plays an important role in the diabetic phenotype in GK rats. Bruning et al. (1997) created a polygenic (or at least digenic) model of NIDDM in mice. The model reproduced the characteristics of the human disease, namely insulin resistance in muscle, fat, and liver, followed by failure of pancreatic beta-cells to compensate adequately for this resistance despite increased insulin secretion. Mice doubly heterozygous for null alleles in the insulin receptor (147670) and insulin receptor substrate-1 (IRS1; 147545) genes exhibited the expected reduction by approximately 50% in expression of these 2 proteins, but a synergism at the level of insulin resistance with 5- to 50-fold elevated plasma insulin levels and comparable levels of beta-cell hyperplasia. At 4 to 6 months of age, 40% of these doubly heterozygote mice became overtly diabetic. Thus, diabetes arose in an age-dependent manner from an interaction between 2 genetically determined, subclinical defects in the insulin signaling cascade, demonstrating the role of epistatic interactions in the pathogenesis of common diseases with nonmendelian genetics. Terauchi et al. (1997) likewise created a polygenic model of NIDDM by heterozygous knockout of the IRS1 gene with heterozygous knockout of the beta-cell GCK gene. They found that the genetic abnormalities, each of which was nondiabetogenic by itself, caused overt diabetes if they coexisted. The Zucker diabetic fatty (ZDF) rat is another animal model of human adipogenic NIDDM. Shimabukuro et al. (1998) demonstrated in islets of obese ZDF rats a pathway of lipotoxicity leading to diabetes. Elevated levels of circulating free fatty acids (Lee et al., 1994) and lipoproteins transport to islets of obese ZDF rats far more free fatty acids than can be oxidized. Because fa/fa islets exhibit a markedly increased lipogenic capacity and a decreased oxidative capacity, unused free fatty acids in islets are esterified and over time an excessive quantity is deposited (Lee et al., 1997). This is associated with an increase in ceramide, inducible NOS expression, and NO production, which causes apoptosis. That troglitazone, an agent that reduces islet fat in ZDF rats (Shimabukuro et al., 1997) and prevents their diabetes (Sreenan et al., 1996), is equally efficacious in human NIDDM suggests a comparable pathway of lipotoxicity to diabetes in humans. Hart et al. (2000) showed that FGF receptors 1 and 2 (136350, 176943), together with ligands FGF1 (131220), FGF2 (134920), FGF4 (164980), FGF5 (165190), FGF7 (148180), and FGF10 (602115), are expressed in adult mouse beta cells, indicating that FGF signaling may have a role in differentiated beta cells. When Hart et al. (2000) perturbed signaling by expressing dominant-negative forms of the receptors, FGFR1C and FGFR2B, in the pancreas, they found that mice with attenuated FGFR1C signaling, but not those with reduced FGFR2B signaling, developed diabetes with age and exhibited a decreased number of beta cells, impaired expression of glucose transporter 2 (138160), and increased proinsulin content in beta cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type II diabetes. Mutations in the homeobox gene IPF1/PDX1 (600733) are linked to diabetes in both mouse and human. Hart et al. (2000) showed that IPF1/PDX1 is required for the expression of FGFR1 signaling components in beta cells, indicating that IPF1/PDX1 acts upstream of FGFR1 signaling in beta cells to maintain proper glucose sensing, insulin processing, and glucose homeostasis. Yuan et al. (2001) demonstrated that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of IKBKB (603258) attenuated insulin signaling in cultured cells, whereas IKKB inhibition reversed insulin resistance. Thus, Yuan et al. (2001) concluded that IKKB, rather than the cyclooxygenases (see 600262), appears to be the relevant molecular target. Heterozygous deletion (IKKB +/-) protected against the development of insulin resistance during high fat feeding and in obese Lep (ob/ob) (see 164160) mice. Yuan et al. (2001) concluded that their findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type II diabetes mellitus and identified the IKKB pathway as a target for insulin sensitization. Scheuner et al. (2005) studied glucose homeostasis in mice with a ser51-to-ala substitution at the phosphorylation site of the translation initiation factor eIF2-alpha (see 603907) and observed that heterozygous mutant mice became obese and diabetic on a high-fat diet. Profound glucose intolerance resulted from reduced insulin secretion accompanied by abnormal distention of the ER lumen, defective trafficking of proinsulin, and a reduced number of insulin granules in beta cells. Scheuner et al. (2005) proposed that translational control couples insulin synthesis with folding capacity to maintain ER integrity and that this signal is essential to prevent diet-induced type II diabetes. In Hmga1 (600701)-deficient mice, Foti et al. (2005) observed decreased insulin receptor expression in muscle, fat, and liver, largely impaired insulin signaling, and severely reduced insulin secretion, causing a phenotype characteristic of human type II diabetes. Matsuzaka et al. (2007) reported that Elovl6 (611546) -/- mice developed obesity and hepatosteatosis when fed a high-fat diet or when mated to leptin-deficient (ob/ob) mice, but showed marked protection from hyperinsulinemia, hyperglycemia, and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate-2 (IRS2; 600797) and suppression of hepatic protein kinase C-epsilon (PRKCE; 176975), resulting in restoration of Akt (see 164730) phosphorylation. Matsuzaka et al. (2007) noted that the Elovl6 -/- mice were unique in that their insulin resistance was reduced without the amelioration of obesity or hepatosteatosis, and concluded that hepatic fatty acid composition is a new determinant for insulin sensitivity that acts independently of cellular energy balance and stress. Misc \- Late onset Lab \- Insulin resistance \- Decreased glucose disposal Endo \- Noninsulin-dependent diabetes mellitus Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DIABETES MELLITUS, NONINSULIN-DEPENDENT	c0011860	26,235	omim	https://www.omim.org/entry/125853	2019-09-22T16:42:18	{"doid": ["9352"], "mesh": ["D003924"], "omim": ["125853"], "icd-10": ["E11"], "synonyms": ["Alternative titles", "DIABETES MELLITUS, TYPE II", "NONINSULIN-DEPENDENT DIABETES MELLITUS", "MATURITY-ONSET DIABETES"]}
Not to be confused with Sickle-cell disease. This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (September 2017) Sick cell syndrome Other namesCell sickness syndrome Sick cell syndrome is a medical condition characterised by reduced functioning of the cellular Na+/K+ pump,[1] which is responsible for maintaining the internal ion homeostasis. The clinical result is a rise in blood K+ level and drop of blood Na+ levels There are a wide range of possible pathological conditions that can cause sick cell syndrome, including: * hypoxia * sepsis * hypovolaemia * malnourishment This syndrome is well known in the field of palliative medicine as many terminal patients develop this condition. ## References[edit] 1. ^ Benito Ruiz, J; Baena Montilla, P; Navarro Monzonis, A (Aug 1990). "Sick cell syndrome in a burned patient". Burns. 16 (4): 309–12. doi:10.1016/0305-4179(90)90147-O. ISSN 0305-4179. PMID 2257076. This article about a disease of the blood or immune 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Sick cell syndrome	c3804995	26,236	wikipedia	https://en.wikipedia.org/wiki/Sick_cell_syndrome	2021-01-18T18:34:38	{"umls": ["C3804995"], "wikidata": ["Q7507600"]}
Abortion in Guam is legal but there were no abortion providers in Guam as of 2018. ## Contents * 1 Terminology * 2 History * 2.1 Abortion access * 2.2 Legislative and judicial history * 2.3 Hospital and clinic history * 3 Statistics * 4 Anti-abortion and abortion rights movements * 5 Footnotes * 6 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] ## History[edit] Abortion, also known as pokká, was first documented in Guam in the 1750s. Chamorro women sought suicide, sterilization, or abortion as they did not wish to birth a child into the "subjugation of the Spaniards".[8] Early methods utilized by Chamorro women to self-induce abortion included consuming drinks made from tree trunks, roots, and leaves.[8] ### Abortion access[edit] During the 1990s, women who needed abortions often traveled to the Philippines to get an abortion as there were no legal options on the island.[9] From 2000 to 2018, two medical providers performed the majority of abortions on Guam. However, after the last doctor providing abortion services retired in June 2018, women were left with few options for legal abortion services. Women seeking abortion may pay out-of-pocket to travel to Hawaii or Japan.[9] ### Legislative and judicial history[edit] As a United States territory, Guam is subject to federal legislation of the United States. In 1990, the Legislature of Guam enacted a law prohibiting abortion in all cases except when there was "substantial risk" to her life or that continuing the pregnancy would "gravely impair" her health. [10][9] This law was challenged by the American Civil Liberties Union and struck down by the ninth circuit court of Guam in a case called Guam Society of Obstetricians and Gynecologists v. Ada in 1997. [10][11][12] In 2012, the Woman's Reproductive Health Information Act was passed, creating new restrictions for abortion provision, including a 13-week gestational age limit, a physician-only requirement, and a 24 hour mandatory waiting period.[13][14] ### Hospital and clinic history[edit] There were no clinics or doctors providing abortion services during much of the 1990s.[9] Since the 2000s and up to 2016, there were two doctors who performed abortions in Guam. That year on November 30, Dr. Edmund Griley at the Guam PolyClinic retired and then Dr. William Freeman at the Women's Clinic retired in June 2018. This left Guam without an abortion provider.[9] Dr. Jeffrey Gabel took over the Women's Clinic in June 2018 and renamed it the Dr. Gabel's Clinic Obstetrics & Gynecology Para Famalao’an but since Gabel is pro-life, he refused to provide abortion services.[9] Guam Memorial Hospital did not openly provide abortions and refused to refer women with life-threatening conditions to other medical facilities for abortions.[9] Guam Regional Medical City also did not have any doctors willing to openly provide abortions and they did not provide referrals to doctors who provided them.[9] Department of Public Health and Social Services also refused to provide abortion referrals.[9] ## Statistics[edit] In 2017, 239 abortions were performed, and 97% of these abortions utilized surgical intervention, such as dilation and curettage or intrauterine saline infusion. All but three abortions were performed at Women's Clinic.[15] As legal abortion is no longer readily available in Guam,[9] the current rate of abortion is not known. Abortions by Type of Procedure (number of cases)[15] Method of Abortion 2017 2016 2015 Uterine curettage or evacuation 219 279 259 Intrauterine Saline Solution Infusion 13 8 3 Medication-induced 3 1 1 Feticidal injection 4 0 0 Not reported 0 1 0 Total Number of Cases 239 289 263 ## Anti-abortion and abortion rights movements[edit] The Catholic Church of Guam is active in support of abortion restrictions through participation in the Rally for Life march.[9] Guam's Governor Lou Leon Guerrero has publicly supported the recruitment of an abortion provider to Guam.[16] ## 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. ^ a b Rubinstein, Donald (1992). "Culture in court : notes and reflections on abortion in Guam". Journal de la Société des Océanistes. 94 (1): 35–44. doi:10.3406/jso.1992.2605. 9. ^ a b c d e f g h i j k "No abortion providers on Guam". Pacific Daily News. Retrieved 2019-05-29. 10. ^ 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. 11. ^ Lewin, Tamar (1990-03-21). "Guam's Abortion Law Tested By A.C.L.U. Lawyer's Speech". The New York Times. ISSN 0362-4331. Retrieved 2020-05-11. 12. ^ Lewis, Neil A.; Times, Special To the New York (1990-08-24). "Judge in Guam Rejects Strict Law on Abortion". The New York Times. ISSN 0362-4331. Retrieved 2020-05-11. 13. ^ "Guam Legal Code" (PDF). 14. ^ Center, Pacific News (2014-03-31). "DPHSS: Enforcement of "The Women's Reproductive Health Information Act " Will Begin June 2". PNC News First. Retrieved 2020-05-11. 15. ^ a b "Guam 2018 Statistical Yearbook \| Statistics for Development Division". sdd.spc.int. Retrieved 2020-05-09. 16. ^ Post, Lannie Walker \| The Guam Daily. "Inquiry into Guam abortion doctor continues". The Guam Daily Post. Retrieved 2020-05-11. 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 * t * e Abortion in Oceania Sovereign states * Australia * Federated States of Micronesia * Fiji * Kiribati * Marshall Islands * Nauru * New Zealand * Palau * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu Associated states of New Zealand * Cook Islands * Niue Dependencies and other territories * American Samoa * Christmas Island * Cocos (Keeling) Islands * Easter Island * French Polynesia * Guam * Hawaii * New Caledonia * Norfolk Island * Northern Mariana Islands * Pitcairn Islands * Tokelau * Wallis and Futuna [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Abortion in Guam	None	26,237	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Guam	2021-01-18T18:55:09	{"wikidata": ["Q64876913"]}
A number sign (#) is used with this entry because hyperparathyroidism-2 with jaw tumors, also known as hyperparathyroidism-jaw tumor syndrome, is caused by heterozygous mutation in the CDC73 gene (607393) on chromosome 1q32. Description Hyperparathyroidism-jaw tumor syndrome is a rare autosomal dominant disorder characterized by synchronous or metachronous occurrence of primary hyperparathyroidism, ossifying fibroma of the maxilla and/or mandible, renal tumor, and uterine tumors. It is associated with increased risk of parathyroid cancer (summary by Shibata et al., 2015). For a discussion of genetic heterogeneity of hyperparathyroidism, see HRPT1 (145000). Clinical Features Although the most common familial form of primary hyperparathyroidism is parathyroid hyperplasia (HRPT1; 145000), a few families have manifested parathyroid adenomas. Mallette et al. (1987) described a family in which 4 members developed cystic parathyroid adenomas. Although calcium levels returned to normal after resection of the adenoma, a second adenoma often developed several years later; thus, Mallette et al. (1987) termed the condition adenomatosis. Each adenoma had a cystic histologic appearance, and 3 of the 4 normal-sized parathyroid glands also contained many cysts. No other endocrine tumors developed, but in 3 of the patients the hyperparathyroidism was complicated by fibrous maxillary or mandibular tumors that resembled ossifying fibromas rather than the brown tumors generally found in patients with hyperparathyroidism. Each patient with an adenoma was hypercalciuric, but 2 were considered obligate carriers of hypocalciuric hypercalcemia (145980). The adenomatosis occurred in a father and 3 sons. A brother and sister of the father had hypercalciuric hypercalcemia, as did the son of 1 of the 3 sons. Jackson (1958) reported a family with hereditary hyperparathyroidism in which 4 of 5 of the affected members of the first generation had jaw tumors. Because 3 affected members of the third generation developed similar jaw tumors which progressed even after surgical correction of their hypercalcemia, the family was reinvestigated. The maxillary and mandibular tumors could be differentiated from the 'brown tumors' of hyperparathyroidism; they were histologically distinct fibroosseous lesions without giant cells. As far as is known, ossified fibrous tumors do not occur in areas other than the jaw, such as the knees or ribs which can be the site of 'brown tumors.' Parathyroid enlargement was mostly uniglandular with multiple tumors found only occasionally. Linkage studies in this and a second family with the same association demonstrated linkage to neither chromosome 11 markers (the site of the gene for MEN1; see 131100) nor markers on chromosome 10 (the site of the gene for MEN2; see 171400). (According to Jackson (1994), linkage studies in 5 families exclude the locus for this disorder, symbolized HRPT2, from the sites of MEN1 and MEN2.) Thus, hereditary hyperparathyroidism with multiple ossifying jaw fibromas may be a genetically distinct disorder. The family of Mallette et al. (1987) was included in the study of Jackson et al. (1990). Other families were reported by Kennett and Pollick (1971), Rosen and Palmer (1981), and Warnakulasuriya et al. (1985). Inoue et al. (1995) reported a 53-year-old Japanese woman diagnosed as having primary hyperparathyroidism caused by hyperplasia of the parathyroid glands and causing renal stones and hypercalcemia. One year after she underwent total parathyroidectomy and implantation of parathyroid tissue, she underwent surgery for a cementifying fibroma. A 19-year-old nephew was found to have elevated serum calcium levels and levels of serum parathyroid hormone and a parathyroid adenoma was removed at surgery. Szabo et al. (1995) found no instance of parathyroid carcinoma in their families; 1 case of this malignancy had been reported by Dinnen et al. (1977). The occurrence of Wilms tumor in 2 female members of unrelated families in their study raised the possibility that Wilms tumor may be a component of the HPT-JT syndrome. Further evidence that parathyroid carcinoma and Wilms tumor are part of the HPT-JT syndrome came from a report by Kakinuma et al. (1994) in which one sib had parathyroid carcinoma, a second had parathyroid adenoma plus Wilms tumor, and a third had parathyroid adenoma plus jaw tumor. Szabo et al. (1995) studied 6 hereditary Wilms tumor families, including 29 affected members, and found no linkage to 1q markers closely linked with HRPT2. Furthermore, 9 parathyroid adenomas and one Wilms tumor from 9 members of 3 HPT-JT families showed no loss of heterozygosity at the HRPT2-linked loci. Teh et al. (1996) reported 2 families with HPT-JT syndrome in which adult renal hamartomas or cystic kidney disease were prominent associated features, possibly representing a new phenotypic variant of the HPT-JT syndrome. In the first family, renal lesions were present in 5 of 6 affected individuals, whereas HPT and jaw tumors (JT) were seen in 4 and 2 cases, respectively. In the second family, JT was found in 3 of the 5 affected individuals, and 2 affected members also exhibited polycystic kidney disease. The possibility of the latter cosegregating as a separate autosomal dominant gene can not be ruled out. A sex-dependent penetrance of primary HPT, resulting in predominantly male-affected cases was evident in the 2 families. Pidwirny et al. (1995) found that the proband in the Canadian family reported by Kennett and Pollick (1971) had died of parathyroid carcinoma, that the family was a branch of a kindred reported by Rosen and Palmer (1981), and that a member of the second branch had also died of parathyroid cancer. This and other experiences established parathyroid cancer as part of the hyperparathyroidism-jaw tumor syndrome occurring in at least 1 patient in 5 (42%) of the 12 known families. Fujikawa et al. (1998) described 2 sisters and a brother, young adults, with hyperparathyroidism due to multiple parathyroid adenomas without evidence of other endocrinologic abnormalities. A 22-year-old woman had 2 parathyroid adenomas complicated by multiple ossifying jaw fibromas. Her sister, aged 29, also suffered from primary hyperparathyroidism associated with 2 parathyroid adenomas, 1 of which was also suspected to be a carcinoma. These 2 woman had unusual multiple small uterine polyps, which were diagnosed as adenomyomatous polyps. Their brother, aged 17, had 2 parathyroid adenomas complicated by urolithiasis. Fujikawa et al. (1998) tabulated the findings in previously reported families. The tabulation indicated that parathyroid lesions tend to be malignant in familial idiopathic hyperparathyroidism. Mapping Szabo et al. (1995) performed genetic linkage studies in 5 families containing a total of 20 individuals with the hereditary hyperparathyroidism-jaw tumor syndrome. They mapped the HRPT2 locus to 1q21-q31 and found a maximum lod score of 6.10 at theta = 0.0 with marker D1S212. Teh et al. (1996) determined that the disease in their 2 kindreds was linked to 5 markers in the 1q21-q32 region (lod scores: 3.2-4.2), whereas linkage to the MEN1 and MEN2 regions was excluded. Meiotic recombinations detected in affected individuals placed the locus telomeric of D1S215, thus narrowing the HRPT2 region from over 60 to approximately 34 cM. Loss of heterozygosity (LOH) was studied in 7 renal hamartomas from 2 affected individuals in the first family, as well as in a jaw tumor and a parathyroid tumor from the second family. All renal hamartomas showed LOH in the 1q21-q32 region. All losses involved the wildtype allele derived from the unaffected parent, suggesting the inactivation of a tumor suppressor gene in this region. Hobbs et al. (1999) studied 2 HPT-JT families identified through the literature. These 2 expanded families and 2 previously reported families were investigated jointly for linkage with 21 new, closely linked markers. Multipoint linkage analysis resulted in a maximum lod score of 7.83 at a recombination fraction of 0.0 for markers D1S2848-D1S191. Recombination events in these families reduced the HRPT2 region to approximately 14.7 cM. In addition, 2 of the 4 families shared a 2.2-cM segment of their affected haplotype, indicating a possible common origin. Combining the linkage data and shared-haplotype data, Hobbs et al. (1999) proposed a 0.7-cM candidate region for HRPT2. Haven et al. (2000) reported a large Dutch kindred in which 13 affected members presented with either parathyroid adenoma or carcinoma; in 5 affected individuals, cystic kidney disease was found. Additionally, pancreatic adenocarcinoma, renal cortical adenoma, papillary renal cell carcinoma, testicular mixed germ cell tumor with major seminoma component, and Hurthle cell thyroid adenoma were also identified. Linkage analysis of the family using MEN1-linked microsatellite markers and mutation analysis excluded the involvement of the MEN1 gene. Using markers from the HPT-JT region in 1q25-q31, cosegregation with the disease was found, with a maximum lod score of 2.41 obtained for 6 markers using the most conservative calculation. Meiotic telomeric recombination between D1S413 and D1S477 was identified in 3 affected individuals, and when combined with previous reports, delineated the HPT-JT region to 14 cM. Carpten et al. (2002) further refined the HRPT2 region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Molecular Genetics Using a positional candidate approach, Carpten et al. (2002) identified a single gene, which they called HPRT2, in which 13 different heterozygous, germline, and activating mutations were found in 14 families with HPT-JT. The proposed role of this gene, CDC73 (607393), as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified 3 somatic inactivating mutations, all located in exon 1. None of these mutations was detected in normal controls, and all were predicted to cause deficient or impaired protein function. INHERITANCE \- Autosomal dominant ABDOMEN Pancreas \- Recurring pancreatitis GENITOURINARY Kidneys \- Renal stones \- Renal hamartomas \- Polycystic kidney disease \- Degenerative cysts SKELETAL Skull \- Multiple ossifying fibromas of the mandible and maxilla ENDOCRINE FEATURES \- Hyperparathyroidism \- Solitary parathyroid adenomas (rarely multiple) NEOPLASIA \- Parathyroid carcinomas \- Wilms tumor \- Pancreatic adenocarcinoma \- Renal cortical adenoma \- Papillary renal cell carcinoma \- Hurthle cell thyroid adenoma LABORATORY ABNORMALITIES \- Hypercalcemia MOLECULAR BASIS \- Caused by mutation in the cell division cycle 73 gene (CDC73, 607393.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPERPARATHYROIDISM 2 WITH JAW TUMORS	c1704981	26,238	omim	https://www.omim.org/entry/145001	2019-09-22T16:39:54	{"doid": ["13543"], "mesh": ["C563273"], "omim": ["145001"], "orphanet": ["99880"], "synonyms": ["Alternative titles", "HYPERPARATHYROIDISM, FAMILIAL PRIMARY, WITH MULTIPLE OSSIFYING JAW FIBROMAS", "HYPERPARATHYROIDISM-JAW TUMOR SYNDROME, HEREDITARY"], "genereviews": ["NBK1294", "NBK3789"]}
Xq12-q13.3 duplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome X, characterized by global developmental delay, autistic behavior, microcephaly and facial dysmorphism (including down-slanting palpebral fissures, depressed nasal bridge, anteverted nares, long philtrum, down-slanting corners of the mouth). Seizures have also been reported in some 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Xq12-q13.3 duplication syndrome	c4707094	26,239	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314389	2021-01-23T17:45:30	{"icd-10": ["Q99.8"], "synonyms": ["Dup(X)(q12-q13.3)"]}
-spermia, Further information: Testicular infertility factors * view * talk * edit Aspermia —lack of semen; anejaculation Asthenozoospermia —sperm motility below lower reference limit Azoospermia —absence of sperm in the ejaculate Hyperspermia —semen volume above higher reference limit Hypospermia —semen volume below lower reference limit Oligozoospermia —total sperm count below lower reference limit Necrozoospermia—absence of living sperm in the ejaculate Teratozoospermia —percent normal forms below lower reference limit Asthenozoospermia (or asthenospermia) is the medical term for reduced sperm motility. Complete asthenozoospermia, that is, 100% immotile spermatozoa in the ejaculate, is reported at a frequency of 1 of 5000 men.[1] Causes of complete asthenozoospermia include metabolic deficiencies, ultrastructural abnormalities of the sperm flagellum (see Primary ciliary dyskinesia) and necrozoospermia.[1] It decreases the sperm quality and is therefore one of the major causes of infertility or reduced fertility in men. A method to increase the chance of pregnancy is ICSI.[1] The percentage of viable spermatozoa in complete asthenozoospermia varies between 0 and 100%.[1] ## Contents * 1 DNA fragmentation * 2 Asthenozoospermia and DHA * 3 References * 4 External links ## DNA fragmentation[edit] Sperm DNA fragmentation level is higher in men with sperm motility defects (asthenozoospermia) than in men with oligozoospermia or teratozoospermia.[2] Among men with asthenozoospermia, 31% were found to have high levels of DNA fragmentation. As reviewed by Wright et al.,[3] high levels of DNA fragmentation have been shown to be a robust indicator of male infertility. ## Asthenozoospermia and DHA[edit] In 2015, Eslamian et al. found a correlation between the composition of the sperm lipid membrane and the odds of having asthenozoospermia. The sperm that have more polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) shown better fertility results. DHA (docosahexaenoic acid) is an acid form by six double bons which allows the fluidity of the membrane, necessary to the fusion with the ovule. Studies in mice have shown that DHA is essential for acrosome reaction and a DHA deficiency results in abnormal sperm morphology, loss of motility and infertility; which can be restored by dietary DHA supplementation. Furthermore, the supplementation with DHA in human has been reported to increase sperm motility. But also, DHA supplement can protect spermatozoa against the damage caused by the cryopresevation process. ## References[edit] 1. ^ a b c d Ortega, C.; Verheyen, G.; Raick, D.; Camus, M.; Devroey, P.; Tournaye, H. (2011). "Absolute asthenozoospermia and ICSI: What are the options?". Human Reproduction Update. 17 (5): 684–692. doi:10.1093/humupd/dmr018. PMID 21816768. 2. ^ Belloc S, Benkhalifa M, Cohen-Bacrie M, Dalleac A, Chahine H, Amar E, Zini A (2014). "Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation". J. Assist. Reprod. Genet. 31 (5): 527–32. doi:10.1007/s10815-014-0194-3. PMC 4016368. PMID 24566945. 3. ^ Wright C, Milne S, Leeson H (2014). "Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility". Reprod. Biomed. Online. 28 (6): 684–703. doi:10.1016/j.rbmo.2014.02.004. PMID 24745838. * González-Ravina Cristina, Aguirre-Lipperheide Mercedes, Pinto Francisco, Martín-Lozano David, Fernández-Sánchez Manuel, Blasco Víctor, Santamaría-López Esther, Candenas Luz (2018). "Effect of dietary supplementation with a highly pure and concentrated docosahexaenoic acid (DHA) supplement on human sperm function". Reproductive Biology. 18 (3): 282–288. doi:10.1016/j.repbio.2018.06.002. hdl:10261/172000. PMID 29934046.CS1 maint: multiple names: authors list (link) * González-Ravina, Cristina; Aguirre-Lipperheide, Mercedes; Pinto, Francisco; Martín-Lozano, David; Fernández-Sánchez, Manuel; Blasco, Víctor; Santamaría-López, Esther; Candenas, Luz (2018). "Effect of dietary supplementation with a highly pure and concentrated docosahexaenoic acid (DHA) supplement on human sperm function" (PDF). Reproductive Biology. 18 (3): 282–288. doi:10.1016/j.repbio.2018.06.002. hdl:10261/172000. PMID 29934046. ## External links[edit] * GP Notebook * Fertility network * v * t * e Male diseases of the pelvis and genitals Internal Testicular * Orchitis * Hydrocele testis * Testicular cancer * Testicular torsion * Male infertility * Aspermia * Asthenozoospermia * Azoospermia * Hyperspermia * Hypospermia * Oligospermia * Necrospermia * Teratospermia Epididymis * Epididymitis * Spermatocele * Hematocele Prostate * Prostatitis * Acute prostatitis * Chronic bacterial prostatitis * Chronic prostatitis/chronic pelvic pain syndrome * Asymptomatic inflammatory prostatitis * Benign prostatic hyperplasia * Prostate cancer Seminal vesicle * Seminal vesiculitis External Penis * Balanoposthitis / Balanitis * Balanitis plasmacellularis * Pseudoepitheliomatous keratotic and micaceous balanitis * Phimosis * Paraphimosis * Priapism * Sexual dysfunction * Erectile dysfunction * Peyronie's disease * Penile cancer * Penile fracture * Balanitis xerotica obliterans Other * Hematospermia * Retrograde ejaculation * Postorgasmic illness syndrome This article related to the genitourinary 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Asthenozoospermia	c3810501	26,240	wikipedia	https://en.wikipedia.org/wiki/Asthenozoospermia	2021-01-18T18:35:09	{"mesh": ["D053627"], "umls": ["C3810501", "C0403823"], "orphanet": ["276234"], "wikidata": ["Q2329041"]}
Adenovirus infection SpecialtyInfectious disease, pediatrics Adenovirus infections most commonly cause illness of the respiratory system; however, depending on the infecting serotype, they may also cause various other illnesses and presentations. ## Contents * 1 Presentations * 1.1 Pharyngoconjunctival fever * 1.2 Adenoviral urethritis * 2 Serotype-specific features * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 References * 8 External links ## Presentations[edit] Apart from respiratory involvement, illnesses and presentations of adenovirus include gastroenteritis,[1] conjunctivitis, cystitis, and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis. Patients with compromised immune systems are especially susceptible to severe complications of adenovirus infection. Acute respiratory disease (ARD), first recognized among military recruits during World War II, can be caused by adenovirus infections during conditions of crowding and stress.[citation needed] ### Pharyngoconjunctival fever[edit] Pharyngoconjunctival fever is a specific presentation of adenovirus infection, manifested as: * high fever that lasts 4–5 days * pharyngitis (sore throat) * conjunctivitis (inflamed eyes, usually without pus formation like pink eye) * enlargement of the lymph nodes of the neck * headache, malaise, and weakness * Incubation period of 5–9 days It usually occurs in the age group 5–18. It is often found in summer camps and during the spring and fall in schools. In Japan, the illness is commonly referred to as "pool fever" as it is often spread via public swimming pools. ### Adenoviral urethritis[edit] Adenovirus infections can occur in the urethra of men.[2][3] This is adenoviral urethritis, and it is classified as a type of non-gonococcal urethritis (NGU). Symptoms of adenoviral urethritis are similar to urethritis of other causes, and can include: * pain during sex or urination * unusual discharge from the penis * inflammation of the urinary meatus * Other non-gonococcal urethritis symptoms ## Serotype-specific features[edit] Although epidemiologic characteristics of the adenoviruses vary by type, all are transmitted by direct contact, fecal-oral transmission, and occasionally waterborne transmission. Some types are capable of establishing persistent asymptomatic infections in tonsils, adenoids, and intestines of infected hosts, and shedding can occur for months or years. Some adenoviruses (e.g., serotypes 1, 2, 5, and 6) have been shown to be endemic in parts of the world where they have been studied, and infection is usually acquired during childhood. Other types cause sporadic infection and occasional outbreaks; for example, epidemic keratoconjunctivitis is associated with adenovirus serotypes 8, 19, and 37. Epidemics of febrile disease with conjunctivitis are associated with waterborne transmission of some adenovirus types, often centering on inadequately chlorinated swimming pools and small lakes. ARD is most often associated with adenovirus types 4 and 7 in the United States. Enteric adenoviruses 40 and 41 cause gastroenteritis, usually in children. For some adenovirus serotypes, the clinical spectrum of disease associated with infection varies depending on the site of infection; for example, infection with adenovirus 7 acquired by inhalation is associated with severe lower respiratory tract disease, whereas oral transmission of the virus typically causes no or mild disease. Outbreaks of adenovirus-associated respiratory disease have been more common in the late winter, spring, and early summer; however, adenovirus infections can occur throughout the year.[4] "Ad14 (for adenovirus serotype 14), has caused at least 140 illnesses in New York, Oregon, Texas and Washington, according to a report from the Centers for Disease Control and Prevention. The illness made headlines in Texas in September 2007, when a so-called "boot camp flu" sickened hundreds at Lackland Air Force Base in San Antonio. A 19-year-old trainee died."[5] Several adenoviruses, including Ad5, Ad9, Ad31, Ad36, Ad37, and SMAM1, have at least some evidence of causation of obesity in animals, adipogenesis in cells, and/or association with human obesity.[6] To date, the most thorough investigations have been conducted for adenovirus serotype 36 (Adv36).[6][7][8] ## Diagnosis[edit] Antigen detection, polymerase chain reaction assay, virus isolation, and serology can be used to identify adenovirus infections. Adenovirus typing is usually accomplished by hemagglutination-inhibition and/or neutralization with type-specific antisera. Since adenovirus can be excreted for prolonged periods, the presence of virus does not necessarily mean it is associated with disease. ## Prevention[edit] See also: Adenovirus vaccine Safe and effective adenovirus vaccines were developed for adenovirus serotypes 4 and 7, but were available only for preventing ARD among US military recruits.[9] Production stopped in 1996[10] and was restarted in 2011. Strict attention to good infection-control practices is effective for stopping transmission in hospitals of adenovirus-associated disease, such as epidemic keratoconjunctivitis. Maintaining adequate levels of chlorination is necessary for preventing swimming pool-associated outbreaks of adenovirus conjunctivitis.[citation needed] ## Treatment[edit] Most infections are mild and require no therapy or only symptomatic treatment. Because there is no virus-specific therapy, serious adenovirus illness can be managed only by treating symptoms and complications of the infection. Deaths are exceedingly rare but have been reported.[11] ## Prognosis[edit] Adenovirus can cause severe necrotizing pneumonia in which all or part of a lung has increased translucency radiographically, which is called Swyer-James Syndrome.[12] Severe adenovirus pneumonia also may result in bronchiolitis obliterans, a subacute inflammatory process in which the small airways are replaced by scar tissue, resulting in a reduction in lung volume and lung compliance.[12] ## References[edit] 1. ^ Wadell G.; et al. (1987). Whelan, Julie; Bock, Gregory (eds.). Novel diarrhoea viruses. New York: Wiley. p. 63. ISBN 978-0-471-91094-7. 2. ^ Bradshaw, C; Denham, I; Fairley, C (December 2002). "Characteristics of adenovirus associated urethritis". Sexually Transmitted Infections. 78 (6): 445–447. doi:10.1136/sti.78.6.445. ISSN 1368-4973. PMC 1758335. PMID 12473808. 3. ^ O'Mahony, C. (March 2006). "Adenoviral non-gonococcal urethritis". International Journal of STD & AIDS. 17 (3): 203–204. doi:10.1258/095646206775809312. ISSN 0956-4624. PMID 16510012. S2CID 34184831. 4. ^ This article incorporates public domain material from the United States Government document: "https://www.cdc.gov/ncidod/dvrd/revb/respiratory/eadfeat.htm". "Archived copy". Archived from the original on July 3, 2007. Retrieved 2007-07-03.CS1 maint: archived copy as title (link) 5. ^ nytimes article New Form of Virus Has Caused 10 Deaths in 18 Months published November 16, 2007 6. ^ a b Voss, Jameson D.; Atkinson, Richard L.; Dhurandhar, Nikhil V. (1 November 2015). "Role of adenoviruses in obesity". Rev. Med. Virol. 25 (6): 379–387. doi:10.1002/rmv.1852. PMID 26352001. 7. ^ "Academic Journals formerly published by NPG". Retrieved 28 December 2016. 8. ^ Dhurandhar, Nikhil V.; Whigham, Leah D.; Abbott, David H.; Schultz-Darken, Nancy J.; Israel, Barbara A.; Bradley, Steven M.; Kemnitz, Joseph W.; Allison, David B.; Atkinson, Richard L. (1 October 2002). "Human Adenovirus Ad-36 Promotes Weight Gain in Male Rhesus and Marmoset Monkeys". J. Nutr. 132 (10): 3155–3160. doi:10.1093/jn/131.10.3155. PMID 12368411. 9. ^ Gray GC. (2006). "Adenovirus transmission—worthy of our attention". J Infect Dis. 194 (7): 871–3. doi:10.1086/507435. PMC 1673215. PMID 16960772. 10. ^ Gray GC, Goswami PR, Malasig MD, et al. (2000). "Adult adenovirus infections: loss of orphaned vaccines precipitates military respiratory disease epidemics". Clin Infect Dis. 31 (3): 663–70. doi:10.1086/313999. PMID 11017812. 11. ^ Centers for Disease Control and Prevention (2001). "Two fatal cases of adenovirus-related illness in previously healthy young adults—Illinois, 2000". MMWR Morb Mortal Wkly Rep. 50 (26): 553–5. PMID 11456329. 12. ^ a b Kliegman, Robert; Richard M Kliegman (2006). Nelson essentials of pediatrics. St. Louis, Mo: Elsevier Saunders. ISBN 978-0-8089-2325-1. ## External links[edit] * Centers for Disease Control and Prevention--National Center for Infectious Diseases—Division of Viral and Rickettsial Diseases, Respiratory and Enteric Viruses Branch Classification D * ICD-10: B97.0 * MeSH: D000257 * v * t * e Infectious diseases – viral systemic diseases Oncovirus DNA virus HBV Hepatocellular carcinoma HPV Cervical cancer Anal cancer Penile cancer Vulvar cancer Vaginal cancer Oropharyngeal cancer KSHV Kaposi's sarcoma EBV Nasopharyngeal carcinoma Burkitt's lymphoma Hodgkin lymphoma Follicular dendritic cell sarcoma Extranodal NK/T-cell lymphoma, nasal type MCPyV Merkel-cell carcinoma RNA virus HCV Hepatocellular carcinoma Splenic marginal zone lymphoma HTLV-I Adult T-cell leukemia/lymphoma Immune disorders * HIV * AIDS Central nervous system Encephalitis/ meningitis DNA virus Human polyomavirus 2 Progressive multifocal leukoencephalopathy RNA virus MeV Subacute sclerosing panencephalitis LCV Lymphocytic choriomeningitis Arbovirus encephalitis Orthomyxoviridae (probable) Encephalitis lethargica RV Rabies Chandipura vesiculovirus Herpesviral meningitis Ramsay Hunt syndrome type 2 Myelitis * Poliovirus * Poliomyelitis * Post-polio syndrome * HTLV-I * Tropical spastic paraparesis Eye * Cytomegalovirus * Cytomegalovirus retinitis * HSV * Herpes of the eye Cardiovascular * CBV * Pericarditis * Myocarditis Respiratory system/ acute viral nasopharyngitis/ viral pneumonia DNA virus * Epstein–Barr virus * EBV infection/Infectious mononucleosis * Cytomegalovirus RNA virus * IV: Human coronavirus 229E/NL63/HKU1/OC43 * Common cold * MERS coronavirus * Middle East respiratory syndrome * SARS coronavirus * Severe acute respiratory syndrome * SARS coronavirus 2 * Coronavirus disease 2019 * V, Orthomyxoviridae: Influenza virus A/B/C/D * Influenza/Avian influenza * V, Paramyxoviridae: Human parainfluenza viruses * Parainfluenza * Human orthopneumovirus * hMPV Human digestive system Pharynx/Esophagus * MuV * Mumps * Cytomegalovirus * Cytomegalovirus esophagitis Gastroenteritis/ diarrhea DNA virus Adenovirus Adenovirus infection RNA virus Rotavirus Norovirus Astrovirus Coronavirus Hepatitis DNA virus HBV (B) RNA virus CBV HAV (A) HCV (C) HDV (D) HEV (E) HGV (G) Pancreatitis * CBV Urogenital * BK virus * MuV * Mumps [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Adenovirus infection	c0001487	26,241	wikipedia	https://en.wikipedia.org/wiki/Adenovirus_infection	2021-01-18T18:53:31	{"mesh": ["D000258"], "icd-10": ["B97.0"], "wikidata": ["Q837054"]}
Blind point of human eye For other uses, see Blind spot (disambiguation). 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: "Blind spot" vision – news · newspapers · books · scholar · JSTOR (November 2011) (Learn how and when to remove this template message) Vertebrate Octopus In vertebrate eyes, the nerve fibers route before the retina, blocking some light and creating a blind spot where the fibers pass through the retina and out of the eye. In octopus eyes, the nerve fibers route behind the retina, and do not block light or disrupt the retina. In the example, 4 denotes the vertebrate blind spot, which is notably absent in the octopus eye. In both images, 1 denotes the retina and 2 the nerve fibers, including the optic nerve (3). Distribution of rods and cones along a line passing through the fovea and the blind spot of a human eye[1] A blind spot, scotoma, is an obscuration of the visual field. A particular blind spot known as the physiological blind spot, "blind point", or punctum caecum in medical literature, is the place in the visual field that corresponds to the lack of light-detecting photoreceptor cells on the optic disc of the retina where the optic nerve passes through the optic disc.[2] Because there are no cells to detect light on the optic disc, the corresponding part of the field of vision is invisible. Some process in our brains interpolates the blind spot based on surrounding detail and information from the other eye, so we do not normally perceive the blind spot. Although all vertebrates have this blind spot, cephalopod eyes, which are only superficially similar, do not. In them, the optic nerve approaches the receptors from behind, so it does not create a break in the retina. The first documented observation of the phenomenon was in the 1660s by Edme Mariotte in France. At the time it was generally thought that the point at which the optic nerve entered the eye should actually be the most sensitive portion of the retina; however, Mariotte's discovery disproved this theory. The blind spot is located about 12–15° temporally and 1.5° below the horizontal and is roughly 7.5° high and 5.5° wide.[3] ## Contents * 1 Blind spot test * 2 See also * 3 References * 4 External links ## Blind spot test[edit] Demonstration of the blind spot R L Instructions: Close one eye and focus the other on the appropriate letter (R for right or L for left). Place your eye a distance from the screen approximately equal to three times the distance between the R and the L. Move your eye towards or away from the screen until you notice the other letter disappear. For example, close your right eye, look at the "L" with your left eye, and the "R" will disappear. ## See also[edit] * Bias blind spot * Filling-in * Horizontal eccentricity ## References[edit] 1. ^ Brian A. Wandell (1 January 1995). Foundations of Vision. Sinauer Associates. ISBN 978-0-87893-853-7. 2. ^ Gregory, R., & Cavanagh, P. (2011). "The Blind Spot". Scholarpedia. Retrieved on 2011-05-21. 3. ^ MIL-STD-1472F, Military Standard, Human Engineering, Design Criteria For Military Systems, Equipment, And Facilities (23 Aug 1999) PDF ## External links[edit] * "Amsler Grid" Test from Ossibus Software * Blind spots * Blind spot map tool * v * t * e Phenomena of the visual system Entoptic phenomena * Blind spot * Phosphene * Floater * Afterimage * Haidinger's brush * Prisoner's cinema * Blue field entoptic phenomenon * Purkinje images Other phenomena * Aura * Form constant * Scintillating scotoma * Palinopsia * Visual snow * Afterimage on empty shape * Cosmic ray visual phenomena * Scotopic sensitivity syndrome * Closed-eye hallucination [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Blind spot (vision)	None	26,242	wikipedia	https://en.wikipedia.org/wiki/Blind_spot_(vision)	2021-01-18T19:05:43	{"wikidata": ["Q371090"]}
Lichen planus (LP) is a common inflammatory dermatosis characterized by the development of pruritic violaceous papules or plaques on mucocutaneous surfaces. Eruptions can involve the face, neck, limbs, back, genitalia, tongue, buccal mucosa, nails, and scalp. LP comprises rare variants affecting the skin and the mucosa. Rare cutaneous LP includes linear LP (referring to blaschkoid and zosteriform distributions of lichenoid lesions), actinic LP, annular LP, atrophic LP, annular atrophic LP, lichen planopilaris (comprising Graham Little-Piccardi-Lassueur syndrome and frontal fibrosing alopecia), lichen planus pigmentosus, and lichen planus pemphigoides (see these terms). Rare mucosal LP includes vulvovaginal gingival syndrome and LP sialadenitis (see these terms). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Rare lichen planus	c0023646	26,243	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254367	2021-01-23T17:32:28	{"gard": ["12344"], "mesh": ["D008010"], "umls": ["C0023646"], "icd-10": ["L43.0", "L43.1", "L43.2", "L43.3", "L43.8", "L43.9", "L66.1"], "synonyms": ["Rare LP"]}
Maternal uniparental disomy of chromosome 4 is an uniparental disomy of maternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only mother is a carrier. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Maternal uniparental disomy of chromosome 4	c4707719	26,244	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96180	2021-01-23T18:01:38	{"icd-10": ["Q99.8"], "synonyms": ["UPD(4)mat"]}
## Summary ### Clinical characteristics. Usher syndrome type I (USH1) is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa (RP). Unless fitted with a cochlear implant, individuals do not typically develop speech. RP, a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity. ### Diagnosis/testing. The diagnosis of USH1 is established in a proband using electrophysiologic and subjective tests of hearing and retinal function. Identification of biallelic pathogenic variants in one of six genes – MYO7A, USH1C, CDH23, PCDH15, USH1G, and CIB2 – establishes the diagnosis if clinical features are inconclusive. Possible digenic inheritance has been reported in a few families. ### Management. Treatment of manifestations: In infants: an initial trial of hearing aids to stimulate residual hearing and accustom the infant to auditory stimulation. Cochlear implantation should be considered as young as medically feasible. Sign language and tactile signs (once visual loss occurs) for families who choose non-auditory communication. Specialized training from educators of the hearing impaired. Vestibular compensation therapy for children with residual balance function and sensory substitution therapy for individuals with complete absence of vestibular function. Standard treatments for retinitis pigmentosa. Surveillance: Annual audiometry and tympanometry in those with cochlear implant or hearing aids to assure adequate auditory stimulation. Annual otoscopic exam with tympanometry in children with profound loss to evaluate for chronic otitis media. Annual ophthalmologic evaluation, fundus photography, visual acuity, visual field testing, electroretinography, optical coherence tomography, and fundus autofluorescence from age 20 years. Agents/circumstances to avoid: Competition in sports requiring acute vision and/or good balance may be difficult and possibly dangerous. Because of the high risk for disorientation when submerged in water, swimming needs to be undertaken with caution. Progressive loss of peripheral vision impairs the ability to safely drive a car. Evaluation of relatives at risk: The hearing of at-risk sibs should be assessed as soon after birth as possible to allow early diagnosis and treatment of hearing loss. ### Genetic counseling. USH1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the USH1-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal diagnosis for a pregnancy at increased risk, and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings Usher syndrome type I (USH1) should be suspected in individuals with: * Congenital (i.e., prelingual) severe-to-profound bilateral sensorineural hearing loss (see Hereditary Hearing Loss and Deafness Overview); * No significant or delayed vestibular responses; * Retinitis pigmentosa (RP); * Normal general health and intellect and otherwise normal physical examination; * A family history consistent with autosomal recessive inheritance. ### Establishing the Diagnosis The diagnosis of USH1 is established in a proband with the above clinical features and family history. Identification of biallelic pathogenic variants in one of the genes listed in Table 1 establishes the diagnosis if clinical features are inconclusive. The phenotype of USH1 is often indistinguishable from many other inherited disorders associated with hearing loss and/or RP; therefore, the recommended molecular genetic testing approaches include use of a multigene panel or comprehensive genomic testing. Note: Single-gene testing is rarely useful and typically NOT recommended. An Usher syndrome multigene panel or a more comprehensive multigene panel (e.g., inherited retinal dystrophy panel, hereditary hearing loss panel) that includes the genes listed in Table 1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. 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 Usher Syndrome Type I (USH1) View in own window Gene 1USH1 SubtypeProportion of USH1 Attributed to Pathogenic Variants 2 in Gene 3Proportion of Pathogenic Variants 2 Detected by Method Sequence analysis 4Gene-targeted deletion/ duplication analysis 5 MYO7AUSH1B53%-70%~98% 6<2% 7 USH1CUSH1C6%-15% 8>98%2 reported 9, 10 CDH23USH1D10%-20%~85% 11<15% 12 PCDH15USH1F7%-12% 13~75%~25% 14, 15 USH1GUSH1GRare (0%-4%)>85%2 reported 15 CIB2USH1JUnknown1 reported 16None reported 16 Unknown 1710%-15% 18NA 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\. Jouret et al [2019] 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice-site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR multiplex, ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Maubaret et al [2005], Jaijo et al [2007], Bonnet et al [2011], Roux et al [2011], Le Quesne Stabej et al [2012] 7\. The majority of reported pathogenic variants are detectable by sequence analysis; however, intragenic multiexon deletions have been reported [Adato et al 1997, Baux et al 2008, Roux et al 2011, Bonnet et al 2016]. 8\. Almost all Usher syndrome type I in the Acadian population is caused by USH1C pathogenic variants. Five pathogenic variants in USH1C have been identified in 53 Acadian individuals with USH1 from Louisiana and Canada [Lentz et al, ongoing Natural History Study, unpublished]. Of these, c.216G>A is the most common variant (95/106 alleles, 90%), followed by c.238dupC (6/106 alleles, 6%). 9\. Sun et al [2018] 10\. Homozygous 11p15-p14 deletion syndrome (see Genetically Related Disorders) is caused by a contiguous gene deletion that includes USH1C and ABCC8 and has been observed in families from Saudi Arabia and Kuwait [Bitner-Glindzicz et al 2000, Al Mutair et al 2013]. 11\. Bonnet et al [2011], Roux et al [2011], Le Quesne Stabej et al [2012] 12\. The majority of reported pathogenic variants are detectable by sequence analysis; however, intragenic deletions and duplications have been reported [Nakanishi et al 2010, Roux et al 2011, Aparisi et al 2014, Bonnet et al 2016]. 13\. p.Arg245Ter (c.733C>T) is detected in a large percentage of Ashkenazi Jewish individuals with PCDH15-Usher syndrome type I. 14\. Roux et al [2011] 15\. Bonnet et al [2016] 16\. Riazuddin et al [2012]. Note: Booth et al [2018] suggest that CIB2 pathogenic variants cause DFNB48 and not USH1J. 17\. USH1E has been mapped to 21q21; USH1H has been mapped to 15q22-q23 [Ahmed et al 2009]; USH1K has been mapped to 10p11.21-q21.1 [Jaworek et al 2012]. 18\. Bonnet et al [2011], Roux et al [2011], Le Quesne Stabej et al [2012], Yoshimura et al [2014], and personal communication with Kerry Goetz at eyeGENE. ## Clinical Characteristics ### Clinical Description Hearing loss. The hearing loss in Usher syndrome type I (USH1) is congenital (i.e., present at birth), bilateral, severe-to-profound sensorineural hearing impairment (SNHI). While congenital SNHI should be identified through universal hearing screening at birth, occasionally false negative screening or missed screening before discharge to home results in delayed diagnosis until speech delay is obvious. Affected individuals do not develop speech unless fitted with cochlear implants. Hearing aids are usually inadequate in individuals with USH1 because of the severity of the hearing loss. Alternatively, sign language and tactile signs (once visual loss occurs) are communication options for families who choose nonauditory communication. Imbalance. The imbalance in individuals with USH1 is associated with the deafness and is a defining feature of this disorder. While the timing and extent of "vestibular areflexia" is not fully understood, children with USH1 typically walk later than usual, at approximately age 18 months to two years. Older children may seem "clumsy" and experience frequent accidental injuries or have difficulty with activities requiring balance, such as riding a bicycle or playing sports. Visual loss. Children with USH1 are often misdiagnosed as having nonsyndromic hearing impairment until delayed walking or tunnel vision and night blindness – early signs of retinitis pigmentosa (RP) – become severe enough to be noticeable, either by parents and teachers or by the individual. The onset of RP in individuals with USH1 is variable but can start in early infancy or childhood. RP is progressive, bilateral, symmetric photoreceptor degeneration of the retina that initiates in the midperiphery; rods (photoreceptors active in the dark-adapted state) are mainly affected first, causing night blindness and constricted visual fields (tunnel vision). Cones (photoreceptors active in the light-adapted state) are affected second and eventually die, resulting in central blindness. Contrast sensitivities, color vision, and mobility may become severely affected as the retinal degeneration progresses. Visual fields become progressively constricted with time. The rate and degree of visual field loss show intra- and interfamilial variability. A visual field of 5-10 degrees ("severe tunnel") is common for a person with USH1 age 30-40 years. Visual impairment worsens significantly each year [Pennings et al 2004]. Individuals with USH1 may become completely blind. Cataracts and/or cystoid macular edema sometimes reduce central vision. These two associated conditions are treatable. Heterozygotes. Heterozygotes are asymptomatic. ### Genotype-Phenotype Correlations A genotype-phenotype correlation has been reported for pathogenic variants in the genes associated with USH1. Homozygous null (e.g., nonsense, frameshift, splicing) variants are associated with USH1, whereas homozygous missense variants that generate partially functional proteins typically cause nonsyndromic hearing impairment or atypical Usher syndrome. This genotype-phenotype correlation suggests that deaf children found to be homozygous for hypomorphic variants in an USH1 gene are unlikely to develop vision loss. USH1C * c.1220delG. Audiometric screening of ten individuals of Yemenite Jewish ancestry revealed that individuals younger than age 40 years had normal hearing while older individuals showed mild-to-severe high-frequency hearing loss. This is the first report of individuals with USH1 and adult-onset hearing loss rather than congenital hearing loss [Khateb et al 2012]. * c.667G>T (p.Gly223Cys). Heterozygous variant reported in individuals with autosomal dominant nonsyndromic hearing impairment from a Korean cohort [Song et al 2020] CDH23. A reduced frequency of null (e.g., nonsense, frameshift, splice) variants in CDH23 was observed in individuals with less severe phenotypes, with approximately 88%, 67%, and 0% of null variants found in persons with typical Usher type I (USH1D), atypical Usher syndrome, and nonsyndromic deafness type 12 (DFNB12), respectively [Bolz et al 2001, Bork et al 2001, Liu et al 2001, Astuto et al 2002, Bork et al 2002, Valero et al 2019]. PCDH15. Hypomorphic variants were associated with nonsyndromic hearing impairment indicating that residual function with some missense variants are sufficient for normal vision but not hearing, while more severe pathogenic variants result in USH1 [Ahmed et al 2001, Alagramam et al 2001, Ahmed et al 2003, Doucette et al 2009]. CIB2. To date all known pathogenic variants (copy number variants, splicing, indels, and missense) identified in CIB2 are associated with DFNB48, except one variant, c.192G>C (p.Glu64Asp), identified in four individuals from a single consanguineous Pakistani family with USH1J [Riazuddin et al 2012]. Booth et al [2018], however, reported three different loss-of-function variants in three families from diverse origins that cause DFNB48 (autosomal recessive nonsyndromic hearing loss) and not USH1. ### Penetrance Penetrance is complete in Usher syndrome type I. ### Nomenclature The numbering system used in Usher syndrome classification (USH1, USH2, and USH3) corresponds with the associated severity of the clinical presentation (i.e., degree of hearing impairment, presence or absence of vestibular areflexia, and age at onset of retinitis pigmentosa). The letters (e.g., USH1C, USH1B) indicate the molecular subtype with biallelic pathogenic variants in one of the related genes listed in Table 1. Note: Gerber et al [2006] provide evidence that the USH1A locus does not exist; six of the nine families from the Bressuire region of France originally reported to map to this locus have been found to have pathogenic variants in MYO7A (USH1B). ### Prevalence In older publications the prevalence of Usher syndrome has been reported to range from 3.2 to 6.2 per 100,000. Usher syndrome was estimated to be responsible for 3%-6% of all childhood deafness and approximately 50% of all deaf-blindness. Many of these estimates were made prior to 1989, when Möller et al [1989] subdivided Usher syndrome into Usher syndromes type I and II, and before the recognition of Usher syndrome type III. The specialized educational requirements of the congenitally deaf have historically rendered the population with Usher syndrome type I more accessible for study by researchers. Persons with Usher syndrome type II or Usher syndrome type III, who communicate orally and who are mainstreamed into regular schools, are not well represented in these estimates. It has been argued that the prevalence of Usher syndrome in the general population may therefore be substantially greater than estimated. A recent study of children with hearing loss in Oregon found pathogenic variants in Usher syndrome-associated genes in 11% and estimated that the prevalence may be as high as one in 6,000 [Kimberling et al 2010]. ## Differential Diagnosis Nonsyndromic hearing loss (NSHL). Often, a family with more than one affected sib is thought to have NSHL (see Hereditary Hearing Loss and Deafness Overview) until the oldest affected sib manifests signs of retinal degeneration (e.g., night blindness, dark adaptation impairment, contrast vision difficulties, visual acuity changes, and visual field narrowing) and is diagnosed with retinitis pigmentosa (RP). Subsequent visual evaluation often reveals the presymptomatic signs of RP in younger affected sibs. While the timing and extent of vestibulopathy related to Usher syndrome is not fully defined, vestibular symptoms in young children thought to have NSHL may also prompt visual evaluation and subsequent genetic testing. Coinheritance of NSHL and RP. Pathogenic variants associated with separate NSHL and RP (e.g., OTOA-NSHL and NR2E3-RP [Neuhaus et al 2017]) can be inherited independently by a single individual whose symptoms can then mimic those of Usher syndrome [Fakin et al 2012]. Larger families lessen the statistical probability of this occurrence because at least one sib is likely to inherit one pathogenic variant without the other. NSHL and RP (or inherited retinal degeneration) are both relatively common, with frequencies of 1:1,000 and 1:3,000, respectively, and are both characterized by extreme genetic heterogeneity (to date, >110 genes have been associated with NSHL, >60 genes have been associated with RP, and >172 genes have been associated with inherited retinal degeneration) [Pagon 1988]. See also Hereditary Hearing Loss and Deafness Overview and RetNet™: Retinal Information Network. Hereditary disorders characterized by both sensorineural hearing impairment (SNHI) and decreased visual acuity to consider in the differential diagnosis of Usher syndrome type I (USH1) are summarized in Table 3. ### Table 3. Genes of Interest in the Differential Diagnosis of Usher Syndrome Type I View in own window Gene(s)DisorderMOIClinical CharacteristicsComment ADGRV1 PDZD7 USH2A WHRNUSH2AR Digenic 1 * Congenital bilateral SNHL (predominantly in the higher frequencies); ranges from mild to severe * Adolescent- to adult-onset RP * Normal vestibular function Children w/USH1 are usually delayed in walking until age 18 mos to 2 yrs because of vestibular involvement, whereas children w/USH2 usually begin walking at ~1 yr. ALMS1Alström syndromeAR * SNHI * Progressive cone-rod dystrophy leading to blindness * Childhood obesity associated w/hyperinsulinemia, & type 2 diabetes * Cardiomyopathy occurs in ~70% of affected persons in infancy or adolescence. * Renal failure & pulmonary, hepatic, & urologic dysfunction are frequent. * Systemic fibrosis develops w/age. CEP250Cone-rod dystrophy and hearing loss 2 (OMIM 618358)AR * Variable onset & severity of hearing loss * Variable onset & severity of visual loss Can be diagnosed as atypical USH1 2 CEP78Cone-rod dystrophy & hearing loss 1 (OMIM 617236)AR * Late-onset hearing loss * Late-onset visual loss Can be diagnosed as atypical USH2 3 CISD2 WFS1Wolfram syndrome (DIDMOAD) (see WFS1 Wolfram Syndrome Spectrum Disorder)ARSevere neurodegenerative disease w/diabetes insipidus, diabetes mellitus, OA, & deafnessAffected persons may also have renal abnormalities, ataxia, dementia, or ID & diverse psychiatric illnesses. CLRN1 HARS1USH3 (OMIM 276902, 614504)AR * Postlingual progressive SNHL * Late-onset RP * Variable impairment of vestibular function Some persons w/USH3 have profound hearing loss & vestibular disturbance & thus may be clinically misdiagnosed as having USH1 or USH2. COL4A3 COL4A4 COL4A5Alport syndromeXL AR AD Digenic * Variable SNHL * Variable ocular anomalies * Progressive deterioration of glomerular basement membranes resulting in progressive renal failure Both Alport syndrome & USH1 have hearing & visual loss, but Alport syndrome also has progressive renal disease. Urinalysis abnormalities in Alport are clinically distinctive. PEX1 PEX6Heimler syndrome (OMIM 234580, 616617)AR * SNHL * Retinal degeneration * Enamel dysplasia & nail abnormalities Both Heimler syndrome & USH1 have hearing & visual loss, but Heimler syndrome also has a defect of the teeth in which the enamel is hypoplastic. PEX1 PEX6 PEX10 (13 genes) 4Zellweger spectrum disorderARSevere neurologic dysfunction, craniofacial abnormalities, liver dysfunction, & absent peroxisomesPersons w/Zellweger syndrome typically die in the 1st yr of life. PEX6Peroxisome biogenesis disorder 4B (OMIM 614863)AD AR * SNHL * RP * Hypotonia Overlapping phenotype w/neonatal adrenoleukodystrophy, infantile Refsum disease, & Zellweger spectrum disorder PRPS1PRPS1 hereditary motor & sensory neuropathy (CMTX5)XL * Deafness * OA * Polyneuropathy Males tend to be severely affected. PRPS1Arts syndromeXL * Hearing impairment * OA * ID, early-onset hypotonia, ataxia, delayed motor development Both Arts syndrome & USH1 have hearing & visual loss, but Arts syndrome also has neurologic & immune system deficits. RPGRRPGR nonsyndromic RP (see Nonsyndromic Retinitis Pigmentosa Overview)XLProgressive RP2% of persons w/RPGR nonsyndromic RP also have ciliary dyskinesia & hearing loss. 5 TIMM8ADeafness-dystonia-optic neuronopathy syndrome (DDON)XL * Males: prelingual or postlingual SNHL in early childhood; slowly progressive ↓ visual acuity from OA beginning at age ~20 yrs; dementia beginning at age ~40 yrs; slowly progressive dystonia or ataxia in the teens * Females: mild hearing impairment & focal dystonia In DDON, appearance of the retina, night vision, & ERG are usually normal; in USH, impaired vision results from retinal dystrophy, which first manifests as impaired dark adaptation. AR = autosomal recessive; CMTX5 = Charcot-Marie-Tooth neuropathy X type 5; DIDMOAD = diabetes insipidus, diabetes mellitus, optic atrophy, and deafness; ID = intellectual disability; MOI = mode of inheritance; OA = optic atrophy; RP = retinitis pigmentosa; SNHI = sensorineural hearing impairment; SNHL = sensorineural hearing loss; USH = Usher syndrome; XL = X-linked; USH1 = Usher syndrome type I; USH2 = Usher syndrome type II; USH3 = Usher syndrome type III 1\. Digenic USH2 is caused by pathogenic variants in ADGRV1 and PDZD7. 2\. Khateb et al [2014], Fuster-García et al [2018] 3\. Nikopoulos et at [2016], Fu et al [2017] 4\. 60.5% of Zellweger spectrum disorder (ZSD) is associated with biallelic pathogenic variants in PEX1, 14.5% with pathogenic variant in PEX6, and 7.6% with pathogenic variants in PEX12. In total, 13 genes are known to be associated with ZSD. 5\. Shu et al [2007] Other. Viral infections, diabetic neuropathy, and syndromes involving mitochondrial defects (see Mitochondrial Disorders Overview) can all produce concurrent symptoms of hearing loss and retinal pigmentary changes that suggest Usher syndrome. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Usher syndrome type I (USH1), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Usher Syndrome Type I View in own window System/ConcernEvaluationComment AudiologyOtoscopy, pure tone audiometry, assessment of speech perceptionConsider ABR, ECOG, & DPOAE. Vestibular functionRotary chair, VNG incl calorics, & computerized posturographyConsider VHIT, vestibular evoked myogenic potentials (cVEMP & oVEMP). OphthalmologyFundus photography, VA, VF (Goldmann perimetry, Humphrey perimetry, dark-adapted rod perimetry), ERG, OCT, & FAF * Fundus photography documents the extent of pigmentation & retinal/RPE atrophy. * VA is often maintained until late in the disease. * VF maps the extent of functional peripheral vision, retinal sensitivities, & functional rod & cone responses. * ERG is often nondetectable at presentation. * OCT allows the determination of "live" photoreceptors (measuring the ellipsoid zone). * FAF can measure the perifoveal hyperfluorescent ring, & lipofuscin disturbance. OtherConsultation w/clinical geneticist &/or genetic counselor ABR = auditory brain stem response; DPOAE = distortion product otoacoustic emission; ECOG = electrocochleography; ERG = electroretinography; FAF = fundus autofluorescence; OCT = optical coherence tomography; RPE = retinal pigment epithelium; VA = visual acuity; VF = visual field; VHIT = vestibular head impulse testing; VNG = videonystagmography ### Treatment of Manifestations ### Table 5. Treatment of Manifestations in Individuals with Usher Syndrome Type I View in own window Manifestation/ ConcernTreatmentConsiderations/Other Hearing loss * An initial trial of hearing aids even w/profound loss stimulates any residual hearing & accustoms the infant to auditory stimulation for auditory/oral language development. * Cochlear implantation should be considered as early as is medically feasible. 1 Hearing aids are usually inadequate in severe-to-profound hearing loss. Sign language such as American Sign Language and tactile signs (once visual loss occurs) are communication options for families who choose nonauditory communication. Specialized training from educators of the hearing impairedRecommended for affected children & all family members to improve communication skills Balance difficulties & ↑ risk of accidental injuryVestibular compensation therapy for children w/residual balance function & sensory substitution therapy for individuals w/complete absence of vestibular functionWell-supervised sports activities may help develop somatosensory component of the balance system. Vision lossSee Nonsyndromic Retinitis Pigmentosa Overview, Management.Adults w/USH1 age >20 yrs use sign language & lip reading for communication. As vision loss progresses, these methods become increasingly difficult & tactile signing may ultimately be required. 1\. Damen et al [2006], Pennings et al [2006], Liu et al [2008] ### Surveillance ### Table 6. Recommended Surveillance for Individuals with Usher Syndrome Type I View in own window System/ConcernEvaluationFrequency Hearing lossAudiometry & tympanometry w/cochlear implant or hearing aids to assure adequate auditory stimulation * For persons w/o profound loss, annual testing allows appropriate hearing aid adjustment. * For cochlear implant recipients, annual follow up is necessary to assure appropriate implant function & programming. * Children w/profound loss & cochlear implants can still develop fluid & chronic ear infection issues, which are less evident to the child because of hearing loss. Annual otoscopic exam w/tympanometry avoids potential serious complications of chronic otitis media. CataractsOphthalmologic evalAnnually from age 20 yrs or from age at diagnosis Cystoid macular edema Retinitis pigmentosaFundus photography, VA, VF (Goldmann perimetry, Humphrey perimetry, dark-adapted rod perimetry), ERG, OCT, & FAF ERG = electroretinography; FAF = fundus autofluorescence; OCT = optical coherence tomography; VA = visual acuity; VF = visual field ### Agents/Circumstances to Avoid Competition in sports requiring acute vision and/or good balance may be difficult and possibly dangerous. Persons with USH1 often become disoriented when submerged in water because they lack the sense of where "up" is; they should therefore exercise caution while swimming. Similarly, the vestibular dysfunction increases the risk of falls when walking on sloped or uneven surfaces. Progressive loss of peripheral vision may eventually impair the ability to safely drive a car. An Esterman visual field test (automated Humphrey, static visual field analyzer) with both eyes open during testing is a helpful measure to assess degrees of peripheral vision along the midline. Night driving is impaired very early. ### Evaluation of Relatives at Risk It is appropriate to evaluate the hearing of all sibs at risk for USH1 as soon after birth as possible to allow early diagnosis and treatment of hearing impairment. Additional evaluations include: * Molecular genetic testing if the pathogenic variants in the family are known; * Auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) if the pathogenic variants in the family are not known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation UshStat® gene replacement of MYO7A – A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of UshStat® in Patients with Usher Syndrome Type 1B. This is an interventional, Phase I/II clinical trial to evaluate the safety and activity of retinal gene therapy to treat RP in individuals with MYO7A-USH1. This trial is active but not recruiting. (See NCT02065011.) QR-421 antisense treatment – A Study to Evaluate Safety and Tolerability of QR-421a in Subjects with RP Due to Mutations in Exon 13 of the USH2A Gene (Stellar). This is an interventional, Phase I/II clinical trial to evaluate the safety of an antisense oligonucleotide (ASO) therapy to treat RP in individuals with USH2 due to specific USH2A pathogenic variants. (See NCT03780257.) C-18-04 antioxidant treatment – Safety and Efficacy of NPI-001 Tablets versus Placebo for Treatment of Retinitis Pigmentosa Associated with Usher Syndrome. This is an interventional, two-year, Phase I/II clinical trial to evaluate the safety and efficacy of NPI-001 tablets in individuals with RP associated with Usher syndrome. This trial is active and recruiting. (See NCT04355689.) CL-17-01 antioxidant treatment – A Phase I, Single- and Multiple-Ascending Dose Study of the Safety and Tolerability of NPI-001 Solution in Healthy Subjects. This clinical trial established that NPI-001 was generally well tolerated in all but the highest dose and determined key pharmacokinetic parameters of the NPI-001 solution. (See ACTRN12617000911392.) Search ClinicalTrials.gov in the US, EU Clinical Trials Register in Europe, and ANZCTR in Australia and New Zealand for access to information on clinical studies for a wide range of diseases and conditions. ### Other Vitamin A supplements. Vitamin A plays an essential role in the visual cycle as the photosensitive intermediate 11 cis retinal. Although treatment with vitamin A palmitate may limit the progression of RP in persons with isolated RP and USH2, no studies have evaluated the effectiveness of vitamin A palmitate in individuals with USH1. Vitamin A is fat soluble and not excreted in the urine. Therefore, high-dose vitamin A dietary supplements should be used only under the direction of a physician because of the need to monitor for harmful side effects such as hepatotoxicity [Sibulesky et al 1999]. Of note, the studies by Berson et al [1993] were performed on individuals older than age 18 years because of the unknown effects of high-dose vitamin A on children. High-dose vitamin A supplementation should not be used by affected pregnant women, as large doses of vitamin A (i.e., above the recommended daily allowance for pregnant or lactating women) may be teratogenic to the developing fetus. Lutein supplements may enhance retinal macular pigment. Lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites accumulate in the human fovea and macula as the macular pigment (MP). They are obtained through dietary sources (green leafy vegetables, yellow and/or orange fruits and vegetables). Inherited retinal dystrophies may cause or be associated with loss of MP [Aleman et al 2001]. Oral administration of lutein (20 mg/day) for seven months had no effect on central vision [Aleman et al 2001]. However, Berson et al [2010] showed that lutein supplementation of 12 mg/day slowed loss of midperipheral visual field among nonsmoking adults with RP taking vitamin A. Omega 3 supplements (e.g., docosahexaenoic acid [DHA]) may replenish membranes of the photoreceptor outer segments, which are largely composed of polyunsaturated fatty acids. Supplementation of DHA significantly elevated blood DHA levels and reduced the rate of progression in final dark-adapted thresholds and visual field sensitivity [Hoffman et al 2015]. N-acetyl-cysteine (NAC) supplements. NAC is a safe oral antioxidant used to treat liver toxicity due to acetaminophen overdose. NAC reduces oxidative damage and increases cone function and survival in animal models of RP [Lee et al 2011]. In a Phase l study, 600 mg, 1200 mg, or 1800 mg were safe in individuals with RP and significant improvements were found in cone function, including visual acuity [Campochiaro et al 2020]. Blueberry extract supplements. Blueberries contain anthocyanins, members of the flavonoid group of phytochemicals, which are powerful antioxidants. No studies have been done on individuals with RP or USH1. Because of their natural source, blueberry extract supplements are probably safe and may be efficacious. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Usher Syndrome Type I	c1568247	26,245	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1265/	2021-01-18T20:51:06	{"synonyms": ["USH1", "Usher 1"]}
Paternal uniparental disomy of chromosome 21 is an uniparental disomy of paternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only father is a carrier. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Paternal uniparental disomy of chromosome 21	c4707801	26,246	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96195	2021-01-23T17:38:01	{"icd-10": ["Q99.8"], "synonyms": ["UPD(21)pat"]}
Branchiogenic deafness syndrome is a multiple congenital anomalies syndrome, described in one family to date, characterized by branchial cysts or fistulae; ear malformations; congenital hearing loss (conductive, sensorineural, and mixed); internal auditory canal hypoplasia; strabismus; trismus; abnormal fifth fingers; vitiliginous lesions, short stature; and mild learning disability. Renal and uretral abnormalities are absent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Branchiogenic deafness syndrome	c1836673	26,247	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50815	2021-01-23T18:37:12	{"mesh": ["C563780"], "omim": ["609166"], "umls": ["C1836673"], "icd-10": ["Q87.0"], "synonyms": ["Branchiogenic hearing loss syndrome", "Mégarbané-Loiselet syndrome"]}
Abortion in Ecuador is illegal except when performed in the case of a threat to the life or health of a pregnant woman (when this threat cannot be averted by other means) or when the pregnancy is the result of a sexual crime against a mentally disabled woman and her legal representative has consented.[1] The Ministry of Public Health provides guidelines on therapeutic abortion. In Ecuador, there is strong political opposition to abortion; in 2013 then president Rafael Correa threatened to resign if the abortion law was liberalized.[2] As of 2015, nearly 100 criminal cases of illegal abortion were under investigation.[3] In 2015, Ecuador was urged by CEDAW to decriminalize abortion in cases of rape and incest (under current law abortion in this case is legal only if the woman is mentally disabled) and severe fetal impairment (which is also illegal).[4] ## See also[edit] * Abortion * Abortion by country * Abortion law ## References[edit] 1. ^ http://www.womenonwaves.org/en/page/4944/ecuador--abortion-law 2. ^ https://www.bbc.com/news/world-latin-america-24499248 3. ^ https://www.hrw.org/news/2015/04/22/ecuador-adopt-un-recommendations-abortion-law 4. ^ https://www.hrw.org/news/2015/04/22/ecuador-adopt-un-recommendations-abortion-law [1] [2] * v * t * e Abortion in South America Sovereign states * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Dependencies and other territories * Falkland Islands * French Guiana * South Georgia and the South Sandwich Islands * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category 1. ^ https://aplicaciones.msp.gob.ec/salud/archivosdigitales/documentosDirecciones/dnn/archivos/ac_00005195_2014%2020%20nov.pdf 2. ^ http://www.womenonwaves.org/article-1572-en.html [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Abortion in Ecuador	None	26,248	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Ecuador	2021-01-18T18:48:21	{"wikidata": ["Q4668456"]}
Bipartite patella Other namesPatella bipartita Bipartite patella as seen from front, right knee left SpecialtyMedical genetics Bipartite patella is a condition where the patella, or kneecap, is composed of two separate bones. Instead of fusing together as normally occurs in early childhood, the bones of the patella remain separated.[1] The condition occurs in approximately 1–2% of the population[2][3][4] and is no more likely to occur in males than females.[3][4] It is often asymptomatic and most commonly diagnosed as an incidental finding,[1][4][5] with about 2% of cases becoming symptomatic.[3][4] Saupe introduced a classification system for Bipartite Patella back in 1921. Type 1: Fragment is located at the bottom of the kneecap (5% of cases) Type 2: Fragment is located on the lateral side of the kneecap (20% of cases) Type 3: Fragment is located on the upper lateral border of the kneecap (75% of cases)[6] ## References[edit] 1. ^ a b "Kneecap (Patella) Injury". About.com. Retrieved 13 April 2014. 2. ^ "Bipartite Patella - Wheeless´ Textbook of Orthopaedics". Duke Orthopaedics. Retrieved 13 April 2014. 3. ^ a b c "Bipartite Patella - Pediatrics - Orthobullets.com". Orthobullets.com. Retrieved 13 April 2014. 4. ^ a b c d "Bipartite Patella \| Radiology Reference Article \| Radiopaedia.org". Orthobullets.com. Retrieved 13 April 2014. 5. ^ Atesok K, Doral MN, Lowe J, Finsterbush A (2008). "Symptomatic bipartite patella: treatment alternatives". J Am Acad Orthop Surg. Journal of the American Academy of Orthopaedic Surgeons. 16 (8): 455–61. doi:10.5435/00124635-200808000-00004. PMID 18664634. S2CID 35458401. 6. ^ "Bipartite Patella - Knee Conditions - Knee-Pain-Explained.com". Knee-Pain-Explained.com. ## External links[edit] Classification D * ICD-10: DQ741H This human musculoskeletal system 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Bipartite patella	c0265666	26,249	wikipedia	https://en.wikipedia.org/wiki/Bipartite_patella	2021-01-18T19:01:22	{"wikidata": ["Q2056680"]}
Aggressive Lymphoma Diffuse Large B-cell Lymphoma SpecialtyHematology and oncology Aggressive lymphoma, also known as high-grade lymphoma, is a group of fast growing Non-Hodgkin Lymphoma.[1] Some common symptoms for aggressive lymphoma are weight loss, night sweats, nausea and recurrent fevers.[2] Since these tumors are fast to grow and spread, immediate intervention is required after diagnosis. There are several subtypes of aggressive lymphoma. These include AIDS-associated lymphoma, angioimmunoblastic lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and peripheral T-cell lymphoma.[1] Diffuse large B-cell lymphoma is the most common subtype as well as the most common type of Non-Hodgkin Lymphoma.[3] Aggressive lymphoma accounts for approximately 60 percent of all Non-Hodgkin Lymphoma cases in the United States.[1] ## Contents * 1 Risk factors * 2 Symptoms & Diagnosis * 3 Types * 3.1 Diffuse large B-cell Lymphoma (DLBCL) * 3.2 Burkitt Lymphoma * 3.3 Peripheral T-cell lymphoma * 3.4 Rarer types of high grade non-Hodgkin lymphoma * 4 Treatment * 5 Prognosis * 6 Research * 7 References ## Risk factors[edit] Some of the risk factors that increase the risk factor of aggressive lymphoma include:[4] * Immunosuppressive medication used for organ transplant patients or autoimmune diseases. * Infection with certain viruses and bacteria such as HIV and Epstein-Barr virus (EBV). * Exposure to chemicals such as insecticides and pesticides. * Older age. ## Symptoms & Diagnosis[edit] The symptoms of aggressive lymphoma are similar to that of low-grade lymphomas. Patients may come in with painless swollen lymph nodes in their neck, armpits or groin. They can also describe symptoms such as abdominal pain, chest pain, persistent fatigue, fever, night sweats and unexplained weight loss depending on the stage of their tumor and its location.[4] Since the signs and symptoms of aggressive lymphoma are similar to that of other types of Non-Hodgkin lymphoma it is important analyze the tumors morphologically and run immunohistochemical tests to ensure correct diagnosis. For aggressive lymphoma, swift and specific treatment dependent upon correct diagnosis can be the difference between life and death for the patient. ## Types[edit] The most common types of high grade non-Hodgkin lymphoma are:[5] ### Diffuse large B-cell Lymphoma (DLBCL)[edit] Diffuse large B cell lymphoma (DLBCL) is a type of high-grade NHL which is the most common type of NHL worldwide at affecting 30-40 percent of all NHL cases.[6] It is more prevalent in elderly patients with a median age of 70 years. Patients most often present with a rapidly growing tumor mass in single or multiple, nodal or extranodal sites. The most commonly diagnosed versions of DLBCL are germinal center B-cell like (GCB) and activated B-cell like (ABC) subtypes.[7] Immunohistochemical and flow cytometry analysis is also necessary for the diagnosis of this disease. The DLBCL cells have found to express B-cell antigens such as CD19, CD20, and CD22 as well as the transcription factors PAX5, BOB.1, and OCT2. CD20 is especially relevant in diagnostics as well as therapeutics because it is the target of the Rituximab humanized monoclonal antibody that is used in the most common treatment strategy.[7] In addition to this, the majority of cells also express surface or cytoplasmic immunoglobulins, specifically IgM, IgG and IgA. While these analyses allow for diagnosis by displaying proof of B-cell lineage, they can also be used in treatment strategy and can give insight into prognosis of the specific case being considered. Burkitt Lymphoma ### Burkitt Lymphoma[edit] Burkitt lymphoma is named after the British surgeon Denis Burkitt. Dr.Burkitt identified this disease in 1956 in children in Africa.[8] In Africa, Burkitt lymphoma is common in children also infected by malaria and Epstein-Barr virus. Outside of Africa, Burkitt lymphoma is less common. In the U.S., about 1,200 people are diagnosed each year, and the disease disproportionately affects those younger than the age of 40.[8] Burkitt lymphoma is especially likely to develop in people infected with HIV, the virus that causes AIDS. Before highly active antiretroviral therapy (HAART) became a widespread treatment for HIV/AIDS, the incidence of Burkitt lymphoma was estimated to be 1,000 times higher in HIV-positive people than in the general population.[8] ### Peripheral T-cell lymphoma[edit] Peripheral T-cell lymphomas are less common accounting for approximately 7% of all non-Hodgkin lymphoma cases.[9] It represents a diverse group of diseases that lacks clear definition. These diseases may involve extranodal sites such as the liver, bone, marrow, intestinal tract and the skin.[9] Due to its difficulties in classification, diagnosis and treatment is often regarded as "orphan diseases".[citation needed] ### Rarer types of high grade non-Hodgkin lymphoma[edit] * AIDS-associated lymphoma * Angioimmunoblastic lymphoma * Central nervous system (CNS) lymphoma * Mantle cell lymphoma (MCL) [1] ## Treatment[edit] For limited high grade lymphoma the typical treatment is chemotherapy and a targeted drug, followed by radiotherapy. While advanced high grade aggressive lymphoma patients receive similar treatments, the duration is extended. For advanced diffuse large B cell lymphoma the standard therapy for patients with DLBCL is the combination use of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).[3] While this commonly used regimen results in 60-70 percent of patients with DLBCL to be cured of disease there is also a group of patients that relapse and do not respond well to R-CHOP. For these patients the current treatment strategies are insufficient in treating their cancer. In addition to this, alternative treatments continue to be research due to the highly toxic nature of R-CHOP.[3] In contrast to mature B-cell neoplasms, therapeutic advances in peripheral T-cell lymphoma have generally lagged behind, particularly with regard to the introduction of immune therapies, which have impacted significantly and favorably on the prognosis of aggressive B cell lymphomas such as diffuse large B-cell lymphoma. As such, it remains a heterogeneous entity with a generally unfavorable prognosis.[10] ## Prognosis[edit] While there is no way of definitively predicting the outcome of an individual’s diagnosis of aggressive lymphoma, there are ways of best guessing the prognosis of the patient. These prognostic factors can be divided into three categories. The first category depends on the patient and can be their age and overall health. The second category is dependent upon the tumor and includes the stage, tumor burden, and extranodal involvement. Finally, the last category is dependent on aggressiveness indicators. Factors such as LDH serum level and proliferative fraction can give insight into the tumor microenvironment and proliferation potential which may impact the prognosis.[7] ## Research[edit] Two promising immunotherapy approaches against diffuse large B-cell lymphoma are chimeric antigen receptor (CAR) T cell therapy and therapeutic blocking of programmed cell death protein 1 pathway (PD-1/PD-L1).[11] While CAR T-cells have shown promising efficacy in patients with DLBCL, there have been some unexpected toxicity related issues that have come up for further research.[11] One proposal to improve research for treatment in aggressive lymphoma is to use canines as model animals. Canine lymphoma prevalence has been increasing over the years similar to the incidence of human lymphoma cases. Lymphoma represents the most frequent hematopoietic cancer in dogs with canine non-Hodgkin lymphoma (cNHL) having the highest incidence at 83% of all hematopoietic cancers.[12] In addition to this diffuse large B-cell lymphoma is the most commonly seen subtype of NHL in both species.[13] The advantages of using canines as model animals include spontaneous disease occurring without an isogenic background or genetic engineering; chronology of disease adapted to lifespan; shared environmental and societal status that allows dogs to be treated as “patients”, while at the same time being able to ethically explore translational innovations that are not possible in human subjects; and organization of dogs into breeds with relatively homogeneous genetic backgrounds and distinct predisposition for lymphomas.[13] In addition to this, there have also been studies that suggest that breed type might influence disease progression and response to therapy which is very promising for human therapeutic research.[13] ## References[edit] 1. ^ a b c d "Treatment for Aggressive NHL". Leukemia and Lymphoma Society. Retrieved 20 April 2020. 2. ^ "Stage 4 Lymphoma". healthline. 3. ^ a b c Li, Shaoying; Young, Ken H.; Medeiros, L. Jeffrey (January 2018). "Diffuse large B-cell lymphoma". Pathology. 50 (1): 74–87. doi:10.1016/j.pathol.2017.09.006. ISSN 0031-3025. PMID 29167021. 4. ^ a b "Non-Hodgkin's lymphoma". Mayo Clinic. 5. ^ "High grade NHL". Cancer Research UK. 6. ^ Schneider, Christof; Pasqualucci, Laura; Dalla-Favera, Riccardo (May 2011). "Molecular pathogenesis of diffuse large B-cell lymphoma". Seminars in Diagnostic Pathology. 28 (2): 167–177. doi:10.1053/j.semdp.2011.04.001. PMC 3562715. PMID 21842702. 7. ^ a b c Martelli, Maurizio; Ferreri, Andrés J. M.; Agostinelli, Claudio; Di Rocco, Alice; Pfreundschuh, Michael; Pileri, Stefano A. (2013-08-01). "Diffuse large B-cell lymphoma". Critical Reviews in Oncology/Hematology. 87 (2): 146–171. doi:10.1016/j.critrevonc.2012.12.009. ISSN 1040-8428. PMID 23375551. 8. ^ a b c "Burkitt Lymphoma". WebMD. 9. ^ a b "Peripheral T-cell lymphoma". Leukemia Foundation. 10. ^ Patel, Moosa (2018). "Peripheral T cell lymphoma". Indian Journal of Medical Research. 147 (5): 439–441. doi:10.4103/ijmr.IJMR_1849_17. ISSN 0971-5916. PMC 6094523. PMID 30082566. 11. ^ a b Zhang, Jun; Medeiros, L. Jeffrey; Young, Ken H. (2018-09-10). "Cancer Immunotherapy in Diffuse Large B-Cell Lymphoma". Frontiers in Oncology. 8: 351. doi:10.3389/fonc.2018.00351. ISSN 2234-943X. PMC 6140403. PMID 30250823. 12. ^ Marconato, Laura; Gelain, Maria Elena; Comazzi, Stefano (March 2013). "The dog as a possible animal model for human non-Hodgkin lymphoma: a review: The dog as model for human non-Hodgkin lymphoma". Hematological Oncology. 31 (1): 1–9. doi:10.1002/hon.2017. PMID 22674797. S2CID 205914765. 13. ^ a b c Ito, Daisuke; Frantz, Aric M.; Modiano, Jaime F. (June 2014). "Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications". Veterinary Immunology and Immunopathology. 159 (3–4): 192–201. doi:10.1016/j.vetimm.2014.02.016. PMC 4994713. PMID 24642290. * Aggressive lymphoma entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Aggressive lymphoma	c1332225	26,250	wikipedia	https://en.wikipedia.org/wiki/Aggressive_lymphoma	2021-01-18T18:59:27	{"wikidata": ["Q4692282"]}
A number sign (#) is used with this entry because of evidence that neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (NDCAGF) is caused by homozygous mutation in the INTS1 gene (611345) on chromosome 7p22. Clinical Features Oegema et al. (2017) reported 3 unrelated Dutch patients, aged 9, 17, and 6 years, with a similar neurodevelopmental disorder. The patients had moderately to severely impaired intellectual development, absent language, and short stature (-3 to -4 SD). Two patients could walk with aid, but 1 was nonambulatory. One patient had seizures and hypoplasia of the cerebellar inferior vermis, whereas the other 2 had no seizures and normal brain imaging. Additional features included cataracts, frontal bossing, hypertelorism, dolichocephaly, pectus abnormalities, and irregularly implanted and overlapping toes. Only 1 patient had renal dysplasia and the other 2 had congenital heart defects. Krall et al. (2019) reported 5 additional patients, including 2 sib pairs, with NDCAGF. The patients had global developmental impairment with mildly delayed walking (around 3 years of age), abnormal gait, hypotonia, and impaired intellectual development with poor or absent speech. Several had features consistent with autism spectrum disorder, and some had feeding difficulties. All patients developed cataracts between 1 and 3 years of age. More variable ocular findings included myopia, microphthalmia, microcornea, and coloboma. Common dysmorphic features included frontal bossing, small palpebral fissures, widely spaced eyes, full cheeks, broad nasal bridge with a broad nasal tip, low-set and simple ears, downturned corners of the mouth, and small chin. Other features included diastema, short neck, pectus deformities, and broad halluces with overlapping toes. One sib pair had thumb abnormalities. Brain imaging was mostly normal, although some patients showed nonspecific abnormalities affecting the hippocampus, corpus callosum, and cerebellum. Zhang et al. (2019) reported a Chinese brother and sister, aged 11 and 5 years, respectively, with NDCAGF. Both had hypotonia, global developmental delay with motor impairment, delayed walking, severely impaired intellectual development with absent language, and short stature; 1 had autistic features. They also had cataracts and strabismus. Dysmorphic features were somewhat variable, but included uneven teeth, hypertelorism, abnormal palmar creases, and pectus deformities. The boy had cryptorchidism and the girl had abnormal genitalia. Brain imaging was normal. Inheritance The transmission pattern of NDCAGF in the families reported by Krall et al. (2019) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 unrelated patients of Dutch ancestry with NDCAGF, Oegema et al. (2017) identified a homozygous nonsense mutation in the INTS1 gene (S1784X; 611345.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. It was not found in the ExAC or gnomAD databases. Additional genomic analysis suggested a common ancestor and a founder effect. Analysis of patient fibroblasts showed significantly decreased mutant INTS1 mRNA, consistent with a loss of function. In 5 patients, including 2 pairs of sibs, with NDCAGF, Krall et al. (2019) identified homozygous or compound heterozygous mutations in the INTS1 gene (see, e.g., 611345.0002-611345.0004). The mutations were found by exome sequencing and confirmed by Sanger sequencing; functional studies of the variants and studies of patient cells were not performed. In 2 sibs, born of unrelated Chinese parents, with NDCAGF, Zhang et al. (2019) identified compound heterozygous mutations in the INTS1 gene (611345.0005 and 611345.0006). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither variant was present in the dbSNP, 1000 Genomes Project, Exome Sequencing Project, or ExAC databases. The variants occurred at conserved residues and both were predicted to be pathogenic according to ACMG guidelines. Functional studies of the variants and studies of patient cells were not performed. Animal Model Krall et al. (2019) found expression of the ints1 gene in the developing eye and brain of zebrafish. Knockdown of ints1 in zebrafish did not result in any gross abnormalities, but there was a subtle increase in lens thickness compared to controls. RT-PCR analysis of mutant fish indicated downregulation of ints1 and other genes in the INT complex. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	NEURODEVELOPMENTAL DISORDER WITH CATARACTS, POOR GROWTH, AND DYSMORPHIC FACIES	None	26,251	omim	https://www.omim.org/entry/618571	2019-09-22T15:41:29	{"omim": ["618571"]}
Microhydranencephaly is a developmental abnormality that affects the brain. Signs and symptoms may include extreme microcephaly, scalp rugae (a series of ridges), profound developmental delay and severe intellectual disability. Imaging studies of the brain generally reveal incomplete brain formation and severe hydrocephalus (accumulation of fluid in the brain). In most cases, the underlying cause is unknown. Rarely, the condition is caused by changes (mutations) in the NDE1 gene and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Microhydranencephaly	c1857977	26,252	gard	https://rarediseases.info.nih.gov/diseases/10216/microhydranencephaly	2021-01-18T17:59:04	{"mesh": ["C537555"], "omim": ["605013"], "umls": ["C1857977"], "synonyms": ["MHAC", "Hydranencephaly and microcephaly"]}
## Description Secundum atrial septal defect (ASD) is a common congenital heart malformation that occurs as an isolated anomaly in 10% of individuals with congenital heart disease. Uncorrected ASD can cause pulmonary overcirculation, right heart volume overload, and premature death (summary by Benson et al., 1998). ### Genetic Heterogeneity of Atrial Septal Defect The ASD1 locus has been mapped to chromosome 5p. Other forms of atrial septal defect that are associated with other congenital heart disease but no conduction defects or noncardiac abnormalities include ASD2 (607941), caused by mutation in the GATA4 gene (600576), and ASD4 (611363), caused by mutation in the TBX20 gene (606061). ASD3 (614089) and ASD5 (612794), in which atrial septal defect is not associated with other cardiac abnormalities, are caused by mutation in the MYH6 (160710) and ACTC1 (102540) genes, respectively. ASD6 (613087), in which atrial septal defect may be associated with aneurysm of the interatrial septum and cardiac arrhythmias, is caused by mutation in the TLL1 gene (606742). ASD7 (108900), in which ASD is often associated with atrioventricular conduction defects, is caused by mutation in the NKX2-5 gene (600584). ASD8 (614433), in which ASD may be associated with other cardiac anomalies, is caused by mutation in the CITED2 gene (602937). ASD9 (614475) is caused by mutation in the GATA6 gene (601656). Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with ASDs. Clinical Features This congenital heart defect is almost always sporadic, but occasional families in which multiple persons have isolated ASD suggest that a single 'major' gene may sometimes be responsible. The family reported by Zuckerman et al. (1962) suggests dominant inheritance. Zetterqvist (1960) reported a family with 8 proved cases and 5 probable cases of ASD of secundum type in 3 generations. Johansson and Sievers (1967) found 6 proved and 1 probable case of ASD in 3 generations. Furthermore, they were able to show that Zetterqvist's and their cases traced their ancestry to a common couple who lived in the 18th century. Zetterqvist et al. (1971) gave a full report on the family which they felt provided strong evidence for the existence of a single major gene as a determining factor. Sanchez-Cascos (1972) examined 109 cases of ASD, 84 of the ostium secundum type and 25 of the ostium primum type; of these, 92 presented ASD as an isolated defect and 17 were associated with other malformations. He concluded, from the incidence of familial aggregation among first-degree relatives of affected cases, from the fact that the sex ratio deviated from 1 for his cases (0.64 males per 1 female), and from other findings, that multifactorial inheritance is consistent with the demonstrated pattern of transmission. He also reported significant dermatoglyphic findings in these ASD cases--a high proportion of whorls and a parallel diminution in the number of ulnar loops. Lynch et al. (1978) restudied a large kindred reported by Zuckerman et al. (1962) and concluded that 2 autosomal dominant forms of ASD occur: one with (108900) and one without prolongation of the PR interval. Li Volti et al. (1991) observed 3 Sicilian families in which 17 persons (10 females and 7 males) had atrial septal defect of the ostium secundum type without conduction defects. There were several instances of male-to-male transmission. Mapping Mohl and Mayr (1977) studied 3 multigeneration families with secundum type ASD and found no recombination with HLA (which is at chromosome 6p21.3). The data yielded a lod score of +3.612 at a recombination fraction of 0.000, but the confidence limits were wide. Insufficient information was given to know whether this was the Holt-Oram syndrome (142900) or ASD with conduction defect (108900) rather than secundum type atrial septal defect. See another report on the ostium secundum type of ASD by the same group (Mohl et al., 1979). Benson et al. (1998) reported an evaluation of 3 families in which individuals in multiple generations had ASD. The most common anomaly was ASD, but other heart defects occurred alone or in association with ASD in individuals from each kindred. In 1 kindred genomewide linkage studies localized a familial ASD gene to chromosome 5p (multipoint lod score = 3.6, theta = 0.0 at D5S406). Of 20 family members with the disease haplotype, 9 had ASD, 8 were clinically unaffected, and 3 had other cardiac defects (aortic stenosis, atrial septal aneurysm, and persistent left superior vena cava). Familial ASD did not map to chromosome 5p in the other 2 families. Thus, they emphasized reduced penetrance, variable expressivity, and genetic heterogeneity of familial atrial septal defects. Cardiac \- Atrial septal defect Inheritance \- Autosomal dominant in occasional families ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ATRIAL SEPTAL DEFECT 1	c0018817	26,253	omim	https://www.omim.org/entry/108800	2019-09-22T16:44:42	{"doid": ["0110106"], "mesh": ["D006344"], "omim": ["108800"], "orphanet": ["1478"], "synonyms": ["Alternative titles", "ASD"]}
## Summary ### Clinical characteristics. MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a multisystem disorder with protean manifestations. The vast majority of affected individuals develop signs and symptoms of MELAS between ages two and 40 years. Common clinical manifestations include stroke-like episodes, encephalopathy with seizures and/or dementia, muscle weakness and exercise intolerance, normal early psychomotor development, recurrent headaches, recurrent vomiting, hearing impairment, peripheral neuropathy, learning disability, and short stature. During the stroke-like episodes neuroimaging shows increased T2-weighted signal areas that do not correspond to the classic vascular distribution (hence the term "stroke-like"). Lactic acidemia is very common and muscle biopsies typically show ragged red fibers. ### Diagnosis/testing. The diagnosis of MELAS is based on meeting clinical diagnostic criteria and identifying a pathogenic variant in one of the genes associated with MELAS. The m.3243A>G pathogenic variant in the mitochondrial gene MT-TL1 is present in approximately 80% of individuals with MELAS. Pathogenic variants in MT-TL1 or other mtDNA genes, particularly MT-ND5, can also cause this disorder. ### Management. Treatment of manifestations: Treatment for MELAS is generally supportive. During the acute stroke-like episode, a bolus of intravenous arginine (500 mg/kg for children or 10 g/m2 body surface area for adults) within three hours of symptom onset is recommended followed by the administration of a similar dosage of intravenous arginine as a continuous infusion over 24 hours for the next three to five days. Coenzyme Q10, L-carnitine, and creatine have been beneficial in some individuals. Sensorineural hearing loss has been treated with cochlear implantation; seizures respond to traditional anticonvulsant therapy (although valproic acid should be avoided). Ptosis, cardiomyopathy, cardiac conduction defects, nephropathy, and migraine headache are treated in the standard manner. Diabetes mellitus is managed by dietary modification, oral hypoglycemic agents, or insulin therapy. Exercise intolerance and weakness may respond to aerobic exercise. Prevention of primary manifestations: Once an individual with MELAS has the first stroke-like episode, arginine should be administered prophylactically to reduce the risk of recurrent stroke-like episodes. A daily dose of 150 to 300 mg/kg/day oral arginine in three divided doses is recommended. Prevention of secondary complications: Because febrile illnesses may trigger acute exacerbations, individuals with MELAS should receive standard childhood vaccinations, flu vaccine, and pneumococcal vaccine. Surveillance: Affected individuals and their at-risk relatives should be followed at regular intervals to monitor progression and the appearance of new symptoms. Annual ophthalmologic, audiology, and cardiologic (electrocardiogram and echocardiogram) evaluations are recommended. Annual urinalysis and fasting blood glucose level are also recommended. Agents/circumstances to avoid: Mitochondrial toxins, including aminoglycoside antibiotics, linezolid, cigarettes, and alcohol; valproic acid for seizure treatment; metformin because of its propensity to cause lactic acidosis; dichloroacetate (DCA) because of increased risk for peripheral neuropathy. Pregnancy management: Affected or at-risk pregnant women should be monitored for diabetes mellitus and respiratory insufficiency, which may require therapeutic interventions ### Genetic counseling. MELAS is caused by pathogenic variants in mtDNA and is transmitted by maternal inheritance. The father of a proband is not at risk of having the mtDNA pathogenic variant. The mother of a proband usually has the mtDNA pathogenic variant and may or may not have symptoms. A man with a mtDNA pathogenic variant cannot transmit the variant to any of his offspring. A woman with a mtDNA pathogenic variant (whether symptomatic or asymptomatic) transmits the variant to all of her offspring. Prenatal testing and preimplantation genetic testing for MELAS is possible if a mtDNA pathogenic variant has been detected in the mother. However, because the mutational load in embryonic and fetal tissues sampled (i.e., amniocytes and chorionic villi) may not correspond to that of all fetal tissues, and because the mutational load in tissues sampled prenatally may shift in utero or after birth as a result of random mitotic segregation, prediction of the phenotype from prenatal studies cannot be made with certainty. ## Diagnosis Clinical diagnostic criteria for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) have been published [Hirano et al 1992, Yatsuga et al 2012] (see Establishing the Diagnosis). ### Suggestive Findings MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) should be suspected in individuals with the following features. #### Clinical Features * Stroke-like episodes before the age of 40 years * Acquired encephalopathy with seizures and/or dementia * Recurrent headaches * Muscle weakness and exercise intolerance * Cortical vision loss * Hemiparesis * Recurrent vomiting * Short stature * Hearing impairment * Normal early psychomotor development * Peripheral neuropathy * Learning disability #### Brain Imaging Brain MRI * During the stroke-like episodes, the affected areas: * Have increased T2 signal; * Do not correspond to the classic vascular distribution (hence the term "stroke-like"); * Are asymmetric; * Typically involve predominantly the posterior cerebrum (temporal, parietal, and occipital lobes); * Can be restricted to cortical areas or involve subcortical white matter [Hirano et al1992, Sproule & Kaufmann 2008]. * Slow spreading of the stroke-like lesions occurs in the weeks following the first symptoms, typically documented by T2-weighted MRI [Iizuka et al 2003]. * Diffusion-weighted MRI shows increased apparent diffusion coefficient (ADC) in the stroke-like lesions of MELAS, in contrast to the decreased ADC seen in ischemic strokes [Kolb et al 2003]. * MR angiography is usually normal and MR spectroscopy shows decreased N-acetylaspartate signals and accumulation of lactate [Sproule & Kaufmann 2008]. Head CT. Basal ganglia calcifications are occasionally seen. #### Electromyography and Nerve Conduction Studies Findings are consistent with a myopathic process, but neuropathy may coexist. Neuropathy can be axonal or mixed axonal and demyelinating [Kärppä et al 2003, Kaufmann et al 2006b]. #### Suggestive Laboratory Findings Lactic acidosis both in blood and CSF. Lactic acidemia is very common. CSF lactate is also elevated in most affected individuals. Lactic acidemia is not specific for MELAS syndrome as it can occur in other mitochondrial diseases, metabolic diseases, and systemic illness. Other situations (unrelated to the diagnosis of MELAS) in which lactate can be elevated are acute neurologic events such as seizure or stroke. On the other hand, lactate level can be normal in a minority of individuals with MELAS syndrome [Hirano & Pavlakis 1994]. Elevated CSF protein rarely surpasses 100 mg/dL. Muscle biopsy * Ragged red fibers (RRFs) with the modified Gomori trichrome stain, which represent mitochondrial proliferation below the plasma membrane of the muscular fibers causing the contour of the muscle fiber to become irregular. These proliferated mitochondria also stain strongly with the succinate dehydrogenase (SDH) stain giving the appearance of ragged blue fibers. Although RRFs are present in many other mitochondrial diseases e.g., MERRF (myoclonic epilepsy with ragged red fibers), most of the RRFs in MELAS stain positively with the cytochrome c oxidase (COX) histochemical stain, unlike other mitochondrial diseases where RRFs do not react with COX. * An overabundance of mitochondria in smooth muscle and endothelial cells of intramuscular blood vessels, best revealed with the SDH stain ("strongly succinate dehydrogenase-reactive blood vessels," or SSVs) * Respiratory chain studies on muscle tissue: typically multiple partial defects, especially involving complex I and/or complex IV. However, biochemical results can also be normal. Note: Muscle biopsy is not required to make this diagnosis; molecular genetic testing is frequently used in lieu of muscle biopsy to establish the diagnosis. ### Establishing the Diagnosis Two sets of clinical diagnostic criteria for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) have been published: I. A clinical diagnosis of MELAS can be made if the following three criteria are met [Hirano et al 1992]: * Stroke-like episodes before age 40 years * Encephalopathy characterized by seizures and/or dementia * Mitochondrial myopathy is evident by the presence of lactic acidosis and/or ragged-red fibers (RRFs) on muscle biopsy. AND at least two of the following criteria are present: * Normal early psychomotor development * Recurrent headaches * Recurrent vomiting episodes II. A clinical diagnosis of MELAS can also be made in an individual with at least two category A and two category B criteria [Yatsuga et al 2012]: Category A criteria * Headaches with vomiting * Seizures * Hemiplegia * Cortical blindness * Acute focal lesions on neuroimaging (see Suggestive Findings, Brain Imaging) Category B criteria * High plasma or cerebrospinal fluid (CSF) lactate * Mitochondrial abnormalities on muscle biopsy (see Suggestive Findings, Suggestive Laboratory Findings). * A MELAS-related pathogenic variant (see Table 1) The diagnosis of MELAS is established in a proband who meets the clinical diagnostic criteria discussed above and who has a pathogenic variant in one of the genes listed in Table 1 identified by molecular genetic testing. Note: Pathogenic variants can usually be detected in mtDNA from leukocytes in individuals with typical MELAS; however, the occurrence of "heteroplasmy" in disorders of mtDNA can result in varying tissue distribution of mutated mtDNA. Hence, the pathogenic variant may be undetectable in mtDNA from leukocytes and may be detected only in other tissues, such as buccal mucosa, cultured skin fibroblasts, hair follicles, urinary sediment, or (most reliably) skeletal muscle. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, concurrent or serial single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with seizures and weakness are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of MELAS, molecular genetic testing approaches can include serial single-gene testing or use of a multigene panel. Serial single-gene testing can be considered if (1) mutation of a particular gene accounts for a large proportion of the condition or (2) clinical findings, laboratory findings, ancestry, or other factors indicate that mutation of a particular gene is most likely. * Typically, blood leukocyte DNA is initially tested for the m.3243A>G pathogenic variant in MT-TL1, which is present in approximately 80% of individuals with typical clinical findings. * If this is normal, targeted testing for the pathogenic variants m.3271T>C and m.3252A>G in MT-TL1 and m.13513G>A in MT-ND5 is considered next. A multigene panel that includes MT-TL1, MT-ND5, and other mtDNA genes of interest (see Table 1 and Differential Diagnosis) may also be considered. Note: (1) The genes included and the sensitivity of multigene panels vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. Entire mitochondrial genome sequencing that includes MT-TL1, MT-ND5, and other mtDNA genes of interest (see Table 1 and Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders characterized by seizures and weakness, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. Many laboratories require that the clinician specify if the mitochondrial genome should be included as part of the comprehensive genomic testing. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Genetic Causes of MELAS View in own window Gene 1, 2% of MELAS Attributed to Pathogenic Variants in This GeneProportion of Pathogenic Variants 3 Detectable by Sequence Analysis 4 MT-TL1>80%100% MT-ND5<10%100% MT-TC MT-TF MT-TH MT-TK MT-TL2 MT-TQ MT-TV MT-TW MT-TS1 MT-TS2 MT-ND1 MT-ND6 MT-CO2 MT-CO3 MT-CYBRare100% Pathogenic variants of any one of the genes included in this table account for >1% of MELAS. 1\. Genes are listed from most frequent to least frequent genetic cause of MELAS. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on pathogenic allelic variants detected. 4\. 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. ## Clinical Characteristics ### Clinical Description MELAS is a multisystem disorder with protean manifestations. The vast majority of affected individuals develop signs and symptoms of MELAS between ages two and 40 years. Childhood is the typical age of onset with 65%-76% of affected individuals presenting at or before age 20 years. Onset of symptoms before age two years or after age 40 years is uncommon (age<2 years: 5%-8% of individuals; age >40 years: 1%-6% of individuals). Individuals with MELAS frequently present with more than one initial clinical manifestation. The most common initial symptoms are seizures, recurrent headaches, stroke-like episodes, cortical vision loss, muscle weakness, recurrent vomiting, and short stature (Table 2). Table 3 summarizes the clinical manifestations of MELAS organized according to their prevalence [Hirano & Pavlakis 1994, Sproule & Kaufmann 2008, Yatsuga et al 2012, El-Hattab et al 2015]. ### Table 2. MELAS: Initial Clinical Manifestations View in own window FrequencyManifestations ≥25% * Seizures * Recurrent headaches * Stroke-like episodes * Cortical vision loss * Muscle weakness * Recurrent vomiting * Short stature 10%-24% * Altered consciousness * Impaired mentation * Hearing impairment * Diabetes mellitus (type 1 or 2) <10% * Developmental delay * Fever ### Table 3. MELAS: Additional Clinical Manifestations View in own window FrequencyManifestations ≥90% * Stroke-like episodes * Dementia * Epilepsy * Lactic acidemia * Ragged red fibers (RRFs) on muscle biopsy 7%-89% * Hemiparesis * Cortical vision loss * Recurrent headaches * Hearing impairment * Muscle weakness 50%-74% * Peripheral neuropathy * Learning disability * Memory impairment * Recurrent vomiting * Short stature 25%-49% * Basal ganglia calcification * Myoclonus * Ataxia * Episodic altered consciousness * Gait disturbance * Depression * Anxiety * Psychotic disorders * Diabetes mellitus (type 1 or 2) <25% * Optic atrophy * Pigmentary retinopathy * Progressive external ophthalmoplegia * Motor developmental delay * Cardiomyopathy * Cardiac conduction abnormalities * Nephropathy * Vitiligo Neurologic manifestations * Stroke-like episodes present clinically with partially reversible aphasia, cortical vision loss, motor weakness, headaches, altered mental status, and seizures with the eventual progressive accumulation of neurologic deficits. * Dementia affects intelligence, language, perception, attention, and memory function. * Both the underlying neurologic dysfunction and the accumulating cortical injuries due to stroke-like episodes contribute to dementia. * Executive function deficits have been observed despite the relative sparing of the frontal lobe on neuroimaging, indicating an additional diffuse neurodegenerative process in addition to the damage caused by the stroke-like episodes [Sproule & Kaufmann 2008]. * Epilepsy * Focal and primary generalized seizures can occur. * Primary generalized seizures in MELAS can occur in the context of normal neuroimaging or be accompanied by neuroimaging abnormalities including stroke-like episodes, white matter lesions, cortical atrophy, and corpus callosum agenesis or hypogenesis (see Suggestive Findings, Brain Imaging). * Seizures can occur in MELAS as a manifestation of a stroke-like episode or independently, and may even induce a stroke-like episode [Finsterer & Zarrouk-Mahjoub 2015]. * Migrainous headaches in the form of recurrent attacks of severe pulsatile headaches with frequent vomiting are typical in individuals with MELAS and can precipitate stroke-like episodes. These headache episodes are often more severe during the stroke-like episodes [Ohno et al 1997]. * Hearing impairment due to sensorineural hearing loss is usually mild, insidiously progressive, and often an early clinical manifestation [Sproule & Kaufmann 2008]. * Peripheral neuropathy is usually a chronic and progressive, sensorimotor, and distal polyneuropathy. Nerve conduction studies typically show an axonal or mixed axonal and demyelinating neuropathy [Kaufmann et al 2006b]. * Early psychomotor development is usually normal, although developmental delay can occasionally occur. * Psychiatric illnesses including depression, bipolar disorder, anxiety, psychosis, and personality changes can occur in MELAS [Anglin et al 2012]. Myopathy presents clinically as muscle weakness and exercise intolerance. Cardiac manifestations * Both dilated and hypertrophic cardiomyopathy have been observed, however, the more typical is a non-obstructive concentric hypertrophy [Sproule & Kaufmann 2008]. * Cardiac conduction abnormalities including Wolff-Parkinson-White syndrome has been reported occasionally [Sproule et al 2007]. Gastrointestinal manifestations. Recurrent or cyclic vomiting is common. Other manifestations include diarrhea, constipation, gastric dysmotility, intestinal pseudo-obstruction, recurrent pancreatitis, and failure to thrive [Fujii et al 2004]. Endocrine manifestations * Diabetes mellitus occurs occasionally, with an average age of onset of 38 years. Diabetes can be type 1 or type 2. Individuals with type 2 diabetes can initially be treated with diet or sulfonylurea, although significant insulinopenia can develop and affected individuals may require insulin therapy (see Management) [Maassen et al 2004]. * Short stature. Individuals with MELAS syndrome are typically shorter than their unaffected family members. Growth hormone deficiency has occasionally been reported [Yorifuji et al 1996]. * Hypothyroidism, hypogonadotropic hypogonadism, and hypoparathyroidism are infrequent manifestations [El-Hattab et al 2015]. Other manifestations * Renal manifestations that may include Fanconi proximal tubulopathy, proteinuria, and focal segmental glomerulosclerosis [Hotta et al 2001] * Pulmonary hypertension [Sproule et al 2008] * Dermatologic manifestations that may include vitiligo, diffuse erythema with reticular pigmentation, and hypertrichosis [Kubota et al 1999] * Chronic anemia [Finsterer 2011] Natural history and life expectancy. The disease progresses over years with episodic deterioration related to stroke-like events. The course varies from individual to individual. * In a cohort of 33 adults with the pathogenic m.3243A>G variant in MT-TL1 who were followed for three years, deterioration of sensorineural function, cardiac left-ventricular hypertrophy, EEG abnormalities, and overall severity were observed [Majamaa-Voltti et al 2006]. * In a natural history study of 31 individuals with MELAS and 54 symptomatic and asymptomatic obligate carrier relatives over a follow-up period of up to 10.6 years, neurologic examination, neuropsychological testing, and daily living scores significantly declined in all affected individuals with MELAS, whereas no significant deterioration occurred in carrier relatives. * The death rate was more than 17-fold higher in fully symptomatic individuals compared to carrier relatives. The average observed age at death in the affected MELAS group was 34.5±19 years (range 10.2-81.8 years). Of the deaths, 22% occurred in those younger than 18 years. * The estimated overall median survival time based on fully symptomatic individuals was 16.9 years from onset of focal neurologic disease [Kaufmann et al 2011]. * A Japanese prospective cohort study of 96 individuals with MELAS confirmed a rapidly progressive course within a five-year interval, with 20.8% of affected individuals dying within a median time of 7.3 years from diagnosis [Yatsuga et al 2012]. ### Causes of Phenotypic Variability For all mtDNA pathogenic variants, clinical expression depends on three factors: * Heteroplasmy. The presence of a mixture of mutated and normal mtDNA * Tissue distribution of mutated mtDNA * Threshold effect. The vulnerability of each tissue to impaired oxidative metabolism While the tissue vulnerability threshold probably does not vary substantially among individuals, mutational load and tissue distribution do vary and may account for the clinical diversity seen in individuals with MELAS. Correlations between the frequency of the more common clinical features and the level of mutated mtDNA in muscle, but not in leukocytes, have been observed [Chinnery et al 1997, Jeppesen et al 2006]. As-yet-undefined nuclear DNA factors may also modify the phenotypic expression of mtDNA pathogenic variants [Moraes et al 1993]. The m.3243A>G pathogenic variant, the most frequent variant associated with MELAS, is associated with diverse clinical manifestations (i.e., progressive external ophthalmoplegia, diabetes mellitus, cardiomyopathy, deafness) that collectively constitute a wide spectrum ranging from MELAS at the severe end to asymptomatic carrier status. More severe phenotypes may be the result of a higher abundance of the pathogenic variant in affected organs [El-Hattab et al 2015]. ### Genotype-Phenotype Correlations No clear genotype-phenotype correlations have been identified (see Causes of Phenotypic Variability). ### Penetrance In mtDNA-related disorders, penetrance typically depends on mutational load and tissue distribution, which show random variation within families (see Causes of Phenotypic Variability). ### Nomenclature Typically designated by the acronym MELAS, this disorder may also be referred to as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. ### Prevalence The prevalence of MELAS has been estimated to be 0.2:100,000 in Japan [Yatsuga et al 2012]. The prevalence of the m.3243A>G pathogenic variant was estimated to be 16:100,000–18:100,000 in Finland [Majamaa et al 1998, Uusimaa et al 2007]. An Australian study found a higher prevalence of the m.3243A>G pathogenic variant: 236:100,000 [Manwaring et al 2007]. ## Differential Diagnosis Clinical manifestations of MELAS can be seen in a wide variety of mitochondrial diseases (see Mitochondrial Disorders Overview). The differential diagnosis of acute stroke includes other causes of stroke in a young person: heart disease, carotid or vertebral diseases, sickle cell disease, vasculopathies, lipoprotein dyscrasias, venous thrombosis, moyamoya disease, complicated migraine (see Familial Hemiplegic Migraine), Fabry disease, and homocystinuria caused by cystathionine beta-synthase deficiency [Meschia & Worrall 2004, Meschia et al 2005]. Besides appropriate specific tests, a maternal history of other problems suggesting mitochondrial dysfunction (short stature, migraine, hearing loss, diabetes mellitus) can help orient the clinician toward the correct diagnosis. A MELAS-like phenotype with defects in nuclear genes including MRM2 [Garone et al 2017], FASTKD2 [Yoo et al 2017], and POLG [Cheldi et al 2013] has been reported. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MELAS, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: ### Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with MELAS View in own window System/ConcernEvaluationComment GrowthMeasurement of height & weight EyesOphthalmology evalTo screen for ptosis, optic atrophy, pigmentary retinopathy, ophthalmoplegia, vision deficits EarsAudiology evalTo detect hearing loss CardiovascularEchocardiogramTo screen for cardiomyopathy 1 ElectrocardiogramTo evaluate for conduction abnormalities 1 RenalUrinalysis & urine amino acid analysisTo evaluate for renal tubulopathy MusculoskeletalPT/OT assessmentFor individuals w/neurologic deficits NeurologicNeurologic evalTo assess for neurologic deficits 2 Head MRI w/MRSTo evaluate for pathologic changes at baseline EEGIf seizures are suspected Neuropsychiatric testingTo assess cognitive abilities & for evidence of dementia EndocrinologicFasting serum glucoseTo screen for diabetes mellitus 3 Glucose tolerance test OtherConsultation w/clinical geneticist &/or genetic counselor OT = occupational therapy; PT = physical therapy 1\. Consider referral to a cardiologist. 2\. Consider referral to a neurologist. 3\. Consider referral to an endocrinologist. ### Treatment of Manifestations Treatment for MELAS is primarily supportive. Arginine therapy. Recommendations for the management of stroke-like episodes in MELAS with arginine have been published. During the acute stroke-like episode, it is recommended to give a bolus of intravenous arginine (500 mg/kg for children or 10 g/m2 body surface area for adults) within three hours of symptom onset followed by the administration of a similar dosage of intravenous arginine as a continuous infusion over 24 hours for the next three to five days. Once an individual with MELAS has the first stroke-like episode, arginine should be administered prophylactically to reduce the risk of recurrent stroke-like episodes (see Prevention of Primary Manifestations). ### Table 6. Treatment of Manifestations in Individuals with MELAS View in own window Manifestation/ConcernTreatmentConsiderations/Other Overall disease processCoQ10 * Children: 5-10 mg/kg/day * Adults: 200–400 mg/dayin 3 divided doses May benefit some individuals 1 L-carnitine * Children: 100 mg/kg/day * Adults: 3 g/day in 3 divided doses Creatine * Children: 100 mg/kg/day * Adults: 2-5 g/day in 3 divided doses PtosisStandard therapyEyelid "crutches," blepharoplasty, or frontalis muscle-eyelid implantation could be considered. Sensorineural hearing lossStandard therapyCochlear implantation successful in some 2 CardiomyopathyStandard pharmacologic therapy 3Per cardiologist Cardiac conduction defects NephropathyStandard therapy Exercise intolerance & weaknessAerobic exercise 4 Stroke-like episodesArginine therapy (see above) 5Physical & occupational therapy after acute phase, as appropriate SeizuresTraditional anticonvulsant therapyAvoid valproic acid. (See Agents/Circumstances to Avoid.) Migraine headachesStandard analgesics Diabetes mellitus 6Dietary modificationMay be particularly successful in thin individuals Oral hypoglycemic agents 7Avoid metformin. (See Agents/Circumstances to Avoid.) Insulin therapy 8Per endocriologist CoQ10 = coenzyme Q10 1\. El-Hattab et al [2015] 2\. Scarpelli et al [2012] 3\. Individuals with MELAS can be suitable candidates for cardiac transplantation. Before transplantation, however, careful consideration of the multisystemic nature of the disease is indicated to determine the suitability of candidates [Bhati et al 2005]. 4\. Taivassalo & Haller [2004] 5\. Koenig et al [2016], El-Hattab et al [2017] 6\. Diabetes can be type 1 or type 2 7\. Typically sulfonylureas 8\. Maassen et al [2004] ### Prevention of Primary Manifestations Once an individual with MELAS has the first stroke-like episode, arginine should be administered prophylactically to reduce the risk of recurrent stroke-like episodes. A daily dose of 150 to 300 mg/kg/day oral arginine in three divided doses is recommended [Koenig et al 2016, El-Hattab et al 2017]. ### Prevention of Secondary Complications Because febrile illnesses may trigger acute exacerbations, individuals with MELAS should receive standard childhood vaccinations, flu vaccine, and pneumococcal vaccine. ### Surveillance Affected individuals and their at-risk relatives should be followed at regular intervals to monitor progression and the appearance of new symptoms. ### Table 7. Recommended Annual Surveillance for Individuals with MELAS View in own window System/ConcernAnnual Evaluation EyesOphthalmology EarsAudiology CardiovascularElectrocardiogram Echocardiogram RenalUrinalysis EndocrinologicFasting blood glucose ### Agents/Circumstances to Avoid Individuals with MELAS should avoid mitochondrial toxins such as: aminoglycoside antibiotics, linezolid, cigarettes, and alcohol. Valproic acid should be avoided in the treatment of seizures [Lin & Thajeb 2007]. Metformin should also be avoided because of its propensity to cause lactic acidosis [Sproule & Kaufmann 2008]. Dichloroacetate, which reduces lactate by activating the pyruvate dehydrogenase enzyme, should be avoided in MELAS syndrome. A study evaluating the effect of dichloroacetate in individuals with MELAS syndrome was terminated because of onset or worsening of peripheral neuropathy, indicating that dichloroacetate can be associated with peripheral nerve toxicity [Kaufmann et al 2006a]. ### Evaluation of Relatives at Risk Molecular genetic testing of at-risk maternal relatives may reveal individuals who have high mutational loads and are thus at risk of developing symptoms. No proven disease-modifying intervention exists at present. However, asymptomatic individuals can undergo regular surveillance for early detection of complications. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Infertility may preclude pregnancy in some affected individuals. Women with MELAS should receive genetic counseling prior to pregnancy. During pregnancy, affected or at-risk women should be monitored for the development of diabetes mellitus and respiratory insufficiency, which may require therapeutic interventions [Díaz-Lobato et al 2005]. ### Therapies Under Investigation The transfer of nuclear DNA from fertilized oocytes or zygotes harboring a mtDNA pathogenic variant to an enucleated recipient cell could theoretically prevent transmission of mtDNA diseases; proof of this concept has been demonstrated in pronuclear transfers from abnormally fertilized zygotes [Craven et al 2010]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MELAS	c0162671	26,254	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1233/	2021-01-18T21:13:52	{"mesh": ["D017241"], "synonyms": []}
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(April 2016) Basaloid squamous cell lung carcinoma SpecialtyOncology Basaloid squamous cell carcinoma (Bas-SqCC) is an uncommon histological variant of lung cancer composed of cells exhibiting cytological and tissue architectural features of both squamous cell lung carcinoma and basal cell carcinoma.[1] ## Contents * 1 Classification * 2 Pathogenesis * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 References * 8 External links ## Classification[edit] Lung cancer is a large and exceptionally heterogeneous family of malignancies.[2] Over 50 different histological variants of lung cancer are explicitly recognized within the fourth (2004) revision of the World Health Organization Classification of Lung Tumours ("WHO-2004").[1] Many of these entities are quite rare, have only been recently described, and remain poorly understood.[3] Basaloid forms of lung carcinoma were first described in the peer-reviewed medical literature by Dr. Elisabeth Brambilla and her colleagues in 1992.[4] In the third revision of the World Health Organization lung tumor typing and classification scheme, published in 1999, basaloid variants of both squamous cell lung carcinoma (SqCC) and large cell lung carcinoma (LCLC) were recognized as distinct entities.[3] In the fourth revision (2004) of the WHO system (currently the world standard) Bas-SqCC is classified as one of four recognized variants of squamous cell lung carcinoma.[1] As a variant of SqCC, it is considered a non-small cell lung cancer (NSCLC). ## Pathogenesis[edit] Both basaloid and squamous cell carcinomas have been shown to arise from pre-malignant lesions of dysplasia in the airways of the lung.[5] After continued exposure to tobacco smoke or other carcinogenic stimuli, cells in areas of severe dysplasia can suffer additional genetic damage that results in progression to a basaloid or squamous cell carcinoma in situ (CIS). CIS is a fully malignant lesion, but by definition, the cancer cells have not yet invaded beyond the tissue delimiting their original site of genesis.[citation needed] ## Diagnosis[edit] Like other forms of lung cancer, Bas-SqCC is ultimately diagnosed after a pathologist examines a tumor sample containing viable malignant cells and tissue under a light microscope and identifies certain particular characteristics.[citation needed] In the case of Bas-SqCC, it is essential that both evidence of squamous differentiation (i.e., intercellular bridges, production of keratin, tonofilament bundles) and basaloid architecture (i.e. prominent peripheral palisading of cell nuclei, organoid/lobular structures) are identified to make a correct diagnosis.[3][6] Immunohistochemical markers that have been suggested to be useful in making an accurate diagnosis of Bas-SqCC include positivity for p63 and high molecular weight keratin (i.e. 34betaE12), and lack of expression of thyroid transcription factor-1 (TTF-1).[7][8][9] Among other pulmonary malignancies, the main differential diagnoses in suspected cases of Bas-SqCC include the high-grade neuroendocrine carcinomas, such as small cell carcinoma and large cell neuroendocrine carcinoma. The issue of differential diagnosis is particularly acute when the pathologist must use a small biopsy specimen or cytology.[8][9] In addition, the basaloid variant of SqCC can be difficult to distinguish from other poorly differentiated squamous cell carcinomas.[10] ## Treatment[edit] For last several decades of the 20th century, all histological variants of NSCLC were generally treated identically. In the last decade, it has become apparent that different variants of malignant tumors generally exhibit diverse genetic, biological, and clinical properties, including response to treatment.[11][12] As patients with uncommon lung tumor variants, including tumors composed of mixtures of histological subtypes, tend to be excluded from clinical trials,[13] the most efficacious treatment regimen(s) for basaloid squamous cell carcinoma remain unknown. In general, these variants appear to be treated according to standard protocols in place for squamous cell carcinoma.[14] ## Prognosis[edit] Like nearly all other forms of NSCLC, the prognosis of basaloid squamous cell carcinoma is quite poor.[15] Although case numbers tend to be rather small, and the published studies statistically underpowered, much (but not all)[14] evidence suggests that basaloid squamous cell lung carcinomas may have a somewhat worse prognosis than "conventional" (i.e. non-basaloid) squamous cell lung carcinomas.[6][16][17] As survival has been noted to be worse in basaloid variants at earlier tumor stages (i.e. Stages I and II), the decreased survival could be attributable to earlier distant metastasis appearing during the natural history of these tumors, as compared to other squamous cell carcinomas and NSCLCs in general.[6] ## Epidemiology[edit] The true incidence and prevalence of basaloid squamous cell lung carcinoma remains unknown, but this form of lung cancer is considered relatively uncommon.[16] In one of the largest studies of this particular variant, Moro-Sibilot and co-workers found a 6.3% prevalence of Bas-SqCC among 1,418 consecutive NSCLC patients at their institution.[6] Basaloid carcinomas of the lung - like nearly all recognized variants of lung cancer - are highly associated with tobacco smoking.[6] Basaloid architecture in pulmonary carcinomas has been shown to be particularly prevalent in smokers with heavy exposure,[6] and squamous cell carcinoma has the strongest association with tobacco exposure than any other major cell type of NSCLC.[18] As compared to other forms of lung cancer, Bas-SqCC often occurs in those who are somewhat older than average.[6] As SqCC is also associated with presentation at somewhat older ages, the true relevance/effect size of the basaloid-age interaction remains unknown.[citation needed] Basaloid squamous cell carcinoma usually begins centrally, in the larger proximal bronchi.[16] Basaloid carcinoma primary in the lung may also occur in a multicentric form.[19] ## References[edit] 1. ^ a b c Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; Harris, Curtis C, eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 978-92-832-2418-1. Archived from the original (PDF) on 23 August 2009. Retrieved 27 March 2010. 2. ^ Roggli VL, Vollmer RT, Greenberg SD, McGavran MH, Spjut HJ, Yesner R (June 1985). "Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases". Hum. Pathol. 16 (6): 569–79. doi:10.1016/S0046-8177(85)80106-4. PMID 2987102. 3. ^ a b c Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y (December 2001). "The new World Health Organization classification of lung tumours". Eur. Respir. J. 18 (6): 1059–68. doi:10.1183/09031936.01.00275301. PMID 11829087. 4. ^ Brambilla E; Moro D; Veale D; et al. (September 1992). "Basal cell (basaloid) carcinoma of the lung: a new morphologic and phenotypic entity with separate prognostic significance". Hum. Pathol. 23 (9): 993–1003. doi:10.1016/0046-8177(92)90260-A. PMID 1381335. 5. ^ Lantuéjoul S, Salameire D, Salon C, Brambilla E (January 2009). "Pulmonary preneoplasia--sequential molecular carcinogenetic events". Histopathology. 54 (1): 43–54. doi:10.1111/j.1365-2559.2008.03182.x. PMID 19187179. S2CID 1027758. 6. ^ a b c d e f g Moro-Sibilot D; Lantuejoul S; Diab S; et al. (April 2008). "Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis". Eur. Respir. J. 31 (4): 854–9. doi:10.1183/09031936.00058507. PMID 18094005. 7. ^ Sturm N; Lantuéjoul S; Laverrière MH; et al. (September 2001). "Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung". Hum. Pathol. 32 (9): 918–25. doi:10.1053/hupa.2001.27110. PMID 11567220. 8. ^ a b Maleki Z (March 2011). "Diagnostic issues with cytopathologic interpretation of lung neoplasms displaying high-grade basaloid or neuroendocrine morphology". Diagn. Cytopathol. 39 (3): 159–67. doi:10.1002/dc.21351. PMID 21319315. S2CID 44844070. 9. ^ a b Crapanzano JP, Loukeris K, Borczuk AC, Saqi A (February 2011). "Cytological, histological, and immunohistochemical findings of pulmonary carcinomas with basaloid features". Diagn. Cytopathol. 39 (2): 92–100. doi:10.1002/dc.21335. PMID 21254456. S2CID 5738451. 10. ^ Wu M; Wang B; Gil J; et al. (May 2003). "p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung". Am. J. Clin. Pathol. 119 (5): 696–702. doi:10.1309/P5AB-R5KQ-89RN-JTFH. PMID 12760288. 11. ^ Rossi G, Marchioni A, Sartori G, Longo L, Piccinini S, Cavazza A (2007). "Histotype in non-small cell lung cancer therapy and staging: The emerging role of an old and underrated factor". Curr Resp Med Rev. 3: 69–77. doi:10.2174/157339807779941820. 12. ^ Vincent MD (August 2009). "Optimizing the management of advanced non-small-cell lung cancer: a personal view". Curr Oncol. 16 (4): 9–21. doi:10.3747/co.v16i4.465. PMC 2722061. PMID 19672420. 13. ^ "Find NCI-Supported Clinical Trials". 2016-06-23. 14. ^ a b Kim DJ, Kim KD, Shin DH, Ro JY, Chung KY (December 2003). "Basaloid carcinoma of the lung: a really dismal histologic variant?". Ann. Thorac. Surg. 76 (6): 1833–7. doi:10.1016/S0003-4975(03)01296-7. PMID 14667594. 15. ^ Merrill RM, Henson DE, Barnes M (September 1999). "Conditional survival among patients with carcinoma of the lung". Chest. 116 (3): 697–703. doi:10.1378/chest.116.3.697. PMID 10492274. 16. ^ a b c Wang LC, Wang L, Kwauk S, et al. (2011). "Analysis on the clinical features of 22 basaloid squamous cell carcinoma of the lung". J Cardiothorac Surg. 6: 10. doi:10.1186/1749-8090-6-10. PMC 3037842. PMID 21269455. 17. ^ Moro D, Brichon PY, Brambilla E, Veale D, Labat F, Brambilla C (June 1994). "Basaloid bronchial carcinoma. A histologic group with a poor prognosis". Cancer. 73 (11): 2734–9. doi:10.1002/1097-0142(19940601)73:11<2734::AID-CNCR2820731114>3.0.CO;2-4. PMID 8194014. 18. ^ Lubin JH, Blot WJ (August 1984). "Assessment of lung cancer risk factors by histologic category". J. Natl. Cancer Inst. 73 (2): 383–9. doi:10.1093/jnci/73.2.383. PMID 6087006. 19. ^ Bhagavathi S, Chang CH (February 2009). "Multicentric basaloid carcinoma of lung clinically mimicking metastatic carcinoma: a case report". Int J Surg Pathol. 17 (1): 68–71. doi:10.1177/1066896908316900. PMID 18480394. S2CID 11868856. ## External links[edit] * Lung Cancer Home Page. The National Cancer Institute site containing further reading and resources about lung cancer. * [1]. World Health Organization Histological Classification of Lung and Pleural Tumours. 4th Edition. * v * t * e Cancer involving the respiratory tract Upper RT Nasal cavity Esthesioneuroblastoma Nasopharynx Nasopharyngeal carcinoma Nasopharyngeal angiofibroma Larynx Laryngeal cancer Laryngeal papillomatosis Lower RT Trachea * Tracheal tumor Lung Non-small-cell lung carcinoma * Squamous-cell carcinoma * Adenocarcinoma (Mucinous cystadenocarcinoma) * Large-cell lung carcinoma * Rhabdoid carcinoma * Sarcomatoid carcinoma * Carcinoid * Salivary gland–like carcinoma * Adenosquamous carcinoma * Papillary adenocarcinoma * Giant-cell carcinoma Small-cell carcinoma * Combined small-cell carcinoma Non-carcinoma * Sarcoma * Lymphoma * Immature teratoma * Melanoma By location * Pancoast tumor * Solitary pulmonary nodule * Central lung * Peripheral lung * Bronchial leiomyoma Pleura * Mesothelioma * Malignant solitary fibrous tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Basaloid squamous cell lung carcinoma	c1710173	26,255	wikipedia	https://en.wikipedia.org/wiki/Basaloid_squamous_cell_lung_carcinoma	2021-01-18T18:38:11	{"wikidata": ["Q4866197"]}
## Clinical Features Kittur et al. (1987) presented the pedigree of an apparently unique family in which 7 members in 3 successive generations suffered from myoglobinuria. A brother and sister presented with episodic myalgia and pigmenturia at age 9 and 18, respectively. In the brother, several such episodes led to acute renal failure and death. Myoglobinuria was precipitated by fever, viral illness, prolonged exercise, or alcohol use. Between episodes, the creatine kinase was elevated, and neurologic examination showed mild weakness and enlarged calf muscles. In both sibs, electromyogram and nerve conduction velocity were normal. A third sib had pigmenturia on exercise. The father and a paternal uncle died of myoglobinuria and acute renal failure in their twenties. The paternal grandmother and a paternal grandaunt also had myoglobinuria. Martin-Du Pan et al. (1997) described a Swiss family in which 10 members in 4 successive generations suffered from episodes of myoglobinuria, in almost all cases induced by febrile illness. In 4 individuals, these episodes led to acute renal failure. In 1 of the patients, a mitochondrial disorder was suspected because of an abnormal increase in lactate levels during an exercise test and because of a subsarcolemmal accumulation of mitochondria in a muscle biopsy associated with a lack of cytochrome C oxidase in some muscle fibers. No mutation in mitochondrial DNA was identified, however. The authors suggested that the myoglobinuria in this family was caused by a nuclear-encoded mutation affecting the respiratory chain. The family contained 2 instances of male-to-male transmission. Inheritance The inheritance pattern of myoglobinuria in the families reported by Kittur et al. (1987) and Martin-Du Pan et al. (1997) was consistent with autosomal dominant inheritance. GU \- Acute renal failure Muscle \- Episodic myalgia \- \- Mild muscle weakness \- Enlarged calf muscles Misc \- Precipitated by fever, viral illness, prolonged exercise, or alcohol use Lab \- Myoglobinuria \- Creatine kinase elevated between episodes Inheritance \- Autosomal dominant type ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MYOGLOBINURIA, AUTOSOMAL DOMINANT	c1834567	26,256	omim	https://www.omim.org/entry/160010	2019-09-22T16:37:51	{"doid": ["0080108"], "mesh": ["C563546"], "omim": ["160010"], "orphanet": ["99846"]}
Genetic hyperferritinemia without iron overload is a rare biological anomaly defined as high serum ferritin levels without elevations of transferrin saturation, tissue or serum iron and characterized by an apparently asymptomatic clinical phenotype. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Genetic hyperferritinemia without iron overload	c4707880	26,257	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254704	2021-01-23T19:01:40	{"synonyms": ["Benign hyperferritinemia"]}
For general background and phenotypic information on stroke, see entry 601367. Mapping Gretarsdottir et al. (2002) reported the results of a genomewide search for susceptibility genes for the common forms of stroke. They cross-matched a population-based list of patients with stroke in Iceland with an extensive computerized genealogy database clustering 476 patients with stroke within 179 extended pedigrees. Linkage to 5q12 was detected, and the lod score of this locus met the criteria for genomewide significance (multipoint allele-sharing lod score of 4.40). A 20-cM region on 5q was physically and genetically mapped to obtain accurate marker order and intermarker distances. This locus on 5q12, which they designated STRK1, did not correspond to known susceptibility loci for stroke or for its risk factors and represented the first mapping of a locus for common stroke. Gretarsdottir et al. (2003) found variation in the PDE4D gene (600129) that showed strong association with stroke, especially for carotid and cardiogenic stroke, the forms related to atherosclerosis. Rosand et al. (2006) noted that 9 studies had been published as follow-up to the report of Gretarsdottir et al. (2002): 5 had claimed replication of the findings and 4 had not. A total of 11 SNPs in the PDE4D gene had been investigated among different phenotypic groups of stroke patients, such as small-vessel, large-vessel, cardioembolic, and all ischemic. Using haplotype data to examine the correlation between these various SNPs, Rosand et al. (2006) found that none of the SNPs was significantly correlated to the at-risk haplotype identified by Gretarsdottir et al. (2002). The authors concluded that the original PDE4D association with stroke should be viewed with caution. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	STROKE, SUSCEPTIBILITY TO, 1	c1847482	26,258	omim	https://www.omim.org/entry/606799	2019-09-22T16:09:59	{"omim": ["606799"], "synonyms": ["Alternative titles", "STRK1"]}
Fissured tongue Other namesScrotal tongue, Lingua plicata, Plicated tongue,[1]:1038 and Furrowed tongue[2]:800 SpecialtyOral medicine Fissured tongue is a benign condition characterized by deep grooves (fissures) in the dorsum of the tongue. Although these grooves may look unsettling, the condition is usually painless. Some individuals may complain of an associated burning sensation.[3] It is a relatively common condition, with a prevalence of between 6.8%[4] and 11%[5] found also in children. Often hereditary, may also be part of degenerative process. The prevalence of the condition increases significantly with age, occurring in 40% of the population after the age of 40.[6] ## Contents * 1 Presentation * 1.1 Associated conditions * 2 Cause * 3 Prevalence * 4 References * 5 External links ## Presentation[edit] The clinical appearance is considerably varied in both the orientation, number, depth and length of the fissure pattern. There are usually multiple grooves/furrows 2–6 mm in depth present. Sometimes there is a large central furrow, with smaller fissures branching perpendicularly. Other patterns may show a mostly dorsolateral position of the fissures (i.e. sideways running grooves on the tongue's upper surface). Some patients may experience burning or soreness. ### Associated conditions[edit] Fissured tongue is seen in Melkersson-Rosenthal syndrome (along with facial nerve paralysis and granulomatous cheilitis). It is also seen in most patients with Down syndrome, in association with geographic tongue, in patients with oral manifestations of psoriasis, and in healthy individuals. Fissured tongue is also sometimes a feature of Cowden's syndrome. ## Cause[edit] The cause is unknown, but it may be partly a genetic trait. Aging and environmental factors may also contribute to the appearance. ## Prevalence[edit] It is a relatively common condition, with an estimated prevalence of 6.8%[4]–11%.[5] Males are more commonly affected. The condition may be seen at any age, but generally affects older people more frequently. The condition also generally becomes more accentuated with age. The prevalence of the condition increases significantly with age, occurring in 40% of the population after the age of 40.[6] ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 3. ^ Scully, Crispian (2008). Oral and maxillofacial medicine: the basis of diagnosis and treatment (2nd ed.). Edinburgh: Churchill Livingstone. ISBN 9780443068188. 4. ^ a b FREQUENCY OF TONGUE ANOMALIES AMONG YEMENI CHILDREN IN DENTAL CLINICS Yemeni Journal for Medical Sciences 5. ^ a b Frequency of Tongue Anomalies in Primary School Of Lahidjan Rabiei M, Mohtashame Amiri Z, Masoodi Rad H, Niazi M, Niazi H. Frequency of Tongue Anomalies in Primary School Of Lahidjan. 3. 2003; 12 (45) :36-42 ] 6. ^ a b Geriatric Nutrition: The Health Professional's Handbook, Ronni Chernoff, (Jones & Bartlett Learning, 2006), page 176 ## External links[edit] Classification D * ICD-10: K14.5 * ICD-9-CM: 529.5, 750.13 * OMIM: 137400 * MeSH: D014063 * DiseasesDB: 32503 External resources * eMedicine: derm/665 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Fissured tongue	c0040412	26,259	wikipedia	https://en.wikipedia.org/wiki/Fissured_tongue	2021-01-18T18:44:56	{"mesh": ["D014063"], "umls": ["C0040412"], "wikidata": ["Q2504473"]}
22q11.2 distal deletion syndrome Other namesDistal del(22)(q11.2)[1] Schematic overview of the 22q11.2 deletion region [2] 22q11.2 distal deletion syndrome is a rare genetic condition caused by a tiny missing part of one of the body’s 46 chromosomes – chromosome 22. 22q11.2 distal deletion syndrome appears to be a recurrent genomic disorder distinct from DiGeorge syndrome (DGS; 188400) and velocardiofacial syndrome (VCFS; 192430).[3] The first published description of a person with a 22q11.2 distal deletion was in 1999.[4] There have since been hundreds of cases reported worldwide. 22q11.2 distal deletion syndrome seems to occur equally often in males and females. There are reports of people who are unaffected by carrying the deletion and only discovered it after their child was diagnosed. It seems that the 22q11.2 distal deletion can be "silent" and it is unknown how many people may have a silent form of this syndrome. ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Research * 6 See also * 7 References * 8 External links ## Presentation[edit] Every 22q11.2 distal deletion is unique, and each person may have different medical and developmental concerns. A number of common features have emerged: * Some children are likely to need support with learning. The amount of support needed by each child will vary * Speech is often delayed and some children have articulation problems * Growth delay both in the womb and after birth * Heart problems * Behavioral difficulties such as difficulties with concentration and anxiety * Subtly unusual facial features. Families may notice similarities between their own child and others with the deletion ## Cause[edit] 22q11.2 distal deletion occurs spontaneously; there is no known environmental cause. The genetic term for this is de novo; both parents typically have normal chromosomes. This is hereditary and people affected by distal deletion syndrome have a 50/50 chance of passing it to their children. De novo 22q11.2 distal deletions are caused by a mistake that is thought to occur when the parents’ sperm or egg cells are formed. At one point in the formation, all the chromosomes including the two chromosome 22s pair up and swap segments. To pair up precisely, each chromosome ‘recognizes’ matching or near-matching DNA sequences on its partner chromosome. However, throughout each chromosome there are many similar DNA sequences that can overlap incorrectly, and pair with the wrong sequence. It is believed that when the exchange of genetic material, known as ‘crossing over’, occurs after mismatching, it is unequal, looping out and excising a length of the chromosome. ## Diagnosis[edit] This section is empty. You can help by adding to it. (January 2018) ## Treatment[edit] This section is empty. You can help by adding to it. (January 2018) ## Research[edit] The features of 22q11.2 distal deletion syndrome are likely to be the result of the loss of a number of different genes found in this region. Most people have an approximately 0.4 to 2.1 Mb deletion (400'000- 2. Millions bases). Although the gene(s) responsible for the clinical features associated with 22q11.2 distal deletion syndrome have not been clearly defined, several potential candidate genes have been suggested. CRKL and MAPK1 genes have been suggested to have a role in the heart anomalies that are common in 22q11.2 distal deletion syndrome. MAPK1 has also been suggested to be associated with placental development and therefore having one copy of this gene missing in 22q11.2 distal deletion syndrome may be linked to the tendency for premature birth and IUGR.[5] The MAPK1 gene in mice has been shown to contribute to social behavior[6] and therefore may play a role in the behavioral problems found in some people with 22q11.2 distal deletion syndrome. Very distal deletions including the SMARCB1 gene are associated with an increased risk of malignant rhabdoid tumors. Very little is known about the magnitude of the risk for malignancy associated with distal 22q11.2 deletion syndrome but it is advised that people with a deletion that includes the SMARCB1 gene undergo careful, prolonged monitoring for this type of tumor. Most persons with 22q11 distal deletions do not have deletion of the SMARCB1 gene. ## See also[edit] * 22q11.2 deletion syndrome ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Distal 22q11.2 microdeletion syndrome". www.orpha.net. Retrieved 26 October 2019. 2. ^ Garavelli, L.; Rosato, S.; Wischmeijer, A.; Gelmini, C.; Esposito, A.; Mazzanti, L.; Franchi, F.; De Crescenzo, A.; Palumbo, O.; Carella, M.; Riccio, A. (2011). "22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review". Mol Syndromol. 2 (1): 35–44. doi:10.1159/000334262. PMC 3343753. PMID 22582037. 3. ^ Ben-Shachar, S; Ou Z; Shaw CA; Belmont JW; Patel MS; Hummel M; Amato S; Tartaglia N; Berg J; Sutton VR; Lalani SR; Chinault AC; Cheung SW; Lupski JR; Patel A (Jan 2008). "22q11.2 distal deletion: a recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome". Am J Hum Genet. 82 (1): 214–21. doi:10.1016/j.ajhg.2007.09.014. PMC 2253964. PMID 18179902. 4. ^ Saitta, SC; McGrath JM; Mensch H; Shaikh TH; Zackai EH; Emanuel BS Am J Hum Genet (August 1999). "A 22q11.2 deletion that excludes UFD1L and CDC45L in a patient with conotruncal and craniofacial defects". Am J Hum Genet. 65 (2): 562–6. doi:10.1086/302514. PMC 1377955. PMID 10417299. 5. ^ Fagberg, CR; Graakjaer J; Heinl UD; Ousager LB; Dreyer I; Kirchhoff M; Rasmussen AA; Lautrup CK; Birkebaek N; Sorensen K. (February 2013). "Heart defects and other features of the 22q11 distal deletion syndrome". Eur J Med Genet. 56 (2): 98–107. doi:10.1016/j.ejmg.2012.09.009. PMID 23063575. 6. ^ Satoh, Y; Endo S; Nakata T; Kobayashi Y; Yamada K; Ikeda T; Takeuchi A; Hiramoto T; Watanabe Y; Kazama T (Aug 2011). "ERK2 contributes to the control of social behaviors in mice". J Neurosci. 31 (33): 11953–67. doi:10.1523/JNEUROSCI.2349-11.2011. PMC 6623182. PMID 21849556. ## External links[edit] Classification D * OMIM: 611867 * MeSH: C567511 * v * t * e Chromosome abnormalities Autosomal Trisomies/Tetrasomies * Down syndrome * 21 * Edwards syndrome * 18 * Patau syndrome * 13 * Trisomy 9 * Tetrasomy 9p * Warkany syndrome 2 * 8 * Cat eye syndrome/Trisomy 22 * 22 * Trisomy 16 Monosomies/deletions * (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) * 1 * Wolf–Hirschhorn syndrome * 4 * Cri du chat syndrome/Chromosome 5q deletion syndrome * 5 * Williams syndrome * 7 * Jacobsen syndrome * 11 * Miller–Dieker syndrome/Smith–Magenis syndrome * 17 * DiGeorge syndrome * 22 * 22q11.2 distal deletion syndrome * 22 * 22q13 deletion syndrome * 22 * genomic imprinting * Angelman syndrome/Prader–Willi syndrome (15) * Distal 18q-/Proximal 18q- X/Y linked Monosomy * Turner syndrome (45,X) Trisomy/tetrasomy, other karyotypes/mosaics * Klinefelter syndrome (47,XXY) * XXYY syndrome (48,XXYY) * XXXY syndrome (48,XXXY) * 49,XXXYY * 49,XXXXY * Triple X syndrome (47,XXX) * Tetrasomy X (48,XXXX) * 49,XXXXX * Jacobs syndrome (47,XYY) * 48,XYYY * 49,XYYYY * 45,X/46,XY * 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid * Burkitt's lymphoma t(8 MYC;14 IGH) * Follicular lymphoma t(14 IGH;18 BCL2) * Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) * Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) * Acute lymphoblastic leukemia Myeloid * Philadelphia chromosome t(9 ABL; 22 BCR) * Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) * Acute promyelocytic leukemia t(15 PML,17 RARA) * Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other * Ewing's sarcoma t(11 FLI1; 22 EWS) * Synovial sarcoma t(x SYT;18 SSX) * Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) * Myxoid liposarcoma t(12 DDIT3; 16 FUS) * Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) * Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other * Fragile X syndrome * Uniparental disomy * XX male syndrome/46,XX testicular disorders of sex development * Marker chromosome * Ring chromosome * 6; 9; 14; 15; 18; 20; 21, 22 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	22q11.2 distal deletion syndrome	c2678480	26,260	wikipedia	https://en.wikipedia.org/wiki/22q11.2_distal_deletion_syndrome	2021-01-18T18:43:42	{"mesh": ["C567511"], "umls": ["C2678480"], "wikidata": ["Q17080095"]}
Keutel syndrome is an inherited condition characterized by cartilage calcification in the ears, nose, larnyx, trachea (voice box), and ribs; pulmonary artery stenoses; brachytelephalangism (short fingers and nails that resemble drumsticks); and facial dysmorphism. Less than 30 cases have been reported in the literature. The majority of affected individuals have been diagnosed during childhood. Other associated features may include hearing loss, recurrent otitis and/or sinusitis, mild intellectual disability, frequent respiratory infections, nasal speech and rarely, seizures, and short stature. This condition is inherited in an autosomal recessive fashion and is caused by mutations in the MGP gene. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Keutel syndrome	c1855607	26,261	gard	https://rarediseases.info.nih.gov/diseases/8449/keutel-syndrome	2021-01-18T17:59:36	{"mesh": ["C536167"], "omim": ["245150"], "umls": ["C1855607"], "orphanet": ["85202"], "synonyms": ["Pulmonic stenosis brachytelephalangism and calcification of cartilages"]}
Hypotrichosis - lymphedema - telangiectasia is an extremely rare syndromic lymphedema disorder characterized by early-onset hypotrichosis, childhood-onset lymphedema, and variable telangiectasia, particularly of the palms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome	c1841989	26,262	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=69735	2021-01-23T17:12:26	{"gard": ["12827"], "mesh": ["C536825"], "omim": ["137940", "607823"], "synonyms": ["Hypotrichosis-lymphedema-telangiectasia-membranoproliferative glomerulonephritis syndrome"]}
## Description Diffuse panbronchiolitis (DPB) is a rare chronic inflammatory obstructive pulmonary disease primarily affecting the respiratory bronchioles. 'Diffuse' refers to the distribution of the lesions throughout both lungs, and 'pan-' refers to the involvement of inflammation in all layers of the respiratory bronchioles. Onset of the disorder occurs in the second to fifth decade of life, and is clinically manifest by chronic cough, exertional dyspnea, and sputum production. Most patients also have chronic paranasal sinusitis. If untreated, the disorder progresses to bronchiectasis, respiratory failure, and death (summary by Poletti et al., 2006). Clinical Features Yamanaka et al. (1969) first described a chronic airway disease in Japan. They termed it diffuse panbronchiolitis to distinguish it from chronic bronchitis. Homma et al. (1983) reported numerous Japanese patients with diffuse panbronchiolitis. Patients with the disease had obstructive respiratory impairment, similar to emphysema, with occasional wheezing and coughing, similar to bronchial asthma. There was often sputum production, resembling chronic bronchitis. In the advanced stages of the disease, there was a large amount of purulent sputum and dilatation of proximal terminal conducting bronchioli, resembling bronchiectasis. Pathologic findings included chronic inflammation, with interstitial infiltration of lymphocytes, plasma cells, and histiocytes, exclusively located in the respiratory bronchioles and associated with thickening of the wall of the respiratory bronchiole. Some had extension of the inflammatory changes toward peribronchiolar tissues. Secondary ectasia of proximal bronchioli occurred in advanced stages. Homma et al. (1983) suggested that diffuse panbronchiolitis belongs to a distinct disease category and should be distinguished from more common diseases, because it often shows rapid progression with fatal outcome. The disease occurred more frequently in males, and onset was unrelated to age. More than 1,000 cases of probable diffuse panbronchiolitis and 82 histologically-confirmed cases had been collected in Japan. Kim et al. (1992) reported 5 Korean unrelated patients, including 2 women, with diffuse panbronchiolitis. Two were histologically proven, and 3 were suspected based on clinical symptoms and radiographic studies. All 5 had the typical respiratory symptoms and signs, including onset in their twenties of progressive wheezing, dyspnea, cough, and sputum production associated with crackles and rhonchi on auscultation. All patients also had a history of chronic sinusitis, and none had a history of smoking. High-resolution CT scan showed hyperinflated lungs with diffuse small nodular densities, 2 to 3 mm in diameter, and thickened bronchial walls, especially in the lower lung fields. Lung biopsies of 2 patients showed thickening of the wall of the bronchioles with infiltration of lymphocytes, plasma cells, and foamy histiocytes, which were also present in adjacent alveolar septa. All patients showed clinical improvement with low-dose erythromycin. Chu et al. (1992) reported a 33-year-old Chinese man who presented with a productive cough of yellowish sputum for several years, and progressive dyspnea on exertion that had been present for 1 year. Physical examination showed clubbing of the fingers and diffuse inspiratory crackles and some rhonchi on auscultation. Plain chest film showed diffuse fine nodular lesions in both lungs, and pulmonary function tests demonstrated obstructive ventilatory impairment. CT scan of the chest showed diffuse fine nodular infiltrations in both lung fields. Arterial blood gas analysis showed mild hypoxemia. Open lung biopsy specimen showed features of diffuse panbronchiolitis. Tsang et al. (1998) reported 7 additional Chinese patients who fulfilled the clinical criteria for DPB, including 3 women. All 7 patients were never smokers. Other Features Other features characteristic of diffuse panbronchiolitis are coexisting sinusitis, as well as infection with Haemophilus influenzae and Pseudomonas aeruginosa. Neutrophils and T lymphocytes, particularly CD8+ cells, together with the cytokines interleukin-8 (IL8; 146930) and macrophage inflammatory protein-1 (CCL3; 182283), are believed to play key roles in the development of DPB (Poletti et al., 2006). Mapping ### Association with HLA on Chromosome 6p21.3 Sugiyama et al. (1990) showed that HLA-B54 (142830), found only in East Asians, was strongly associated with diffuse panbronchiolitis (relative risk of 13.30; corrected p value less than 1.08 x 10(-10)). This positive association was further confirmed at the nucleotide-sequence level in a larger study by Keicho et al. (1998). Among 76 Japanese patients, 37% had the HLA-B5401 allele that is conserved in East Asians, as compared with 15% of 110 healthy volunteers (p = 0.0004). In addition, 4% of the patients possessed HLA-B5504, which is also unique to Asians, compared to no controls with HLA-B5504. In the Korean population, Park et al. (1999) showed that HLA-A (142800) was most significantly associated with DPB. Among 30 patients, there was an increased frequency of HLA-A11 (53.3%) compared to controls (17.5%; p = 1.2 x 10(-4); odds ratio (OR) of 5.4). HLA-B55 also showed a significant positive disease association (16.7% vs 3.5%; p = 0.05; OR, 5.5). The observations of Korean and Japanese associations with HLA suggested to the authors that the candidate gene(s) responsible for the disease susceptibility is located within the MHC class I region, most probably between HLA-A and HLA-B. Keicho et al. (2000) hypothesized that a founder mutation of a putative disease-susceptibility gene located between the HLA-B and HLA-A loci occurred on an ancestral chromosome bearing HLA-B54 and HLA-A11 in East Asia. They considered it conceivable that different historic recombination events around the disease locus resulted in disease associations with HLA-B54 in Japanese and HLA-A11 in Koreans. To test this hypothesis, Keicho et al. (2000) analyzed 14 genetic markers in the HLA class I region, including 9 highly polymorphic microsatellites, in 92 Japanese patients and 93 healthy controls. Seven markers, including B54 and A11, were significantly associated with the disease. All the haplotypes observed seemed to have diverged from a common ancestral haplotype in East Asians and shared a specific segment containing 3 consecutive markers between the S (CDSN; 602593) and GTF2H4 (601760) loci in the class I region. Of 20 Korean patients with diffuse panbronchiolitis, 17 also shared the combination of the disease-associated marker loci within the candidate region. Keicho et al. (2000) interpreted the results as indicating that an HLA-associated major histocompatibility gene for diffuse panbronchiolitis is located within the class I region 300-kb telomeric of the HLA-B locus on chromosome 6p21.3. ### Association Pending Confirmation In a Japanese population, Emi et al. (1999) demonstrated an association between a specific allele at the IL8 locus (146930) on chromosome 4q12-q13 and diffuse panbronchiolitis. Clinical Management Long-term treatment with macrolide antibiotics have resulted in significant improvement in the prognosis of this potentially fatal disease. The effect is attributed to an antiinflammatory and immunoregulatory action (Poletti et al., 2006). Population Genetics Diffuse panbronchiolitis predominantly affects East Asians, occurring with a frequency of 11 per 100,000 in the Japanese population (Homma et al., 1983). The disease has also been reported in Korea (Kim et al., 1992) and China (Chu et al., 1992; Tsang et al., 1998). A few cases have been reported outside Asia, notably in Asian emigrants (Hoiby, 1994; Corne, 1996). INHERITANCE \- Multifactorial RESPIRATORY \- Obstructive respiratory impairment \- Wheezing \- Cough \- Sputum production Nasopharynx \- Paranasal sinusitis, chronic Lung \- Rhonchi \- Crackles \- Chronic inflammation in the bronchioles \- Infiltration of plasma cells, lymphocytes, and histiocytes \- Foamy macrophages \- Thickening of the bronchiole wall \- Peribronchiolar tissue may be involved \- Bronchiole ectasia \- Bronchiectasis \- Hyperinflated lungs \- Disseminated small nodular shadows on x-ray \- Pathology is more severe in the lower lobes than in the upper lobes LABORATORY ABNORMALITIES \- Hypoxemia MISCELLANEOUS \- Onset in the second to fifth decade \- Progressive disorder \- Fatal outcome if untreated \- Increased frequency among individuals of East Asian descent ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan	PANBRONCHIOLITIS, DIFFUSE	c0878555	26,263	omim	https://www.omim.org/entry/604809	2019-09-22T16:11:48	{"mesh": ["C536174"], "omim": ["604809"], "orphanet": ["171700"], "synonyms": ["Alternative titles", "DPB", "PBLT"]}
Human disease (bacterial infection) For the band, see Impetigo (band). Impetigo Other namesSchool sores,[1] impetigo contagiosa A case of impetigo on the chin Pronunciation * /ɪmpɪˈtaɪɡoʊ/ SpecialtyDermatology, Infectious disease SymptomsYellowish skin crusts, painful[2][3] ComplicationsCellulitis, poststreptococcal glomerulonephritis[3] Usual onsetYoung children[3] DurationLess than 3 weeks[3] CausesStaphylococcus aureus or Streptococcus pyogenes which spreads by direct contact[3] Risk factorsDay care, crowding, poor nutrition, diabetes mellitus, contact sports, breaks in the skin[3][4] PreventionHand washing, avoiding infected people, cleaning injuries[3] TreatmentBased on symptoms[3] MedicationAntibiotics (mupirocin, fusidic acid, cephalexin)[3][5] Frequency140 million (2010)[6] Impetigo is a bacterial infection that involves the superficial skin.[2] The most common presentation is yellowish crusts on the face, arms, or legs.[2] Less commonly there may be large blisters which affect the groin or armpits.[2] The lesions may be painful or itchy.[3] Fever is uncommon.[3] It is typically due to either Staphylococcus aureus or Streptococcus pyogenes.[3] Risk factors include attending day care, crowding, poor nutrition, diabetes mellitus, contact sports, and breaks in the skin such as from mosquito bites, eczema, scabies, or herpes.[3][4] With contact it can spread around or between people.[3] Diagnosis is typically based on the symptoms and appearance.[3] Prevention is by hand washing, avoiding people who are infected, and cleaning injuries.[3] Treatment is typically with antibiotic creams such as mupirocin or fusidic acid.[3][5] Antibiotics by mouth, such as cephalexin, may be used if large areas are affected.[3] Antibiotic-resistant forms have been found.[3] Impetigo affected about 140 million people (2% of the world population) in 2010.[6] It can occur at any age, but is most common in young children.[3] In some places the condition is also known as "school sores".[1] Without treatment people typically get better within three weeks.[3] Recurring infections can occur due to colonization of the nose by the bacteria.[7][8] Complications may include cellulitis or poststreptococcal glomerulonephritis.[3] The name is from the Latin impetere meaning "attack".[9] ## Contents * 1 Signs and symptoms * 1.1 Contagious impetigo * 1.2 Bullous impetigo * 1.3 Ecthyma * 2 Causes * 2.1 Predisposing factors * 2.2 Transmission * 3 Diagnosis * 3.1 Differential diagnosis * 4 Prevention * 5 Treatment * 5.1 Alternative medicine * 6 Prognosis * 7 Epidemiology * 8 History * 9 References * 10 External links ## Signs and symptoms[edit] ### Contagious impetigo[edit] This most common form of impetigo, also called nonbullous impetigo, most often begins as a red sore near the nose or mouth which soon breaks, leaking pus or fluid, and forms a honey-colored scab,[10] followed by a red mark which heals without leaving a scar. Sores are not painful, but they may be itchy. Lymph nodes in the affected area may be swollen, but fever is rare. Touching or scratching the sores may easily spread the infection to other parts of the body.[11] Skin ulcers with redness and scarring also may result from scratching or abrading the skin.[citation needed] * Illustration of a woman with a severe facial impetigo. * Impetigo on the back of the neck. * A severe case of facial impetigo. ### Bullous impetigo[edit] Bullous impetigo after the bulla have broken Bullous impetigo, mainly seen in children younger than 2 years, involves painless, fluid-filled blisters, mostly on the arms, legs, and trunk, surrounded by red and itchy (but not sore) skin. The blisters may be large or small. After they break, they form yellow scabs.[11] ### Ecthyma[edit] Ecthyma, the nonbullous form of impetigo, produces painful fluid- or pus-filled sores with redness of skin, usually on the arms and legs, become ulcers that penetrate deeper into the dermis. After they break open, they form hard, thick, gray-yellow scabs, which sometimes leave scars. Ecthyma may be accompanied by swollen lymph nodes in the affected area.[11] ## Causes[edit] Impetigo is primarily caused by Staphylococcus aureus, and sometimes by Streptococcus pyogenes.[12] Both bullous and nonbullous are primarily caused by S. aureus, with Streptococcus also commonly being involved in the nonbullous form.[13] ### Predisposing factors[edit] Impetigo is more likely to infect children ages 2–5, especially those that attend school or day care.[3][14][1] 70% of cases are the nonbullous form and 30% are the bullous form.[3] Other factors can increase the risk of contracting impetigo such as diabetes mellitus, dermatitis, immunodeficiency disorders, and other irritable skin disorders.[15] Impetigo occurs more frequently among people who live in warm climates.[16] ### Transmission[edit] The infection is spread by direct contact with lesions or with nasal carriers. The incubation period is 1–3 days after exposure to Streptococcus and 4–10 days for Staphylococcus.[17] Dried streptococci in the air are not infectious to intact skin. Scratching may spread the lesions.[citation needed] ## Diagnosis[edit] Impetigo is usually diagnosed based on its appearance. It generally appears as honey-colored scabs formed from dried serum, and is often found on the arms, legs, or face.[12] If a visual diagnosis is unclear a culture may be done to test for resistant bacteria.[18] ### Differential diagnosis[edit] Other conditions that can result in symptoms similar to the common form include contact dermatitis, herpes simplex virus, discoid lupus, and scabies.[3] Other conditions that can result in symptoms similar to the blistering form include other bullous skin diseases, burns, and necrotizing fasciitis.[3] ## Prevention[edit] To prevent the spread of impetigo the skin and any open wounds should be kept clean and covered. Care should be taken to keep fluids from an infected person away from the skin of a non-infected person. Washing hands, linens, and affected areas will lower the likelihood of contact with infected fluids. Scratching can spread the sores; keeping nails short will reduce the chances of spreading. Infected people should avoid contact with others and eliminate sharing of clothing or linens.[19] Children with impetigo can return to school 24 hours after starting antibiotic therapy as long as their draining lesions are covered.[20] ## Treatment[edit] Antibiotics, either as a cream or by mouth, are usually prescribed. Mild cases may be treated with mupirocin ointments. In 95% of cases, a single 7-day antibiotic course results in resolution in children.[20][21] It has been advocated that topical antiseptics are inferior to topical antibiotics, and therefore should not be used as a replacement.[3] However, the National Institute for Health and Care Excellence (NICE) as of February 2020 recommends a hydrogen peroxide 1% cream antiseptic rather than topical antibiotics for localised non-bullous impetigo in otherwise well individuals.[22] This recommendation is part of an effort to reduce the overuse of antimicrobials that may contribute to the development of resistant organisms[23] such as MRSA. More severe cases require oral antibiotics, such as dicloxacillin, flucloxacillin, or erythromycin. Alternatively, amoxicillin combined with clavulanate potassium, cephalosporins (first-generation) and many others may also be used as an antibiotic treatment. Alternatives for people who are seriously allergic to penicillin or infections with methicillin-resistant Staphococcus aureus include doxycycline, clindamycin, and trimethoprim-sulphamethoxazole, although doxycycline should not be used in children under the age of eight years old due to the risk of drug-induced tooth discolouration.[20] When streptococci alone are the cause, penicillin is the drug of choice. When the condition presents with ulcers, valacyclovir, an antiviral, may be given in case a viral infection is causing the ulcer. ### Alternative medicine[edit] There is not enough evidence to recommend alternative medicine such as tea tree oil or honey.[3] ## Prognosis[edit] Without treatment, individuals with impetigo typically get better within three weeks.[3] Complications may include cellulitis or poststreptococcal glomerulonephritis.[3] Rheumatic fever does not appear to be related.[3] ## Epidemiology[edit] Globally, impetigo affects more than 162 million children in low to middle income countries.[24] The rates are highest in countries with low available resources and is especially prevalent in the region of Oceania.[24] The tropical climate and high population in lower socioeconomic regions contribute to these high rates.[25] Children under the age of 4 in the United Kingdom are 2.8% more likely than average to contract impetigo; this decreases to 1.6% for children up to 15-years-old.[26] As age increases, the rate of impetigo declines, but all ages are still susceptible.[25] ## History[edit] Impetigo was originally described and differentiated by William Tilbury Fox.[27] The word "impetigo" is the generic Latin word for "skin eruption", and stems from the verb impetere, "to attack" (as in "impetus").[28] Before the discovery of antibiotics, the disease was treated with an application of the antiseptic gentian violet, which was an effective treatment.[29] ## References[edit] 1. ^ a b c "Impetigo - school sores". Bettel Health Channel. Archived from the original on 5 July 2017. Retrieved 10 May 2017. 2. ^ a b c d Ibrahim, F; Khan, T; Pujalte, GG (December 2015). "Bacterial Skin Infections". Primary Care. 42 (4): 485–99. doi:10.1016/j.pop.2015.08.001. PMID 26612370. 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 Hartman-Adams, H; Banvard, C; Juckett, G (15 August 2014). "Impetigo: diagnosis and treatment". American Family Physician. 90 (4): 229–35. PMID 25250996. 4. ^ a b Adams, BB (2002). "Dermatologic disorders of the athlete". Sports Medicine. 32 (5): 309–21. doi:10.2165/00007256-200232050-00003. PMID 11929358. S2CID 34948265. 5. ^ a b Koning, S; van der Sande, R; Verhagen, AP; van Suijlekom-Smit, LW; Morris, AD; Butler, CC; Berger, M; van der Wouden, JC (18 January 2012). "Interventions for impetigo". The Cochrane Database of Systematic Reviews. 1: CD003261. doi:10.1002/14651858.CD003261.pub3. PMC 7025440. PMID 22258953. 6. ^ a b Vos, T (Dec 15, 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607. 7. ^ "Impetigo symptoms and treatments". www.nhsinform.scot. Retrieved 2020-05-26. 8. ^ "Impetigo and Ecthyma - Skin Disorders". Merck Manuals Consumer Version. Retrieved 2020-05-26. 9. ^ Limited, Wordsworth Editions (1993). Concise English Dictionary. Wordsworth Editions. p. 452. ISBN 9781840224979. Archived from the original on 2016-10-03. 10. ^ Cole C, Gazewood J (2007). "Diagnosis and treatment of impetigo". Am Fam Physician. 75 (6): 859–64. ISSN 0002-838X. PMID 17390597. Archived from the original on 2015-04-30. 11. ^ a b c Mayo Clinic staff (5 October 2010). "Impetigo". Mayo Clinic Health Information. Mayo Clinic. Archived from the original on 28 November 2012. Retrieved 25 August 2012. 12. ^ a b Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 843 ISBN 978-1-4160-2973-1 13. ^ Stulberg DL, Penrod MA, Blatny RA (2002). "Common bacterial skin infections". American Family Physician. 66 (1): 119–24. PMID 12126026. Archived from the original on 2007-09-29. 14. ^ "Impetigo (school sores)". www.health.govt.nz. Ministry of Health. Retrieved 14 September 2017. 15. ^ "Impetigo". Healthline. Archived from the original on 7 October 2016. Retrieved 7 October 2016. 16. ^ Tamparo, Carol; Lewis, Marcia (2011). Diseases of the Human Body. Philadelphia, PA: F.A. Davis Company. p. 194. ISBN 9780803625051. 17. ^ "ISDH: Impetigo". state.in.us. Archived from the original on 11 December 2014. Retrieved 11 December 2014. 18. ^ "Impetigo: MedlinePlus Medical Encyclopedia". medlineplus.gov. Archived from the original on 2016-11-07. 19. ^ "Self-management - Impetigo - Mayo Clinic". www.mayoclinic.org. Archived from the original on 16 October 2016. Retrieved 7 October 2016. 20. ^ a b c Baddour, Larry. "Impetigo". UpToDate. Retrieved 2018-08-15. 21. ^ Fleisher, Gary R.; Ludwig, Stephen (2010-01-01). Textbook of Pediatric Emergency Medicine. Lippincott Williams & Wilkins. p. 925. ISBN 9781605471594. Archived from the original on 2017-09-08. 22. ^ "Impetigo: antimicrobial prescribing - NICE guideline [NG153]". www.nice.org.uk. Retrieved 2020-05-26. 23. ^ Mahase, Elisabeth (15 August 2019). "Doctors should treat impetigo with antiseptics not antibiotics, says NICE". BMJ. 366: l5162. doi:10.1136/bmj.l5162. ISSN 1756-1833. PMID 31416810. S2CID 201018620. 24. ^ a b Bowen, Asha; Mahe, Antoine; Hay, Roderick; Andrews, Ross; Steer, Andrew; Tong, Steven; Carapetis, Jonathan (2015). "The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma". PLOS ONE. 10 (8): e0136789. Bibcode:2015PLoSO..1036789B. doi:10.1371/journal.pone.0136789. PMC 4552802. PMID 26317533. 25. ^ a b Romani, Lucia; Steer, Andrew; Whitfeld, Margot; Kaldor, John (2015). "Prevalence of scabies and impetigo worldwide: a systematic review". The Lancet Infectious Diseases. 15 (8): 960–7. doi:10.1016/S1473-3099(15)00132-2. PMID 26088526. 26. ^ George, Ajay; Rubin, Greg (2003). "A systematic review and meta-analysis of treatments for impetigo". British Journal of General Practice. 53 (491): 480–7. PMC 1314624. PMID 12939895. 27. ^ "Impetigo". The British Medical Journal. 1 (4185): 448. 1941. doi:10.1136/bmj.1.4185.445-a. JSTOR 20319413. S2CID 214846855. 28. ^ The Barnhart Concise Dictionary of Etymology. Harper Collins. 1995. ISBN 978-0-06-270084-1. 29. ^ MacDonald RS (October 2004). "Treatment of impetigo: Paint it blue". BMJ. 329 (7472): 979. doi:10.1136/bmj.329.7472.979. PMC 524121. PMID 15499130. ## External links[edit] * Impetigo at Curlie * Impetigo and Ecthyma at Merck Manual of Diagnosis and Therapy Professional Edition Classification D * ICD-10: L01 * ICD-9-CM: 684 * MeSH: D007169 * DiseasesDB: 6753 External resources * MedlinePlus: 000860 * eMedicine: derm/195 emerg/283 med/1163 ped/1172 * Patient UK: Impetigo * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Bacterial skin disease Gram +ve Firmicutes * Staphylococcus * Staphylococcal scalded skin syndrome * Impetigo * Toxic shock syndrome * Streptococcus * Impetigo * Cutaneous group B streptococcal infection * Streptococcal intertrigo * Cutaneous Streptococcus iniae infection * Erysipelas / Chronic recurrent erysipelas * Scarlet fever * Corynebacterium * Erythrasma * Listeriosis * Clostridium * Gas gangrene * Dermatitis gangrenosa * Mycoplasma * Erysipeloid of Rosenbach Actinobacteria * Mycobacterium-related: Aquarium granuloma * Borderline lepromatous leprosy * Borderline leprosy * Borderline tuberculoid leprosy * Buruli ulcer * Erythema induratum * Histoid leprosy * Lepromatous leprosy * Leprosy * Lichen scrofulosorum * Lupus vulgaris * Miliary tuberculosis * Mycobacterium avium-intracellulare complex infection * Mycobacterium haemophilum infection * Mycobacterium kansasii infection * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Rapid growing mycobacterium infection * Scrofuloderma * Tuberculosis cutis orificialis * Tuberculosis verrucosa cutis * Tuberculous cellulitis * Tuberculous gumma * Tuberculoid leprosy * Cutaneous actinomycosis * Nocardiosis * Cutaneous diphtheria infection * Arcanobacterium haemolyticum infection * Group JK corynebacterium sepsis Gram -ve Proteobacteria * α: Endemic typhus * Epidemic typhus * Scrub typhus * North Asian tick typhus * Queensland tick typhus * Flying squirrel typhus * Trench fever * Bacillary angiomatosis * African tick bite fever * American tick bite fever * Rickettsia aeschlimannii infection * Rickettsialpox * Rocky Mountain spotted fever * Human granulocytotropic anaplasmosis * Human monocytotropic ehrlichiosis * Flea-borne spotted fever * Japanese spotted fever * Mediterranean spotted fever * Flinders Island spotted fever * Verruga peruana * Brill–Zinsser disease * Brucellosis * Cat-scratch disease * Oroya fever * Ehrlichiosis ewingii infection * β: Gonococcemia/Gonorrhea/Primary gonococcal dermatitis * Melioidosis * Cutaneous Pasteurella hemolytica infection * Meningococcemia * Glanders * Chromobacteriosis infection * γ: Pasteurellosis * Tularemia * Vibrio vulnificus * Rhinoscleroma * Haemophilus influenzae cellulitis * Pseudomonal pyoderma / Pseudomonas hot-foot syndrome / Hot tub folliculitis / Ecthyma gangrenosum / Green nail syndrome * Q fever * Salmonellosis * Shigellosis * Plague * Granuloma inguinale * Chancroid * Aeromonas infection * ε: Helicobacter cellulitis Other * Syphilid * Syphilis * Chancre * Yaws * Pinta * Bejel * Chlamydia infection * Leptospirosis * Rat-bite fever * Lyme disease * Lymphogranuloma venereum Unspecified pathogen * Abscess * Periapical abscess * Boil/furuncle * Hospital furunculosis * Carbuncle * Cellulitis * Paronychia / Pyogenic paronychia * Perianal cellulitis * Acute lymphadenitis * Pilonidal cyst * Pyoderma * Folliculitis * Superficial pustular folliculitis * Sycosis vulgaris * Pimple * Ecthyma * Pitted keratolysis * Trichomycosis axillaris * Necrotizing fascitis * Gangrene * Chronic undermining burrowing ulcers * Fournier gangrene * Elephantiasis nostras * Blistering distal dactylitis * Botryomycosis * Malakoplakia * Gram-negative folliculitis * Gram-negative toe web infection * Pyomyositis * Blastomycosis-like pyoderma * Bullous impetigo * Chronic lymphangitis * Recurrent toxin-mediated perineal erythema * Tick-borne lymphadenopathy * Tropical ulcer [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Impetigo	c0021099	26,264	wikipedia	https://en.wikipedia.org/wiki/Impetigo	2021-01-18T18:55:45	{"mesh": ["D007169"], "umls": ["C0021099"], "wikidata": ["Q28971"]}
Lamellar ichthyosis is a rare genetic condition that affects the skin. Infants affected by lamellar ichthyosis are generally born with a shiny, waxy layer of skin (called a collodian membrane) that is typically shed within the first two weeks of life. The skin beneath the collodian membrane is red and scaly. Other signs and symptoms of the condition may include ectropion, lips that turn outwards, hair loss, palmoplantar hyperkeratosis (thick skin on the palms of the hands and/or soles of the feet), nail abnormalities, dehydration and respiratory problems. Although the condition may be caused by changes (mutations) in one of several different genes, approximately 90% of cases are caused by mutations in the TGM1 gene. Lamellar ichthyosis is generally inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Lamellar ichthyosis	c0079154	26,265	gard	https://rarediseases.info.nih.gov/diseases/10803/lamellar-ichthyosis	2021-01-18T17:59:32	{"mesh": ["D017490"], "icd-10": ["Q80.2"], "orphanet": ["313"], "synonyms": ["Classic lamellar ichthyosis", "Congenital lamellar ichthyosis", "LI"]}
Aldred syndrome Other namesRetinitis pigmentosa and intellectual disability due to Xp11.3 microdeletion Aldred syndrome is an X-linked recessive genetic disorder. It is mainly characterized by a form of mental retardation and retinitis pigmentosa. The syndrome was first described by geneticist Micheala Aldred in 1994.[1] ## Cause[edit] Aldred syndrome is caused by a deletion on the p11.3 area of the X-chromosome.[2] ## References[edit] 1. ^ Aldred, M. A.; Dry, K. L.; Knight-Jones, E. B.; Hardwick, L. J.; Teague, P. W.; Lester, D. H.; Brown, J.; Spowart, G.; Carothers, A. D. (November 1994). "Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa". American Journal of Human Genetics. 55 (5): 916–922. ISSN 0002-9297. PMC 1918325. PMID 7977353. 2. ^ "OMIM Entry - # 300578 - CHROMOSOME Xp11.3 DELETION SYNDROME". omim.org. Retrieved 2019-04-28. ## External links[edit] Classification D * ICD-10: H35.5 * OMIM: 300578 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Aldred syndrome	c1845136	26,266	wikipedia	https://en.wikipedia.org/wiki/Aldred_syndrome	2021-01-18T18:53:11	{"gard": ["8360"], "mesh": ["C564481"], "umls": ["C1845136", "C0795873"], "orphanet": ["85332"], "wikidata": ["Q42593774"]}
Schaeffer's sign Differential diagnosisPyramidal tract lesion Schaeffer's sign is a clinical sign in which squeezing the Achilles tendon elicits an extensor plantar reflex. It is found in patients with pyramidal tract lesions, and is one of a number of Babinski-like responses.[1] The sign takes its name from the German neurologist Max Schaeffer (1852-1923). ## References[edit] 1. ^ Kumar SP, Ramasubramanian D (December 2000). "The Babinski sign--a reappraisal". Neurol India. 48 (4): 314–8. PMID 11146592. Retrieved 2009-04-13. ## External links[edit] * Schäffer's reflex at Who Named It? 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Schaeffer's sign	None	26,267	wikipedia	https://en.wikipedia.org/wiki/Schaeffer%27s_sign	2021-01-18T18:28:22	{"wikidata": ["Q4393824"]}
For a phenotypic description and a discussion of genetic heterogeneity of the branchiootic syndrome, see BOS1 (602588). Clinical Features Marres and Cremers (1991) described a kindred in which 20 of 74 persons in 3 generations had external ear anomalies, preauricular sinuses (or cysts), and commissural lip pits, either in combination or separately. The external ear anomaly was relatively minor and was found in 12 persons. Eleven persons had unilateral or bilateral preauricular sinus. Two individuals without sinus or ear pit had a palpable preauricular cyst. Eight persons had one or more commissural lip pits, which had not been noticed before the study. Although Marres and Cremers (1991) had considered the disorder in their family to be distinct because of the absence of cervical fistulae and renal abnormalities and the presence of commissural lip pits, the report by Kumar et al. (2000) suggested that commissural lip pits may not be a true component of the syndrome; one individual who had not inherited the chromosome segment responsible in other affected members had only lip pits. Baker (1966) found commissural lip pits in 12% of Caucasoids and 20% of blacks. Congenital preauricular sinuses occurred more frequently in persons with pits than in those without pits. Mapping In a large family with BO syndrome, Kumar et al. (1998) excluded linkage to the 8q13 region previously identified in families with BOS1. Using a genomewide search strategy in the family reported by Marres and Cremers (1991) and Kumar et al. (1998), Kumar et al. (2000) identified genetic linkage, with a maximum lod score of 4.81 at a recombination fraction of zero, between the BO phenotype and the polymorphic marker D1S2757 in the 1q31 region. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- External ear anomaly \- Preauricular sinuses or cysts \- Congenital hearing loss Mouth \- Commissural lip pits ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	BRANCHIOOTIC SYNDROME 2	c1865143	26,268	omim	https://www.omim.org/entry/120502	2019-09-22T16:43:02	{"doid": ["0060232"], "mesh": ["C537104"], "omim": ["602588", "120502"], "orphanet": ["52429"], "synonyms": ["Alternative titles", "BO SYNDROME 2"]}
A number sign (#) is used with this entry because of the evidence that systemic nonneuropathic amyloidosis can be the result of mutation in the apolipoprotein A1 gene (APOA1; 107680), the fibrinogen alpha-chain gene (FGA; 134820), or the lysozyme gene (LYZ; 153450) Heterozygous mutation in the beta-2-microglobulin gene (B2M; 109700) has been reported to result in systemic nonneuropathic amyloidosis. One such family has been reported. Clinical Features Ostertag (1932, 1950) reported on a family with visceral amyloidosis. A woman, 3 of her children, and 1 of her grandchildren were affected with chronic nephropathy, arterial hypertension, and hepatosplenomegaly. Albuminuria, hematuria and pitting edema were early signs. The age of onset was variable. Death occurred about 10 years after onset. The visceral involvement by amyloid was found to be extensive. Maxwell and Kimbell (1936) described 3 brothers who died of visceral, especially renal, amyloidosis in their 40s. Chronic weakness, edema, proteinuria, and hepatosplenomegaly were features. McKusick (1974) followed up on the family reported by Maxwell and Kimbell (1936). The father of the 3 affected brothers died at age 72 after an automobile accident and their mother died suddenly at age 87 after being in apparent good health. A son of one of the brothers had frequent bouts of unexplained fever in childhood (as did his father and 2 uncles), accompanied at times by nonspecific rash. At the age of 35, proteinuria was discovered and renal amyloidosis was diagnosed by renal biopsy. For 2 years thereafter he displayed the nephrotic syndrome, followed in the next 2 years by uremia from which he died at age 39. Autopsy revealed amyloidosis, most striking in the kidneys but also involving the adrenal glands and spleen. Although some features of the family of Maxwell and Kimbell (1936) are similar to those of urticaria, deafness and amyloidosis (191900), no deafness was present in their family. Weiss and Page (1974) reported a family with 2 definite and 4 probable cases in 3 generations. Mornaghi et al. (1981, 1982) reported rapidly progressive biopsy-proved renal amyloidosis in 3 brothers, aged 49, 52 and 55, of Irish-American origin. None had evidence of a plasma cell dyscrasia, a monoclonal serum or urine protein, or any underlying chronic disease. Immunoperoxidase staining of 1 pulmonary and 1 renal biopsy specimen was negative for amyloid A (AA), amyloid L (AL) and prealbumin. The authors concluded that the disorder in the 3 brothers closely resembled that described by Ostertag (1932). Studying the proband of a kindred with the familial amyloidosis of Ostertag, Lanham et al. (1982) demonstrated permanganate-sensitive congophilia of the amyloid but found no immunofluorescent staining for amyloid A or prealbumin. They concluded that this amyloid may be chemically distinct from previously characterized forms. Libbey and Talbert (1987) described a case of nephropathic amyloidosis, presumably of the Ostertag type. In their case, the amyloid showed no staining for light chains or prealbumin. Involvement of the liver was associated with cholestasis. In the kindred reported by Lanham et al. (1982), 6 members in 2 generations showed the onset of renal disease between ages 23 and 45 years. The deposition of amyloid is characteristically interstitial rather than glomerular as seen in other forms of amyloidosis. The proband had the sicca syndrome. The details of their patient's family history were not given by Libbey and Talbert (1987). Zalin et al. (1991) described yet another family with the Ostertag type of familial nephropathic nonneuropathic amyloidosis. Petechial skin rash was a striking feature, and petechial hemorrhages were induced by minimal abrasion. Extensive amyloid deposition in the lungs was illustrated. Zalin et al. (1991) reported that the amyloid deposits contained apolipoprotein A-I; however, it was later shown that the disorder in this family was caused by a mutation in lysozyme (see 153450.0001). Vella et al. (2002) reported 2 patients with glaucoma due to primary nonneuropathic amyloidosis. Glaucoma complicating amyloidosis had been documented previously in familial amyloidotic polyneuropathy, and in association with primary localized orbital amyloidosis. One of their patients developed orbital amyloidoma and secondary glaucoma. After a sudden worsening of visual acuity, papilledema was found and (nonarteritic) anterior ischemic optic neuropathy was diagnosed. Tumor debulking and orbital decompression were performed. Tumor histology showed massive deposits of amyloid containing lambda chains. Postoperatively, glaucoma was controllable with topical therapy. The other patient had a 2-year history of weakness, persistent abdominal pain, paresthesias, and weight loss, and a 20-year history of open-angle glaucoma. This patient was found to have primary systemic amyloidosis on liver and rectal biopsies. Echocardiography showed restrictive cardiomyopathy with a diffuse hyperrefractile 'granular sparkling appearance.' Intraocular pressure was normal on topical therapy and ocular fundus examination showed hard drusen-like deposits bilaterally. The patient's course improved after 15 cycles of melphalan-prednisone treatment over 24 months. The authors stated that the incidence of primary amyloidosis-associated glaucoma might be underestimated because glaucoma in Western Europe and North America is less commonly treated surgically. Molecular Genetics In the family with hereditary nonneuropathic systemic amyloidosis previously studied by Zalin et al. (1991) and in another unrelated English family with the disease, Pepys et al. (1993) identified heterozygosity for 2 missense mutations in the LYZ gene, respectively (153450.0001 and 153450.0002). In a Peruvian family in which a brother and sister and the son of the brother died from renal amyloidosis, Benson et al. (1993) identified a mutation in the fibrinogen A alpha polypeptide gene (FGA; 134820.0012). In 2 large American kindreds of Irish descent with nephrotic syndrome due to renal amyloidosis, Uemichi et al. (1993, 1994) identified a missense mutation in the FGA gene (E526V; 134820.0013). In an American kindred with hereditary renal amyloidosis, Uemichi et al. (1996) identified a 1-bp deletion in the FGA gene (134820.0016), causing a frameshift and termination sequence at codon 548. In a French kindred with autosomal dominant hereditary renal amyloidosis, Asl et al. (1997) identified a different 1-bp deletion in the FGA gene, also resulting in termination at codon 548 (134820.0018). Systemic amyloidosis is the diagnosis in 2.5% of all renal biopsies, according to Davison (1985), and is the cause of death in more than 1 in 1,500 persons in the United Kingdom annually. Acquired monoclonal immunoglobulin light-chain amyloidosis (AL; see 254500), formerly known as primary amyloidosis, is the most common form of systemic amyloidosis and can respond to chemotherapy directed at the underlying plasma cell dyscrasia. Lachmann et al. (2002) studied 350 patients with systemic amyloidosis in whom a diagnosis of the AL type of the disorder had been suggested by clinical and laboratory data and by the apparent absence of a family history. They identified amyloidogenic mutations in 34 (9.7%) of the patients, all of whom had the diagnosis of hereditary amyloidosis confirmed by additional investigations. In 18 (5.1%) of the 350 patients, the E526V mutation in the FGA gene was identified; 13 of the patients had missense mutations in the transthyretin gene (176300); 2 patients had missense mutations in the APOA1 gene (107680); and 1 patient had the D67H mutation in the lysozyme gene (153450.0002). All 18 patients with the FGA E526V mutation were of northern European ancestry, and although none was aware of any relevant family history, genealogic studies revealed that 2 were cousins and that ancestors of 2 other patients lived in adjacent villages. A fifth patient retrospectively ascertained that her dizygotic twin had died of renal failure at the age of 76 years. The median age of the 18 patients at the time of presentation was 59 years; the youngest was in her thirties and the oldest was 78 years old. All presented with isolated renal dysfunction and proteinuria, and most had moderate hypertension; all had renal amyloid deposits, and splenic amyloid was present in all but 1 of the patients. Spontaneous splenic rupture occurred in 2 patients. Granel et al. (2005) described a patient diagnosed with systemic digestive and 'medullar' amyloidosis. (Grateau (2006) stated that the term 'medullar' referred to the involvement of bone marrow.) Primary (AL) amyloidosis was initially suspected, but results of immunohistochemical staining were negative for immunoglobulin kappa/lambda light chains. The results of a complementary search for lysozyme amyloidosis were positive in colonic mucosa. A missense mutation, a T-to-A transversion at the first nucleotide of codon 64 (W64R; 153450.0005), was found in the LYZ gene. Granel et al. (2005) pointed out that an incorrect diagnosis could have been made if complete analysis of the amyloid deposits had not been performed, and that amyloidoses of different types, i.e., AA, AL, transthyretin, lysozyme, or fibrinogen, can produce similar visceral involvement, but prognosis and treatment are completely different. In 4 affected members of a family with autosomal dominant visceral amyloidosis, Valleix et al. (2012) identified a heterozygous mutation in the B2M gene (D76N; 109700.0002). Studies on the recombinant D76N protein showed reduced stability of the fully folded mutant protein and significantly increased conversion of the mutant protein into fibrils with amyloid-like properties under physiologic conditions, whereas the wildtype protein did not aggregate at all. In mid-adult life, the patients developed slowly progressive chronic diarrhea with weight loss and sicca syndrome. One had sensorimotor axonal polyneuropathy and orthostatic hypotension and 2 had severe autonomic neuropathy. Postmortem examination of 1 patient, who died at age 70 years, showed extensive B2M-containing amyloid deposits in the spleen, liver, heart, salivary glands, and nerves. Colonic biopsy from another affected individual also contained B2M-containing amyloid deposits. Amyloid scintigraphy of 2 patients showed a heavy visceral amyloid burden in the spleen and adrenal glands, but not in heart. Valleix et al. (2012) noted that the amyloid deposition in this family was different from that observed in dialysis-related amyloidosis, in which B2M-amyloid accumulates around bones and joints. In addition, serum B2M was not increased in the patients with familial disease, whereas it is increased in those with dialysis-related amyloidosis. Clinical Management Bodin et al. (2010) demonstrated that administration of anti-human serum amyloid P component (SAP; 104770) antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. GU \- Nephropathy with hematuria \- Nephrotic syndrome \- Uremia Neuro \- Nonneuropathic Lab \- Generalized amyloid deposition \- Proteinuria \- Hematuria Skin \- Pitting edema \- Petechial skin rash Endocrine \- Hypertension Inheritance \- Autosomal dominant Misc \- Chronic weakness GI \- Hepatomegaly \- Cholestasis \- Splenomegaly ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	AMYLOIDOSIS, FAMILIAL VISCERAL	c0268389	26,269	omim	https://www.omim.org/entry/105200	2019-09-22T16:45:14	{"doid": ["0050636"], "mesh": ["C538249"], "omim": ["105200"], "orphanet": ["85450"], "synonyms": ["Familial renal amyloidosis", "AMYLOIDOSIS VIII", "GERMAN TYPE AMYLOIDOSIS", "Alternative titles", "Hereditary amyloid nephropathy", "AMYLOIDOSIS, SYSTEMIC NONNEUROPATHIC", "AMYLOIDOSIS, FAMILIAL RENAL", "Amyloidosis, Ostertag type", "Familial amyloid nephropathy", "Hereditary renal amyloidosis", "OSTERTAG TYPE AMYLOIDOSIS"]}
A rare, chronic cutaneous lupus erythematosus disease characterized by red or violaceous, initially pruritic (evolving to painful) papules and plaques located on acral areas (especially dorsal aspects of fingers and toes, while the nose and ear involvement is uncommon), exacerbated by cold and damp conditions, with fissuring and ulceration occasionally observed. Coexistence of discoid lupus erythematosus lesions elsewhere on the body and occasional progression to systemic lupus erythematosus may be associated. Histological examination and direct immunofluorescence studies reveal nonspecific inflammatory lupus erythematosus changes while results of cryoglobulin and cold agglutinin studies are negative. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Chilblain lupus	c0024145	26,270	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90280	2021-01-23T19:10:44	{"mesh": ["C535924"], "umls": ["C0024145"], "icd-10": ["L93.2"]}
Nemaline myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face, neck, and limbs. This weakness can worsen over time. Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). Mutations in at least six genes can cause nemaline myopathy. Some individuals with nemaline myopathy do not have an identified mutation. The genetic cause of the disorder is unknown in these individuals. Nemaline myopathy is usually inherited in an autosomal recessive pattern. Less often, this condition is inherited in an autosomal dominant pattern. Nemaline myopathy is divided into six types. You can search for information about a particular type of nemaline myopathy from the GARD Home page. Enter the name of the condition in the GARD search box and then select the type from the drop down menu. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Nemaline myopathy	c0206157	26,271	gard	https://rarediseases.info.nih.gov/diseases/12033/nemaline-myopathy	2021-01-18T17:58:47	{"mesh": ["D017696"], "orphanet": ["607"], "synonyms": ["Nemaline body disease", "Nemaline rod disease", "Rod body disease", "Rod-body myopathy", "Rod myopathy", "Congenital rod disease", "Nemaline rod myopathy", "NM"]}
Mucolipidosis III (ML III) is a rare and progressive metabolic disorder that involves our body’s ability to break down certain fats (mucolipids). Symptoms typically present around age 3 and include developmental delay, joint pain, thickened skin, heart valve abnormalities, and intellectual disabilities or learning problems. Many individuals with ML III develop low bone density (osteoporosis), which causes pain and may lead to bone fractures. Heart deformities and repeated respiratory infections can reduce the individual’s ability to breathe effectively and may result in death during mid-adulthood. ML III is caused by mutation in the GNPTAB gene, and is inherited in an autosomal recessive manner. Mucolipidosis III is diagnosed by testing the blood or urine for high levels of mucolipids, and the diagnosis can be confirmed by genetic testing. Treatment is focused on relieving the individual symptoms of each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mucolipidosis III alpha/beta	c0033788	26,272	gard	https://rarediseases.info.nih.gov/diseases/3806/mucolipidosis-iii-alphabeta	2021-01-18T17:58:57	{"mesh": ["D009081"], "omim": ["252600"], "umls": ["C0033788"], "orphanet": ["577"], "synonyms": ["ML3", "ML 3 A", "Pseudo-Hurler polydystrophy", "Mucolipidosis type 3A"]}
Atrial enlargement SpecialtyCardiology Atrial enlargement refers to a condition where the left atrium or right atrium of the heart is larger than would be expected. It can also affect both atria.[1] Types include: * Left atrial enlargement * Right atrial enlargement ## References[edit] 1. ^ "ECG Learning Center - An introduction to clinical electrocardiography". library.med.utah.edu. * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever This cardiovascular system 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Atrial enlargement	c0741276	26,273	wikipedia	https://en.wikipedia.org/wiki/Atrial_enlargement	2021-01-18T19:04:53	{"umls": ["C0741276"], "wikidata": ["Q4817543"]}
The King-Denborough syndrome (KDS) is a congenital myopathy associated with susceptibility to malignant hyperthermia, skeletal abnormalities and dysmorphic features with characteristic facial appearance. Although the cause of King-Denborough syndrome is not fully understood, at least some cases have been attributed to the ryanodine receptor gene (RYR1), which has been tied to malignant hyperthermia and central core 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	King Denborough syndrome	c1840365	26,274	gard	https://rarediseases.info.nih.gov/diseases/8433/king-denborough-syndrome	2021-01-18T17:59:36	{"mesh": ["C536883"], "omim": ["145600"], "orphanet": ["99741"], "synonyms": ["Anesthetic-induced malignant hyperpyrexia in children", "King syndrome"]}
## Description Focal epithelial hyperplasia is a benign hyperplasia of the oral mucosa induced by human papillomavirus (HPV) (Premoli-De-Percoco et al., 1993). Clinical Features Premoli-De-Percoco et al. (1993) demonstrated a familial aggregation of oral FEH in a Venezuelan family. DNA sequences of HPV were demonstrated in the affected individuals. HPV13 and HPV32 have been demonstrated as etiologic agents; HPV13 was demonstrated in this kindred. (See 226400 and 305350 for possible examples of skin disorders (epidermodysplasia verruciformis) due to genetic susceptibility to HPV.) In 2 of 4 sibs born of Mexican-American parents of Navajo and Comanche Native American lineage, Mealey et al. (1993) described FEH in association with leukocyte adhesion deficiency (116920). Population Genetics Oral focal epithelial hyperplasia is found predominantly in Eskimos and American Indians (Archard et al., 1965; Gomez et al., 1969). Inheritance The transmission pattern of focal epithelial hyperplasia in the family reported by Premoli-De-Percoco et al. (1993) was consistent with autosomal recessive inheritance. Misc \- Susceptibility to oral human papillomavirus (HPV) infection Mouth \- Focal epithelial hyperplasia of oral mucosa 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	FOCAL EPITHELIAL HYPERPLASIA, ORAL	c0206067	26,275	omim	https://www.omim.org/entry/229045	2019-09-22T16:27:52	{"doid": ["5362"], "mesh": ["D017573"], "omim": ["229045"], "synonyms": ["Alternative titles", "FEH, ORAL", "HECK DISEASE"]}
A number sign (#) is used with this entry because of evidence that ovarian dysgenesis-6 (ODG6) is caused by homozygous mutation in the NUP107 gene (607617) on chromosome 12q15. One such family has been reported. Description Ovarian dysgenesis-6 is characterized by absence of spontaneous pubertal development in females with elevated gonadotropin levels, small uterus, and absence of ovarian tissue on imaging studies. Males appear to be unaffected (Weinberg-Shukron et al., 2015). For a discussion of genetic heterogeneity of ovarian dysgenesis, see ODG1 (233300). Clinical Features Weinberg-Shukron et al. (2015) studied a girl from a large consanguineous Palestinian family who presented at age 15 years with absence of spontaneous puberty and had minimal breast development, pubertal hair at Tanner stage II, primary amenorrhea, and elevated luteinizing hormone (LH; see 152780) and follicle-stimulating hormone (FSH; see 136530) levels. Ultrasound and MRI of the pelvis showed a relatively small uterus, and ovaries were not detected. After 24 months of hormone replacement therapy, she had achieved mean familial height, secondary sexual characteristics, and regular menstruation. She had an affected younger sister and 3 affected female cousins, who all presented with absence of spontaneous puberty and elevated gonadotropic hormones, with small uterus and absent ovaries on imaging studies. All men in the family had normal pubertal development, and married men had multiple children. Inheritance The transmission pattern of ovarian dysgenesis in the family reported by Weinberg-Shukron et al. (2015) was consistent with autosomal recessive inheritance. Mapping In a large Palestinian family in which 5 females had ovarian dysgenesis, Weinberg-Shukron et al. (2015) performed homozygosity mapping and identified 2 large regions of homozygosity, spanning a total of 9.3 Mb, on chromosomes 4 (chr4:152,221,451-157,617,198, GRCh37) and 12 (chr12:68,756,371-72,742,353, GRCh37). There were no obvious functional candidate genes in either region. Molecular Genetics In 2 affected cousins from a large Palestinian family with ovarian dysgenesis, Weinberg-Shukron et al. (2015) performed whole-exome sequencing and identified homozygosity for a missense mutation (D447N; 607617.0005) that segregated with disease in the family and was not found in 150 ethnically matched controls. Although male fertility appeared to be normal in the family, there were no homozygotes among the male family members tested. INHERITANCE \- Autosomal recessive GENITOURINARY Internal Genitalia (Female) \- Absent or streak ovaries \- Small uterus ENDOCRINE FEATURES \- No spontaneous puberty \- Elevated luteinizing hormone (LH, see 152780 ) levels \- Elevated follicle-stimulating hormone (FSH, see 136530 ) levels MISCELLANEOUS \- Male fertility does not appear to be affected \- Based on report of one Palestinian family (last curated August 2018) MOLECULAR BASIS \- Caused by mutation in the 107-kD nucleoporin gene (NUP107, 607617.0005 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	OVARIAN DYSGENESIS 6	c0685837	26,276	omim	https://www.omim.org/entry/618078	2019-09-22T15:43:43	{"doid": ["0080498"], "mesh": ["D023961"], "omim": ["618078"], "orphanet": ["243"]}
2-Hydroxyglutaric aciduria Alpha-Hydroxyglutaric acid 2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in ones urine. It is either autosomal recessive or autosomal dominant.[1] ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 3.1 Classification * 3.1.1 L-2-hydroxyglutaric aciduria * 3.1.2 D-2-hydroxyglutaric aciduria * 3.1.3 Combined D-2- and L-2-hydroxyglutaric aciduria * 4 Treatment * 5 See also * 6 References * 7 External links ## Presentation[edit] The signs/symptoms of this condition are consistent with the following:[2] * Intellectual disability, * Muscular hypotonia * Encephalitis * Seizures * Aphasia ## Cause[edit] This section is empty. You can help by adding to it. (January 2017) Most forms of 2-Hydroxyglutaric aciduria have an autosomal recessive pattern of inheritance. ## Diagnosis[edit] ### Classification[edit] 2-hydroxyglutaric aciduria is an organic aciduria, and because of the stereoisomeric property of 2-hydroxyglutarate different variants of this disorder are distinguished: #### L-2-hydroxyglutaric aciduria[edit] The L-2 form is more common, severe, and mainly affects the central nervous system. The basal ganglia are affected, and cystic cavitations in the white matter of the brain are common, beginning in infancy. This form is chronic, with early symptoms such as hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.[3] It is associated with L2HGDH, which encodes L-2-hydroxyglutarate dehydrogenase.[4] L-2-hydroxyglutarate is produced by promiscuous action of malate dehydrogenase on 2-oxoglutarate, and L-2-hydroxyglutarate dehydrogenase is an example of a metabolite repair enzyme that oxidizes L-2-hydroxyglutarate back to 2-oxoglutarate.[5] #### D-2-hydroxyglutaric aciduria[edit] The D2 form is rare, with symptoms including macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness.[6] It is caused by recessive mutations in D2HGDH[7] (type I) or by dominant gain-of-function mutations in IDH2[8] (type II). #### Combined D-2- and L-2-hydroxyglutaric aciduria[edit] The combined form is characterized by severe early-onset epileptic encephalopathy and absence of developmental progress.[9] It is caused by recessive mutations in SLC25A1 encoding the mitochondrial citrate carrier.[10] ## Treatment[edit] The treatment of 2-Hydroxyglutaric aciduria is based on seizure control, the prognosis depends on how severe the condition is.[11] ## See also[edit] * 2-hydroxyglutarate synthase * 2-hydroxyglutarate dehydrogenase * Hydroxyacid-oxoacid transhydrogenase * Alpha-Hydroxyglutaric acid ## References[edit] 1. ^ Reference, Genetics Home. "2-hydroxyglutaric aciduria". Genetics Home Reference. Retrieved 25 January 2017. 2. ^ "L-2-hydroxyglutaric aciduria \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 25 January 2017. 3. ^ Seijo-Martinez M, Navarro C, Castro del Rio M, Vila O, Puig M, Ribes A, Butron M (2005). "L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings". Arch. Neurol. 62 (4): 666–670. doi:10.1001/archneur.62.4.666. PMID 15824270. 4. ^ Topçu M, Jobard F, Halliez S, et al. (November 2004). "L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1". Hum. Mol. Genet. 13 (22): 2803–11. doi:10.1093/hmg/ddh300. PMID 15385440. 5. ^ Van Schaftingen, E.; Rzem, R.; Veiga-da-Cunha, M. (2009-04-01). "L: -2-Hydroxyglutaric aciduria, a disorder of metabolite repair". Journal of Inherited Metabolic Disease. 32 (2): 135–142. doi:10.1007/s10545-008-1042-3. ISSN 1573-2665. PMID 19020988. S2CID 27702186. 6. ^ Nyhan WL, Shelton GD, Jakobs C, Holmes B, Bowe C, Curry CJ, Vance C, Duran M, Sweetman L (1995). "D-2-hydroxyglutaric aciduria". J. Child Neurol. 10 (2): 137–142. doi:10.1177/088307389501000216. PMID 7782605. S2CID 19395651. 7. ^ Struys EA, Salomons GS, Achouri Y, Van Schaftingen E, Grosso S, Craigen WJ, Verhoeven NM, Jakobs C (Jan 2005). "Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria". Am J Hum Genet. 76 (2): 358–60. doi:10.1086/427890. PMC 1196381. PMID 15609246. 8. ^ Kranendijk M, Struys EA, van Schaftingen E, et al. (2010). "IDH2 mutations in patients with D-2-hydroxyglutaric aciduria". Science. 330 (6002): 336. Bibcode:2010Sci...330..336K. doi:10.1126/science.1192632. PMID 20847235. S2CID 206527781. 9. ^ Muntau A, Röschinger W, Merkenschlager A, van der Knaap MS, et al. (2000). "Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria?". Neuropediatrics. 31 (3): 137–40. doi:10.1055/s-2000-7497. PMID 10963100. 10. ^ Nota B; et al. (2013). "Deficiency in SLC25A1, Encoding the Mitochondrial Citrate Carrier, Causes Combined D-2- and L-2-Hydroxyglutaric Aciduria". The American Journal of Human Genetics. 92 (4): 627–631. doi:10.1016/j.ajhg.2013.03.009. PMC 3617390. PMID 23561848. 11. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: D 2 hydroxyglutaric aciduria". www.orpha.net. Retrieved 25 January 2017. ## External links[edit] Classification D * OMIM: 600721 236792 613657 615182 * DiseasesDB: 34515 * SNOMED CT: 698870008 External resources * Orphanet: 19 * 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 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[Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	2-Hydroxyglutaric aciduria	c2746066	26,277	wikipedia	https://en.wikipedia.org/wiki/2-Hydroxyglutaric_aciduria	2021-01-18T18:31:02	{"gard": ["10761"], "mesh": ["C535306"], "umls": ["C2746066"], "orphanet": ["19"], "wikidata": ["Q4596888"]}
Kleine–Levin syndrome Other namesFamilial hibernation syndrome[1] SpecialtyNeurology Kleine–Levin syndrome (KLS) is a rare disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Many patients also experience hyperphagia, hypersexuality and other symptoms. Patients generally experience recurrent episodes of the condition for more than a decade and may return at a later age. Individual episodes generally last more than a week, sometimes lasting for months. The condition greatly affects the personal, professional, and social lives of sufferers. The severity of symptoms and the course of the syndrome vary between sufferers. Patients commonly have about 20 episodes over about a decade. Several months generally elapse between episodes. The onset of the condition usually follows a viral infection; several different viruses have been observed to trigger KLS. It is generally only diagnosed after similar conditions have been excluded; MRI, CT scans, lumbar puncture, and toxicology tests are used to rule out other possibilities. The syndrome's mechanism is not known, but the thalamus is thought to possibly play a role. SPECT has shown thalamic hypoperfusion of patients during episodes. KLS is very rare, occurring at a rate of 1 in 1 million, which limits research into genetic factors. The condition primarily affects adolescent males, though females can also be affected and the age of onset varies. There is no known cure, and there is little evidence supporting drug treatment. Lithium has been reported to have limited effects in case reports, decreasing the length of episodes and duration between them in some patients.[2] Stimulants have been shown to promote wakefulness during episodes, but they do not counteract cognitive symptoms or decrease the duration of episodes. The condition is named after Willi Kleine and Max Levin,[3] who described cases of the disease in the early 20th century. It was added to the International Classification of Sleep Disorders in 1990. ## Contents * 1 Symptoms * 2 Cause * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 History * 9 References * 10 Bibliography * 11 External links ## Symptoms[edit] Patients with Kleine–Levin syndrome (KLS) experience recurring episodes of prolonged sleep (hypersomnia).[4] In most cases, patients sleep 15 to 21 hours a day during episodes.[5] Excessive appetite (hyperphagia) and unusual cravings are present in half to two thirds of cases.[5][6][7] About half of patients, mainly male patients, experience dramatically increased sexual urges (hypersexuality).[8][6] Several other symptoms usually accompany the syndrome, including marked changes in mood and cognitive ability.[4] Derealization and severe apathy are present in at least 80 percent of cases.[9] About one third of patients experience hallucinations or delusions.[6] Depression and anxiety occur less commonly; one study found them in about 25 percent of patients.[9] Individuals usually cannot remember what happened during episodes.[5] Repetitive behaviors and headaches are commonly reported.[6] Some patients act very childlike during episodes,[10] and communication skills and coordination sometimes suffer.[5] Sleep studies of KLS show varying results based on the amount of time the patient is observed. Slow wave sleep is often reduced at the beginning of episodes, and REM sleep is reduced near the end.[11] Conversely, REM sleep is often normal at the beginning, and slow wave sleep is often normal by the conclusion.[12] Stage two non-rapid eye movement sleep is often interrupted during KLS. Studies also show that stage one and three non-rapid eye movement sleep become more efficient when the episodes end.[13] The Multiple Sleep Latency Test has yielded inconsistent results when given to KLS patients.[14] In many cases, hours are spent in a withdrawn sleep-like state while awake during episodes.[11] Most sleep studies have been performed while subject is near the end of their episodes.[12] Some patients experience brief insomnia and become very happy and talkative after the episode ends.[5] The first time a patient experiences KLS, it usually occurs along with symptoms that are similar to those of the flu or encephalitis. In at least 75 percent of cases, symptoms occur after an airway infection or a fever. Viruses observed before the development of the condition include Epstein-Barr virus, varicella zoster virus, herpes zoster virus, influenza A virus subtypes, and adenovirus. Several days after symptoms first occur, patients become very tired.[8] In cases that occur after an infection, KLS usually starts within three to five days for teenagers and fewer for children.[15] In other cases, alcohol consumption, head injury, or international travel precede symptoms.[8][13] Lifestyle habits, such as stress, alcohol abuse and lack of sleep and stress, have also been proposed as possible triggers.[4] First episodes of KLS are preceded by a clear event in about 90 percent of cases.[7] Recurrences generally do not have clear triggers; only about 15 percent have a precipitating event.[16] The condition generally disrupts the social lives and academic or professional obligations of sufferers.[4][8] Some patients also gain weight during episodes.[8] The most severe cases cause a long-term impact on mood and cognitive attention.[8] In rare cases, patients experience long-term memory problems.[5] In patients with KLS, MRI and CT scans show normal brain morphology. When SPECT is performed, hypoperfusion can often be observed in the brain,[17] particularly in the thalamic and frontotemporal areas.[7] The hypoperfusion is significantly diminished between episodes.[18] Serum biology, c-reactive proteins and leptins, the hormonal pituitary axis, and protein in the cerebral spinal fluid (CSF) are normal in KLS patients.[19] ## Cause[edit] It is not known what causes KLS, but several mechanisms have been proposed. One possible explanation is hypothalamic or circadian dysfunction.[4] The thalamus probably plays a role in the out-of-control sleeping,[20] and patients with diencephalic–hypothalamic dysfunction caused by tumors experience symptoms similar to those of KLS patients.[4] Specifically, the medial temporal regions of the thalamus may be involved,[21] although examinations of KLS patients have not consistently found abnormalities in this area.[7] The temporal lobe also appears to play a role in the condition, possibly causing cognitive difficulties. The apathy and disinhibition found in some KLS sufferers suggest that the condition may include frontal lobe dysfunction as well. The involvement of the thalamus, temporal lobe, and frontal lobe of the brain suggests that there is a multifocal, localized encephalopathy. There are also persistent subclinical abnormalities in KLS sufferers.[20] Another possible explanation concerns the metabolism of serotonin and dopamine. An imbalance in the neurotransmitter pathways of these chemicals could play a role.[4] Viral infections have also been suggested as a possible cause. Evidence for their role includes lesions found in autopsies.[4] CSF samples from KLS patients indicate that the condition has a different cause than influenza-associated encephalopathy.[15] Triggers of KLS may also affect the blood-brain barrier, which could play a role in the condition.[20] There is limited evidence of what role hypocretin may play, although it often influences hypersomnia.[15] Androgen might (indirectly) block melatonin receptors, possibly by means of vasodilation, and cause cholinergic abnormalities in some cases of Kleine–Levin syndrome.[22] Because KLS occurs at a much higher rate in Jews and in some families, it is likely that there is some genetic component in addition to environmental factors.[20] Genetic studies hold promise for understanding the disease, but they have yielded inconsistent results[19] and few patients are available for testing.[20] Epilepsy and depression do not appear to cause KLS. The condition's rapid onset after infections indicates that the immune system is not to blame.[20] One study has suggested a link to the gene LMOD3 on chromosome 3.[23] ## Diagnosis[edit] KLS can be diagnosed when there is confusion, apathy, or derealization in addition to frequent bouts of extreme tiredness and prolonged sleep.[8] The earliest it can be diagnosed is the second episode, this is not common.[15] The condition is generally treated as a diagnosis of exclusion.[7] Because KLS is rare, other conditions with similar symptoms are usually considered first.[17] MRIs can determine if the symptoms are caused by certain brain disorders, stroke, and multiple sclerosis. Lumbar puncture can determine if encephalitis is the cause. KLS must be differentiated from substance abuse by toxicology tests.[17] The use of electroencephalography (EEG) can exclude temporal status epilepticus from consideration. EEGs are normal in about 70% of KLS patients, but background slowing may sometimes be detected.[17][11] In addition, low-frequency high-amplitude waves can be observed during waking hours.[11] Initially, KLS appears similar to bipolar depression.[7] Patients with frontal-lobe syndromes and Klüver-Bucy syndrome also display similar symptoms, but these conditions can be differentiated by the presence of brain lesions.[17] KLS should also be distinguished from very rare cases of menstruation-caused hypersomnia.[6] ## Prevention[edit] Lithium is the only drug that appears to have a preventive effect. In two studies of more than 100 patients, lithium helped prevent recurrence of symptoms in 20% to 40% of cases. The recommended blood level of lithium for KLS patients is 0.8–1.2 mEq/ml. It is not known if other mood stabilizers have an effect on the condition.[24] Anti-depressants do not prevent recurrence.[4] ## Treatment[edit] Several drug therapies have been used on patients with KLS, but none of them have been subject to randomized controlled trials. A 2016 Cochrane Review concluded that "No evidence indicates that pharmacological treatment for Kleine-Levin syndrome is effective and safe".[4] In several cases, stimulants, including modafinil,[7] have been reported to have a limited effect on patients, often alleviating sleepiness.[4] They can cause behavioral problems,[19] but they may pose fewer issues if used in older patients with mild symptoms.[24] In some case reports, lithium has been reported to decrease the length of episodes and the severity of their symptoms and to increase the time between episodes.[4] It has been reported to be effective in about 25 to 60 percent of cases. Its use carries the risk of side effects in the thyroid or kidneys. Anti-psychotics and benzodiazepines can help alleviate psychotic and anxiety related symptoms, respectively.[19] Carbamazepine has been reported to be less effective than lithium but more effective than some drugs in its class.[20] Electroconvulsive therapy is not effective and worsens symptoms.[7] KLS patients generally do not need to be admitted to hospitals. It is recommended that caregivers reassure them and encourage them to maintain sleep hygiene.[19] It may also be necessary for patients to be prevented from putting themselves in dangerous situations, such as driving.[24] ## Prognosis[edit] The frequency of KLS episodes can vary from attacks one week in length occurring twice a year to dozens of episodes that follow each other in close succession.[8] The median duration of KLS episodes is about ten days, but some last several weeks or months. A study of 108 patients found an average of 19 episodes over the duration of the disease.[8] Another study found a median of 3.5 months between episodes.[21] Outside of episodes, there is no disturbance in patients' sleep patterns and they are generally asymptomatic.[8][5] Patients do not experience the same symptoms in each episode.[6] About 80 percent of patients are adolescents when they first experience KLS. On some occasions though, its first occurrence comes in childhood or adulthood.[8] In most adolescent-onset patients, symptoms cease by the time they are 30 years old. A French study of 108 patients found a median duration of 13 years,[8] but a review of 186 cases found a median duration of 8 years.[21] Unusually young or old patients and those who experience hypersexuality tend to have a more severe course. Patients who initially have frequent attacks generally see the disease cease earlier than others.[8] The condition spontaneously resolves,[8] and the patient is considered to be cured if there have been no symptoms for six years.[7] ## Epidemiology[edit] Population-based studies of KLS have not been performed. Its prevalence is about 1 case per million people.[7] In France, KLS has a prevalence of 1.5 per million people. It occurs most frequently among Jews in the US and Israel. First-degree relatives of people who have suffered from the syndrome are much more likely than the general population to suffer from it, although only in about one percent of cases do family members contract it. About 70 to 90 percent of patients are male. Patients with the syndrome are more likely than the general population to have genetic disorders, and about a third of people with the syndrome encountered some form of birth difficulty.[25] In a study of 186 older patients, about ten percent had preexisting psychiatric issues.[5] One study found that about ten percent of patients had a neurological condition before KLS developed.[7] The condition does not appear to occur most frequently in one season.[10] ## History[edit] In 1815, there was a report of a young man who showed excessive appetite and prolonged sleep after experiencing a fever; this may have been an early description of the condition.[26] Another case with similar symptoms was described by Brierre de Boismont in 1862.[21] Five patients with symptoms of persistent sleepiness were described in detail in 1925 by Willi Kleine, a neurologist from Frankfurt. This report was followed four years later by details of a similar case by New York-based psychiatrist Max Levin. In 1935, Levin published information about several more cases, including one described by Kleine. Levin noted that some patients displayed an intense appetite in addition to their persistent tiredness. MacDonald Critchley, who first wrote about the condition in 1942,[21] described 11 cases he had examined and reviewed 15 other published cases in a 1962 publication. In the report, which included patients he had examined in the Royal Navy during World War II,[7] he observed that irritability and depersonalization often occurred while patients were awake. He named the condition Kleine–Levin syndrome and noted four common traits: hypersexuality, adolescent onset, spontaneous resolution, and compulsive eating.[21] He believed that the condition only affected males, but later studies showed some female patients.[27] In the 1970s, several psychoanalytic and psychodynamic explanations for the condition were proposed.[28] In 1980, a Hawaiian–Caucasian family was found in which nine family members suffered from the condition.[21] Diagnostic criteria for KLS was established by Schmidt in 1990, and the International Classification of Sleep Disorders further refined them.[4] KLS is classified as a sleep disorder,[11] specifically one of recurrent hypersomnia.[7] Before 2005, hyperphagia and hypersexuality were thought to occur in all cases. That was changed with the guidelines published that year, which noted that they did not always occur.[5] ## References[edit] 1. ^ "Kleine Levin syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 21 March 2019. 2. ^ Poppe, M, Friebel, D, Reuner, U, Todt, H, Koch, R, and Heubner, G. The Kleine-Levin syndrome – effects of treatment with lithium. Neuropediatrics 2003;34:113-9 3. ^ Levin, M. (1936). Periodic somnolence and morbid hunger: a new syndrome. Brain, 59(4), 494–504. 4. ^ a b c d e f g h i j k l m de Oliveira, Marcio M.; Conti, Cristiane; Prado, Gilmar F. (2016-05-06). "Pharmacological treatment for Kleine-Levin syndrome". The Cochrane Database of Systematic Reviews (5): CD006685. doi:10.1002/14651858.CD006685.pub4. ISSN 1469-493X. PMC 7386458. PMID 27153153. 5. ^ a b c d e f g h i Arnulf, Rico & Mignot 2012, p. 920. 6. ^ a b c d e f Arnulf, Rico & Mignot 2012, p. 921. 7. ^ a b c d e f g h i j k l m Ramdurg 2010. 8. ^ a b c d e f g h i j k l m n Arnulf, Rico & Mignot 2012, p. 919. 9. ^ a b Huang, Lakkis & Guilleminault 2010, p. 558. 10. ^ a b Billiard et al. 2011. 11. ^ a b c d e Arnulf, Rico & Mignot 2012, p. 923. 12. ^ a b Huang, Lakkis & Guilleminault 2010, p. 559. 13. ^ a b Gupta, Lahan & Srivastava 2011. 14. ^ Frenette & Kushida 2009, p. 364. 15. ^ a b c d Kodaira & Yamamoto 2012. 16. ^ Frenette & Kushida 2009, p. 363. 17. ^ a b c d e Arnulf, Rico & Mignot 2012, p. 922. 18. ^ Huang, Lakkis & Guilleminault 2010, p. 560. 19. ^ a b c d e Arnulf, Rico & Mignot 2012, p. 924. 20. ^ a b c d e f g Arnulf, Rico & Mignot 2012, p. 925. 21. ^ a b c d e f g Pearce 2008. 22. ^ Brown 1993. sfn error: no target: CITEREFBrown1993 (help) 23. ^ Al Shareef SM, Basit S, Pfister C, Pradervand S, Lecendreux M, Mayer G, Dauvilliers Y, Salpietro V, Houlden H, BaHammam AS, Tafti M (2018) Kleine-Levin syndrome is associated with LMOD3 variants. J Sleep Res e12718 24. ^ a b c Mignot 2012. 25. ^ Arnulf, Rico & Mignot 2012, p. 918. 26. ^ Oliveira, Conti & Prado 2013. sfn error: no target: CITEREFOliveiraContiPrado2013 (help) 27. ^ Huang, Lakkis & Guilleminault 2010, p. 557. 28. ^ Arnulf et al. 2005. ## Bibliography[edit] * Arnulf, Isabelle; Rico, Thomas; Mignot, Emmanuel (2012). "Diagnosis, Disease Course, and Management of Patients with Kleine-Levin Syndrome". The Lancet Neurology. 11 (10): 918–28. doi:10.1016/S1474-4422(12)70187-4. PMID 22995695. * Arnulf, Isabelle; Zeitzer, J. M.; Farber, N.; Mignot, Emmanuel (2005). "Kleine–Levin Syndrome: a Systematic Review of 186 Cases in the Literature". Brain. 128 (12): 2763–76. doi:10.1093/brain/awh620. PMID 16230322. * Billiard, Michel; Jaussent, Isabelle; Dauvilliers, Yves; Besset, Alain (2011). "Recurrent Hypersomnia: a Review of 339 Cases". Sleep Medicine Reviews. 15 (4): 247–57. doi:10.1016/j.smrv.2010.08.001. PMID 20970360. * Frenette, Eric; Kushida, Clete (2009). "Primary Hypersomnias of Central Origin". Seminars in Neurology. 29 (4): 354–67. doi:10.1055/s-0029-1237114. PMID 19742411. * Gupta, Ravi; Lahan, Vivekananda; Srivastava, Malini (2011). "Kleine-Levin Syndrome and Idiopathic Hypersomnia: Spectrum Disorders". Indian Journal of Psychological Medicine. 33 (2): 194–98. doi:10.4103/0253-7176.92048. PMC 3271500. PMID 22345850. * Huang, Yu-Shu; Lakkis, Clair; Guilleminault, Christian (2010). "Kleine-Levin Syndrome: Current Status". Medical Clinics of North America. 94 (3): 557–62. doi:10.1016/j.mcna.2010.02.011. PMID 20451032. * Kodaira, Minori; Yamamoto, Kanji (2012). "First Attack of Kleine-Levin Syndrome Triggered by Influenza B Mimicking Influenza-associated Encephalopathy". Internal Medicine. 51 (12): 1605–8. doi:10.2169/internalmedicine.51.7051. PMID 22728499. * Mignot, Emmanuel (2012). "A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes". Neurotherapeutics. 9 (4): 739–52. doi:10.1007/s13311-012-0150-9. PMC 3480574. PMID 23065655. * Oliveira, Marcio; Conti, Cristiane; Prado, Gilmar (2016) [2013]. "Pharmacological Treatment for Kleine-Levin Syndrome". Cochrane Database of Systematic Reviews. 5: CD006685. doi:10.1002/14651858.CD006685.pub4. PMC 7386458. PMID 27153153. * Pearce, J. M. (2008). "Kleine–Levin Syndrome: History and Brief Review". European Neurology. 60 (4): 212–4. doi:10.1159/000148694. PMID 18667831. * Ramdurg, Santosh (2010). "Kleine–Levin Syndrome: Etiology, Diagnosis, and Treatment". Annals of Indian Academy of Neurology. 13 (4): 241–6. doi:10.4103/0972-2327.74185. PMC 3021925. PMID 21264130. ## External links[edit] Classification D * ICD-10: G47.8 * ICD-9-CM: 327.13 * OMIM: 148840 * MeSH: D017593 * DiseasesDB: 29520 External resources * Orphanet: 33543 * kleine_levin at NINDS * Story of young man with Kleine–Levin syndrome at The New York Times * v * t * e Sleep and sleep disorders Stages of sleep cycles * Rapid eye movement (REM) * Non-rapid eye movement * Slow-wave Brain waves * Alpha wave * Beta wave * Delta wave * Gamma wave * K-complex * Mu rhythm * PGO waves * Sensorimotor rhythm * Sleep spindle * Theta wave Sleep disorders Dyssomnia * Excessive daytime sleepiness * Hypersomnia * Insomnia * Kleine–Levin syndrome * Narcolepsy * Night eating syndrome * Nocturia * Sleep apnea * Catathrenia * Central hypoventilation syndrome * Obesity hypoventilation syndrome * Obstructive sleep apnea * Periodic breathing * Sleep state misperception Circadian rhythm disorders * Advanced sleep phase disorder * Cyclic alternating pattern * Delayed sleep phase disorder * Irregular sleep–wake rhythm * Jet lag * Non-24-hour sleep–wake disorder * Shift work sleep disorder Parasomnia * Bruxism * Nightmare disorder * Night terror * Periodic limb movement disorder * Rapid eye movement sleep behavior disorder * Sleepwalking * Somniloquy Benign phenomena * Dreams * Exploding head syndrome * Hypnic jerk * Hypnagogia / Sleep onset * Hypnopompic state * Sleep paralysis * Sleep inertia * Somnolence * Nocturnal clitoral tumescence * Nocturnal penile tumescence * Nocturnal emission Treatment * Sleep diary * Sleep hygiene * Sleep induction * Hypnosis * Lullaby * Somnology * Polysomnography Other * Sleep medicine * Behavioral sleep medicine * Sleep study Daily life * Bed * Bunk bed * Daybed * Four-poster bed * Futon * Hammock * Mattress * Sleeping bag * Bed bug * Bedding * Bedroom * Bedtime * Bedtime story * Bedtime toy * Biphasic and polyphasic sleep * Chronotype * Dream diary * Microsleep * Mouth breathing * Nap * Nightwear * Power nap * Second wind * Siesta * Sleep and creativity * Sleep and learning * Sleep deprivation / Sleep debt * Sleeping while on duty * Sleepover * Snoring [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Kleine–Levin syndrome	c0206085	26,278	wikipedia	https://en.wikipedia.org/wiki/Kleine%E2%80%93Levin_syndrome	2021-01-18T18:51:31	{"gard": ["3117"], "mesh": ["D017593"], "umls": ["C0206085"], "icd-9": ["327.13"], "icd-10": ["G47.8"], "orphanet": ["33543"], "wikidata": ["Q613809"]}
A number sign (#) is used with this entry because of evidence that pityriasis rubra pilaris (PRP) is caused by heterozygous mutation in the CARD14 gene (607211) on chromosome 17q25. Description Pityriasis rubra pilaris is an uncommon skin disorder characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic, although up to 6.5% of PRP-affected individuals report a positive family history. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression: the disorder is usually present at birth or appears during the first years of life and is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema, with only a modest response to treatment (summary by Fuchs-Telem et al., 2012). Clinical Features Pityriasis rubra pilaris is 'characterized by scaly and horny productions situated chiefly in the sebaceous follicles and by a more or less generalized hyperemia' to use the words of DeVergie who first described it (Zeisler, 1923) in a man and his son and 2 daughters. The lesions consist 'of acuminate follicular plugging about the dorsal aspects of the hands and feet, and large plaquelike, scaling psoriasiform lesions of the extensor surfaces of the arms, legs and thighs as well as the neck and calves.' Weiner and Levin (1943) reported a mother and 4 of her children with PRP. The mother and her affected father, brother, and sister had previously been reported by Zeisler (1923). The patients studied by Weiner and Levin (1943) all had onset of skin lesions between the first and second year of life, and the disorder became more intense with age. Characteristically the lesions were less intense during warm weather, particularly in childhood, but never resolved completely. All of the affected individuals were otherwise healthy. The mother and her 15-year-old son had acuminate follicular plugging on the dorsa of the hands and feet, with plaque-like, scaling psoriasiform lesions of the extensor surfaces of the arms, legs, and thighs as well as the neck and calves. There was some involvement of the face in both, and the mother had the characteristic waxy yellow appearance of her palms and soles. Her 3 daughters, aged 13, 12, and 8 years, had lesions of less severity in direct proportion to their ages, and no psoriasiform plaques were present. Weiner and Levin (1943) followed the patients for 2 years and observed that treatment with vitamin A and carotene resulted in improvement of lesions beyond that occurring seasonally, but the lesions never completely cleared, and the lesions always recurred when treatment was stopped. Beamer et al. (1972) contrasted the acquired and hereditary forms of pityriasis rubra pilaris, stating that the hereditary form tends to be less severe and more limited in extent. Kint et al. (1972) described 6 affected individuals over 3 generations of a family with PRP. Onset of disease was between 4 months and 10 years of age, and there was variable expressivity and incomplete penetrance. A biopsy of affected skin from the proband, a 5-year-old girl, revealed hyperkeratosis with focal parakeratosis, follicular plugging, and moderate acanthosis. A perivascular infiltrate in the upper dermis consisted primarily of lymphocytes and histiocytes. In 4 individuals from 3 generations of a family of Ukrainian ancestry, Vanderhooft et al. (1995) described the clinical features of pityriasis rubra pilaris. There was one instance of male-to-male transmission. All affected individuals demonstrated erythematous scaly skin with follicular prominence and islands of sparing. Immunocytochemistry and immunoblot analysis suggested abnormality of keratins. Sehgal et al. (2000) described a 55-year-old mother and 33-year-old son with PRP, as well as 2 sporadic patients. The mother and son both had onset of PRP in childhood, with lesions beginning on the head. They reported seasonal exacerbations and relative remissions. Examination revealed erythematous and scaly follicular papules, some of which coalesced to form plaques. The lesions were innumerable and occupied the skin of the neck, chest, upper extremities, abdomen, thighs, legs, and dorsa of the feet. Dorsa of the fingers, palms, and soles showed conspicuous 'islets of sparing.' The nails were brittle, discolored, and had subungual hyperkeratotic pitting and transverse ridging. Histopathology showed mild to moderate hyperkeratosis with focal parakeratosis and hypergranulosis. There was associated mild acanthosis apparent in the form of broad and blunted rete ridges, and focal keratotic plugging was a regular feature. Focal collections of mononuclear cells were seen in the dermis, and acute inflammatory changes were striking, with mild spongiosis in elongated rete ridges. Sehgal et al. (2000) noted that the clinical features and microscopic findings in sporadic and familial PRP are similar. Sehgal et al. (2002) examined a 45-year-old man with a 2-year history of PRP, as well as his affected 42-year-old sister and 38-year-old brother. All 3 had erythematous and scaly papules conforming to a follicular and/or extra-follicular pattern, coalescing in places to form plaques. The majority of the lesions were covered with grayish-white scales. The lesions were located on the neck, chest, upper extremities. abdomen, thighs, legs, and dorsae of the hands and feet. There was conspicuous presence of apparently normal skin in 'islets of sparing.' Nails, palms, and soles were also spared. Histologic sections of lesion biopsies showed changes typical of PRP and were identical in all 3 patients. Thomson and Moss (2007) reported a mother and 2 daughters with PRP. The 33-year-old mother developed PRP at age 12 years; there was no prior family history of PRP, psoriasis (see 177900), or atopy (see 147050). She presented with a cephalocaudal eruption of follicular hyperkeratotic papules progressing to generalized erythroderma with islands of sparing. She also had a scaly scalp, yellow thickening of the palms and soles, and subungual hyperkeratosis. The clinical diagnosis of PRP was supported by histologic findings of hyperkeratosis, patchy parakeratosis varying in both horizontal and vertical planes, and follicular plugging. Her first daughter was born with thick scales on the scalp and areas of superficial peeling on the face, palms, soles, and genital region. Within weeks she developed follicular erythematous papules on the face, trunk, and limbs, which enlarged into pink plaques with a scaly edge. There was no palmoplantar thickening. A skin biopsy was consistent with PRP, showing orthokeratosis and parakeratosis alternating in both the vertical and horizontal directions, lipping of the follicular ostia, and associated follicular plugging. The second daughter was born with similar clinical findings to those of her sister, although she was less severely affected. At the ages of 9 months and 3 years, respectively, the girls' skin disease was well-controlled on emollients and intermittent use of mild topical steroids, and the older daughter's skin was mostly clear. Fuchs-Telem et al. (2012) studied 4 families segregating autosomal dominant PRP. Age of onset ranged from 4 to 36 months of age. All affected individuals showed well-demarcated erythematous plaques coalescing into large areas interspersed with islands of normal skin, follicular papules or accentuation, palmoplantar keratoderma, and a lack of psoriasis-associated nail changes. Histopathology of skin lesions showed alternating orthokeratosis and parakeratosis, acanthosis with broadening of the rete ridges, follicular plugging, lymphocytic infiltrate in the dermis, and a lack of neutrophils in the epidermis. Sehgal and Srivastava (2006) noted that Western blot analysis of involved skin in PRP has shown expression of keratin 17, 16, and 6, indicating keratinocyte activation. ### Classification Griffiths (1984, 1992) devised a classification of both sporadic and familial cases of PRP based on age of onset, clinical features, and prognosis, along with a relative frequency of each type: type I, or classic adult PRP, present in 55% of cases; type II, or atypical adult PRP, present in 5%; type III, or classic juvenile PRP, present in 10%; type IV, or circumscribed juvenile PRP, present in 25%; and type V, or atypical juvenile PRP, present in 5%. Fuchs-Telem et al. (2012) stated that familial PRP belongs to the type V group. It is usually present at birth or appears during the first years of life and runs a chronic course. It is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema. Response to treatment is disappointing. Inheritance Sehgal and Srivastava (2006) stated that the pattern of inheritance of PRP is largely autosomal dominant with variable expressivity but noted that autosomal recessive inheritance had also been reported. Mapping Fuchs-Telem et al. (2012) genotyped members of a family segregating autosomal dominant pityriasis rubra pilaris and identified 2 regions of interest. Fine mapping using microsatellite markers in this family and 2 additional families with PRP revealed linkage in all 3 families to chromosome 17q25.3, with a combined lod score of 3.73. Critical recombination events set the 5-Mb disease interval between markers D17S722 and D17S668. Molecular Genetics After next-generation sequencing failed to identify the proximal cause of autosomal dominant pityriasis rubra pilaris mapping to chromosome 17q25 in 3 families, Fuchs-Telem et al. (2012) sequenced functionally relevant candidate exons within the critical interval and identified heterozygosity for a missense mutation and a nonsense mutation in the CARD14 gene (607211.0006 and 607211.0007, respectively) that segregated with disease in each family. In 2 patients from a fourth family with PRP, they identified a heterozygous splice site mutation (607211.0008). Fuchs-Telem et al. (2012) noted that penetrance was incomplete in some of the families, suggesting a possible role for additional modifying traits, epigenetic factors, or environmental elements in determining the phenotypic expression of the causative mutations. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Scaly scalp (in some patients) Eyes \- Ectropion, bilateral (in some patients) SKIN, NAILS, & HAIR Skin \- Papules, keratotic follicular \- Plaques, erythematous, covered with fine powdery scales \- Islands of uninvolved skin \- Palmoplantar keratoderma Skin Histology \- Hyperkeratosis, mild to moderate \- Focal parakeratosis \- Focal orthokeratosis \- Focal hypergranulosis \- Mild acanthosis, with broad and blunted rete ridges \- Focal keratotic plugging \- Mononuclear cell infiltrate in the dermis Nails \- Discoloration, yellow-brown \- Subungual hyperkeratosis \- Nail plate thickening \- Splinter hemorrhages \- Transverse ridging MISCELLANEOUS \- Male-to-female ratio of 3:2 in childhood cases \- Disease usually progresses in a cephalocaudal direction \- Nails, palms, and soles are spared in some patients \- The familial form of pityriasis rubra pilaris is generally resistant to treatment and persists MOLECULAR BASIS \- Caused by mutation in the caspase recruitment domain-containing protein 14 gene (CARD14, 607211.0006 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PITYRIASIS RUBRA PILARIS	c0032027	26,279	omim	https://www.omim.org/entry/173200	2019-09-22T16:36:15	{"doid": ["9212"], "mesh": ["D010916"], "omim": ["173200"], "icd-9": ["696.4"], "icd-10": ["L44.0"], "orphanet": ["2897"]}
Thyroid hemiagenesis is a form of thyroid dysgenesis (see this term) characterized by an absence of half of the thyroid gland that is usually asymptomatic but may result in primary congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth. ## Epidemiology Thyroid hemiagenesis is estimated to occur in 1/500-1/2,000 individuals. ## Clinical description In symptomatic cases, clinical features and signs may include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Slow linear growth and developmental delay may also occur. ## Etiology Thyroid hemiagenesis has been reported in mice with compound heterozygous FOXE1/NKX2-1 and PAX8 gene (14q13 and 2q12-q14) mutations. ## Genetic counseling Some familial cases have been reported, suggesting genetic factors but to date none have been identified in humans. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Thyroid hemiagenesis	c1869118	26,280	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95719	2021-01-23T17:34:39	{"mesh": ["C566852"], "omim": ["218700"], "icd-10": ["E03.1"]}
A rare radiation-induced disorder characterized by impairment of the peripheral nervous system at the level of the brachial or lumbosacral plexus following radiation therapy. Onset of symptoms can occur between several months up to decades after the last dose of radiation. Patients with radiation-induced brachial plexopathy typically present with mostly unilateral progressive paresthesia, followed by weakness, atrophy, and pain. Symptoms in radiation-induced lumbosacral plexopathy include more variable combinations of numbness, paresthesia, pain, and weakness, and are more often bilateral. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Radiation-induced plexopathy	None	26,281	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=521123	2021-01-23T18:00:04	{}
A pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive spastic gait, extensor plantar responses, brisk tendon reflexes in arms and legs, decreased vibration sense at ankles and urinary dysfunction. Ankle clonus is also reported in some 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal dominant spastic paraplegia type 37	c2936880	26,282	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171612	2021-01-23T17:03:23	{"mesh": ["C567931"], "omim": ["611945"], "umls": ["C2936880"], "icd-10": ["G11.4"], "synonyms": ["SPG37"]}
A multiple congenital anomaly disorder characterized by anonychia congenita totalis and microcephaly, and normal intelligence along with some minor anomalies including single transverse palmar creases, fifth-finger clinodactyly and widely-spaced teeth. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Anonychia-microcephaly syndrome	c2931373	26,283	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1094	2021-01-23T17:50:16	{"gard": ["5123"], "mesh": ["C536948"], "omim": ["607214"], "umls": ["C2931373"], "icd-10": ["Q87.8"], "synonyms": ["Teebi-Kaurah syndrome"]}
Brodsky et al. (1977) described a family in which a short PR interval in the electrocardiogram occurred in members in 3 generations with male-to-male transmission. Several members of the family with short PR had paroxysmal or chronic atrial fibrillation or paroxysmal atrial tachycardia from an early age. Five members of the family had short PR intervals but had not yet shown tachyarrhythmia. The proband, aged 18, had left ventricular dysfunction during paroxysmal atrial tachycardia. Both were reversed with administration of digoxin and propranolol. This condition may represent a variant of the Lown-Ganong-Levine syndrome; several affected relatives were described but not studied extensively in the original report (Lown et al., 1952). Noting the evidence for genetic factors in atrioventricular conduction time (108980), one wonders whether the affected persons in the family of Brodsky et al. (1977) represented a 'tail' of the distribution for a multifactorial trait. Two families with multiple generations affected by late-onset, chronic atrial fibrillation in the absence of organic heart disease may represent a related disorder (Gould, 1957; Phair, 1963). The Wolff-Parkinson-White syndrome (194200) is another syndrome of short PR interval with proneness to supraventricular tachycardia. Cardiac \- Paroxysmal or chronic atrial fibrillation \- Paroxysmal atrial tachycardia Lab \- Electrocardiographic short PR interval Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ATRIAL TACHYARRHYTHMIA WITH SHORT PR INTERVAL	c1862387	26,284	omim	https://www.omim.org/entry/108950	2019-09-22T16:44:37	{"doid": ["13087"], "mesh": ["C566237"], "omim": ["108950"], "orphanet": ["844"]}
Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. Subtle abnormalities indicating changes in vision may occur in a person's forties or fifties. Distorted vision and vision loss usually become noticeable in a person's sixties or seventies and tend to worsen over time. Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but slow adjustment of vision to darkness (dark adaptation) and reduced dim light (scotopic) vision often occur in the early stages of the disease. Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The most advanced stage of dry age-related macular degeneration is known as geographic atrophy, in which areas of the macula waste away (atrophy), resulting in severe vision loss. Dry age-related macular degeneration typically affects vision in both eyes, although vision loss often occurs in one eye before the other. In 10 to 15 percent of affected individuals, the dry form progresses to the wet form of age-related macular degeneration. The wet form is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted. The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. ## Frequency It is estimated that 8 percent of people around the world have signs of age-related macular degeneration. The condition currently affects about 11 million Americans and 170 million people worldwide, and the prevalence is expected to increase over the coming decades as the proportion of older people in the population increases. For reasons that are unclear, age-related macular degeneration affects individuals of European descent more frequently than African Americans in the United States. ## Causes Age-related macular degeneration results from a combination of genetic and environmental factors. Many of these factors have been identified, but some remain unknown. Researchers have considered changes in many genes as possible risk factors for age-related macular degeneration. The best-studied of these genes are involved in a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH gene, contribute to a person's risk of developing age-related macular degeneration. It is unclear how these genetic changes are related to the retinal damage and vision loss characteristic of this condition. Changes on the long (q) arm of chromosome 10 in a region known as 10q26 are also associated with an increased risk of age-related macular degeneration. The 10q26 region contains two genes of interest, ARMS2 and HTRA1. Changes in both genes have been studied as possible risk factors for the disease. However, because the two genes are so close together, it is difficult to tell which gene is associated with age-related macular degeneration risk, or whether increased risk results from variations in both genes. Other genes that are associated with age-related macular degeneration include genes involved in transporting and processing high-density lipoproteins (HDL, also known as "good" cholesterol) and genes that have been associated with other forms of macular disease. Researchers have also examined nongenetic factors that contribute to the risk of age-related macular degeneration. Age appears to be the most important risk factor; the chance of developing the condition increases significantly as a person gets older. Smoking is another established risk factor for age-related macular degeneration. Other factors that may increase the risk of this condition include high blood pressure; heart disease; a diet that is high in fat, high in easily digested foods (high glycemic index), or low in certain nutrients (such as antioxidants and zinc); obesity; and exposure to ultraviolet (UV) rays from sunlight. However, it is unclear how these factors influence the risk of developing age-related macular degeneration. ### Learn more about the genes associated with Age-related macular degeneration * ABCA4 * APOE * ARMS2 * ASPM * BEST1 * C2 * C3 * CFH * CFHR5 * CFI * CST3 * ELOVL4 * ERCC6 * F13B * FBLN5 * HTRA1 * LIPC Additional Information from NCBI Gene: * C9 * CETP * CFB * CFHR1 * CFHR2 * CFHR3 * CFHR4 * COL10A1 * COL8A1 * CX3CR1 * FILIP1L * FRK * HMCN1 * MAP2 * TIMP3 * TNFRSF10A * VEGFA ## Inheritance Pattern Age-related macular degeneration usually does not have a clear-cut pattern of inheritance, although the condition appears to run in families in some cases. An estimated 15 to 20 percent of people with age-related macular degeneration have at least one first-degree relative (such as a sibling or parent) with 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Age-related macular degeneration	c1864205	26,285	medlineplus	https://medlineplus.gov/genetics/condition/age-related-macular-degeneration/	2021-01-27T08:25:05	{"gard": ["10260"], "mesh": ["C566411"], "omim": ["603075", "611488", "611953", "613784", "615439", "615489", "615591", "153800", "610698", "613761", "613757", "610149", "613778", "611378", "608895"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that Schinzel-Giedion midface retraction syndrome is caused by heterozygous de novo mutation in the SETBP1 gene (611060) on chromosome 18q12. Description Schinzel-Giedion syndrome is a highly recognizable syndrome characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, and cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia (summary by Hoischen et al., 2010). Clinical Features Schinzel and Giedion (1978) described a unique syndrome in brother and sister, who lived 24 hours and 16 months, respectively. Severe midface retraction, multiple skull anomalies (short and sclerotic base, multiple wormian bones, wide cranial sutures and fontanels), congenital heart defect, hydronephrosis, clubfeet, and hypertrichosis were features. Long tubular bones also showed increased density. Another syndrome carries Schinzel's name (181450), and Giedion's is combined with Langer's for a disorder resembling the trichorhinophalangeal syndrome (150230). Despite these possibilities for confusion, I have assigned the above designation for want of a better one (VAM). Donnai and Harris (1979) reported a case in which multiple telangiectases were observed over the nose and cheeks. By personal communication and observation, Schinzel (1982) was aware of a total of 8 other unreported cases, all sporadic, including at least 2 offspring of consanguineous parents. Al-Gazali et al. (1988) reported 3 cases. Hypoplasia of dermal ridges and genital anomalies were mentioned as abnormalities. The skeletal abnormalities also included broad ribs and hypoplasia of the distal phalanges. Two of the 7 children reported in the literature died in the neonatal period, and the remainder developed intractable epilepsy and spasticity along with profound growth and developmental retardation. Al-Gazali et al. (1990) reviewed 5 previously reported cases and 5 new cases. They stated that consanguinity in fact had not been observed, but that 2 sibs of unlike sex are known. Thus, a dominant disorder with gonadal mosaicism in one parent or an unbalanced structural chromosome abnormality that went undetected by present methods cannot be excluded. Maclennan et al. (1991) described increasing ventriculomegaly, intraventricular bands, and subependymal pseudocysts in an affected infant born prematurely who died at the age of 9 weeks. Robin et al. (1993) described malignant sacrococcygeal teratoma discovered soon after birth. They pointed out that Burck (1982) described hepatoblastoma in this disorder and suggested that embryonal malignancy may be a common complication. Labrune et al. (1994) added 3 new cases to the 13 previously reported. Rodriguez et al. (1994) reported the third example of a postmortem study. In addition to having the major manifestations of the syndrome, the 11-month-old boy with SGS had a primitive neuroectodermal tumor in the lumbosacral region, bilateral syndactyly of the hands and feet, and brain anomalies. Rodriguez et al. (1994) commented that of 19 SGS patients reported, 4 had syndactyly and 3 had embryonal tumors; the 3 published necropsy studies showed brain anomalies. They noted that the only familial cases were the affected sibs in the initial report by Schinzel and Giedion (1978). Antich et al. (1995) reported the cases of a brother and sister. The sister had a malignant sacrococcygeal teratoma (the third case of malignancy in Schinzel-Giedion syndrome). The brother died shortly after birth. McPherson et al. (1998) reported a fourth patient with Schinzel-Giedion syndrome and a sacrococcygeal tumor (the previous cases being those of Robin et al. (1993), Rodriguez et al. (1994), and Antich et al. (1995)). Santos et al. (1994) described a girl with characteristic manifestations of SGS (including typical face, skeletal abnormalities, and hydronephrosis) who also had hypothyroidism and diabetes insipidus. The TSH value in her newborn period was normal. MRI of her brain at 9 months of age showed malformation of the posterior fossa and arachnoid cysts in both temporal regions and in the left cerebellar hemisphere. The brainstem seemed to be pushed backwards by an anterior cyst, and the pituitary stalk was stretched. Santos et al. (1994) suggested that hypothyroidism and diabetes insipidus were secondary to these central defects. Okamoto et al. (1995) reported a patient they claimed to be the twenty-first in the literature and the first reported instance of the syndrome in an Oriental patient. Elliott et al. (1996) described a male infant who, in addition to typical manifestations (characteristic face, choanal stenosis, tricuspid regurgitation, hypospadias), had seizures, hearing loss, camptodactyly, and dysplastic sternum. Autopsy disclosed small brain with diminution of white matter (but no evidence of any brain storage), hypoplastic corpus callosum, steatosis of liver, and lipid vacuolization of the zona fasciculata of the adrenals. Shah et al. (1999) reported a case of Schinzel-Giedion syndrome with serial cranial MRI studies consistent with a progressive neurodegenerative process affecting both gray and white matter. Although the authors thought that these studies, along with the coarse facial features, skeletal abnormality, and progressive neurologic deterioration, suggested a storage or metabolic neurodegenerative process, the results of their metabolic studies were normal. Minn et al. (2002) described 2 unrelated children born of nonconsanguineous parents with SGS and identical clinical findings: megacalycosis and progressive neurodegeneration with infantile spasms and hypsarrhythmic activity. Alacrimia and corneal hypoesthesia were observed. Computed tomography of the temporal bone showed a 'tuning-fork' malformation of the stapes in both children. Bilateral megacalycosis, as opposed to hydronephrosis, is a nonobstructive dilatation of the calyces, assumed to be the result of an underdevelopment of the renal medullary pyramids. Megaureter is a common associated feature and was present in 1 of the cases of Minn et al. (2002). Megacalycosis had been previously observed by Herman et al. (1993) and Rittinger et al. (1999). Like Minn et al. (2002), Manouvrier-Hanu (2003) described alacrima with corneal hypoesthesia as a valuable diagnostic sign in Schinzel-Giedion syndrome. Lehman et al. (2008) described what they stated was the forty-sixth reported patient with Schinzel-Giedion syndrome, a male infant born of nonconsanguineous Persian parents, in whom the previously unreported feature of splenopancreatic fusion was found on autopsy. Suphapeetiporn et al. (2011) reported 2 male Thai patients with Schinzel-Giedion syndrome who displayed some features not previously reported in the disorder, including very short epiglottis, vocal cord paralysis, radioulnar synostosis, and possible hypothyroidism. Diagnosis Lehman et al. (2008) reviewed previously reported cases and proposed diagnostic criteria for the syndrome consisting of a mandatory facial phenotype involving prominent forehead, midface retraction, and short, upturned nose; developmental delay (excepting neonates); and either hydronephrosis or 2 of the 4 typical skeletal malformations, i.e., sclerotic skull base, wide occipital synchondrosis, increased cortical density or thickness, or broad ribs. Mapping Hoischen et al. (2010) sequenced the 37-Mb exomes of 4 unrelated individuals with Schinzel-Giedion syndrome and identified 12 genes for which all 4 patients carried variants. Only 2 genes, CTBP2 (602619) and SETBP1 (611060), showed variants at different genomic positions, suggesting that these represented causative variants rather than simply unidentified SNPs. The CTBP2 gene was excluded from further analysis because it contained numerous variants found during different in-house exome sequencing experiments, considered possibly due to highly homologous sequences from other genomic loci. Molecular Genetics In 4 unrelated individuals with Schinzel-Giedion syndrome, Hoischen et al. (2010) sequenced the candidate gene SETBP1 and identified de novo heterozygous mutations in all 4 individuals; using Sanger sequencing, they identified de novo heterozygous SETBP1 mutations in 8 of 9 additional individuals with Schinzel-Giedion syndrome (611060.0001-611060.0005). None of the mutations were found in available parents or in 188 control chromosomes. All 13 patients fulfilled the diagnostic criteria proposed by Lehman et al. (2008) and were of European descent from various parts of the world, including 7 from Europe, 3 from New Zealand, 2 from Australia, and 1 from the United States. In 2 unrelated Thai male infants who fulfilled the diagnostic criteria for Schinzel-Giedion syndrome, Suphapeetiporn et al. (2011) identified heterozygosity for the G870S mutation in the SETBP1 gene (611060.0005). INHERITANCE \- Autosomal dominant GROWTH Weight \- Failure to thrive Other \- Postnatal growth deficiency HEAD & NECK Head \- Widely patent fontanels and sutures \- Metopic suture extends to nasal root Face \- Coarse facies \- High, protruding forehead \- Midface hypoplasia \- Facial hemangioma Ears \- Low-set ears Eyes \- Shallow orbits \- Proptosis \- Hypertelorism Nose \- Short nose \- Low nasal bridge \- Anteverted nares Mouth \- Macroglossia Neck \- Short neck CARDIOVASCULAR Heart \- Atrial septal defect RESPIRATORY Nasopharynx \- Choanal stenosis CHEST Ribs Sternum Clavicles & Scapulae \- Hypoplastic first ribs \- Broad ribs \- Long clavicles \- Short sternum Breasts \- Hypoplastic nipples GENITOURINARY External Genitalia (Male) \- Hypospadias \- Short penis \- Hypoplastic scrotum External Genitalia (Female) \- Hypoplastic labia majora \- Hypoplastic labia minora \- Deep interlabial sulcus \- Hymenal atresia \- Short perineum Internal Genitalia (Female) \- Bicornuate uterus Kidneys \- Hydronephrosis Ureters \- Ureteral stenosis \- Hydroureter SKELETAL Skull \- Steep short base of skull \- Sclerotic skull base \- Wormian bones \- Wide occipital synchondrosis Pelvis \- Hypoplastic/aplastic pubic bones Limbs \- Broad cortex of long bones \- Increased density of long bones \- Tibial bowing \- Mesomelic brachymelia \- Wide distal metaphysis of femur Hands \- Hypoplastic dermal ridges \- Transverse palmar creases \- Distal phalangeal hypoplasia \- Postaxial polydactyly \- Short first metacarpals Feet \- Talipes equinovarus \- Fifth toe overlapping fourth \- Distal phalangeal hypoplasia SKIN, NAILS, & HAIR Skin \- Hypertrichosis \- Facial hemangioma \- Hypoplastic dermal ridges \- Transverse palmar creases Nails \- Hyperconvex nails NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures \- Opisthotonus \- Spasticity \- Hypsarrhythmia \- Cerebral atrophy \- Ventriculomegaly \- Thin corpus callosum NEOPLASIA \- Embryonal tumors \- Hepatoblastoma \- Sacrococcygeal teratoma MISCELLANEOUS \- Most cases result from de novo mutations MOLECULAR BASIS \- Caused by mutation in the SET-binding protein-1 gene (SETBP1, 611060.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME	c0265227	26,286	omim	https://www.omim.org/entry/269150	2019-09-22T16:22:30	{"mesh": ["C536632"], "omim": ["269150"], "orphanet": ["798"], "synonyms": ["Alternative titles", "SGS"]}
Infantile neuronal ceroid lipofuscinosis Other namesSantavuori disease, Hagberg-Santavuori disease, Santavuori-Haltia disease, Infantile Finnish type neuronal ceroid lipofuscinosis, Balkan disease SpecialtyEndocrinology Infantile neuronal ceroid lipofuscinoses (INCL) or Santavuori disease[1] or Hagberg-Santavuori disease[2] or Santavuori-Haltia disease[2] or Infantile Finnish type neuronal ceroid lipofuscinosis[3] or Balkan disease[3] is a form of NCL and inherited as a recessive autosomal genetic trait. The disorder is progressive, degenerative and fatal, extremely rare worldwide – with approximately 60 official cases reported by 1982,[4] perhaps 100 sufferers in total today[citation needed] – but relatively common in Finland due to the local founder effect. ## Contents * 1 Presentation * 2 Causes * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Presentation[edit] The development of children born with INCL is normal for the first 8–18 months, but will then flounder and start to regress both physically and mentally. Motor skills and speech are lost, and optic atrophy causes blindness. A variety of neurological symptoms, such as epilepsy and myoclonic seizures, appear. The senses of hearing and touch remain unaffected. The average lifespan of an INCL child is 9–11 years. ## Causes[edit] It has been associated with palmitoyl-protein thioesterase.[5] ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2017) ## Treatment[edit] Treatment is limited. Drugs can alleviate the symptoms, such as sleep difficulties and epilepsy. Physiotherapy helps affected children retain the ability to remain upright for as long as possible, and prevents some of the pain. Recent attempts to treat INCL with cystagon have been unsuccessful. ## See also[edit] * FAIDD (The Finnish Association on Intellectual and Developmental Disabilities) ## References[edit] 1. ^ Santavuori P, Haltia M, Rapola J (October 1974). "Infantile type of so-called neuronal ceroid-lipofuscinosis". Dev Med Child Neurol. 16 (5): 644–53. doi:10.1111/j.1469-8749.1974.tb04183.x. PMID 4371326. S2CID 23169241. 2. ^ a b ORPHA:79263 3. ^ a b Classic Infantile CLN1 Disease 4. ^ Baumann RJ, Markesbery WR (November 1982). "Santavuori disease: diagnosis by leukocyte ultrastructure". Neurology. 32 (11): 1277–81. doi:10.1212/wnl.32.11.1277. PMID 6890163. S2CID 30186235. 5. ^ Voznyi YV, Keulemans JL, Mancini GM, et al. (June 1999). "A new simple enzyme assay for pre- and postnatal diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) and its variants". J. Med. Genet. 36 (6): 471–4. doi:10.1136/jmg.36.6.471 (inactive 2021-01-10). PMC 1734393. PMID 10874636.CS1 maint: DOI inactive as of January 2021 (link) ## External links[edit] Classification D * ICD-10: E75.4 * OMIM: 256730 * MeSH: D009472 * DiseasesDB: 31533 * GeneReviews/NCBI/NIH/UW entry on Neuronal Ceroid-Lipofuscinosis * An overview (in Finnish) * The INCL organization of Finland (in Finnish) * v * t * e Lysosomal storage diseases: Inborn errors of lipid metabolism (Lipid storage disorders) Sphingolipidoses (to ceramide) From ganglioside (gangliosidoses) * Ganglioside: GM1 gangliosidoses * GM2 gangliosidoses (Sandhoff disease * Tay–Sachs disease * AB variant) From globoside * Globotriaosylceramide: Fabry's disease From sphingomyelin * Sphingomyelin: phospholipid: Niemann–Pick disease (SMPD1-associated * type C) * Glucocerebroside: Gaucher's disease From sulfatide (sulfatidoses * leukodystrophy) * Sulfatide: Metachromatic leukodystrophy * Multiple sulfatase deficiency * Galactocerebroside: Krabbe disease To sphingosine * Ceramide: Farber disease NCL * Infantile * Jansky–Bielschowsky disease * Batten disease Other * Cerebrotendineous xanthomatosis * Cholesteryl ester storage disease (Lysosomal acid lipase deficiency/Wolman disease) * Sea-blue histiocytosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Infantile neuronal ceroid lipofuscinosis	c0268281	26,287	wikipedia	https://en.wikipedia.org/wiki/Infantile_neuronal_ceroid_lipofuscinosis	2021-01-18T18:50:05	{"mesh": ["D009472"], "wikidata": ["Q4357262"]}
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a disorder that affects vision and also causes an abnormal curvature of the spine (scoliosis). People with this condition are unable to move their eyes side-to-side (horizontally). As a result, affected individuals must turn their head instead of moving their eyes to track moving objects. Up-and-down (vertical) eye movements are typically normal. In people with HGPPS, an abnormal side-to-side curvature of the spine develops in infancy or childhood. It tends to be moderate to severe and worsens over time. Because the abnormal spine position can be painful and interfere with movement, it is often treated with surgery early in life. ## Frequency HGPPS has been reported in several dozen families worldwide. ## Causes HGPPS is caused by mutations in the ROBO3 gene. This gene provides instructions for making a protein that is important for the normal development of certain nerve pathways in the brain. These include motor nerve pathways, which transmit information about voluntary muscle movement, and sensory nerve pathways, which transmit information about sensory input (such as touch, pain, and temperature). For the brain and the body to communicate effectively, these nerve pathways must cross from one side of the body to the other in the brainstem, a region that connects the upper parts of the brain with the spinal cord. The ROBO3 protein plays a critical role in ensuring that motor and sensory nerve pathways cross over in the brainstem. In people with HGPPS, these pathways do not cross over, but stay on the same side of the body. Researchers believe that this miswiring in the brainstem is the underlying cause of the eye movement abnormalities associated with the disorder. The cause of progressive scoliosis in HGPPS is unclear. Researchers are working to determine why the effects of ROBO3 mutations appear to be limited to horizontal eye movement and scoliosis. ### Learn more about the gene associated with Horizontal gaze palsy with progressive scoliosis * ROBO3 ## 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Horizontal gaze palsy with progressive scoliosis	c4551964	26,288	medlineplus	https://medlineplus.gov/genetics/condition/horizontal-gaze-palsy-with-progressive-scoliosis/	2021-01-27T08:25:44	{"gard": ["12682"], "mesh": ["C564593"], "omim": ["607313"], "synonyms": []}
Maternal uniparental disomy of chromosome 22 is a uniparental disomy of maternal origin that does not seem to have an adverse impact on the phenotype of an individual. There is a possibility of homozygosity for a recessive disease mutation for which the mother is a carrier and specific phenotype depends on the inherited disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Maternal uniparental disomy of chromosome 22	None	26,289	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96188	2021-01-23T18:01:38	{"icd-10": ["Q99.8"], "synonyms": ["UPD(22)mat"]}
A number sign (#) is used with this entry because autosomal dominant deafness-17 (DFNA17) is caused by heterozygous mutation in the MYH9 gene (160775) on chromosome 22q12. Clinical Features Lalwani et al. (1999) studied a 5-generation American family, previously reported by Lalwani et al. (1997), with deafness caused by cochleosaccular degeneration (CSD). CSD is the most common histopathologic finding in cases of profound congenital deafness and is estimated to occur in approximately 70% of cases. CSD was first described by Scheibe (1892) and is commonly known as Scheibe dysplasia. It affects structures that are derived from the pars inferior of the otocyst. Thus, the membranous cochlea and saccule are affected, but the osseous labyrinth, the membranous utricle, and the semicircular canals are normal. The family studied by Lalwani et al. (1997, 1999) had been identified through a temporal bone database; because there is no clinically available test to diagnose CSD, postmortem histologic examination of the temporal bone is required. The affected family members exhibited nonsyndromic hearing loss with an autosomal dominant mode of transmission; there was no pigmentary abnormality. The hearing impairment began at age 10 years and involved only the high frequencies; by the third decade of life, affected family members had moderate to severe deafness. Hildebrand et al. (2006) reported a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17. The self-reported age of onset ranged from 6 years to the mid-twenties. The hearing loss was progressive with a general trend of initial mild high-frequency loss during childhood and adolescence and with a flattening of the audiogram over time. The hearing loss became severe to profound by the second to third decades, although there was some intrafamilial variability. Dantas et al. (2014) reported a Brazilian family in which 10 members had autosomal dominant progressive bilateral hearing loss affecting all frequencies, with age of onset ranging from the first to the fifth decade. Three other family members had a distinct hearing loss phenotype, affecting only high frequencies with onset at about age 40. Clinical Management Hildebrand et al. (2006) reported that 5 individuals in their Australian family received cochlear implants with excellent results and noted the contrast between the results of cochlear implant in their family and the poor results after cochlear implant reported in 1 patient from the family of Lalwani et al. (2000). Hildebrand et al. (2006) speculated that early intervention plays an important role in the therapeutic response. Mapping Lalwani et al. (1999) mapped the nonsyndromic hereditary hearing impairment in the family studied by them to chromosome 22q12.2-q13.3 by linkage analysis. In a Brazilian family in which 10 members had hearing loss at all frequencies and 3 others had hearing loss at high frequencies, Dantas et al. (2014) found linkage to chromosome 14 (lod = 2.1) and to chromosome 22 (lod = 1.9). Molecular Genetics DFNA17 maps to the same region as MYH9 (160775), a nonmuscle-myosin heavy-chain gene. Because of the importance of myosins in hearing, Lalwani et al. (2000) tested MYH9 as a candidate gene for DFNA17. Expression of MYH9 in the rat cochlea was confirmed using RT-PCR and immunohistochemistry analysis. MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of MYH9 in the family previously studied by Lalwani et al. (1997, 1999) demonstrated that a heterozygous mutation (R705H; 160775.0008) cosegregated with deafness. In affected members of a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17, Hildebrand et al. (2006) identified a heterozygous R705H mutation in the MYH9 gene. In a Brazilian family in which 10 members had nonsyndromic hearing loss at all frequencies, Dantas et al. (2014) identified heterozygosity for the same R705H mutation in the MYH9 gene. The mutation segregated with the phenotype in the family. Three other members of this family with hearing loss at high frequencies did not have the mutation. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, high-frequency (onset in childhood-adolescence) \- Deafness, moderate-severe (onset in third decade) \- Cochleosaccular dysplasia \- Organ of Corti degeneration MISCELLANEOUS \- Onset of hearing loss in late childhood or adolescence MOLECULAR BASIS \- Caused by mutation in the myosin, heavy chain 9, nonmuscle gene (MYH9, 160775.0008 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS, AUTOSOMAL DOMINANT 17	c1863659	26,290	omim	https://www.omim.org/entry/603622	2019-09-22T16:12:49	{"doid": ["0110548"], "mesh": ["C535507"], "omim": ["603622"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]}
A number sign (#) is used with this entry because of evidence that axonal Charcot-Marie-Tooth disease type 2Y (CMT2Y) is caused by heterozygous mutation in the VCP gene (601023) on chromosome 9p13. Description Charcot-Marie-Tooth disease type 2Y is an autosomal dominant peripheral neuropathy characterized by distal muscle weakness and atrophy associated with length-dependent sensory loss. Most patients have involvement of both the lower and upper limbs. The age at onset and the severity of the disorder are highly variable (summary by Gonzalez et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). Clinical Features Gonzalez et al. (2014) reported a family in which 5 living individuals had axonal Charcot-Marie-Tooth disease with highly variable severity. The patients were first cousins and ranged in age from 48 to 66 years. The most severely affected individual developed gait and running difficulties due to muscle weakness and distal sensory impairment in early childhood. She also had foot deformities requiring arthrodesis, and later needed forearm crutches for mobility. She had long-standing dysarthria, dyspnea, and mood and behavioral abnormalities. A first cousin developed walking difficulties requiring orthotics in her early twenties. The 3 remaining patients had onset of balance problems, difficulties with fine movements of the hands, and distal sensory impairment after age 50. All patients had absent Achilles reflexes and distal muscle atrophy, and most had foot abnormalities, including pes cavus and high arches. Four of the 5 had distal weakness affecting the upper limb associated with atrophy of the hand muscles. One patient had proximal weakness of the lower limbs; none had proximal weakness of the upper limbs. Electrophysiologic studies showed intermediate slowing of nerve conduction velocities, consistent with an axonal neuropathy. Sural nerve biopsy was not reported. The overall disability was considered mild in 2 patients, moderate in 2 patients, and severe in 1. The deceased mothers of the patients were identical twins who reportedly had high arches and hammertoes and developed weakness and sensory loss in their fourth and fifth decades of life. Jerath et al. (2015) reported a 60-year-old man of Dutch and Italian descent with CMT2Y. He had a long-standing history of toe-walking and high arches since childhood, but had normal developmental milestones and played ice hockey into his fifties. He then noticed progressive paresthesias in the distal lower limbs, followed by weakness and cramping of the distal upper and lower limbs, frequent falls, and unsteady gait. He also complained of memory and word-finding difficulties. Neurologic examination showed scapular winging and proximal upper limb weakness, lordosis, pes cavus, hammertoes, tight heel cords, and proximal and distal lower limb weakness. He had a wide-based gait and was unable to walk long distances. Reflexes were decreased or absent. Electrophysiologic studies were consistent with an axonal sensorimotor neuropathy with variably decreased amplitudes and prolonged latencies. Serum creatine kinase was increased, and muscle biopsy showed chronic active neurogenic atrophy. Family history revealed a deceased father with amyotrophic lateral sclerosis, dementia, and Paget disease of bone, a sister with flat, narrow feet, and a daughter with high arches and toe-walking. There was no family history of inclusion body myositis. The phenotype in the proband was complex and seemed to represent an entity along the spectrum of a lower motor neuron syndrome and axonal neuropathy. Jerath et al. (2015) commented on the phenotypic variability associated with VCP mutations. Inheritance The transmission pattern of CMT2Y in the family reported by Gonzalez et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In 5 affected members of a family with CMT2Y, Gonzalez et al. (2014) identified a heterozygous missense mutation in the VCP gene (E185K; 601023.0010). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that the variant impaired autophagic function of VCP, leading to the accumulation of immature autophagosomes. ATPase function of the variant was normal. In a 60-year-old man of Dutch and Italian descent with CMT2Y, Jerath et al. (2015) identified a heterozygous missense mutation in the VCP gene (G97E; 601023.0011). In vitro functional expression studies showed that the mutant protein had increased ATPase activity compared to wildtype. The mutation was found by exome sequencing. INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes cavus \- High arches \- Hammertoes MUSCLE, SOFT TISSUES \- Distal muscle weakness due to peripheral neuropathy, lower and upper limbs \- Distal muscle atrophy due to peripheral neuropathy, lower and upper limbs \- Difficulties walking and running \- Muscle biopsy shows neurogenic atrophy (1 patient) NEUROLOGIC Peripheral Nervous System \- Axonal sensorimotor peripheral neuropathy \- Distal sensory impairment \- Hypo- or areflexia \- Balance difficulties LABORATORY ABNORMALITIES \- Increased serum creatine kinase (1 patient) MISCELLANEOUS \- One family and 1 unrelated patient have been reported (last curated December 2015) \- Highly variable severity \- Progressive disorder \- Age at onset ranges from early childhood to after age 50 years MOLECULAR BASIS \- Caused by mutation in the valosin-containing protein gene (VCP, 601023.0010 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2Y	c4225244	26,291	omim	https://www.omim.org/entry/616687	2019-09-22T15:48:18	{"doid": ["0110168"], "omim": ["616687"], "orphanet": ["435387"], "synonyms": ["Autosomal dominant Charcot-Marie-Tooth disease type 2 due to VCP mutation", "Alternative titles", "CMT2 due to VCP mutation", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2Y", "CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2Y", "CMT2Y"]}
A rare distal arthrogryposis syndrome characterized by multiple pterygia (typically involving the neck, axilla and popliteal areas), joint contractures, ptosis, camptodactyly of the hands with hypoplastic flexion creases, vertebral fusions, severe scoliosis and short stature. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal dominant multiple pterygium syndrome	c1867440	26,292	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65743	2021-01-23T18:15:33	{"mesh": ["C566739"], "omim": ["178110"], "umls": ["C1867440"], "icd-10": ["Q79.8"], "synonyms": ["Distal arthrogryposis type 8"]}
Abortion in Egypt is prohibited by Articles 260–264 of the Penal Code of 1937.[1][2] However, under Article 61 of the Penal Code, exceptions may be granted in cases of necessity, which has typically been interpreted to permit an abortion necessary to save the life of the pregnant woman. In some cases, this exception has been extended to cases where the pregnancy poses dangers to the pregnant woman's health, and to cases of foetal impairment.[3] A physician can only perform an abortion in such cases when two specialists approve, unless the woman's life is in imminent danger.[4] Any person who induces an abortion may be imprisoned, and physicians who do so may be sentenced to prison. Convictions are uncommon, because the prosecution must prove that the woman was pregnant and the means by which the pregnancy was interrupted.[3][1] In 1998, Muhammad Sayyid Tantawy, the Grand Imam of al-Azhar, issued a fatwa calling for access to abortion for unmarried women who had been raped. In 2004 he approved a draft bill that would permit abortion in the case of rape; the bill was unsuccessful.[5] Despite legal restrictions, abortions are common. In a 2000 study of 1025 women from six villages in Upper Egypt, 416 were found to have had at least one abortion; among this group, there were 265 abortions per 1000 live births.[6] Abortions are carried out by indigenous methods, at clandestine clinics, or at great expense by private gynecologists.[7] In addition, unsafe abortions are common: a 1998 study found that about 20% of obstetric hospital admissions were for post-abortion treatment. One study estimated that between 1995 and 2000, there were 2,079,216 abortions, and 2,542 maternal deaths due to unsafe abortions.[5] ## References[edit] 1. ^ a b "EGYPT. Penal Code of 31 July 1937". Harvard School of Public Health. Archived from the original on 2017-03-16. Retrieved 16 March 2017. 2. ^ Atighetchi, Dariusch (2007). Islamic bioethics: problems and perspectives. Dordrecht: Springer. pp. 126–127. ISBN 9781402049613. Retrieved 10 January 2018. 3. ^ a b "Egypt". Abortion Policies: A Global Review (DOC). 2. United Nations Population Division. 2002. Retrieved 14 March 2017. 4. ^ "EGYPT. Code of Ethics, Regulation No. 238 of 21 March 2003 of the Ministry of Health and Population". Harvard School of Public Health. Archived from the original on 2017-03-16. Retrieved 16 March 2017. 5. ^ a b Hessini, Leila (May 2007). "Abortion and Islam: Policies and Practice in the Middle East and North Africa". Reproductive Health Matters. 15 (29): 75–84. doi:10.1016/S0968-8080(06)29279-6. PMID 17512379. 6. ^ Yassin, KM (July 2000). "Incidence and socioeconomic determinants of abortion in rural Upper Egypt". Public Health. 114 (4): 269–272. doi:10.1016/s0033-3506(00)00343-7. 7. ^ Lane, Sandra D.; Jok, Jok Madut; El-Mouelhy, Mawaheb T. (October 1998). "Buying safety: The economics of reproductive risk and abortion in Egypt". Social Science & Medicine. 47 (8): 1089–1099. doi:10.1016/S0277-9536(98)00129-4. * v * t * e Abortion in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * 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active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Abortion in Egypt	None	26,293	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Egypt	2021-01-18T19:07:05	{"wikidata": ["Q30314347"]}
In 4 female sibs, Winter et al. (1968) observed renal hypoplasia or aplasia, anomalies of the internal genitalia, especially vaginal atresia, and, in the 2 surviving sisters in whom it could be investigated, anomaly of the ossicles of the middle ear. Turner (1970) described a similarly affected patient. Pathologic findings in 2 sisters of the Winter kindred had been reported by Schmidt et al. (1952). GU \- Renal aplasia/hypoplasia \- Vaginal atresia Inheritance \- Autosomal recessive Ears \- Hearing loss \- Abnormal middle ear ossicles ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	RENAL, GENITAL, AND MIDDLE EAR ANOMALIES	c1849432	26,294	omim	https://www.omim.org/entry/267400	2019-09-22T16:22:46	{"mesh": ["C564849"], "omim": ["267400"], "orphanet": ["1092"]}
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: "Ornithine translocase deficiency" – news · newspapers · books · scholar · JSTOR (March 2008) (Learn how and when to remove this template message) Ornithine translocase deficiency Other namesHHH syndrome, ORNT1 deficiency, ornithine carrier deficiency, triple H syndrome Ornithine Ornithine translocase deficiency, also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome,[1] is a rare autosomal recessive[2] urea cycle disorder affecting the enzyme ornithine translocase, which causes ammonia to accumulate in the blood, a condition called hyperammonemia. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia. ## Contents * 1 Pathophysiology * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 Further reading * 7 External links ## Pathophysiology[edit] Ornithine translocase deficiency has an autosomal recessive pattern of inheritance. Mutations in SLC25A15 cause ornithine translocase deficiency.[3] Ornithine translocase deficiency belongs to a class of metabolic disorders referred to as urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. The SLC25A15 gene provides instructions for making a protein called a mitochondrial ornithine transporter. This protein is needed to move a molecule called ornithine within the mitochondria (the energy-producing centers in cells). Specifically, this protein transports ornithine across the inner membrane of mitochondria to the region called the mitochondrial matrix, where it participates in the urea cycle. Mutations in the SLC25A15 gene result in a mitochondrial ornithine transporter that is unstable or the wrong shape, and which cannot bring ornithine to the mitochondrial matrix. This failure of ornithine transport causes an interruption of the urea cycle and the accumulation of ammonia, resulting in the signs and symptoms of ornithine translocase deficiency.[citation needed] This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder. ## Diagnosis[edit] Clinical findings in HHH syndrome are non-specific. If the disorder is suspected, laboratory testing can provide diagnostic information. Plasma amino acid analysis will show elevated ornithine levels, and urine amino acids will detect homocitrulline. Orotic acid may also be elevated. Ammonia levels can be variably elevated. If these findings are present, molecular testing may provide additional confirmatory information.[citation needed] ## Treatment[edit] Treatments include discontinuation of protein intake, intravenous infusion of glucose and, as needed, infusion of supplemental arginine and the ammonia removal drugs, sodium phenylacetate and sodium benzoate. ## See also[edit] * Ornithine transcarbamylase deficiency * Inborn errors of metabolism * Ornithine aminotransferase deficiency (gyrate atrophy of the choroid and retina) ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 238970 2. ^ Hommes FA, Roesel RA, Metoki K, Hartlage PL, Dyken PR (Feb 1986). "Studies on a case of HHH-syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria)". Neuropediatrics. 17 (1): 48–52. doi:10.1055/s-2008-1052499. ISSN 0174-304X. PMID 3960284. 3. ^ Smith, L. D.; Garg, U. (2017-01-01), Garg, Uttam; Smith, Laurie D. (eds.), "Chapter 5 - Urea cycle and other disorders of hyperammonemia", Biomarkers in Inborn Errors of Metabolism, San Diego: Elsevier, pp. 103–123, doi:10.1016/b978-0-12-802896-4.00004-3, ISBN 978-0-12-802896-4, retrieved 2020-11-10 * Charles Scriver, Beaudet, A.L., Valle, D., Sly, W.S., Vogelstein, B., Childs, B., Kinzler, K.W. (accessed 2007). New York: McGraw-Hill. Summaries of 255 chapters, full text through many universities. There is also the OMMBID blog. ## Further reading[edit] * Ornithine translocase deficiency at NLM Genetics Home Reference ## External links[edit] Classification D * ICD-9-CM: 270.6 * OMIM: 238970 * MeSH: C538380 * DiseasesDB: 29849 External resources * Orphanet: 415 * 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ornithine translocase deficiency	c0268540	26,295	wikipedia	https://en.wikipedia.org/wiki/Ornithine_translocase_deficiency	2021-01-18T18:57:21	{"gard": ["2830"], "mesh": ["C538380"], "umls": ["C0268540"], "icd-9": ["270.6"], "orphanet": ["415"], "wikidata": ["Q7103627"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-22 (SCAR22) is caused by homozygous mutation in the VWA3B gene (614884) on chromosome 2q11. One such family has been reported. Clinical Features Kawarai et al. (2016) reported 3 brothers, born of consanguineous Japanese parents, with intellectual disability associated with adult-onset cerebellar ataxia. Following normal early development, the patients showed variable severity of intellectual disability. Two attended a school for handicapped children and 1 completed junior high school. Full-scale IQ ranged from 48 to 81. Cerebellar ataxia manifested at around 40 years of age, with dysarthria and gait instability with falls. Initial neurologic examination showed pyramidal signs, including hyperreflexia and spasticity of the lower limbs, as well as cerebellar signs, such as dysmetria and nystagmus. Features that appeared later included truncal ataxia and intention tremor. The disorder was slowly progressive, and a walking aid or wheelchair was needed when the patients reached their late sixties. Brain imaging of 1 patient at age 68 showed cerebellar atrophy and thin corpus callosum. Inheritance The transmission pattern of SCAR22 in the family reported by Kawarai et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 brothers, born of consanguineous Japanese parents, with SCAR22, Kawarai et al. (2016) identified a homozygous missense mutation in the VWA3B gene (K622T; 614884.0001). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability. Sequencing the VWA3B gene in 26 other consanguineous families with cerebellar degeneration found several SNPs, but no clearly pathogenic mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus NEUROLOGIC Central Nervous System \- Intellectual disability \- Cerebellar ataxia \- Truncal ataxia \- Gait instability \- Dysmetria \- Dysarthria \- Intention tremor \- Pyramidal signs \- Spasticity \- Hyperreflexia \- Cerebellar atrophy \- Thin corpus callosum MISCELLANEOUS \- Onset of intellectual disability in childhood \- Onset of ataxia around age 40 years \- Slow progression \- One consanguineous Japanese family has been reported (last curated May 2016) MOLECULAR BASIS \- Caused by mutation in the von Willebrand factor A domain-containing protein 3B gene (VWA3B, 614884.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 22	c4310781	26,296	omim	https://www.omim.org/entry/616948	2019-09-22T15:47:24	{"omim": ["616948"]}
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1X (CMD1X) is caused by compound heterozygous mutation in the gene encoding fukutin (FKTN; 607440) on chromosome 9q31. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Murakami et al. (2006) described 6 Japanese patients from 4 families with dilated cardiomyopathy and mild or no limb-girdle muscle involvement, normal intelligence, and no history of seizures. One patient died at age 12 years from rapidly progressive CMD, and another underwent cardiac transplantation at age 18 years. Skeletal muscle biopsies from the patients showed minimal dystrophic features but altered glycosylation of alpha-dystroglycan (128239) and reduced laminin (see 150240)-binding ability. Cardiac muscle biopsy in 1 patient showed altered glycosylation of alpha-dystroglycan similar to that seen in Fukuyama-type congenital muscular dystrophy (253800). Molecular Genetics Murakami et al. (2006) analyzed the FKTN gene in 6 Japanese patients with CMD and mild or no limb-girdle muscle involvement and identified compound heterozygosity in all for a 3-kb retrotransposal insertion (607440.0001) and another missense mutation (607440.0010 or 607440.0011, respectively). INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Cardiomyopathy, dilated MUSCLE, SOFT TISSUES \- Proximal muscle weakness, mild MOLECULAR BASIS \- Caused by mutation in the fukutin gene (FKTN, 607440.0001 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CARDIOMYOPATHY, DILATED, 1X	c0340427	26,297	omim	https://www.omim.org/entry/611615	2019-09-22T16:03:06	{"doid": ["0110444"], "mesh": ["C536231"], "omim": ["611615"], "orphanet": ["154"], "synonyms": ["Alternative titles", "CARDIOMYOPATHY, DILATED, WITH MILD OR NO PROXIMAL MUSCLE WEAKNESS"]}
A rare soft tissue sarcoma characterized by a malignant space-occupying lesion most commonly located in the retroperitoneum or the inferior vena cava, but also other soft tissues, and composed of cells showing distinct features of smooth muscle cells. The tumor presents with mass effect depending on the location. It is capable of both local recurrence and distant metastasis, while lymph node metastasis is rare. Prognosis largely depends on tumor location and size. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Leiomyosarcoma	c0023269	26,298	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=64720	2021-01-23T18:09:00	{"gard": ["6880"], "mesh": ["D007890"], "umls": ["C0023269"], "icd-10": ["C49.9"]}
Chronic recurrent multifocal osteomyelitis (CRMO) causes abnormal inflammation to occur in and around the bones. Symptoms usually begin in childhood but can occur at any age. Symptoms may include episodes of pain and joint swelling, skin redness, and sometimes a fever. In some cases, CRMO leads to abnormal bone growth, bone deformity, and fractures. Symptoms can last for years, and may go away on their own. CRMO may occur alone or with other skin or bowel inflammation conditions. In rare cases, CRMO occurs as part of one of these genetic syndromes: Majeed syndrome, DIRA or PAPA syndrome. The cause of CRMO is unknown, but a genetic influence is thought to be involved. Diagnosis of CRMO is based on the symptoms, clinical exam, and imaging studies. Other more common conditions may need to be excluded before a diagnosis of CRMO can be made. Treatment is focused on managing the symptoms and include medications such as non-steroidal anti-inflammatories, corticosteroids, and other drugs that reduce inflammation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Chronic recurrent multifocal osteomyelitis	c0410422	26,299	gard	https://rarediseases.info.nih.gov/diseases/6108/chronic-recurrent-multifocal-osteomyelitis	2021-01-18T18:01:18	{"mesh": ["C535456"], "omim": ["259680"], "umls": ["C0410422"], "orphanet": ["324964"], "synonyms": ["CRMO", "Multifocal osteomyelitis, chronic", "Chronic multifocal osteomyelitis", "CMO", "Chronic nonbacterial osteomyelitis/Chronic recurrent multifocal osteomyelitis", "CNO/CRMO"]}

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