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text stringlengths 297 230k	title stringlengths 4 145	cui stringlengths 4 10	idx int64 0 30.7k	source stringclasses 6 values	source_url stringlengths 33 155	retrieved_date timestamp[s]	classification_map stringlengths 2 1.45k
A rare genetic syndromic intellectual disability characterized by language delay and mild to moderate intellectual disability associated with truncal obesity, congenital nonprogressive retinal dystrophy with poor night vision and reduced visual acuity, and micropenis in males. Cataracts may occur in the second or third decade of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	MORM syndrome	c1857802	24,800	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75858	2021-01-23T17:37:48	{"gard": ["10121"], "mesh": ["C536984"], "omim": ["610156"], "umls": ["C1857802"], "synonyms": ["Intellectual disability-truncal obesity-retinal dystrophy-micropenis syndrome"]}
A rare, severe, genetic, intestinal disease characterized by congenital absence of heparan sulfate from small intestine epithelium manifesting with secretory diarrhea and massive enteric protein loss. Patients present intolerance to enteral feeds during the first few weeks to months of life. Apart from absence of heparan sulfate from the basolateral surface of small intestine enterocytes, small bowel biopsy is otherwise normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Congenital enterocyte heparan sulfate deficiency	c4511238	24,801	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=103910	2021-01-23T17:06:12	{"icd-10": ["P78.3"]}
Clinical syndrome Brainstem death is a clinical syndrome defined by the absence of reflexes with pathways through the brainstem—the "stalk" of the brain, which connects the spinal cord to the mid-brain, cerebellum and cerebral hemispheres—in a deeply comatose, ventilator-dependent patient. Identification of this state carries a very grave prognosis for survival; cessation of heartbeat often occurs within a few days although it may continue for weeks if intensive support is maintained.[1] In the United Kingdom, the formal diagnosis of brainstem death by the procedure laid down in the official Code of Practice[1] permits the diagnosis and certification of death on the premise that a person is dead when consciousness and the ability to breathe are permanently lost, regardless of continuing life in the body and parts of the brain, and that death of the brainstem alone is sufficient to produce this state.[2] This concept of brainstem death is also accepted as grounds for pronouncing death for legal purposes in India[3] and Trinidad & Tobago.[4] Elsewhere in the world the concept upon which the certification of death on neurological grounds is based is that of permanent cessation of all function in all parts of the brain—whole brain death—with which the British concept should not be confused. The United States' President's Council on Bioethics made it clear, for example, in its White Paper of December 2008, that the British concept and clinical criteria are not considered sufficient for the diagnosis of death in the United States of America.[5] ## Contents * 1 Evolution of diagnostic criteria * 2 Diagnosis * 3 Prognosis and management * 4 Criticism * 5 References * 6 External links ## Evolution of diagnostic criteria[edit] The United Kingdom (UK) criteria were first published by the Conference of Medical Royal Colleges (with advice from the Transplant Advisory Panel) in 1976, as prognostic guidelines.[6] They were drafted in response to a perceived need for guidance in the management of deeply comatose patients with severe brain damage who were being kept alive by mechanical ventilators but showing no signs of recovery. The Conference sought "to establish diagnostic criteria of such rigour that on their fulfilment the mechanical ventilator can be switched off, in the secure knowledge that there is no possible chance of recovery". The published criteria—negative responses to bedside tests of some reflexes with pathways through the brainstem and a specified challenge to the brainstem respiratory centre, with caveats about exclusion of endocrine influences, metabolic factors and drug effects—were held to be "sufficient to distinguish between those patients who retain the functional capacity to have a chance of even partial recovery and those where no such possibility exists". Recognition of that state required the withdrawal of fruitless further artificial support so that death might be allowed to occur, thus "sparing relatives from the further emotional trauma of sterile hope".[6] In 1979, the Conference of Medical Royal Colleges promulgated its conclusion that identification of the state defined by those same criteria—then thought sufficient for a diagnosis of brain death—"means that the patient is dead".[7] Death certification on those criteria has continued in the United Kingdom (where there is no statutory legal definition of death) since that time, particularly for organ transplantation purposes, although the conceptual basis for that use has changed. In 1995, after a review by a Working Group of the Royal College of Physicians of London, the Conference of Medical Royal Colleges[2] formally adopted the "more correct" term for the syndrome, "brainstem death"—championed by Pallis in a set of 1982 articles in the British Medical Journal[8]—and advanced a new definition of human death as the basis for equating this syndrome with the death of the person. The suggested new definition of death was the "irreversible loss of the capacity for consciousness, combined with irreversible loss of the capacity to breathe". It was stated that the irreversible cessation of brainstem function will produce this state and "therefore brainstem death is equivalent to the death of the individual".[2] ## Diagnosis[edit] In the UK, the formal rules for the diagnosis of brainstem death have undergone only minor modifications since they were first published[6] in 1976. The most recent revision of the UK's Department of Health Code of Practice governing use of that procedure for the diagnosis of death[1] reaffirms the preconditions for its consideration. These are: 1. There should be no doubt that the patient's condition – deeply comatose, unresponsive and requiring artificial ventilation—is due to irreversible brain damage of known cause. 2. There should be no evidence that this state is due to depressant drugs. 3. Primary hypothermia as the cause of unconsciousness must have been excluded, and 4. Potentially reversible circulatory, metabolic and endocrine disturbances likewise. 5. Potentially reversible causes of apnoea (dependence on the ventilator), such as muscle relaxants and cervical cord injury, must be excluded. With these pre-conditions satisfied, the definitive criteria are: 1. Fixed pupils which do not respond to sharp changes in the intensity of incident light. 2. No corneal reflex. 3. Absent oculovestibular reflexes – no eye movements following the slow injection of at least 50ml of ice-cold water into each ear in turn (the caloric reflex test). 4. No response to supraorbital pressure. 5. No cough reflex to bronchial stimulation or gagging response to pharyngeal stimulation. 6. No observed respiratory effort in response to disconnection of the ventilator for long enough (typically 5 minutes) to ensure elevation of the arterial partial pressure of carbon dioxide to at least 6.0 kPa (6.5 kPa in patients with chronic carbon dioxide retention). Adequate oxygenation is ensured by pre-oxygenation and diffusion oxygenation during the disconnection (so the brainstem respiratory centre is not challenged by the ultimate, anoxic, drive stimulus). This test—the apnoea test—is dangerous – and may prove lethal.[9][10][11][12] Two doctors, of specified status and experience, are required to act together to diagnose death on these criteria and the tests must be repeated after "a short period of time ... to allow return of the patient's arterial blood gases and baseline parameters to the pre-test state". These criteria for the diagnosis of death are not applicable to infants below the age of two months. ## Prognosis and management[edit] With due regard for the cause of the coma, and the rapidity of its onset, testing for the purpose of diagnosing death on brainstem death grounds may be delayed beyond the stage where brainstem reflexes may be absent only temporarily – because the cerebral blood flow is inadequate to support synaptic function although there is still sufficient blood flow to keep brain cells alive[9] and capable of recovery. There has recently been renewed interest in the possibility of neuronal protection during this phase by use of moderate hypothermia and by correction of the neuroendocrine abnormalities commonly seen in this early stage.[13] Published studies of patients meeting the criteria for brainstem death or whole brain death – the American standard which includes brainstem death diagnosed by similar means – record that even if ventilation is continued after diagnosis, the heart stops beating within only a few hours or days.[14] However, there have been some very long-term survivals[15] and it is noteworthy that expert management can maintain the bodily functions of pregnant brain dead women for long enough to bring them to term.[16] ## Criticism[edit] The diagnostic criteria were originally published for the purpose of identifying a clinical state associated with a fatal prognosis (see above). The change of use, in the UK, to criteria for the diagnosis of death itself was protested from the first.[17][18] The initial basis for the change of use was the claim that satisfaction of the criteria sufficed for the diagnosis of the death of the brain as a whole, despite the persistence of demonstrable activity in parts of the brain.[19] In 1995, that claim was abandoned[7] and the diagnosis of death (acceptable for legal purposes in the UK in the context of organ procurement for transplantation) by the specified testing of brainstem functions was based on a new definition of death, viz. the permanent loss of the capacity for consciousness and spontaneous breathing. There are doubts that this concept is generally understood and accepted and that the specified testing is stringent enough to determine that state. It is, however, associated with substantial risk of exacerbating the brain damage and even causing the death of the apparently dying patient so tested (see "the apnoea test" above). This raises ethical problems which seem not to have been addressed. It has been argued that sound scientific support is lacking for the claim that the specified purely bedside tests have the power to diagnose true and total death of the brainstem, the necessary condition for the assumption of permanent loss of the intrinsically untestable consciousness-arousal function of those elements of the reticular formation which lie within the brainstem (there are elements also within the higher brain).[19] Knowledge of this arousal system is based upon the findings from animal experiments[20][21][22] as illuminated by pathological studies in humans.[23] The current neurological consensus is that the arousal of consciousness depends upon reticular components which reside in the midbrain, diencephalon and pons.[24][25] It is said that the midbrain reticular formation may be viewed as a driving centre for the higher structures, loss of which produces a state in which the cortex appears, on the basis of electroencephalographic (EEG) studies, to be awaiting the command or ability to function. The role of diencephalic (higher brain) involvement is stated to be uncertain and we are reminded that the arousal system is best regarded as a physiological rather than a precise anatomical entity. There should, perhaps, also be a caveat about possible arousal mechanisms involving the first and second cranial nerves (serving sight and smell) which are not tested when diagnosing brainstem death but which were described in cats in 1935 and 1938.[20] In humans, light flashes have been observed to disturb the sleep-like EEG activity persisting after the loss of all brainstem reflexes and of spontaneous respiration.[26] There is also concern about the permanence of consciousness loss, based on studies in cats, dogs and monkeys which recovered consciousness days or weeks after being rendered comatose by brainstem ablation and on human studies of brainstem stroke syndrome raising thoughts about the "plasticity" of the nervous system.[23] Other theories of consciousness place more stress on the thalamocortical system.[27] Perhaps the most objective statement to be made is that consciousness is not currently understood. That being so, proper caution must be exercised in accepting a diagnosis of its permanent loss before all cerebral blood flow has permanently ceased. The ability to breathe spontaneously depends upon functioning elements in the medulla – the 'respiratory centre'. In the UK, establishing a neurological diagnosis of death involves challenging this centre with the strong stimulus offered by an unusually high concentration of carbon dioxide in the arterial blood, but it is not challenged by the more powerful drive stimulus provided by anoxia – although the effect of that ultimate stimulus is sometimes seen after final disconnection of the ventilator in the form of agonal gasps. No testing of testable brain stem functions such as oesophageal and cardiovascular regulation is specified in the UK Code of Practice for the diagnosis of death on neurological grounds. There is published evidence[28][29][30] strongly suggestive of the persistence of brainstem blood pressure control in organ donors. A small minority of medical practitioners working in the UK have argued that neither requirement of the UK Health Department's Code of Practice basis for the equation of brainstem death with death is satisfied by its current diagnostic protocol[1] and that in terms of its ability to diagnose de facto brainstem death it falls far short. ## References[edit] 1. ^ a b c d A Code of Practice for the Diagnosis and Confirmation of Death. Academy of Medical Royal Colleges, 70 Wimpole Street, London, 2008 2. ^ a b c Criteria for the diagnosis of brain stem death. J Roy Coll Physns of London 1995;29:381–2 3. ^ The Transplantation of Human Organs Act, 1994. Act No.42 of 1994. s. 2 4. ^ Human Tissue Transplant Act 2000. s. 19(1) 5. ^ Controversies In The Determination Of Death (PDF) (Report). Washington, D.C.: President's Council on Bioethics. December 2008. p. 66. hdl:10822/559343. Archived (PDF) from the original on 2018-05-17. 6. ^ a b c Conference of Medical Royal Colleges and their Faculties in the UK. BMJ 1976;2:1187–8 7. ^ a b Conference of Medical Royal Colleges and their Faculties in the UK. BMJ 1979;1:332. 8. ^ Pallis, C. From Brain Death to Brain Stem Death, BMJ, 285, November 1982 9. ^ a b Coimbra CG. Implications of ischemic penumbra for the diagnosis of brain death. Brazilian Journal of Medical and Biological Research 1999;32:1479–87 10. ^ Coimbra CG. The apnea test – a bedside lethal 'disaster' to avoid a legal 'disaster' in the operating room. In Finis Vitae – is brain death still life? pp.113–45 11. ^ Saposnik G et al. Problems associated with the apnea test in the diagnosis of brain death. Neurology India 2004;52:342–45 12. ^ Yingying S et al. Diagnosis of brain death : confirmatory tests after clinical test. Chin Med J 2014;127:1272–77 13. ^ Coimbra CG. Are 'brain dead' (or 'brain stem dead') patients neurologically recoverable? In Finis Vitae—'brain death' is not true death. Eds. De Mattei R, Byrne PA. Life Guardian Foundation, Oregon, Ohio, 2009, pp. 313–378 14. ^ Pallis C, Harley DH. ABC of brain stem death. BMJ Publishing Group, 1996, p.30 15. ^ Shewmon DA. 'Brain body' disconnection : implications for the theoretical basis of 'brain death'. In Finis Vitae – is brain death still life? Ed. De Mattei R. Consiglio Nazionale delle Richerche. Rubbettino, 2006, pp. 211–250 16. ^ Powner DJ, Bernstein IM. Extended somatic support for pregnant women after brain death. Crit Care Med 2003;31:1241–49 17. ^ Evans DW, Lum LC. Cardiac transplantation. Lancet 1980;1:933–4 18. ^ Evans DW, Lum LC. Brain death. Lancet 1980;2:1022 19. ^ a b Evans DW. The demise of 'brain death' in Britain. In Beyond brain death—the case against brain based criteria for human death. Eds. Potts M, Byrne PA, Nilges RG. Kluwer Academic Publishers, 2006, pp. 139–158 20. ^ a b G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalog Clin neurophysiol 1949;1:455–73 21. ^ Ward AA. The relationship between the bulbar-reticular suppressor region and the EEG. Clin Neurophysiol 1949;1:120 22. ^ Lindsley DB et al. Effect upon the EEG of acute injury to the brain stem activating system. EEG Clin Neurophysiol 1949;1:475–8627 23. ^ a b Parvizi J, Damasio AR. Neuroanatomical correlates of brainstem coma. Brain 2003;126:1524–36 24. ^ Textbook of clinical neurology, 2nd Edn. Ed. Goetz CG. Elsevier Science, 2003 25. ^ Bleck TP. In Textbook of clinical neurology, 3rd Edn. Ed. Goetz CG. Elsevier Science, 2007 26. ^ Zwarts MJ, Kornips FHM. Clinical brainstem death with preserved electroencephalographic activity and visual evoked response. Arch Neurol 2001;58:1010 27. ^ Tononi G. An information integration theory of consciousness. BMC Neuroscience 2004;5:42 28. ^ Hall GM et al. Hypothalamic-pituitary function in the 'brain dead' patient. Lancet 1980;2:1259 29. ^ Wetzel RC et al. Hemodynamic responses in brain dead organ donor patients. Anesthesia and Analgesia 1985;64:125–8 30. ^ Pennefather SH, Dark JH, Bullock RE. Haemodynamic responses to surgery in brain-dead organ donors. Anaesthesia 1993;48:1034–38 ## External links[edit] * Great Ormond Street Hospital for Children * v * t * e Death In medicine Cell death * Necrosis * Avascular necrosis * Coagulative necrosis * Liquefactive necrosis * Gangrenous necrosis * Caseous necrosis * Fat necrosis * Fibrinoid necrosis * Temporal lobe necrosis * Programmed cell death * AICD * Anoikis * Apoptosis * Autophagy * Intrinsic apoptosis * Necroptosis * Paraptosis * Parthanatos * Phenoptosis * Pseudoapoptosis * Pyroptosis * Autolysis * Autoschizis * Eschar * Immunogenic cell death * Ischemic cell death * Pyknosis * Karyorrhexis * Karyolysis * Mitotic catastrophe * Suicide gene * Abortion * Accidental death * Autopsy * Brain death * Brainstem death * Clinical death * DOA * Death by natural causes * Death rattle * Dysthanasia * End-of-life care * Euthanasia * Lazarus sign * Lazarus syndrome * Medical definition of death * Organ donation * Terminal illness * Unnatural death Lists * Causes of death by rate * Expressions related to death * Natural disasters * People by cause of death * Premature obituaries * Preventable causes of death * Notable deaths by year * Unusual deaths Mortality * Birthday effect * Child mortality * Gompertz–Makeham law of mortality * Infant mortality * Karoshi * Maternal death * Maternal mortality in fiction * Memento mori * Micromort * Mortality displacement * Mortality rate * RAMR * Mortality salience * Perinatal mortality After death Body Stages * Pallor mortis * Algor mortis * Rigor mortis * Livor mortis * Putrefaction * Decomposition * Skeletonization * Fossilization Preservation * Cryopreservation * Cryonics * Neuropreservation * Embalming * Maceration * Mummification * Plastination * Prosection * Taxidermy Disposal * Burial * Natural burial * Cremation * Dismemberment * Excarnation * Promession * Resomation * Beating heart cadaver * Body donation * Cadaveric spasm * Coffin birth * Death erection * Dissection * Gibbeting * Postmortem caloricity * Post-mortem interval Other aspects * Afterlife * Cemetery * Consciousness * Customs * Crematorium * Examination * Funeral * Grief * Intermediate state * Internet * Mourning * Online mourning * Obituary * Vigil Paranormal * Ghosts * Near-death experience * Near-death studies * Necromancy * Out-of-body experience * Reincarnation research * Séance Legal * Abortion law * Administration * Capital punishment * Cause of death * Civil death * Coroner * Death-qualified jury * Death certificate * Declared death in absentia * Death row * Dying declaration * Inquest * Legal death * Murder * Necropolitics * Prohibition of death * Right to die * Suspicious death * Trust law * Will Fields * Forensic pathology * Funeral director * Mortuary science * Necrobiology * Post-mortem chemistry * Post-mortem photography * Taphonomy * Biostratinomy * Thanatology Other * Apparent death * Dark tourism * Darwin Awards * Death and culture * Death anniversary * Death anxiety * Death deity * Personification of death * Dying-and-rising god * Psychopomp * Death camp * Death drive * Death education * Death from laughter * Death hoax * Death knell * Death march * Death messenger * Death notification * Death panel * Death poem * Death pose * Death-positive movement * Death squad * Death threat * Death trajectory * Dignified death * Extinction * Fan death * Festival of the Dead * Fascination with death * Hierarchy of death * Homicide * Last rites * Martyr * Megadeath * Museum of Death * Necronym * Necrophilia * Necrophobia * The Order of the Good Death * Predation * Sacrifice * human * Suicide * Assisted suicide * Thanatosensitivity * The Goodbye Family * Category * Outline * v * t * e Disorders of consciousness Unconsciousness * Minimally conscious state * Persistent vegetative state * Obtundation * Coma * Brain stem death * Stupor * Sopor * Sleep * Somnolence * Cataplexy Syncope * Heat syncope * Vasovagal episode Alteration of consciousness * Locked-in syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Brainstem death	c0394019	24,802	wikipedia	https://en.wikipedia.org/wiki/Brainstem_death	2021-01-18T18:49:07	{"wikidata": ["Q16971792"]}
A number sign (#) is used with this entry because of evidence that phosphohydroxylysinuria is caused by compound heterozygous mutation in the AGXTL2 gene (PHYKPL; 614683) on chromosome 5q35. One such patient has been reported. Description Phosphohydroxylysinuria is characterized by elevated phosphohydroxylysine in the urine. There is no clinical phenotype associated with this finding other than the urinary metabolites. This was confirmed by population genetic studies performed by Veiga-da-Cunha et al. (2013) (Hamosh, 2013). Clinical Features Dorland et al. (1990) reported 2 unrelated patients with neurologic abnormalities and an abnormal ninydrin-positive compound in the urine. The first patient was a Turkish girl, 1 of 5 children. She had a measles infection at the age of 2 and developed neurologic deterioration including seizures and ataxia at the age of 6. CSF showed anti-measles antibody, which established the diagnosis of subacute sclerotic panencephalitis. Her condition deteriorated and she died at the age of 7. The second patient was a boy who developed tonic-clonic seizures and cyanosis with a shigella infection at the age of 4 years. He had no long-term sequelae at age 17 but had not been followed up since childhood. The abnormal ninydrin-positive compound, which was persistently present in urine in both patients, was shown to be O-phosphohydroxylysine by FAB mass spectrometry and NMR spectroscopy. Veiga-da-Cunha et al. (2013) described a previously unreported patient who had been evaluated by the same laboratory as the patients reported by Dorland et al. (1990). This patient developed a severe phenotype reminiscent of Ehlers-Danlos syndrome at the age of 4, with extreme hyperlaxity of the joints leading to immobility and limited mobility as a teenager. She had no neurologic problems but did have severe growth retardation with low final height. Cardiac evaluation was normal. She achieved normal educational milestones. Urinary phosphohydroxylysine was 5 mmol/mol creatinine in the patient and undetectable in control samples. Population Genetics Veiga-da-Cunha et al. (2013) reported allele frequencies of 0.007 and 0.001 for the heterozygous missense mutations E437V and G240R, respectively, found in their patient with phosphohydroxylysinuria. These frequencies suggested that phosphohydroxylysinuria should be found in at least 1/16,000 subjects in the European population. This rather high frequency agreed with the identification of 2 patients in a screening for inborn errors of metabolism performed on 8,000 subjects in the Netherlands by Duran et al. (1994). Molecular Genetics Veiga-da-Cunha et al. (2013) sequenced the AGXT2L2 gene in their patient with phosphohydroxylysinuria and detected compound heterozygous missense mutations at conserved residues (see 614683.0001, 614683.0002). Functional studies showed that these mutations resulted in an insoluble, nonfunctional protein. Veiga-da-Cunha et al. (2013) noted that the patients reported by Dorland et al. (1990) had neurologic problems which were likely caused by infections, whereas their patient had a different phenotype with no neurologic symptoms. They concluded that phosphohydroxylysinuria is unlikely to be the cause of the phenotype in the 3 patients and more likely to be a harmless metabolic abnormality. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	PHOSPHOHYDROXYLYSINURIA	c3554344	24,803	omim	https://www.omim.org/entry/615011	2019-09-22T15:53:30	{"omim": ["615011"]}
Olive quick decline syndrome An olive grove infested with Xylella fastidiosa in Puglia, Italy in 2019 Common namesOQDS Causal agentsXylella fastidiosa HostsOlive trees VectorsMeadow froghopper DistributionSouthern Italy SymptomsDieback of the leaves, twigs and branches An infected olive grove in Italy in 2019 Disease of olive trees Olive quick decline syndrome (OQDS) (in Italian: Complesso da Disseccamento Rapido dell'Olivo, CDRO or CoDiRo) is a wasting disease of olive trees which causes dieback of the leaves, twigs and branches so that the trees no longer produce crops of olives. The main cause is a strain of the bacterium, Xylella fastidiosa, which is spread by plant-sucking insects such as the meadow froghopper. The bacteria restrict the flow of sap within the tree and so choke its extremities.[1] ## Impact[edit] The disease is particularly affecting olive groves in Southern Italy. It was first detected in Italy in 2013,[2] in the Salento Peninsula; by late 2013, it was estimated that approximately 8,000 hectares were affected.[3] The disease currently threatens olive groves and oil production in Italy, Greece, and Spain, which together account for 95% of European oil production[4][5] One 2020 model predicts a potential economic impact of the disease for Italy over 50 years between 1.9 billion to 5.6 billion Euros.[4] In addition to Europe, the disease has also been detected in olive crops in California, Argentina and Brazil.[6] ## Symptoms[edit] Symptoms include leaf scorch and desiccation of twigs and branches, beginning at the upper part of the crown and then moving to the rest of the tree, which acquires a burned look.[7] ## References[edit] 1. ^ Olive Quick Decline Syndrome (PDF), Primary Industries and Regions SA, 2017 2. ^ Stokstad, Erik (8 May 2015). "Italy's olives under siege". Science. 348 (6235): 620. doi:10.1126/science.348.6235.620. ISSN 0036-8075. PMID 25953988. 3. ^ Martelli, Giovanni P. (1 February 2016). "The current status of the quick decline syndrome of olive in southern Italy". Phytoparasitica. 44 (1): 1–10. doi:10.1007/s12600-015-0498-6. ISSN 1876-7184. S2CID 18746881. 4. ^ a b Schneider, Kevin; Werf, Wopke van der; Cendoya, Martina; Mourits, Monique; Navas-Cortés, Juan A.; Vicent, Antonio; Lansink, Alfons Oude (28 April 2020). "Impact of Xylella fastidiosa subspecies pauca in European olives". Proceedings of the National Academy of Sciences. 117 (17): 9250–9259. doi:10.1073/pnas.1912206117. ISSN 0027-8424. PMC 7196823. PMID 32284411. 5. ^ McGrath, Matt (13 April 2020). "Deadly olive tree disease 'could cost billions'". BBC News. Retrieved 5 May 2020. 6. ^ Saponari, M.; Boscia, D.; Altamura, G.; Loconsole, G.; Zicca, S.; D’Attoma, G.; Morelli, M.; Palmisano, F.; Saponari, A.; Tavano, D.; Savino, V. N. (18 December 2017). "Isolation and pathogenicity of Xylella fastidiosa associated to the olive quick decline syndrome in southern Italy". Scientific Reports. 7 (1): 17723. doi:10.1038/s41598-017-17957-z. ISSN 2045-2322. PMC 5735170. PMID 29255232. 7. ^ Martelli, G. P.; Boscia, D.; Porcelli, F.; Saponari, M. (1 February 2016). "The olive quick decline syndrome in south-east Italy: a threatening phytosanitary emergency". European Journal of Plant Pathology. 144 (2): 235–243. doi:10.1007/s10658-015-0784-7. ISSN 1573-8469. S2CID 16126474. This plant disease article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Olive quick decline syndrome	None	24,804	wikipedia	https://en.wikipedia.org/wiki/Olive_quick_decline_syndrome	2021-01-18T18:32:52	{"wikidata": ["Q19850514"]}
A number sign (#) is used with this entry because myofibrillar myopathy-1 (MFM1) is caused by heterozygous, homozygous, or compound heterozygous mutation in the desmin gene (DES; 125660) on chromosome 2q35. Description Myofibrillar myopathy (MFM) is a noncommittal term that refers to a group of morphologically homogeneous, but genetically heterogeneous chronic neuromuscular disorders. The morphologic changes in skeletal muscle in MFM result from disintegration of the sarcomeric Z disc and the myofibrils, followed by abnormal ectopic accumulation of multiple proteins involved in the structure of the Z disc, including desmin, alpha-B-crystallin (CRYAB; 123590), dystrophin (300377), and myotilin (TTID; 604103). ### Genetic Heterogeneity of Myofibrillar Myopathy Other forms of MFM include MFM2 (608810), caused by mutation in the CRYAB gene (123590); MFM3 (609200) (182920), caused by mutation in the MYOT gene (604103); MFM4 (609452), caused by mutation in the ZASP gene (LDB3; 605906); MFM5 (609524), caused by mutation in the FLNC gene (102565); MFM6 (612954), caused by mutation in the BAG3 gene (603883); MFM7 (617114), caused by mutation in the KY gene (605739); MFM8 (617258), caused by mutation in the PYROXD1 gene (617220); and MFM9 (603689), caused by mutation in the TTN gene (188840). 'Desmin-related myopathy' is another term referring to MFM in which there are intrasarcoplasmic aggregates of desmin, usually in addition to other sarcomeric proteins. Rigid spine syndrome (602771), caused by mutation in the SEPN1 gene (606210), is another desmin-related myopathy. Goebel (1995) provided a review of desmin-related myopathy. Clinical Features Desmin-related MFM is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. Autosomal dominant and autosomal recessive forms have been reported. Approximately one-third of DRMs are thought to be caused by mutations in the desmin gene (Ferreiro et al., 2004). Clark et al. (1978) described a large kindred with an autosomal dominant benign myopathy of late-adult onset (average age 53 years) characterized by mild weakness of the pelvic and shoulder girdles. Light microscopy identified myofibrillar cytoplasmic inclusions in type 1 muscle fibers in all 3 symptomatic and in 4 of 7 asymptomatic members. Ultrastructural characteristics showed Z band material and aggregates of actin (ACTA1; 102610) and myosin (MYH1; 160730). Porte et al. (1980) and Stoeckel et al. (1981) reported 3 brothers with a familial cardiomyopathy characterized by aberrant accumulation of desmin-type intermediate filaments within cardiac muscle cells. The 3 brothers were admitted to hospital at ages 23, 29, and 24, respectively, with complete AV block requiring implantation of a pacemaker. Concentric and obstructive ventricular hypertrophy was demonstrated. The parents and a fourth brother had no signs of cardiomyopathy. Wolburg et al. (1982) reported 2 unrelated patients with a slowly progressive myopathy characterized by dense granular inclusions in skeletal muscle and subsarcolemmal filamentous bodies as well as streaming and disintegration of the Z discs. Among the offspring of second-cousin parents, Vajsar et al. (1993) described a brother and sister who developed symptoms of cardiomyopathy at the age of 2 and 5 years, respectively, and slowly progressive muscle weakness a few years later. Skeletal muscle biopsy specimens showed subsarcolemmal crescents of dark eosinophilic material in both type 1 and type 2 fibers that stained positively for desmin and ubiquitin (191339). Ultrastructurally, the subsarcolemmal deposits consisted of aggregates of granular and filamentous material arising from Z bands. Horowitz and Schmalbruch (1994) provided follow-up of an Ashkenazi Jewish family with autosomal dominant myopathy originally described by Milhorat and Wolff (1943). The 6-generation family had early- to mid-adult onset of gait disturbances due to symmetric weakness in distal leg muscles, which progressed over 5 to 10 years to involve all extremities and bulbar, respiratory, and facial muscles. There was loss of leg reflexes with preservation of arm reflexes until late in the disorder. Laboratory examination showed a 3- to 5-fold increase in serum creatine kinase levels. There was frequent cardiac involvement with arrhythmias, conduction block, and congestive heart failure, resulting in a shortened life span. In addition to typical myopathic features and rimmed vacuoles on muscle biopsy, desmin was present as abundant granulofilamentous deposits in the form of reticular meshworks between individual myofibrils or adjacent to the sarcolemma. Abe et al. (1993) described a family in which 12 members of 4 successive generations suffered from weakness and atrophy of muscles in the distal extremities, neck, thorax, and shoulder girdle. Male-to-male transmission was observed. The mean age at onset was 42 years, and the patients became disabled after 5 to 10 years due to chronic respiratory failure. The level of serum creatine kinase was normal or slightly elevated. Electromyogram showed a predominant myopathic change with a slight neurogenic change. Autopsy, performed in 2 cases, revealed numerous cytoplasmic bodies in skeletal muscles; smooth and cardiac muscles were also affected. Cytoplasmic bodies were present predominantly in type 1 fibers in skeletal muscle. Electron microscopic examination showed dense central cores of myofilaments surrounded by radiating filaments. Ariza et al. (1995) described a patient with severe generalized myopathy affecting skeletal, cardiac, and smooth muscle. At age 19 years, the patient exhibited generalized muscle weakness; at 28 years, respiratory failure and intestinal pseudoobstruction led to death. Biopsies from skeletal muscle, myocardium, and intestinal muscle revealed numerous atrophic fibers and frequent misplacement of nuclei to the interior of the cells with subsarcolemmal eosinophilic masses. Immunohistochemistry was positive for desmin and negative for vimentin; antidesmin staining was patchy with extensive areas lacking staining and immunoreactive aggregates in other regions. Electron microscopy revealed classic features of desminopathies and abnormalities similar to those observed in desmin-null mutant mice. In the mice, myofibrils are fragile upon mechanical stress, and muscle weakness develops with age. Messina et al. (1997) observed dilated cardiomyopathy with conduction defect and adult-onset limb-girdle muscular dystrophy in an extensively affected 4-generation family. Twenty-five members were identified as affected on the basis of the presence of cardiac conduction defects, cardiomyopathy, and/or proximal muscle weakness. The proband underwent evaluation for cardiac transplantation at the age of 37 years. Symptoms of muscle weakness had been noted as early as age 17 years. Dyspnea on exertion had been present since age 25 years. A pacemaker had been implanted at age 29 years because of syncopal episodes due to complete heart block. All 4 chambers of the heart were dilated on echocardiography. Laboratory studies showed increased serum creatine kinase, and muscle biopsies showed dystrophic changes. The proband's father died at age 49 years of congestive heart failure and arrhythmia. In follow-up of this family, Greenberg et al. (2012) stated that the proband eventually underwent cardiac transplantation. He had progressive proximal limb weakness, greater in the legs, and mildly increased serum creatine kinase at age 40 years. Endomyocardial biopsy showed fibrosis and myocyte hypertrophy. Skeletal muscle biopsy showed abundant dense cytoplasmic inclusions that occasionally stained with menadione-linked nitro blue tetrazolium, consistent with reducing bodies. There was variation in fiber size, internal nuclei, mild endomysial fibrosis, rare vacuoles, and isolated degenerating fibers. Electron microscopy showed that the inclusions were composed of fibrils and granulofilamentous material. Laser capture microdissection and mass spectrometric analysis identified desmin in the inclusions. Goldfarb et al. (1998) reported 2 unrelated families with a cardiac and skeletal myopathy. In 1 family, 2 of 3 sibs developed proximal muscle weakness and wasting in their twenties or thirties. Weakness slowly progressed to involve the entirety of the limbs and eventually spread to the neck, bulbar, and facial muscles. Electrocardiograms of each patient showed right bundle branch block. In both affected sibs, an accumulation of amorphous material immunoreactive for desmin, dystrophin (300377), and vimentin (193060) was observed in the cytoplasm of the skeletal muscle cells. An uncle and the father of the patients had an identical condition. In the second family, 3 of 4 sibs developed complete atrioventricular conduction block requiring a permanent pacemaker at 2, 9, and 10 years of age. Between 20 and 24 years of age, all 3 sibs developed progressive muscle weakness and atrophy with swelling and breathing difficulties. The 2 older sibs died of progressive fibrosis of the cardiac conduction system and cardiomyopathy at 28 and 30 years of age. The surviving sib developed congestive heart failure secondary to restrictive cardiomyopathy. Examination of tissue from all 3 patients showed intracytoplasmic accumulation of amorphous desmin- and dystrophin-immunoreactive material with a characteristic subsarcolemmal distribution. There was no case of a similar disease in the extended family. Inheritance appeared to be autosomal dominant in the first family and autosomal recessive in the second family. Melberg et al. (1999) studied 12 patients from a Swedish family with myopathy and cardiomyopathy, and reviewed the medical records of 2 affected deceased members. Twelve patients, including the deceased individuals, had myopathy. The distribution of weakness was axial in mildly affected patients, axial and predominantly distal in moderately affected persons, and generalized in severely affected patients. The electromyogram showed signs of myopathy in 10 patients. Muscle biopsy specimens showed myopathic changes, rimmed vacuoles, and accumulation of desmin, dystrophin, and other proteins. Electron microscopy demonstrated granulofilamentous changes and disorganization of myofibrils. Several patients had episodes of chest pain or palpitations. Three men had arrhythmogenic right ventricular cardiomyopathy (ARVC). Nonsustained ventricular tachycardia, atrial flutter, and dilatation of the ventricles mainly affecting the right ventricle were documented. Two of the men had a pacemaker implanted because of atrial ventricular block and sick sinus syndrome (see 608567). Inheritance was autosomal dominant with variable onset and severity of skeletal muscle and cardiac involvement. Onset of muscle weakness was between the third and sixth decades. One of the deceased patients was found to have dilatation of the right ventricle, which on histologic examination, showed fibrofatty replacement of the myocardium, extending from the epicardium to the endocardium. Similar but less extensive changes were present in the left ventricle. Park et al. (2000) reported a patient who presented at age 24 years with difficulty climbing steps due to weakness in the legs. A year later, she experienced dizziness and syncopal episodes and was found to have atrioventricular conduction block requiring a permanent pacemaker. At age 29 years, distal and proximal muscle weakness in the arms and legs and mild neck and facial weakness were found. No other family members were affected. A homozygous mutation in the DES gene (125660.0007) was identified. Kaminska et al. (2004) reported 2 Polish families with skeletal myopathy without cardiac involvement. In the first family, a mother, her daughter, niece, and nephew had onset of gait disturbance and bilateral weakness in the legs between 39 and 45 years of age. A brother and sister in the second family presented with difficulty climbing stairs and raising their arms between 31 and 33 years of age. Progression was slower than that in the first family. Both families had the same deletion in the DES gene (125660.0012). Bar et al. (2007) reported a French family in which at least 6 members spanning 3 generations had desmin-related myopathy inherited in an autosomal dominant pattern. The proband had onset of proximal and distal lower limb weakness and dyspnea on exertion at age 35 years, followed by proximal upper limb weakness a year later. He had increased serum creatine kinase and became wheelchair-bound at age 44 years. He underwent tracheostomy for nocturnal ventilatory assistance at age 46 years. A year later, he had a pacemaker implanted for bradyarrhythmia. Of note, the patient had repetitive episodes of diarrhea and constipation during the disease course, indicating smooth muscle involvement. His mother and 2 maternal aunts died of heart failure. Bergman et al. (2007) studied 2 distantly related 4-generation Dutch families segregating autosomal dominant desmin-related myopathy, in which a total of 15 patients exhibited a highly heterogeneous clinical picture, varying from isolated dilated cardiomyopathy to a more generalized skeletal myopathy and mild respiratory problems. The female proband of the first family presented at 30 years of age with myopathy and later developed cardiac arrhythmias, requiring pacemaker placement at 45 years of age. The male proband of the second family presented with arrhythmias at 31 years of age and developed slowly progressive weakness of the proximal leg muscles starting at age 52. Overall, 13 (87%) of 15 presumably affected family members presented with cardiac problems between the ages of 25 and 60 years, consisting mainly of cardiac conduction defects. Skeletal muscle weakness beginning in either proximal or distal musculature was present in 6 (40%) of the affected individuals, with onset between 30 and 58 years of age. Mild respiratory function disturbance was found in 2 patients. Causes of death, occurring between 31 and 76 years of age, were presumably heart attack in 6 patients, heart failure in 3 patients, sudden cardiac death in 1 patient, and unknown in 1 patient. Skeletal muscle biopsy showed increased variation in muscle fiber size and fatty degeneration in both probands, with endomysial fibrosis and central nuclei observed as well in the male proband. Desmin staining showed an irregular pattern in both patients. Endomyocardial biopsy in the female proband's affected sister showed hypertrophic cardiomyocytes as well as degenerating cardiomyocytes with central vacuolar changes; staining revealed dense aggregates of desmin and variable patterns of p62 (SQSTM1; 601530), ranging from fine granular staining and small dense inclusions to muscle fibers that were almost completely filled. Postmortem skeletal muscle biopsy demonstrated severe muscle pathology with vacuolar changes, and desmin staining ranged from small clumps on a normal-appearing background to fibers showing complete and intense staining. Bergman et al. (2007) noted that these families illustrated the broad intrafamilial variability of desmin-related myopathy, since 6 affected individuals exhibited isolated cardiac conduction disease or heart failure, whereas 1 family member presented with skeletal muscle weakness as the only feature. Pica et al. (2008) reported a 39-year-old Chinese man who presented with complete heart block requiring pacemaker insertion following a syncopal episode. Examination revealed mild and symmetric weakness of both proximal and distal muscles; bilateral elbow flexion contractures of 20 degrees were also noted. Serum CK was elevated, and electromyography was consistent with myopathy. Echocardiography showed no evidence of cardiomyopathy. Family evaluation revealed a brother with a similar distribution as well as severity of muscle weakness and elevated CK levels, whereas the patient's mother and a sister had very mild proximal and distal weakness, with CK values just above the upper limits of normal. His brother also reported 2 episodes of unexplained syncope, and the affected sister reported episodes of palpitations. Van Tintelen et al. (2009) restudied the Dutch kindred with MFM1 reported by Bergman et al. (2007) and expanded it to include 3 distantly related families. The authors described 2 more affected Dutch families whose ancestors could be traced to the same small, poorly populated region in which the common ancestral couple of the large Dutch kindred had lived. The 27 affected individuals demonstrated a fully penetrant yet variable phenotype: all had predominantly cardiac involvement characterized by high-grade atrioventricular (AV) block at young ages and significant right ventricular involvement, including right bundle branch block (RBBB) in 10 patients, sometimes as a first manifestation, and right ventricular heart failure in 6 patients. Two of the latter patients fulfilled the criteria for ARVC. Immunofluorescence analysis of patient myocardia showed normal amounts of the major desmosomal proteins, but intercalated discs were more convoluted and elongated and had a zigzag appearance compared to controls. Otten et al. (2010) reported a Dutch family with desmin-related myopathy and ARVC. The proband, who had had palpitations since childhood, presented at 36 years of age with decreased leg strength. At age 39, he had atrial fibrillation, and 2 years later electrocardiogram showed first-degree AV block, sinus arrests, premature ventricular contractions, negative T waves in multiple leads, and an epsilon wave. At age 42, he collapsed and required resuscitation, after which a cardioverter-defibrillator was implanted. Echocardiography showed right ventricular dilation with hypokinesia and akinesia, consistent with a diagnosis of ARVC. Skeletal muscle biopsy at age 44 demonstrated desminopathy; the weakness of his leg musculature was progressive, with eventual involvement of his hand and diaphragmatic muscles. A brother of the patient also experienced loss of leg strength at age 41, and muscle biopsy at age 43 showed desminopathy; cardiac evaluation at age 46 showed first-degree AV block and slightly decreased left ventricular function, consistent with incipient cardiomyopathy. Their father had progressive loss of leg strength and was wheelchair-dependent when he died at age 59 from pneumonia; he had never undergone cardiac evaluation. Van Spaendonck-Zwarts et al. (2011) performed a metaanalysis of 159 patients with 40 different DES mutations reported in the literature. Familial disease was documented in 54%. Neurologic signs were present in 74%, cardiac signs in 74%, and both neurologic and cardiac signs in 49%. Isolated neurologic signs were found in 22%, and isolated cardiac signs in 22%. More than 70% of carriers exhibited myopathy or muscular weakness, with normal creatine kinase levels present in one third of them. Up to 50% of carriers had cardiomyopathy, mostly dilated cardiomyopathy, and about 60% had cardiac conduction disease or arrhythmias, with atrioventricular block as an important hallmark. Respiratory insufficiency was suggested in 26%. Symptoms generally started during the thirties. A quarter of carriers died at a mean age of 49 years. Sudden cardiac death occurred in 2 patients with a pacemaker, suggesting a ventricular tachyarrhythmia as cause of death. The findings emphasized the importance of cardiac monitoring in these patients. Cetin et al. (2013) reported 2 Turkish sibs, born of consanguineous parents, with young-adult onset of what the authors described as progressive limb-girdle muscular dystrophy, formerly designated as LGMD2R. The 39-year-old proband had developed progressive proximal muscle weakness of the arms and legs at age 15 years. He had mild facial muscle weakness and mild scapular winging but severe limb weakness and was wheelchair-bound since age 33 years. He had no subjective cardiac complaints or cardiomyopathy, but studies showed incomplete right bundle branch block and rare ventricular extrasystoles. Cognition was normal and he had no bulbar symptoms. Muscle biopsy showed dystrophic features with variation in fiber size, internal nuclei, and fibrosis, but no evidence of myofibrillar disruption or aggregation of abnormal proteins. There was a predominance of type 2 fibers. His 45-year-old sister had similar muscle complaints with proximal muscle weakness starting at age 27 years. She became wheelchair-bound most of the time at age 43, and could only walk a few steps at age 46. She had rare ventricular extrasystoles and echocardiography showed normal left ventricular function with mild tricuspid insufficiency; there was no evidence of cardiomyopathy. Mapping By linkage analysis of the large family with autosomal dominant myopathy reported by Horowitz and Schmalbruch (1994), Saavedra-Matiz et al. (2000) mapped the disease locus to a 17-cM region on chromosome 2q bounded by DNA markers D2S2248 and D2S401. The region colocalized on the radiation hybrid map with the desmin gene. Molecular Genetics In affected members of a family with autosomal dominant inheritance of a desmin-related cardioskeletal myopathy, Goldfarb et al. (1998) identified a heterozygous mutation in the desmin gene (125660.0001). In 3 affected members of a second family with apparent autosomal recessive inheritance of a more severe disorder, Goldfarb et al. (1998) identified compound heterozygosity for 2 mutations in the desmin gene (125660.0002; 125660.0003). Several older unaffected family members carried 1 of the mutations. Park et al. (2000) reported splice site mutations in the desmin gene causing deletion of exon 3 (125660.0008; 125660.0009) in 2 individuals with cardiac and skeletal myopathy. In the patient reported by Ariza et al. (1995), Munoz-Marmol et al. (1998) identified a homozygous 21-bp deletion in the DES gene (125660.0004). In affected members of the large, 6-generation Ashkenazi Jewish family with desmin-related myopathy reported by Horowitz and Schmalbruch (1994), Sjoberg et al. (1999) identified a heterozygous mutation in the desmin gene (125660.0006). In 6 patients from 4 unrelated families with desmin-related myopathy, Bar et al. (2007) identified mutations in the DES gene (see, e.g., 125660.0015). In affected members of 2 distantly related Dutch families segregating autosomal dominant desmin-related myopathy with a highly heterogeneous clinical picture, varying from isolated dilated cardiomyopathy to more generalized skeletal myopathy and mild respiratory problems, Bergman et al. (2007) identified heterozygosity for a missense mutation in the DES gene (S13F; 125660.0019) that was not found in unaffected family members or in 216 ethnically matched controls. In 4 affected members of a 2-generation Chinese family with desmin-related myopathy, Pica et al. (2008) identified heterozygosity for the S13F mutation in the DES gene. Van Tintelen et al. (2009) restudied the Dutch kindred with MFM1 previously reported by Bergman et al. (2007), now expanded to 3 distantly related families. The authors described 2 more affected Dutch families whose ancestors could be traced to the same small, poorly populated region in which the common ancestral couple of the large Dutch kindred had lived. All 27 affected individuals were heterozygous for the S13F mutation, and demonstrated a fully penetrant yet variable predominantly cardiologic phenotype, characterized by conduction disease at an early age and right ventricular involvement, including RBBB and/or right ventricular tachycardias and ARVC phenocopies. Based on haplotype analysis, the mutation was estimated to be between 220 and 495 years old. In a female patient who had recurrent episodes of syncope from infancy and an aggressive course leading to the devastation of cardiac, skeletal, and smooth musculature, and death from cardiac failure at age 20 years, Pinol-Ripoll et al. (2009) identified homozygosity for the same 21-bp deletion in the DES gene that was previously found by Munoz-Marmol et al. (1998) in the patient reported by Ariza et al. (1995). Pinol-Ripoll et al. (2009) stated that this was the youngest known molecularly identified patient with desminopathy. In a Dutch patient with desmin-related myopathy and arrhythmogenic right ventricular cardiomyopathy (ARVC), Otten et al. (2010) identified heterozygosity for a missense mutation in the DES gene (N342D; 125660.0020). In affected members of a large family with autosomal dominant limb-girdle muscular dystrophy and cardiomyopathy (Messina et al., 1997), Greenberg et al. (2012) identified a heterozygous mutation in the desmin gene (125660.0008). The mutation was found after laser capture microdissection of skeletal muscle and mass spectrometry-based proteomics identified desmin as the major constituent of cytoplasmic inclusions. Initial mapping studies on this family by Messina et al. (1997) had found linkage to chromosome 6q23, and the locus was designated 'LGMD1D.' Subsequent mapping by Greenberg et al. (2012) excluded 6q23 due to absence of cosegregation of this locus with the phenotype in affected family members. By exome sequencing in the Swedish family with myofibrillar myopathy and ARVC reported by Melberg et al. (1999), Hedberg et al. (2012) identified a heterozygous mutation in the DES gene (P419S; 125660.0017) in affected members. In 2 sibs with MFM1 who were diagnosed with a form of limb-girdle muscular dystrophy, Cetin et al. (2013) identified a homozygous splice site mutation in the DES gene (125660.0018). The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder and was not found in several control databases. The mutant protein was expressed in patient skeletal muscle, which had normal myofibrillar organization, but confocal laser scanning microscopy showed a disruption in binding between desmin and lamin B (LMNB1; 150340), which is a component of the nuclear lamina. Genotype/Phenotype Correlations Van Spaendonck-Zwarts et al. (2011) performed a metaanalysis of 159 patients with 40 different DES mutations reported in the literature. The majority of DES mutations were missense mutations, mostly located in the 2B domain. Mutations in the 2B domain were predominant in patients with an isolated neurologic phenotype, whereas head and tail domain mutations were predominant in patients with an isolated cardiac phenotype. Nomenclature Selcen et al. (2004) noted that the pathologic findings in myofibrillar myopathy have been described in the past in various ways, including 'inclusion bodies,' 'intrasarcoplasmic dense granulofilamentous material,' 'spheroid bodies,' 'sarcoplasmic bodies,' 'cytoplasmic bodies,' 'Mallory body-like inclusions,' and 'subsarcolemmal vermiform deposits.' Autosomal dominant inclusion body myopathy had previously been referred to in OMIM as IBM1 to distinguish it in particular from autosomal recessive IBM2 (see 605820), which is caused by mutation in the GNE gene (603824) on chromosome 9p13.3. Since then, autosomal dominant inclusion body myopathy has been found to be a genetically heterogeneous condition and is referred to as myofibrillar myopathy. The symbol 'LGMD1D' had previously been used in OMIM for a form of limb-girdle muscular dystrophy mapping to chromosome 7q; however, according to the report of the 105th ENMC workshop, the form of LGMD mapping to chromosome 7q has been designated 'LGMD1E' (603511) (Bushby and Beckmann, 2003). The symbol 'LGMD1D' was later used for a form of LGMD and cardiomyopathy mapped to 6q23 in 1 family (Messina et al., 1997); however, the disorder in that family was later mapped to 2q35 and found to be caused by mutation in the desmin gene (Greenberg et al., 2012). Limb-girdle muscular dystrophy-2R (LGMD2R) was reclassified as a form of myofibrillar myopathy caused by mutation in the DES gene by Straub et al. (2018). The symbol 'ARVD7' was initially used for a form of myofibrillar myopathy with arrhythmogenic right ventricular dysplasia identified in a large Swedish family and mapped to chromosome 10q22 by Melberg et al. (1999) and Kuhl et al. (2008). Reevaluation of that family by Hedberg et al. (2012) found that affected individuals carried a heterozygous mutation in the DES gene (P419S; 125660.0017) on chromosome 2, indicating that this family has myofibrillar myopathy-1. Animal Model Shelton et al. (2004) reported myofibrillar myopathy with accumulations of desmin and other proteins in an Australian shepherd dog. The dog presented at age 1 year with chronic lameness, contractures, exercise intolerance, cardiomyopathy, and increased serum creatine kinase. INHERITANCE \- Autosomal dominant \- Autosomal recessive CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy \- Dilated cardiomyopathy \- Restrictive heart failure \- Conduction abnormalities \- Arrhythmias RESPIRATORY \- Respiratory muscle weakness ABDOMEN Gastrointestinal \- Constipation due to smooth muscle involvement \- Diarrhea due to smooth muscle involvement MUSCLE, SOFT TISSUES \- Distal muscle weakness occurs initially \- Proximal muscle weakness occurs later \- Affected muscles show atrophy \- Neck muscle weakness \- Facial weakness \- Bulbar weakness \- Hyporeflexia in lower limbs \- Smooth muscle may also become involved \- EMG shows myopathy \- Biopsy shows degenerative changes consistent with myopathy \- Intrasarcoplasmic dense granulofilamentous aggregates that are immunoreactive with desmin MISCELLANEOUS \- Variable phenotype \- Onset usually in second or third decades \- Autosomal dominant and autosomal recessive forms MOLECULAR BASIS \- Caused by mutation in the desmin gene (DES, 125660.0001 ) ▲ 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	MYOPATHY, MYOFIBRILLAR, 1	c1832370	24,805	omim	https://www.omim.org/entry/601419	2019-09-22T16:14:47	{"doid": ["0080092"], "mesh": ["C563319"], "omim": ["615325", "601419"], "orphanet": ["363543", "98909"], "synonyms": ["DESMINOPATHY, PRIMARY", "INCLUSION BODY MYOPATHY 1, AUTOSOMAL DOMINANT, FORMERLY", "ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 7, FORMERLY", "CMD1F AND LGMD1D, FORMERLY", "DESMIN-RELATED MYOPATHY WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY", "ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 7, FORMERLY", "CARDIOMYOPATHY, DILATED, 1F AND LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 1D, FORMERLY", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2R, FORMERLY", "Autosomal recessive limb-girdle muscular dystrophy due to desmin deficiency", "CARDIOMYOPATHY, DILATED, WITH CONDUCTION DEFECT AND MUSCULAR DYSTROPHY", "Alternative titles", "DESMIN-RELATED MYOPATHY", "MYOPATHY, MYOFIBRILLAR, DESMIN-RELATED", "LGMD2R", "MYOFIBRILLAR MYOPATHY WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY"]}
Abortion in Idaho is legal. 45% of adults said in a poll by Pew Research that abortion should be legal in all or most cases. Idaho passed a law in the 2000s banning abortions after 22 weeks because it was alleged that a fetus can feel pain. Mandatory informed consent laws were in place by 2007. The cut off point for getting a legal abortion in the state was generally some point between week 24 and 28. This period uses a standard defined by the United States Supreme Court in 1973 with the Roe v. Wade ruling. The number of abortion clinics in the state has been declining in recent years, going from fifteen in 1982 to nine in 1992 to three in 2014, and remaining at that number in 2016 and 2017. Because of this, some women went to Emerg-A-Care in Jackson Hole, Wyoming to get abortions. There were 801 legal abortions in 2000, 738 in 2001, 911 in 2003, 1,767 in 2014 and 1,695 in 2015. Both abortion rights activists and anti-abortion rights activists have been active in Idaho. ## Contents * 1 Terminology * 2 Context * 3 History * 3.1 Legislative history * 3.2 Judicial history * 3.3 Clinic history * 4 Statistics * 5 Abortion rights views and activities * 5.1 Protests * 6 Anti-abortion views and activities * 7 Footnotes * 8 References ## Terminology[edit] Main article: Abortion See also: Definitions of abortion The abortion debate most commonly relates to the "induced abortion" of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[note 1] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[1] Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[2][3] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[4][5] Both "pro-choice" and "pro-life" are examples of terms labeled as political framing: they are terms which purposely try to define their philosophies in the best possible light, while by definition attempting to describe their opposition in the worst possible light. "Pro-choice" implies that the alternative viewpoint is "anti-choice", while "pro-life" implies the alternative viewpoint is "pro-death" or "anti-life".[6] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[7] ## Context[edit] See also: Abortion in the United States Free birth control correlates to teenage girls having a fewer pregnancies and fewer abortions. A 2014 New England Journal of Medicine study found such a link. At the same time, a 2011 study by Center for Reproductive Rights and Ibis Reproductive Health also found that states with more abortion restrictions have higher rates of maternal death, higher rates of uninsured pregnant women, higher rates of infant and child deaths, higher rates of teen drug and alcohol abuse, and lower rates of cancer screening.[8] According to a 2017 report from the Center for Reproductive Rights and Ibis Reproductive Health, states that tried to pass additional constraints on a women's ability to access legal abortions had fewer policies supporting women's health, maternal health and children's health. These states also tended to resist expanding Medicaid, family leave, medical leave, and sex education in public schools.[9] According to Megan Donovan, a senior policy manager at the Guttmacher Institute, states have legislation seeking to protect a woman's right to access abortion services have the lowest rates of infant mortality in the United States.[9] Poor women in the United States had problems paying for menstrual pads and tampons in 2018 and 2019. Almost two-thirds of American women could not pay for them. These were not available through the federal Women, Infants, and Children Program (WIC).[10] Lack of menstrual supplies has an economic impact on poor women. A study in St. Louis found that 36% had to miss days of work because they lacked adequate menstrual hygiene supplies during their period. This was on top of the fact that many had other menstrual issues including bleeding, cramps and other menstrual induced health issues.[10] This state was one of a majority that taxed essential hygiene products like tampons and menstrual pads as of November 2018.[11][12][13][14] ## History[edit] ### Legislative history[edit] By 1950, the state legislature passed a law stating that a woman who had an abortion or actively sought to have an abortion regardless of whether she went through with it were guilty of a criminal offense.[15] The state passed a law in the 2000s banning abortions after 22 weeks because they alleged that fetus can feel pain.[16] The state was one of 23 states in 2007 to have a detailed abortion-specific informed consent requirement.[17] In the informed consent materials given to women in Idaho, Oklahoma, South Dakota and Texas required by statute, the materials used graphic and inflammatory language.[18] Idaho was the only state of 23 with detailed informed consent requirements by statute that did not require the woman be told how far advanced her pregnancy was.[18] Georgia, Michigan, Arkansas and Idaho all required in 2007 that women must be provided by an abortion clinic with the option to view an image their fetus if an ultrasound is used prior to the abortion taking place.[18] As of May 14, 2019, the state prohibited abortions after the fetus was viable, generally some point between week 24 and 28. This period uses a standard defined by the United States Supreme Court in 1973 with the Roe v. Wade ruling.[19] On March 24, 2020 Governor Little signed S1385 into law which is a trigger law that if states are allowed to ban abortion, then abortion will be illegal in Idaho except for cases of the life of the mother, rape or incest.[20][21][22] ### Judicial history[edit] The United States Supreme Court's decision in 1973's Roe v. Wade ruling meant the state could no longer regulate abortion in the first trimester.[15] ### Clinic history[edit] Number of abortion clinics in Idaho by year See also: Abortion clinic Between 1982 and 1992, the number of abortion clinics in the state decreased by six, going from fifteen in 1982 to nine in 1992.[23] In 2014, there were three abortion clinics in the state.[24] In 2014, 95% of the counties in the state did not have an abortion clinic. That year, 68% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[25] In March 2016, there were three Planned Parenthood clinics in the state.[26] In 2017, there were three Planned Parenthood clinics in a state with a population of 365,502 women aged 15 – 49 of which 3 offered abortion services.[27] Emerg-A-Care in Jackson Hole, Wyoming also served women from Eastern Idaho in 2017.[28] ## Statistics[edit] In the period between 1972 and 1974, there was only no recorded illegal abortion death in the state.[clarification needed][29] In 1990, 106,000 women in the state faced the risk of an unintended pregnancy.[23] The lowest number of legal induced abortions by state in 2000 occurred in Idaho with 801, while South Dakota was second with 878, and North Dakota was third with 1,341.[30] Idaho had the fewest induced abortions in 2001 with 738, while South Dakota was second with 895, and North Dakota was third with 1,216. Idaho had the lowest induced abortion to live birth ration at 36 per 1,000 live births while New York City had the highest at 767. Based on the ratio of number of women aged 15–44 years, Idaho had the lowest rate of induced abortions at 3 per 1,000 women while the District of Columbia had the highest at 37 per 1,000.[31] In 2003, the state of South Dakota had the lowest number of legal induced abortions with 819. Idaho was second with 911, while North Dakota was third with 1,354. Idaho had the lowest ratio of induced abortions to live births at 42 per 1,000 in 2003 while New York City had the highest at 758 to 1,000.[32] In 2010, the state had zero publicly funded abortions.[33] In 2013, among white women aged 15–19, there were abortions 170, zero abortions for black women aged 15–19, forty abortions for Hispanic women aged 15–19, and 20 abortions for women of all other races.[34] In 2014, 45% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[35] In 2017, the state had an infant mortality rate of 4.6 deaths per 1,000 live births.[9] Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[36] Census division and state Number Rate % change 1992–1996 1992 1995 1996 1992 1995 1996 US Total 1,528,930 1,363,690 1,365,730 25.9 22.9 22.9 –12 Mountain 69,600 63,390 67,020 21 17.9 18.6 –12 Arizona 20,600 18,120 19,310 24.1 19.1 19.8 –18 Colorado 19,880 15,690 18,310 23.6 18 20.9 –12 Idaho 1,710 1,500 1,600 7.2 5.8 6.1 –15 Montana 3,300 3,010 2,900 18.2 16.2 15.6 –14 Nevada 13,300 15,600 15,450 44.2 46.7 44.6 1 New Mexico 6,410 5,450 5,470 17.7 14.4 14.4 –19 Utah 3,940 3,740 3,700 9.3 8.1 7.8 –16 Wyoming 460 280 280 4.3 2.7 2.7 –37 Number, rate, and ratio of reported abortions, by reporting area of residence and occurrence and by percentage of abortions obtained by out-of-state residents, US CDC estimates Location Residence Occurrence % obtained by out-of-state residents Year Ref No. Rate^ Ratio^^ No. Rate^ Ratio^^ Idaho 1,710 7.2 1992 [36] Idaho 1,500 5.8 1995 [36] Idaho 1,600 6.1 1996 [36] Idaho 1,767 5.6 77 1,353 4.3 59 5.2 2014 [37] Idaho 1,695 5.3 74 1,272 4 56 4.6 2015 [38] Idaho 1,725 5.4 77 1,289 4.0 57 3.4 2016 [39] ^number of abortions per 1,000 women aged 15–44; ^^number of abortions per 1,000 live births ## Abortion rights views and activities[edit] ### Protests[edit] Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[40] ## Anti-abortion views and activities[edit] The Boise March for Life takes place every January on the weekend anniversary of Roe v. Wade to commemorate the over 50 million unborn children that have been lost since the Supreme Court ruling. The march and rally that follows are a celebration of life and demonstration in the belief that all life is sacred. Shelley Shannon attempted to set fires at abortion clinics in Oregon, California, Idaho and Nevada during the late 1980s and early 1990s and eventually plead guilty for these cases of arson. In 1993, she would be found guilty of attempted murder of Dr. George Tiller in 1993 at his Wichita, Kansas clinic.[41] ## Footnotes[edit] 1. ^ According to the Supreme Court's decision in Roe v. Wade: > (a) For the stage prior to approximately the end of the first trimester, the abortion decision and its effectuation must be left to the medical judgement of the pregnant woman's attending physician. (b) For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. (c) For the stage subsequent to viability, the State in promoting its interest in the potentiality of human life may, if it chooses, regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgement, for the preservation of the life or health of the mother. Likewise, Black's Law Dictionary defines abortion as "knowing destruction" or "intentional expulsion or removal". ## References[edit] 1. ^ Watson, Katie (20 Dec 2019). "Why We Should Stop Using the Term "Elective Abortion"". AMA Journal of Ethics. 20: E1175-1180. doi:10.1001/amajethics.2018.1175. PMID 30585581. Retrieved 17 May 2019. 2. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1). 3. ^ "The Roberts Court Takes on Abortion". New York Times. November 5, 2006. Retrieved January 18, 2008. 4. ^ Brennan 'Dehumanizing the vulnerable' 2000 5. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review. 6. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on 2011-07-27. Retrieved 2011-11-16. 7. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007. 8. ^ Castillo, Stephanie (2014-10-03). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Retrieved 2019-05-27. 9. ^ a b c "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved 2019-05-25. 10. ^ a b Mundell, E.J. (January 16, 2019). "Two-Thirds of Poor U.S. Women Can't Afford Menstrual Pads, Tampons: Study". US News & World Report. Retrieved May 26, 2019. 11. ^ Larimer, Sarah (January 8, 2016). "The 'tampon tax,' explained". The Washington Post. Archived from the original on December 11, 2016. Retrieved December 10, 2016. 12. ^ Bowerman, Mary (July 25, 2016). "The 'tampon tax' and what it means for you". USA Today. Archived from the original on December 11, 2016. Retrieved December 10, 2016. 13. ^ Hillin, Taryn. "These are the U.S. states that tax women for having periods". Splinter. Retrieved 2017-12-15. 14. ^ "Election Results 2018: Nevada Ballot Questions 1-6". KNTV. Retrieved 2018-11-07. 15. ^ a b Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66: 1774–1831. 16. ^ Times, The New York. "Abortion Restrictions in States". archive.nytimes.com. Retrieved 2019-05-25. 17. ^ "State Policy On Informed Consent for Abortion" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019. 18. ^ a b c "State Abortion Counseling Policies and the Fundamental Principles of Informed Consent". Guttmacher Institute. 2007-11-12. Retrieved 2019-05-22. 19. ^ Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24. 20. ^ "'Trigger law' to ban abortion passes Senate". 21. ^ "Idaho governor signs bill outlawing abortion if Roe v. Wade is reversed". 22. ^ "Senate Bill S1385 2020 Session". 23. ^ 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. 24. ^ Gould, Rebecca Harrington, Skye. "The number of abortion clinics in the US has plunged in the last decade — here's how many are in each state". Business Insider. Retrieved 2019-05-23. 25. ^ businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved 2019-05-24. 26. ^ Bohatch, Emily. "27 states with the most Planned Parenthood clinics". thestate. Retrieved 2019-05-24. 27. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved 2019-05-23. 28. ^ McCann, Allison (May 23, 2017). "Seven states have only one remaining abortion clinic. We talked to the people keeping them open". Vice News. Retrieved 2019-05-23. 29. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687. 30. ^ "Abortion Surveillance --- United States, 2000". www.cdc.gov. Retrieved 2019-05-25. 31. ^ "Abortion Surveillance --- United States, 2001". www.cdc.gov. Retrieved 2019-05-25. 32. ^ "Abortion Surveillance --- United States, 2003". www.cdc.gov. Retrieved 2019-05-25. 33. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved 2019-05-24. 34. ^ "No. of abortions among women aged 15–19, by state of residence, 2013 by racial group". Guttmacher Data Center. Retrieved 2019-05-24. 35. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics". Pew Research Center. Retrieved 2019-05-23. 36. ^ a b c d "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Retrieved 2019-06-02. 37. ^ Jatlaoui, Tara C. (2017). "Abortion Surveillance — United States, 2014". MMWR. Surveillance Summaries. 66 (24): 1–48. doi:10.15585/mmwr.ss6624a1. ISSN 1546-0738. PMID 29166366. 38. ^ Jatlaoui, Tara C. (2018). "Abortion Surveillance — United States, 2015". MMWR. Surveillance Summaries. 67 (13): 1–45. doi:10.15585/mmwr.ss6713a1. ISSN 1546-0738. PMC 6289084. PMID 30462632. 39. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738. 40. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA Today. Retrieved 2019-05-25. 41. ^ Jacobson, Mireille; Royer, Heather (December 2010). "Aftershocks: The Impact of Clinic Violence on Abortion Services". American Economic Journal: Applied Economics. 3: 189–223. doi:10.1257/app.3.1.189. Abortion in the United States by state States * Alabama * Alaska * Arizona * Arkansas * California * Colorado * Connecticut * Delaware * Florida * Georgia * Hawaii * Idaho * Illinois * Indiana * Iowa * Kansas * Kentucky * Louisiana * Maine * Maryland * Massachusetts * Michigan * Minnesota * Mississippi * Missouri * Montana * Nebraska * Nevada * New Hampshire * New Jersey * New Mexico * New York * North Carolina * North Dakota * Ohio * Oklahoma * Oregon * Pennsylvania * Rhode Island * South Carolina * South Dakota * Tennessee * Texas * Utah * Vermont * Virginia * Washington * West Virginia * Wisconsin * Wyoming Federal district Washington, D.C. Insular areas * American Samoa * Guam * Northern Mariana Islands * Puerto Rico * U.S. Virgin Islands [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Abortion in Idaho	None	24,806	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Idaho	2021-01-18T18:58:49	{"wikidata": ["Q64876915"]}
Kaler-Garrity-Stern syndrome is a rare syndrome, described in two sisters of Mennonite descent, characterized by sparse hair, osteopenia, intellectual disability, minor facial abnormalities, joint laxity and hypotonia. There have been no further descriptions in the literature since 1992. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Osteopenia-intellectual disability-sparse hair syndrome	c1850140	24,807	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2324	2021-01-23T18:38:07	{"gard": ["354"], "mesh": ["C537706"], "omim": ["259690"], "umls": ["C1850140"], "synonyms": ["Kaler-Garrity-Stern syndrome"]}
A number sign (#) is used with this entry because immunoglobulin kappa light chain deficiency (IGKCD) can be caused by compound heterozygous mutation in the immunoglobulin kappa constant region gene (IGKC; 147200) on chromosome 2p11. Clinical Features In a female offspring of an uncle-niece marriage, Bernier et al. (1972) observed deficient synthesis of kappa chain-bearing immunoglobulins. She also had recurrent respiratory infections and diarrhea. Zegers et al. (1976) observed complete absence of immunoglobulin kappa chains in a male patient with cystic fibrosis (219700) in whom kappa chains were absent in serum immunoglobulins and in blood and bone marrow lymphocytes. Lymphocytes stimulated by pokeweed mitogen produced no kappa chains. A sister, who also had cystic fibrosis, showed partial deficiency of kappa chains. Sera from the patient's parents and another sib had approximately normal amounts of kappa chains. The patient's immune responses to a variety of antigens were normal, suggesting that kappa deficiency has little effect on health. Zegers et al. (1976) noted that a few individuals with reduced kappa chains had been described (Bernier et al., 1972; Barandun et al., 1976). Mapping Kappa light chain deficiency results from mutation in the IGKC gene, which Gross (2011) mapped to chromosome 2p11.2. Molecular Genetics Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete kappa chain deficiency in the patient reported by Zegers et al. (1976). They identified compound heterozygosity for 2 point mutations in the IGKC gene, resulting in loss of an invariant tryptophan in one allele (W148R; 147200.0004) and an invariant cysteine in the other allele (C194G; 147200.0005). Both mutations were predicted to abolish formation of stable intradomain disulfide bonds. INHERITANCE \- Autosomal recessive RESPIRATORY \- Recurrent infections (in 1 patient) ABDOMEN Gastrointestinal \- Diarrhea (in 1 patient) IMMUNOLOGY \- Immunoglobulin kappa light chain deficiency MISCELLANEOUS \- Very few patients reported \- One patient studied at molecular level (as of July 2011) MOLECULAR BASIS \- Caused by mutation in the immunoglobulin kappa constant region gene (IGKC, 147200.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY	c3279824	24,808	omim	https://www.omim.org/entry/614102	2019-09-22T15:56:28	{"mesh": ["C564131"], "omim": ["614102"], "orphanet": ["183675"], "synonyms": ["Alternative titles", "KAPPA CHAIN DEFICIENCY"]}
Hantavirus pulmonary syndrome (HPS) is a severe, respiratory disease caused by infection with a hantavirus. People can become infected with a hantavirus through contact with hantavirus-infected rodents or their saliva, urine and/or droppings. Early symptoms universally include fatigue, fever and muscle aches (especially in the thighs, hips, and/or back), and sometimes include headaches, dizziness, chills, and abdominal problems such as nausea, vomiting, diarrhea, and pain. Later symptoms of the syndrome occur 4 to 10 days after initial onset and include coughing and shortness of breath. HPS can be fatal; approximately 38% of individuals with HPS do not survive. There is no cure or specific treatment for HPS, but early diagnosis and treatment in intensive care may increase the chance of recovery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Hantavirus pulmonary syndrome	c0243025	24,809	gard	https://rarediseases.info.nih.gov/diseases/69/hantavirus-pulmonary-syndrome	2021-01-18T18:00:10	{"mesh": ["D018804"], "umls": ["C0243025"], "synonyms": ["HPS", "Hantavirus", "Hantavirus-associated respiratory distress syndrome", "HARDS", "Four corners hantavirus"]}
A number sign (#) is used with this entry because of evidence that congenital hydrocephalus-1 (HYC1) is caused by homozygous mutation in the CCDC88C gene (611204) on chromosome 14q32. Description Congenital hydrocephalus-1 is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). ### Genetic Heterogeneity of Congenital Hydrocephalus See also HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p23, and HYC3 (617967), caused by mutation in the WDR81 gene (614218) on chromosome 17p13. An X-linked form of congenital hydrocephalus (HSAS, HYCX; 307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28. Clinical Features Ekici et al. (2010) reported a girl, born of consanguineous parents of Algerian origin, with congenital nonsyndromic hydrocephalus. Fetal ultrasound at 25 weeks' gestation showed enlarged ventricles. Brain MRI at age 3 days showed dilatation of the lateral ventricles with normal third and fourth ventricles. A diverticulum-like pouch extended from the medial-posterior aspect of the left lateral ventricle into the interhemispheric space, extending through the tentorium into the infratentorial space, leading to mild compression of the upper cerebellar vermis. The posterior fossa was markedly enlarged with supra- and retrocerebellar fluid accumulation. Communication between the fourth ventricle and the cisterna magna was normal. The child had seizures, but showed no other malformations, dysmorphism, or neurologic anomalies. At age 3 years, she showed normal psychomotor development. An earlier pregnancy of these parents had been terminated due to ventricular enlargement detected on prenatal ultrasound. Drielsma et al. (2012) reported 2 unrelated consanguineous families with autosomal recessive nonsyndromic hydrocephalus. In 1 Ashkenazi Jewish family, 4 sibs had congenital hydrocephalus and seizures. The head circumferences at birth ranged from 39.5 to 49 cm, and all were delivered by cesarean section. Two had midline cystic structures and 1 had an extra-axial parietal cyst, but none had an enlarged fourth ventricle. One child had biparietal polymicrogyria. All were developmentally delayed, with moderate to severe mental retardation and motor impairment; one 18-year-old was severely affected and only able to sit. In the second family, a first-cousin couple of Palestinian origin underwent 5 terminations of pregnancy following the diagnosis of marked ventricular dilatation at mid-gestation. The couple also had a twin miscarriage at 10 weeks' gestation. Wallis et al. (2018) reported 5 patients with HYC1 from 2 consanguineous families (one from Saudi Arabia and one form Morocco) and reviewed clinical findings in previously reported patients. Most patients had evidence of proximal obstruction at the level of the aqueduct and absence of significant malformations outside the brain. Two patients, including 1 reported by Wallis et al. (2018), met their early childhood milestones. Four of 6 individuals with evidence of developmental delay came from a single family reported by Drielsma et al. (2012); these patients had a focal seizure disorder and required at least 1 shunt revision, and 1 patient had biparietal polymicrogyria. Wallis et al. (2018) suggested that normal developmental outcomes were more likely in patients without additional brain malformations who received a shunt in the first few weeks of life, did not require multiple surgical revisions, and had a more distal truncating variant of the CCD88C gene. Inheritance Schockaert and Janssens (1952) observed 4 sibs, including a female, with hydrocephalus. Abdul-Karim et al. (1964) reported 2 instances of consanguineous unions, each of which resulted in 3 affected sibs. I have knowledge of an Amish family in which 1 female and 2 male sibs have hydrocephalus. The family studied by Mehne (1961) was non-Amish, living in Indiana. Borle (1953) reviewed the instances of familial hydrocephalus and Gellman (1959) reviewed those of hydrocephalus in twins. In a study of hydrocephalus in a 20-year period in Victoria, Australia, Halliday et al. (1986) observed possible autosomal recessive inheritance in 2 families out of 91. In a report on X-linked hydrocephalus (307000), Varadi et al. (1987) stated that they had seen 6 families with isolated hydrocephalus of which 4 appeared to be autosomal recessive and 2 X-linked recessive. Varadi et al. (1988) reported on 261 prospectively ascertained pregnancies studied to determine the recurrence risk of congenital hydrocephalus. Their results suggested that the recurrence risk is about 4%, and that 'apart from the X-linked recessive cases, ventriculomegaly is mostly multifactorially determined.' Teebi and Naguib (1988) observed nonsyndromic hydrocephalus in 4 sibs of a consanguineous Arab family in Kuwait. The Arnold-Chiari malformation was confirmed in 1 by autopsy and was suspected in the other 3. Chow et al. (1990) reported a brother and sister who presented in the neonatal period with hydrocephalus due to obstruction of the third ventricle. Zlotogora et al. (1994) suggested that an autosomal recessive form of hydrocephalus with prenatal onset is particularly frequent among Palestinian Arabs. Among 14 families in which more than 1 child was diagnosed with hydrocephalus of prenatal onset, in 7, only males were affected: in 2, X-linked hydrocephalus was diagnosed, while X-linked inheritance was suspected in 3 other families. These 5 families were of Jewish origin. In all 8 families of Arab origin, the parents of the affected children were consanguineous. Mapping By homozygosity mapping of a large consanguineous family of Algerian origin with nonsyndromic hydrocephalus, Ekici et al. (2010) found linkage to a 3.37-Mb region on chromosome 14 between SNPs rs41463644 and rs7148382 (maximum lod score close to 3). Molecular Genetics In a girl, born of consanguineous parents, with nonsyndromic hydrocephalus, Ekici et al. (2010) identified a homozygous splice site mutation in the CCDC88C gene (611204.0001), resulting in premature termination. An affected fetus, a sib of the girl, was also found to carry this homozygous mutation. The mutation was found by homozygosity mapping followed by candidate gene sequencing. Protein and gene expression profiling indicated disturbed regulation of the WNT (see, e.g., WNT3A, 606359) signaling pathway. In affected members of 2 unrelated families with congenital hydrocephalus, Drielsma et al. (2012) identified 2 different homozygous mutations in the CCDC88C gene (611204.0002-611204.0003). In 2 consanguineous families with congenital hydrocephalus, Wallis et al. (2018) identified homozygous mutations in the CCDC88C gene (see, e.g., 611204.0005). The mutations, which were identified by next-generation sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Animal Model The H-Tx rat strain has prenatal hydrocephalus associated with obstruction of the cerebral aqueduct (Jones and Bucknall, 1988). Linkage studies by Jones et al. (2001) showed that hydrocephalus in the rat is associated with several different chromosomes. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Hydrocephalus \- Enlarged ventricles \- Mental retardation \- Poor motor development \- Seizures MISCELLANEOUS \- Onset in utero \- One patient with normal psychomotor development has been reported (last curated December 2012) MOLECULAR BASIS \- Caused by mutation in the coiled-coil domain-containing protein 88C (CCDC88C, 611204.0001 ) ▲ 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	HYDROCEPHALUS, CONGENITAL, 1	c0020256	24,810	omim	https://www.omim.org/entry/236600	2019-09-22T16:27:02	{"doid": ["10908"], "mesh": ["D006849"], "omim": ["236600"], "orphanet": ["2185", "269510"], "synonyms": ["Alternative titles", "HYDROCEPHALY", "VENTRICULOMEGALY", "HYDROCEPHALUS, NONSYNDROMIC, AUTOSOMAL RECESSIVE 1, FORMERLY"]}
A number sign (#) is used with this entry because of evidence that Hermansky-Pudlak syndrome-7 (HPS7) is caused by homozygous mutation in the DTNBP1 gene (607145) on chromosome 6p22. For a phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (203300). Clinical Features Li et al. (2003) identified a 48-year-old Portuguese woman with Hermansky-Pudlak syndrome. She exhibited oculocutaneous albinism, ease of bruising, and a bleeding tendency. Bleeding time was 13 minutes, and platelet aggregation indicated a storage-pool deficiency. The woman had mild shortness of breath on exertion and reduced lung compliance but otherwise normal pulmonary function and high resolution computed tomography (CT) chest scans, and had no muscle weakness or ataxia. Her parents were first cousins. Lowe et al. (2013) reported a 77-year-old Caucasian woman, born of consanguineous parents, with HPS. The patient had a lifelong bleeding tendency, including spontaneous epistaxis, prolonged bleeding after dental extractions and minor surgical procedures, menorrhagia, heavy postpartum bleeding, and perirectal bleeding. She also had pale skin and hair, as well as lifelong reduced visual acuity and nystagmus. She had no evidence of pulmonary disease but did have granulomatous colitis diagnosed as Crohn disease. Platelet studies showed impaired aggregation responses and a lack of dense granule secretion. Bryan et al. (2017) reported a 6-year-old Paraguayan boy with HPS. The boy had ocular albinism, nystagmus, and easy bruising with trauma-induced intracranial hemorrhage. He had some skin and hair pigmentation but was paler than his parents. Electron microscopy showed absent dense granules, and platelet aggregation studies were abnormal. He had delayed motor and language development, fundus hypopigmentation, foveal hypoplasia, optic nerve hypoplasia, and hyperopic astigmatism. He had no recurrent or unusual infections. There was no interstitial lung disease on imaging and lung function was normal. There was no known history of consanguinity. Inheritance The transmission pattern of HPS7 in the families reported by Li et al. (2003) and Lowe et al. (2013) was consistent with autosomal recessive inheritance. Mapping The gene mutant in HPS7, DTNBP1, maps to chromosome 6p22.3 (Li et al., 2003). Swank et al. (1991) demonstrated that the 'sandy' (sdy) mutant mouse is a valid model for human HPS and mapped the sdy locus to mouse chromosome 13. Molecular Genetics Li et al. (2003) showed that mutation in the dysbindin gene, Dtnbp1, causes the sdy phenotype in mice. In a 48-year-old Portuguese woman with Hermansky-Pudlak syndrome, Li et al. (2003) identified homozygosity for a nonsense mutation in the DTNBP1 gene (Q103X; 607145.0001). In a 77-year-old Caucasian woman, born of consanguineous parents, with HPS7, Lowe et al. (2013) identified a homozygous truncating mutation in the DTNBP1 gene (W59X; 607145.0002). The mutation was found by autozygosity mapping with microsatellite markers followed by direct sequencing of the candidate DTNBP1 gene. In a 6-year-old Paraguayan boy with HPS7, Bryan et al. (2017) identified homozygosity for the previously identified Q103X mutation in the DTNBP1 gene. Patient fibroblasts showed normal DTNBP1 mRNA expression but negligible dysbindin protein expression. Animal Model In mice, at least 16 loci are associated with HPS, including 'sandy' (sdy) (Swank et al., 1991). Li et al. (2003) showed that the sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1. They confirmed that mutation of dysbindin causes the sdy phenotype and that dysbindin is important for normal platelet-dense granule and melanosome biogenesis. Li et al. (2003) showed that dysbindin is a component of the biogenesis of lysosome-related organelles complex-1 (BLOC1), which regulates trafficking to lysosome-related organelles and includes the proteins pallidin (604310), muted (607289), and cappuccino (605695), all of which are associated with Hermansky-Pudlak syndrome in mice. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Decreased visual acuity \- Ocular albinism \- Nystagmus Nose \- Epistaxis RESPIRATORY Lung \- Decreased lung compliance (1 patient) ABDOMEN Gastrointestinal \- Granulomatous colitis (1 patient) SKIN, NAILS, & HAIR Skin \- Pale skin \- Cutaneous albinism Hair \- Pale hair HEMATOLOGY \- Bleeding tendency due to platelet defect \- Defective platelet aggregation \- Lack of dense granules in platelets MISCELLANEOUS \- Onset in childhood \- Two unrelated patients have been reported (last curated January 2015) MOLECULAR BASIS \- Caused by mutation in the dystrobrevin-binding protein 1 gene (DTNBP1, 607145.0001 ) ▲ 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	HERMANSKY-PUDLAK SYNDROME 7	c0079504	24,811	omim	https://www.omim.org/entry/614076	2019-09-22T15:56:42	{"doid": ["0060545"], "mesh": ["D022861"], "omim": ["614076"], "orphanet": ["231531", "79430"], "synonyms": ["HPS7"], "genereviews": ["NBK1287"]}
A number sign (#) is used with this entry because X-linked Alport syndrome-1 (ATS1) is caused by mutation in the gene encoding the alpha-5 chain of basement membrane collagen type IV (COL4A5; 303630) on Xq22. Description Alport syndrome is an inherited disorder of the basement membrane, resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and variable ocular anomalies (review by Kashtan, 1999). ### Genetic Heterogeneity of Alport Syndrome Alport syndrome is a genetically heterogeneous disorder, with all forms resulting from mutations in genes encoding type IV collagen, which is a major structural component of the basement membrane. Approximately 85% of cases of Alport syndrome are X-linked and about 15% are autosomal recessive (ATS2; 203780); autosomal dominant inheritance (ATS3; 104200) is rare (Kashtan, 1999). See also benign familial hematuria (BFH; 141200), a phenotypically similar, but milder disorder. Alport syndrome is also a feature of 2 contiguous gene deletion syndromes involving the COL4A5 gene: Alport syndrome and diffuse leiomyomatosis (308940) and Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis (AMME; 300194). Clinical Features Alport (1927) reported a family in which affected individuals showed progressive renal disease with hematuria and deafness. Affected males died early of uremia, while females lived to old age. The report of Alport (1927) was the fourth concerning a single pedigree that was also studied by Guthrie (1902), Kendall and Hertz, 1912, and Hurst (1923) (review by Cohen et al., 1961). The renal disease became evident as recurrent microscopic or gross hematuria as early as childhood, earlier in males than in females. Progression to renal failure was gradual and usually occurred in males by the fifth decade. The renal histology was nonspecific; both glomerular and interstitial abnormalities, including foam cells, were observed. Although initially reported as a dominant trait with possible partial sex-linkage, it later became apparent that this was an X-linked dominant condition (Cohen et al., 1961; O'Neill et al., 1978; Evans et al., 1980). Perkoff et al. (1951, 1958) reported a large Utah kindred with hereditary chronic interstitial nephritis associated with sensorineural deafness. The kindred was further studied by O'Neill et al. (1978), who observed X-linked inheritance. Men were more severely affected than women. Microscopic hematuria was found to be the most reliable urinary criterion of hereditary nephritis in both males and females. The hematuria was often accompanied by red cell casts, indicating that the renal lesion was a glomerulitis. There were striking urinary abnormalities in early childhood which progressed to renal failure in adulthood. Affected women had less obvious urinary findings and rarely developed uremia. O'Neill et al. (1978) reported another large kindred with X-linked hereditary nephritis without hearing difficulties. Iversen (1974) described the characteristic course of Alport syndrome in males: 'In connection with one of the infectious diseases of childhood or a common cold in early childhood or adolescence, he will suddenly begin to suffer from massive haematuria or headache or oedema of the face. The urine shows haematuria and/or proteinuria and often also cylindruria and leukocyturia. These urinary signs may in one and the same patient vary in degree during the following months, and in some patients they may almost disappear, but they may become more pronounced again during the next infectious disease or after physical strain. There may be more or less pronounced hypertension....Most boys with this disease die from uraemia during adolescence.' There may also be secondary involvement of a transplanted kidney. Zhou et al. (1992) reported a 27-year-old male who developed hematuria in childhood and terminal renal failure at the age of 25 years. He had no hearing loss or ocular lesions. Electron microscopy demonstrated splitting of the lamina densa of the glomerular basement membrane (GBM). The proband's mother had had persistent microscopic hematuria since the age of 40 years but no other manifestations. Smeets et al. (1992) reported a boy with severe Alport syndrome who developed end-stage renal disease (ESRD) by age 17, accompanied by deafness. Transplantation with the kidney of an unrelated donor was followed by rapidly progressive antiglomerular basement membrane nephritis, leading to loss of the transplant almost 7 months after grafting. His affected maternal grandfather died from renal failure at the age of 26 years. His mother and sister both displayed hematuria. Guo et al. (1995) reported a woman who presented at the age of 19 years with microscopic hematuria and nephrotic syndrome. The diagnosis of Alport syndrome was confirmed by the finding of typical glomerular basement membrane abnormalities on a renal biopsy taken at that age. There was progressive renal failure, and she began chronic hemodialysis at age 30. A cadaveric kidney transplantation was done 2 years later. Family history showed that her father had sensorineural hearing loss and died at age 36 of renal failure. An elder sister had microscopic hematuria, proteinuria with normal kidney function, and hearing loss. Molecular genetic studies identified 2 mutations in cis in the COL4A5 gene (303630.0012), and skewed X-inactivation studies showed favoring of the mutant allele. Turco et al. (1995) reported a man with late-onset Alport syndrome confirmed by genetic analysis (G54D; 303630.0013). Microhematuria was first discovered at age 22 years. He reached end-stage renal disease at age 40, and had a successful transplant at age 41. He also had bilateral sensorineural hearing loss and subcapsular posterior lens opacities. The proband had 2 daughters, aged 15 and 13 years. Since age 2, the older daughter had had mild irregular microhematuria with normal renal function; a renal biopsy at age 8 showed a thinning of the glomerular basement membrane. In the other daughter, microhematuria was discovered at age 7. Ocular and auditory assessments were normal in both sisters. The proband's mother was known to have microhematuria. ### Clinical Variability Hasstedt et al. (1986) tested for clinical and genetic heterogeneity among 23 Utah kindreds with Alport syndrome. End-stage renal disease had occurred in 72 (49%) of 148 known affected males and in 13 (8%) of 171 known affected females. No father-son affected pairs occurred in any of the kindreds, and there was no evidence for autosomal inheritance. Eighty-four percent of daughters of affected fathers were affected, and 49% of sons and 48% of daughters of affected mothers were affected. One of 3 clinical phenotypes occurred in each of the 23 kindreds: juvenile Alport syndrome with deafness, adult Alport syndrome with deafness, or adult Alport syndrome without deafness or other defects. There was some evidence for intrakindred phenotypic heterogeneity for onset of ESRD: the age of 31 years for ESRD was taken as the divide between the juvenile and adult forms. M'Rad et al. (1992) reviewed 31 families with Alport syndrome. Although there was clinical variability in ophthalmic signs and the age of development of end-stage renal disease, homogeneity tests failed to show evidence of genetic heterogeneity. All were consistent with X-linked inheritance, which was confirmed by linkage studies. ### Evidence for Digenic Inheritance Mencarelli et al. (2015) identified 8 patients with mutations in COL4A4 (120131) and COL4A5, with phenotypes including hematuria with proteinuria in 6 individuals and end-stage renal disease in 2 individuals. Other Features Ocular abnormalities have been observed in some patients (Arnott et al., 1966). Nielsen (1978) suggested that anterior lenticonus may be a specific sign of Alport syndrome, since all recently reported cases (e.g., Arnott et al. (1966)) had been associated with hereditary nephropathy. Govan (1983) described anterior lenticonus and retinal flecks in the macular and midperipheral retina as characteristic ophthalmic findings in Alport syndrome. The findings provided further evidence that Alport syndrome is a hereditary disorder of basement membranes. Streeten et al. (1987) concluded that the anterior capsule of the lens 'is clearly fragile in this disease, forming the basis for the progressive lenticonus and anterior polar cataract. These abnormalities correlate well with a defect in the type IV collagen molecule.' Burke et al. (1991) described bilateral corneal epithelial erosions in Alport syndrome. Their patient was a 25-year-old man who had recurrent episodes of pain in 1 or both eyes, which awakened him at night, and were associated with lacrimation, photophobia, and blurred vision. Proteinuria and microscopic hematuria had been recognized by age 12 months, and bilateral sensorineural hearing loss since age 11 years. Colville and Savige (1997) reviewed the ocular manifestations of Alport syndrome. They stated that the typical ocular associations are a dot-and-fleck retinopathy, which occurs in approximately 85% of affected adult males, anterior lenticonus, which occurs in approximately 25%, and rare posterior polymorphous corneal dystrophy. The ocular manifestations were identical to those found in the autosomal forms of Alport syndrome. Rhys et al. (1997) observed 3 brothers with Alport syndrome and a history of spontaneous attacks of recurrent corneal erosion. In 2 of them, 2 episodes over a period of 1 to 3 years had occurred; the third brother had approximately 60 episodes over the previous 10 years. Further studies showed that 7 of 41 patients with Alport syndrome and renal failure had a history of corneal erosion first manifest between ages 12 and 21 years, compared to 1 of 67 control patients transplanted for another form of nephropathy (p = 0.003). Ohkubo et al. (2003) found immunohistochemical evidence that normal anterior lens capsules expressed all of the A4 collagen chains. Similar studies of the anterior lens capsule of a patient with Alport syndrome who had anterior lenticonus showed lack of immunoreactivity to the COL4A3 to COL4A6 (303631) chains. The patient had a nonsense mutation in the COL4A5 gene (R1677X; 303630.0015). Inheritance O'Neill et al. (1978) identified 150 affected persons in 2 kindreds with hereditary nephritis and concluded that the inheritance of the disorder was consistent with an X-linked pattern. Hasstedt and Atkin (1983) restudied the Utah kindred, 'family P,' that was the subject of the studies of Perkoff et al. (1951, 1958). Penetrance was estimated as 0.85 in females and 1.0 in males. Reexamination of segregation showed no excess of affected offspring of affected parents and no difference in penetrance in daughters of symptomatic and asymptomatic mothers. An unexplained deficiency of sons of affected mothers was found. Mapping In affected Utah kindreds, Menlove et al. (1984, 1985) mapped the locus for X-linked Alport syndrome to the proximal part of chromosome Xq near the centromere. They found 2 of 21 recombinants with DXS3, which is located at Xq21.3-q22 (maximum lod = 9.1; theta = 0.16). They found a maximum lod score of 2.5 at theta 0.18 for linkage with DXS1, which is located at Xp11-q13. These authors referred to the disorder as 'Alport syndrome-like hereditary nephritis,' based on the assumption that the disorder originally described by Alport was autosomal dominant. Atkin et al. (1988) reported on the typing of 261 members of 3 large kindreds with Alport syndrome using 5 DNA markers. Lod scores in excess of 3.0 were found on the long arm of the X chromosome. Two types of Alport syndrome were represented by 3 kindreds: affected males in 1 kindred developed deafness in addition to nephritis, but deafness was absent in affected members of the other 2 kindreds. However, there was no evidence of linkage heterogeneity among these families. Flinter et al. (1989) found linkage to DXS17 (maximum lod score = 4.72 at theta = 0.06). Flinter and Bobrow (1988) studied 41 families and concluded that Alport syndrome may be less heterogeneous than previously thought. All of the families had 'classic' Alport syndrome, with pedigrees compatible with X-linked inheritance. They confirmed linkage to Xq markers. Szpiro-Tapia et al. (1988) presented additional data strongly supporting the assignment of the Alport syndrome gene to proximal Xq. The locus was designated 'ATS' by HGM10 in New Haven (1989). Hertz et al. (1991) presented data on the order of multiple DNA markers in relation to ATS in the proximal portion of Xq in 12 Danish families with classic ATS or progressive hereditary nephritis without deafness. M'Rad et al. (1992) reviewed 31 families with Alport syndrome. Although there was clinical variability in ophthalmic signs and the age of development of end-stage renal disease, homogeneity tests failed to show evidence of genetic heterogeneity. Concordant data indicated the localization of the Alport gene between DXS17 and DXS11. Four deletions and 1 single base mutation of the COL4A5 gene were detected. Pathogenesis Miller et al. (1970) showed that the vestibular neuroepithelium as well as that of the cochlea is involved in Alport syndrome. Myers and Tyler (1972) found variability in the histologic findings of the ear in Alport syndrome. In 2 cases with severe deafness, 1 had had a histologically normal inner ear, whereas the other had a marked reduction in spinal ganglion cochlear neurons. Spear (1973) suggested that a primary structural abnormality of basement membranes underlies the phenotype of Alport syndrome. Churg and Sherman (1973) stated that the ultrastructural changes of the glomerular basement membrane, which is irregularly thickened and attenuated, are specific for Alport syndrome. Immunofluorescence studies provided little evidence for an immunologic basis for renal damage. In a study by Waldherr (1982), Alport syndrome comprised at least a sixth of familial glomerular disease, which itself was responsible for 6.3% of his biopsy material. Yoshikawa et al. (1982) reported the pathologic findings of 38 patients with familial hematuria, including those with Alport syndrome. The most common abnormality on electron microscopy, found in 27 of 31 biopsies, was complex replication of the lamina densa of the capillary basement membrane to form a 'basket weave' pattern. These changes could be seen in children under age 5 years. If neurosensory deafness or heavy proteinuria was present, the patient generally ran a progressive clinical course and fell within the spectrum of Alport syndrome. In contrast, patients from families without deafness, heavy proteinuria, or chronic renal failure showed a nonprogressive course consistent with benign familial hematuria (141200). Their biopsies showed little or no glomerular changes other than attenuation of the lamina densa on electron microscopy. By indirect immunofluorescence of kidney biopsies from 7 males from 5 families with Alport syndrome, Jeraj et al. (1983) found absence of the glomerular basement membrane antigen targeted in the autoimmune disorder Goodpasture syndrome (233450), which is characterized by glomerulonephritis and lung disease. However, the antigen was detected in 2 affected women, an unaffected male, and 13 normal controls. The specificity of the finding was supported by persistence of other glomerular basement membrane antigens, and the findings were compatible with X-linked inheritance. IgG in sera from patients with Goodpasture syndrome does not bind to the GBM of some patients with Alport syndrome. The epitopes reactive with anti-GBM antibodies are located in the noncollagenous globular domain of type IV collagen. Treatment with acid-urea favors exposure of this epitope. Kashtan et al. (1986) found that FNS, a serum from an Alport patient who developed anti-GBM nephritis in a renal allograft, reacted with acid-urea-treated epidermal basement membrane (EBM) from 12 controls and 9 unaffected male relatives of Alport patients, but did not react with EBM from 8 affected males. In 5 affected females, 'interrupted' reactivity of FNS with EBM was observed, i.e., there were gaps, regions of nonreactive EBM separating regions of reactive EBM. The immunofluorescent stains of basement membrane demonstrated the Lyon phenomenon of X inactivation in a particularly graphic manner. Goodpasture sera (GPS), containing antibodies, were not discriminating; whereas FNS did not stain renal basement membrane from 5 affected males, GPS stained EBM, tubular basement membrane, and Bowman capsules of affected males. These studies indicated that the FNS antigen is apparently distinct from the Goodpasture antigen. The distribution in altered expression of FNS in type IV collagen was consistent with X-linked dominant inheritance. Turner et al. (1992) identified COL4A3 (120070), which maps to chromosome 2q36 and not to the X chromosome, as the antigen targeted in Goodpasture syndrome. In a retrospective, double-blind study, Savage et al. (1986) examined paraffin-embedded renal biopsy sections from 44 children with hematuria to see whether a mouse monoclonal antibody (MCA-P1) against GBM could identify a subgroup of patients with Alport syndrome in which the Goodpasture antigen was abnormal. Strong linear binding of MCA-P1 to GBM was found in all 29 patients without evidence of hereditary nephritis and in 2 with possible but not definite hereditary nephritis. In contrast, 12 of 13 patients with strong evidence of hereditary nephritis showed no binding (9) or greatly reduced binding (3). Thus, abnormal antigenicity of the basement membrane in hereditary nephritis, as reported by McCoy et al. (1982), was confirmed. Savage et al. (1987) concluded that the inherited defect in hereditary nephritis affects Goodpasture antigen secondarily. Serum amyloid P component (SAP; 104770) has been found to be a constituent of normal GBM. Melvin et al. (1986) showed that SAP and Goodpasture antigen are closely associated in the GBM and that SAP is also absent in patients with Alport-type hereditary nephritis who lack Goodpasture antigen. Yoshikawa et al. (1987) reviewed 48 children with hematuria and ultrastructural changes of the GBM, a characteristic of hereditary nephritis. In 30 cases, there was hematuria in at least 1 other member of the family; in the other 18 cases, there was no familial incidence. There were no differences between the 2 groups with regard to clinical and pathologic findings. At the latest follow-up, 6 boys with familial hematuria and 3 boys with nonfamilial hematuria had reduced renal function, and 9 boys with familial hematuria and 4 boys and 1 girl with nonfamilial hematuria had sensorineural deafness. Knebelmann et al. (1996) reported that 16 of 18 patients with Alport syndrome who were tested had abnormal glomerular basement antigenicity. They demonstrated that even a subtle modification of the alpha-5 chain of collagen IV, such as a glycine substitution in the collagenous domain, could be associated with lack of immunologic expression of the alpha-3, alpha-4, and alpha-5 chains. Normal glomerular capillaries filter plasma through a basement membrane rich in the alpha-3, alpha-4, and alpha-5 chains of type IV collagen. Kalluri et al. (1997) showed that these 3 isoforms are absent biochemically from the glomeruli of patients with X-linked Alport syndrome. Instead, their glomerular basement membranes retain a fetal distribution of the alpha-1 and alpha-2 isoforms of type IV collagen because they fail to switch their alpha-chain use developmentally. The anomalous persistence of these fetal isoforms in the GBM confers an increase in susceptibility to proteolytic attack by collagenases and cathepsins. The authors speculated that the incorporation of the cysteine-rich alpha-3, alpha-4, and alpha-5 chains into specialized basement membranes like the GBM may have evolved to enhance their resistance to proteolytic degradation at the site of glomerular filtration. The absence of these potentially protective collagen IV isoforms in GBM from X-linked Alport syndrome patients may explain the progressive basement membrane splitting and increased damage as the kidneys deteriorate in these patients. Meleg-Smith et al. (1998) studied renal biopsy specimens from 8 female patients with a clinical presentation suggestive of Alport syndrome. Two patients were 7 and 36 years of age; 6 were between 12 and 15 years of age. Light microscopy and immunohistochemistry using a monoclonal antibody to COL4A5 were used to define expression of the protein in the glomerular basement membrane. To describe the variability of the ultrastructural GBM changes, they developed a semiquantitative Alport Index. Despite the wide variability, they concluded that renal biopsy can identify female patients heterozygous for X-linked Alport syndrome. The predominant ultrastructural change in females was thin basement membrane. Clinical Management ### Complications of Renal Transplant Milliner et al. (1982) estimated that approximately 1 to 5% of Alport syndrome patients who receive transplants develop a specific antiglomerular basement membrane (anti-GBM) nephritis, subsequently leading to loss of the renal graft. Patients with Alport syndrome constituted 2.3% of the transplant population at the Mayo Clinic. Gobel et al. (1992) studied graft survival and course of renal function in 30 Alport syndrome patients who had had kidney transplants and compared them with nondiabetic, age- and sex-matched patients, transplanted on a date closest to that of an Alport syndrome patient. Patient survival was better in the Alport syndrome group, and first graft survival was the same in the 2 groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 ATS patients. Anti-GBM nephritis was not detected in any of them, and no graft was lost due to anti-GBM nephritis. Gobel et al. (1992) concluded that allograft anti-GBM nephritis is a rare complication in patients with Alport syndrome. In a review of mutations that had been identified in the type IV collagen genes in patients with Alport syndrome, Lemmink et al. (1997) found data on 46 patients with transplants, among whom there were 41 with a COL4A5 mutation, 4 with a COL4A3 (120070) mutation, and 1 with a COL4A4 (120131) mutation. All patients except 1 had juvenile Alport syndrome. A specific anti-GBM nephritis was detected in 9 patients with transplants (20% of the total number of transplants). Of these 9, 8 carried large deletions or premature stop codons, which were predicted to result in COL4A3 or COL4A5 proteins truncated within the noncollagenous (NC) domain. The exception was a splice site mutation resulting in an mRNA without exon 38. Four patients identified with COL4A3 mutations had had transplants, and 3 of them developed an anti-GBM nephritis. These data suggested that Alport syndrome patients with a type IV collagen mutation resulting in absence of the NC domain have an increased risk of developing anti-GBM nephritis after renal transplantation. Molecular Genetics Suspicion that the mutation responsible for Alport syndrome might reside in the gene for the alpha-5 chain of collagen IV was raised by the demonstration that the COL4A5 gene maps to Xq22-q23, the same region known to contain the locus for the X-linked form of Alport syndrome (Myers et al., 1990). Barker et al. (1990) identified 3 different structural anomalies in the COL4A5 gene (303630.0001-303630.0003) in affected members of 3 Utah kindreds with X-linked Alport syndrome. Zhou et al. (1992) demonstrated that juvenile-onset Alport syndrome without hearing loss or ocular lesions is also due to mutation in the COL4A5 gene (303630.0006). Renieri et al. (1996) used SSCP analysis of the entire coding sequence of the COL4A5 gene to search for mutations in 201 unrelated Italian patients with Alport syndrome. A causative mutation was found in only 45% of individuals. The authors noted that SSCP analysis can potentially detect 80% of mutations. They suggested that their failure to detect a higher percentage of mutations in these patients may indicate that disease-causing mutations occur not only in the exons but also in the promoter region, within introns, or in alternatively spliced exons. They commented that an alternative explanation could be the involvement of other genes within the Xq region. Knebelmann et al. (1996) screened 48 of the 51 exons of the COL4A5 gene by SSCP analysis and identified 64 mutations and 10 sequence variants among 131 unrelated Alport syndrome patients, which represents a mutation detection rate of approximately 50%. They reported that all different types of mutations were observed in juvenile-type Alport syndrome whereas only glycine substitutions and splicing mutations were observed in adult-type Alport syndrome. Barker et al. (1996) identified a novel mutation in the COL4A5 gene (L1649R; 303630.0014) in Alport syndrome patients. In contrast to most described COL4A5 mutations in Alport syndrome, each of which accounts for the disease in a single family, the L1649R mutation was found in over 7% of the 121 families studied. In males with the L1649R mutation, renal failure preceded hearing loss by approximately 10 years, and the cumulative frequency of hearing loss was 60% by age 60. Barker et al. (1996) noted that substantial variability occurs in the ages at appearance of end-stage renal disease and functional hearing loss among individuals with identical mutations, emphasizing the fallibility of generalizations about the phenotype associated with a specific mutation that is observed in only a small number of Alport syndrome patients. Cytogenetics Hertz et al. (2005) reported a 32-year-old man with Alport syndrome in whom no mutation in COL4A5 was found by SSCP, although there was an abnormal band pattern on Southern blot analysis. Long-range and inverse PCR revealed an inversion on the long arm of the X chromosome with a proximal breakpoint within intron 8 of the COL4A5 gene. Hertz et al. (2005) stated that this was the first report of inversion of the X chromosome associated with Alport syndrome. History Guthrie (1902) reported a family in which 12 individuals showed recurrent hematuria. At the time of this report, none of the affected individuals exhibited evidence of chronic renal damage. Hurst (1923) described the development of uremia in several members of this family. Alport (1927) reported that many family members showed deafness as well as renal disease, and that affected males died of uremia whereas affected females lived to old age. As a result, Alport's name became synonymous with a familial progressive nephropathy, first manifested by hematuria and associated with deafness, that is particularly severe in affected males. A kindred reported by Ohlsson (1963) differed from others reported in that myopia was a conspicuous feature and the impairment of renal function in the affected males was relatively mild, even in 2 over age 30 years. Devriendt et al. (1998) suggested that the brothers reported by Ohlsson (1963) may have had Donnai-Barrow syndrome (222448). Miyoshi et al. (1975) found antithyroid antibodies in the serum of multiple persons with Alport syndrome in 2 Japanese kindreds. Hyperthyroidism was present in 1 and histologic changes of thyroiditis in a second. They proposed that Alport syndrome may be an immunologic disorder. Atkin et al. (1986) proposed the existence of 6 subtypes of Alport syndrome among reported kindreds: I, classic juvenile Alport syndrome with deafness; II, X-linked juvenile Alport syndrome with deafness; III, X-linked adult Alport syndrome with deafness; IV, X-linked adult Alport syndrome without deafness or other defect, that is, purely renal disease; V, autosomal Alport syndrome with deafness and thrombocytopathia (see 155100); and VI, autosomal recessive juvenile Alport syndrome with deafness (203780). A possibly distinct entity was hereditary nephritis without deafness (161900) reported by Reyersbach and Butler (1954) and Dockhorn (1967). Animal Model Baumal et al. (1991) reported study of the apparently homologous disorder in a family of Samoyed dogs. The authenticity of the model was established by demonstration of mutation in the COL4A5 gene (Zheng et al., 1992). Lees et al. (1999) described an X-linked form of hereditary nephritis in a family of mixed breed dogs located in Navasota, Texas. The glomerular basement membrane of Navasota (NAV) hereditary nephritis males was shown to undergo ultrastructural changes identical to those observed in Alport syndrome and in Samoyed hereditary glomerular nephritis. A hereditary nephritis in English cocker spaniels (Robinson et al., 1985; Steward and MacDougall, 1984) appears to be a model of autosomal recessive Alport syndrome (Lees et al. (1997, 1998)). NAV dogs exhibit typical clinical, histologic, immunochemical, and genetic features of X-linked Alport syndrome. In a colony of NAV dogs, Cox et al. (2003) identified the causative mutation: a 10-bp deletion in exon 9 of the COL4A5 gene, resulting in a frameshift and premature stop codon. Another form of canine X-linked Alport syndrome had been reported by Bernard and Valli (1977) and shown by Zheng et al. (1994) to be caused by a G-to-T substitution in exon 35 of COL4A5, causing a premature stop codon. Kalluri et al. (1997) developed a new mouse model of human anti-GBM disease to characterize better the genetic determinants of cell-mediated injury. The findings in studies of the model suggested that anti-GBM antibodies in mice facilitate disease only in MHC haplotypes capable of generating nephritogenic lymphocytes with special T-cell repertoires. INHERITANCE \- X-linked dominant HEAD & NECK Ears \- Deafness, sensorineural, especially affecting high frequencies (in about 55% of males and 45% of females) Eyes \- Anterior lenticonus \- Lens opacities \- Cataracts \- Myopia \- Pigmentary changes ('flecks') in the perimacular region \- Corneal endothelial vesicles \- Corneal erosions CARDIOVASCULAR Vascular \- Hypertension GENITOURINARY Kidneys \- Glomerulonephropathy \- End-stage renal failure \- Thinning of the glomerular basement membrane (early in the disease) \- Thickening of the glomerular basement membrane (later in the disease) \- Splitting of the glomerular basement membrane \- Diffuse lamellation of the glomerular basement membrane LABORATORY ABNORMALITIES \- Hematuria, gross and microscopic \- Proteinuria \- Nephrotic syndrome MISCELLANEOUS \- Males more severely affected than females \- Affected males show onset of hematuria in first year of life \- Progressive disorder \- Hearing loss occurs in late childhood \- Female carriers may show intermittent hematuria \- About 15% of female carriers develop renal insufficiency in the second or third decade \- About 1 to 5% of patients who undergo renal transplantation develop anti-glomerular basement membrane nephritis \- Estimated gene carrier frequency of 1 in 5,000 \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the collagen, type IV, alpha-5 gene (COL4A5, 303630.0001 ) ▲ 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	ALPORT SYNDROME 1, X-LINKED	c1567741	24,812	omim	https://www.omim.org/entry/301050	2019-09-22T16:18:49	{"doid": ["0110034"], "mesh": ["D009394"], "omim": ["301050"], "orphanet": ["63", "88917"], "synonyms": ["Alternative titles", "ATS", "NEPHROPATHY AND DEAFNESS, X-LINKED"], "genereviews": ["NBK1207"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-50 (DFNA50) is caused by heterozygous mutation in a microRNA, MIRN96 (611606), on chromosome 7q32. Description Autosomal dominant deafness-50 is a form of nonsyndromic hearing loss. Hearing impairment shows postlingual onset and is progressive (summary by Mencia et al., 2009). Clinical Features Modamio-Hoybjor et al. (2004) identified a large Spanish family segregating autosomal dominant postlingual, progressive, nonsyndromic all-frequency hearing loss. Of 74 family members, 37 were affected. The earliest clinical evidence of hearing loss in the family was obtained for 2 subjects at the age of 12 years. Hearing loss was initially mild, affecting all frequencies, and progressed to severe or profound in the seventh decade. Mencia et al. (2009) identified a second family with autosomal dominant progressive hearing loss. Middle and high frequencies were affected. Onset of hearing loss was earlier than in the family studied by Modamio-Hoybjor et al. (2004), beginning at 2 to 3 years of age in the proband, with progression to a severe form in the third decade. Inheritance The transmission pattern of nonsyndromic hearing loss in the families reported by Modamio-Hoybjor et al. (2004) and Mencia et al. (2009) was consistent with autosomal dominant inheritance. Mapping Using linkage analysis in a large 5-generation Spanish family with progressive nonsyndromic autosomal dominant hearing loss, Modamio-Hoybjor et al. (2004) mapped the phenotype to chromosome 7q32. A maximum 2-point lod score of 10.66 (theta = 0) was achieved at marker D7S530. Further genotyping delimited the DFNA50 locus to a critical interval of 3.8 cM between markers D7S1875 and D7S2519, between the DFNB17 (603010) and DFNB13 (603098) loci. Molecular Genetics In 2 families with autosomal dominant nonsyndromic hearing loss, Mencia et al. (2009) identified 2 independent heterozygous point mutations in the seed region of MIRN96 (611606) as the cause of the disorder. This was the first study to implicate a miRNA in a mendelian disorder. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural, progressive (all frequencies) \- Tinnitus, bilateral (in some patients) MISCELLANEOUS \- Earliest age of onset 12 years of age \- Initial hearing loss is mild progressing to severe or profound by the seventh decade \- Mutations have been identified in Spanish families MOLECULAR BASIS \- Caused by mutation in the micro RNA 96 (MIR96, 611606.0001 ) ▲ 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	DEAFNESS, AUTOSOMAL DOMINANT 50	c3888123	24,813	omim	https://www.omim.org/entry/613074	2019-09-22T15:59:53	{"doid": ["0110576"], "omim": ["613074"], "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 Fanconi anemia of complementation group Q (FANCQ) is caused by compound heterozygous mutation in the ERCC4 gene (133520) on chromosome 16p13. Description Fanconi anemia (FA) is a rare genomic instability disorder characterized by bone marrow failure, congenital malformations, hypersensitivity to DNA interstrand crosslink-inducing agents, chromosome fragility, and high susceptibility to cancer (summary by Bogliolo et al., 2013). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650. Clinical Features Bogliolo et al. (2013) reported 2 unrelated patients, of Spanish and German origin, respectively, with an unclassified form of Fanconi anemia. The first patient presented in the neonatal period with bilateral absent thumbs, microsomy, esophageal atresia, a ventrally translocated anus, and dysplastic, low-set ears. She did not have skin hyperpigmentation, photosensitivity, sunlight-induced scarring, or atrophy. She developed bone marrow failure at age 2 years and died from complications of a bone marrow transplant at age 4 years. The second patient was diagnosed at age 5 years due to the presence of multiple FA features such as perinatal growth retardation, short stature, microcephaly, cafe-au-lait spots, an ostium primum defect, biliary atresia with liver fibrosis, and bone marrow failure. The patient had red hair and pale skin, but had no spontaneous or UV light-induced skin lesions. Laboratory studies of cells derived from both patients showed increased chromosome breakage in response to certain agents, such as diepoxybutane, mitomycin-C, and melphalan, indicating a defect in interstrand crosslink (ICL) DNA repair. In contrast, patient cells did not show increased sensitivity to UV-induced damage, suggesting that nucleotide excision repair (NER) was intact. Inheritance The transmission pattern of FANCQ in the families reported by Bogliolo et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics By exome sequencing of a girl with Fanconi anemia, Bogliolo et al. (2013) identified compound heterozygous mutations in the ERCC4 gene (133520.0004 and 133520.0005). Direct sequencing of this gene in 18 patients with unclassified Fanconi anemia revealed 1 patient with compound heterozygous mutations (133520.0006 and 133520.0007). Transduction of wildtype ERCC4 into patient cells complemented the mitomycin-C sensitivity. Detailed cellular studies showed that the Fanconi anemia cells with ERCC4 mutations were completely deficient in ICL repair, but retained significant levels of NER activity to prevent skin photosensitivity from UV damage. Functional studies showed that the mutations resulted either in impaired nuclease incision activity or in abnormal aggregation of the protein in the cytoplasm. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Growth retardation HEAD & NECK Head \- Microcephaly Ears \- Low-set ears ABDOMEN Liver \- Biliary atresia Gastrointestinal \- Esophageal atresia SKELETAL Hands \- Absent thumbs HEMATOLOGY \- Bone marrow failure LABORATORY ABNORMALITIES \- Patient cells show increased chromosome breakage MISCELLANEOUS \- Two unrelated patients have been reported (last curated June 2013) \- Onset in infancy \- Variable phenotype MOLECULAR BASIS \- Caused by mutation in the excision-repair cross-complementing group 4 gene (ERCC4, 133520.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	FANCONI ANEMIA, COMPLEMENTATION GROUP Q	c0015625	24,814	omim	https://www.omim.org/entry/615272	2019-09-22T15:52:44	{"doid": ["0111093"], "mesh": ["D005199"], "omim": ["615272"], "orphanet": ["84"], "genereviews": ["NBK1401", "NBK5192"]}
Congenital adrenal hyperplasia (CAH) is an inherited endocrine disorder caused by a steroidogenic enzyme deficiency that is characterized by adrenal insufficiency and variable degrees of hyper or hypo androgeny manifestations, depending of the type and the severity of the disease. ## Epidemiology The estimated prevalence is 1/10,000 and annual incidence ranges from 1/5,000 to 1/15,000. ## Clinical description The most frequent form of CAH is classical CAH due to a 21-hydroxylase deficiency which can further be divided into simple virilizing, salt wasting or non-classical types (see these terms). Girls present at birth with ambiguous genitalia and variable levels of virilization. They have a normal uterus but abnormal vaginal development. The external genitalia in boys are normal. Salt wasting forms of CAH lead to symptoms of dehydration and hypotension in the first few weeks of life and can be life threatening. Premature pubarche can be seen in children as well as accelerated growth velocity and accelerated skeletal maturation (leading to short stature in adulthood). NCAH is often not diagnosed until adolescence when the first symptoms appear. Manifestations seen in females are hirsutism, acne, anovulation and menstrual irregularities. Males (and some females) are asymptomatic. Hirsutism continues in adulthood and women can suffer from chronic anovulation and fertility problems. Other rare forms can present with arterial hypertension, craniofacial malformations and sexual ambiguity in both sexes. ## Etiology In 90-95% of cases, CAH is caused by a mutation in the CYP21A2 gene located on chromosome 6p21.3 which encodes for an enzyme that controls cortisol and aldosterone production. Other genes are less frequently involved and result in the following variants of CAH: CAH due to 17-alpha-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, 11-beta-hydroxylase deficiency, cytochrome P450 oxidoreductase deficiency and congenital lipoid adrenal hyperplasia (see these terms). ## Diagnostic methods Diagnosis of girls with classical CAH is usually at birth when ambiguous genitalia are present. Babies can be screened for CAH in order to identify those with the classical forms by measuring 17-hydroxy-progesterone (17-OHP) levels. Genetic screening also confirms a diagnosis of CAH by identifying those with a CAH related gene mutation. In most European countries there are National systematic screening programs in place to diagnose CAH at birth. ## Differential diagnosis In adult females a tumor of the ovaries or adrenal glands can mimic the clinical manifestations of CAH. Polycystic ovarian syndrome (PCOS) is another differential diagnosis. ## Antenatal diagnosis Antenatal diagnosis is possible by screening for a disease causing gene by amniocentesis or chorionic villus sampling. ## Genetic counseling CAH is an autosomal recessive disorder and genetic counselling can be offered to parents with CAH. Dexamethasone can be given to pregnant women at risk of having offspring with the mutation (when fetus is female) in order to prevent virilization in girls. ## Management and treatment Lifelong hormone replacement therapy is needed to treat adrenal insufficiency and to decrease elevated androgen hormone levels. It is essential in allowing for normal growth and puberty in children. Hydrocortisone regulates menstrual cycles and promotes fertility in adult females. Hydrocortisone is usually given to children as glucocorticoid replacement therapy and 9 alpha-fludrocortisone acetate for mineralocorticoid replacement. Regular follow-up by a specialist is important so that dosage is monitored and modified if needed. Vaginoplasty can be performed in the first year of life. Psychological support is often needed. Methods of hair removal treat hirsutism. Menstrual cycles can sometimes be regulated with oral contraceptives. ## Prognosis With proper treatment patients may have a normal life expectancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Congenital adrenal hyperplasia	c0001627	24,815	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=418	2021-01-23T19:01:11	{"gard": ["1467"], "mesh": ["D000312"], "omim": ["201710", "201810", "201910", "202010", "202110", "613571"], "umls": ["C0001627"], "icd-10": ["E25.0"], "synonyms": ["CAH"]}
Zika virus disease is an emerging Aedes mosquito-born virus disease characterized by a clinical course that may be asymptomatic or mild with fever, conjunctivitis, muscle and joint pain, headache, exanthema, but may also be associated with severe neurological (meningitis, meningoencephalitis and myelitis) and auto-immune (Guillain-Barre syndrome) complications, as well as a potential increase of birth defects (microcephaly) if the infection occurs during pregnancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Zika virus disease	c0276289	24,816	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=448237	2021-01-23T19:10:55	{"gard": ["12894"], "mesh": ["D000071243"], "icd-10": ["U06"], "synonyms": ["Zika virus infection"]}
Multiple endocrine neoplasia 2B (MEN2B) syndrome is a rare aggressive form of MEN2 (see this term) characterized by medullary thyroid carcinoma (MTC, see this term), pheochromocytoma (see this term), mucosal ganglioneuroma, and marfanoid habitus. ## Epidemiology The exact prevalence of MEN2B is unknown but it accounts for 5 to 10% of all cases of MEN2 syndrome, providing estimated prevalence of 1/700,000 to 1/350,000. ## Clinical description Onset usually occurs earlier than MEN2A (see this term) and most frequently in infants and young children. Chronic constipation, abdominal distension, diarrhea, or megacolon at birth are often the initial manifestations of the disease due to ganglioneuromatosis of the gastrointestinal tract. Patients also exhibit mucosal neuromas of the lips, eyelids, and tongue, bumpy lips, and marfanoid habitus (with skeletal abnormalities and joint laxity). MEN2B has a higher mortality rate than MEN2A. Unlike MEN2A, MEN2B follows a more severe course and hyperparathyroidism is not found. Pheochromocytoma occurs in 50% of patients. ## Etiology A single mutation at codon 918 in the tyrosine kinase domain of the RET proto-oncogene (10q11.2) has been associated with the MEN2B phenotype. ## Genetic counseling Transmission is autosomal dominant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Multiple endocrine neoplasia type 2B	c0025269	24,817	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247709	2021-01-23T17:44:32	{"gard": ["10225"], "mesh": ["D018814"], "omim": ["162300"], "umls": ["C0025269"], "icd-10": ["D44.8"], "synonyms": ["MEN2B", "Multiple endocrine neoplasia type 3", "Wagenmann-Froboese syndrome"]}
A number sign (#) is used with this entry because of evidence that achondrogenesis type II (ACG2) is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13. For a general phenotypic description and discussion of genetic heterogeneity of achondrogenesis, see ACG1A (200600). Description Achondrogenesis type II is characterized by severe micromelic dwarfism with small chest and prominent abdomen, incomplete ossification of the vertebral bodies, and disorganization of the costochondral junction. This form is an autosomal dominant trait occurring mostly as new mutations. However, somatic and germline mosaicism have been reported (summary by Comstock et al., 2010). Clinical Features Spranger et al. (1974) distinguished 2 forms of achondrogenesis, which they called types I and II. Type I was subdivided into type IA (200600) and IB (600972). In type I, the ribs tend to be thin, often with multiple fractures. This finding led Harris et al. (1972) to refer to it as pseudoachondrogenesis with fractures. Indeed, it might be confused with the broad-bone form of osteogenesis imperfecta (166210). Type II achondrogenesis is characterized by virtual absence of ossification in the vertebral column, sacrum and pubic bones. Saldino (1971) reported on this form. In both forms the trunk is short with prominent abdomen and hydropic appearance. Micromelia is striking. In both, death occurs in utero or the early neonatal period. Chen et al. (1981) reported 2 cases and reviewed reported cases in extenso. As compared with type I, the cases of type II, or Langer-Saldino type, showed fewer stillbirths, longer survival, longer gestational period, larger size of baby, longer limbs, and characteristic craniofacial features (prominent forehead, flat face, micrognathia). Spranger (1985) introduced the concept of 'bone dysplasia families' as exemplified by the similar pattern of radiographically demonstrated skeletal abnormalities, called dysostosis multiplex, produced by a variety of lysosomal storage diseases. The concept postulates that the developing skeleton reacts in a stereotypic fashion to heterogeneous disturbances of a single metabolic pathway. Spranger (1985) defined one such family as consisting of type II achondrogenesis, hypochondrogenesis, and spondyloepiphyseal dysplasia congenita, the 3 disorders constituting a spectrum of decreasing severity. This family of disorders may be etiologically more intimately related than are the various conditions that produce dysostosis multiplex, since there is evidence of abnormality of type II collagen in SED congenita (Murray and Rimoin, 1988). Hypochondrogenesis (Hendrickx et al., 1983) may bear the same relationship to achondrogenesis that hypochondroplasia does to achondroplasia, i.e., it may be an allelic variant. Stanescu et al. (1977) described 3 cases and introduced the term hypochondrogenesis. Borochowitz et al. (1986) favored the view that hypochondrogenesis and achondrogenesis of the Langer-Saldino type are part of the spectrum of severity of the same disorder. Maroteaux et al. (1991) reiterated the view that hypochondrogenesis is an allelic form of the Langer-Saldino type of achondrogenesis, a conclusion that is probably supported by the finding of abnormalities of type II collagen in these cases. Superti-Furga (1996) suggested that hypochondrogenesis should be considered separately from achondrogenesis type II because the phenotype can be much milder. As in achondrogenesis type II, all cases represent de novo autosomal dominant mutations in the COL2A1 gene. Biochemical Features In a case of lethal short-limbed dwarfism, Eyre et al. (1986) found that the cartilage in all sites had an abnormal gelatinous texture and translucent appearance. No type II collagen was detected at any site; type I was the predominant collagen present. However, cartilage-specific proteoglycans appeared to be abundant. Eyre et al. (1986) suggested that chondrogenesis imperfecta might be a satisfactory designation. Horton et al. (1987) studied growth cartilage in 7 cases of what they designated achondrogenesis type II. The normal architecture of the epiphyseal and growth plate cartilage was replaced by morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to enlarged chondrocytes. Extracellular matrix in the latter area was more abundant than in the former and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen and other constituents. Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations might indicate a defect in the biosynthesis of type II collagen or in chondrocyte differentiation. Godfrey et al. (1988) described the clinical, radiographic, histologic, and ultrastructural abnormalities in a mild case of type II achondrogenesis-hypochondrogenesis fitting the classification criteria of Whitley-Gorlin prototype IV (Whitley and Gorlin, 1983). Immunohistochemical studies using a monoclonal antibody against type II collagen showed intense staining of small, rounded-to-oval structures within chondrocytes, strongly suggesting intracellular accumulation of this collagen type, probably in the distended cisternae of the rough endoplasmic reticulum observed in all chondrocytes by electron-microscopic studies. These observations raised the possibility of an abnormal type II collagen produced by, and accumulating within, chondrocytes. Godfrey and Hollister (1988) presented evidence that the patient they studied was heterozygous for an abnormal pro-alpha-1 (II) chain which impaired the assembly and/or folding of type II collagen. Feshchenko et al. (1989) described absence of type II collagen and a quantitative and qualitative change in proteoglycans in hyaline cartilage of the ribs and knee joint in a stillborn female with type II achondrogenesis. As they pointed out, studies in both parents would help in connection with the question of whether this represented homozygosity for a mutation located in the COL2A1 gene. Other Features Potocki et al. (1995) reported defects in cardiac septation in 2 infants with hypochondrogenesis. One infant had a complete AV canal defect. The second had a secundum type atrial septal defect. Potocki et al. (1995) raised the question whether type II collagen may function in human cardiogenesis even though it is not detected in myocardium. Rittler and Orioli (1995) described postaxial polydactyly of the feet in a severely affected newborn with achondrogenesis type II. The possibility that it represented a contiguous gene syndrome due to a deletion on chromosome 12 was raised. Inheritance Faivre et al. (2004) reported the recurrence of achondrogenesis type II in 2 successive pregnancies of a healthy, nonconsanguineous young couple. In the second fetus a G316D mutation in the COL2A1 gene (120140.0038) was detected. A heterozygous mutation was not found in either parent. Faivre et al. (2004) concluded that recurrence was due to germline mosaicism in 1 parent. Forzano et al. (2007) reported another family with recurrence of achondrogenesis type II in 3 fetuses. Genetic analysis provided proof of somatic mosaicism for a COL2A1 mutation in the father (G346V; 120140.0053). Comstock et al. (2010) reported another family in which 2 fetuses had achondrogenesis type II. Molecular analysis confirmed a heterozygous mutation in the COL2A1 gene in the second affected fetus, but molecular studies could not be completed on the first fetus. Neither parent was affected, although the father reportedly was born with clubfoot. The parents had 6 healthy term gestations and 1 spontaneous first-trimester loss. Overall, the findings suggested germline mosaicism, which increased the recurrence risk from background risk in this family. Molecular Genetics In a case of type II achondrogenesis-hypochondrogenesis, Vissing et al. (1989) demonstrated heterozygosity for a missense mutation in the COL2A1 gene (120140.0002). In an infant with a severe form of skeletal dysplasia who required continuous respiratory support until his death at 3 months of age, Bogaert et al. (1992) demonstrated a mutation in the COL2A1 gene (120140.0009). History Early editions of OMIM had designated type II achondrogenesis as type IB and had incorrectly cataloged it as an autosomal recessive disorder. ### Achondrogenesis Types III and IV On radiologic grounds, Whitley and Gorlin (1983) identified 4 subtypes of achondrogenesis. Their achondrogenesis type I was the Parenti-Fraccaro type, called type I in other classifications; however, they divided the classic type II (Langer-Saldino type) into 3 types called II, III, and IV. They introduced the 'femoral cylinder index,' or CI(femur): length/width. Their types I and II have the same CI(femur), namely 1.0 to 2.8, and both have crenated ilia and stellate long bones, but multiple rib fractures, characteristic of type I, are not found in type II. Type III has unfractured ribs, halberd ilia, mushroom-stem long bones, and a CI(femur) of 2.8 to 4.9. Type IV has unfractured ribs, sculpted ilia, well-developed long bones, and a CI(femur) of 4.9 to 8.0. Whitley and Gorlin (1983) suggested that 'achondrogenesis type IV...should be considered synonymous with hypochondrogenesis until there are sufficient criteria to distinguish the suspected genetic heterogeneity.' In a survey of lethal osteochondrodysplasias in the county of Fyn (Funen), Denmark, Andersen (1989) identified new cases of type III achondrogenesis. Superti-Furga (1996) stated that the radiologic classification devised by Whitley and Gorlin (1983) did not prove helpful and was abandoned. Animal Model On histologic grounds, the bulldog calf appears to be an authentic model of the Langer-Saldino type of achondrogenesis. Abnormalities of type II collagen were demonstrated by Sanford et al. (1989), although no abnormality of the COL2A1 gene or its mRNA transcripts could be demonstrated. INHERITANCE \- Autosomal dominant GROWTH Height \- Dwarfism, marked micromelic HEAD & NECK Mouth \- Cleft palate Neck \- Cystic hygroma CHEST External Features \- Barrel-shaped chest \- Short trunk Ribs Sternum Clavicles & Scapulae \- Short, horizontal ribs \- Normal clavicles ABDOMEN External Features \- Distended abdomen SKELETAL Skull \- Enlarged calvaria with normal ossification Spine \- Absent vertebral body mineralization Pelvis \- Non-ossified sacrum, ischial, and pubic bones \- Small iliac wings with concave inferior and medial margin Limbs \- Very short, broad tubular bones \- Flared, cupped metaphyses Hands \- Short tubular bones Feet \- Non-ossified talus and calcaneus \- Short tubular bones PRENATAL MANIFESTATIONS \- Fetal hydrops Amniotic Fluid \- Polyhydramnios Delivery \- Stillborn or death shortly after birth MISCELLANEOUS \- Most cases result from de novo mutations \- Stillborn or death shortly after birth \- Hypochondrogenesis represents clinical variability within the achondrogenesis-hypochondrogenesis spectrum MOLECULAR BASIS \- Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1, 120140.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	ACHONDROGENESIS, TYPE II	c0220685	24,818	omim	https://www.omim.org/entry/200610	2019-09-22T16:31:39	{"doid": ["0080056"], "mesh": ["C536017"], "omim": ["200610"], "icd-10": ["Q77.0"], "orphanet": ["93296", "932", "93297"], "synonyms": ["Alternative titles", "ACHONDROGENESIS, LANGER-SALDINO TYPE", "CHONDROGENESIS IMPERFECTA", "ACHONDROGENESIS, TYPE IB, FORMERLY"], "genereviews": ["NBK540447"]}
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-36 (COXPD36) is caused by compound heterozygous mutation in the MRPS2 gene (611971) on chromosome 9q34. For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). Clinical Features Gardeitchik et al. (2018) reported 2 unrelated patients, an 11-year-old girl of Austrian descent and an 11-year-old boy of Tunisian descent, with a relatively mild multisystem disease resulting from mitochondrial dysfunction. The patients presented in infancy with delayed psychomotor development and hypotonia, followed by speech delay associated with sensorineural hearing loss and episodic hypoglycemia. The girl had intellectual disability and mild dysmorphic features, including low-set ears, upslanting palpebral fissures, skin wrinkling, and strabismus. At age 11 years, the boy had a normal appearance, but moderate intellectual disability, frequent headaches, weakness of the lower limbs, and exercise intolerance. Both patients had normal brain MRI. Laboratory studies in both patients showed increased lactate, increased urinary Krebs cycle intermediates, such as 2-oxoglutaric aciduria, and decreased activities of multiple oxidative phosphorylation enzyme complexes (OXPHOS) in various tissues. The disorder was not progressive, and Gardeitchik et al. (2018) commented that these patients were at the less severe end of the clinical spectrum of mitochondrial disorders. Inheritance The transmission pattern of COXPD36 in the families reported by Gardeitchik et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 unrelated children with COXPD36, Gardeitchik et al. (2018) identified compound heterozygous or homozygous missense mutations in the MRPS2 gene (611971.0001-611971.0003). The mutations, which were found by exome sequencing, segregated with the disorder in the families. Patient fibroblasts showed decreased levels of the MRPS2 protein, as well as decreased levels of certain other MRPS proteins and the mt-DNA-encoded 12S rRNA, which are part of the smaller mitochondrial-specific ribosomal subunit 28S (mt-SSU). Complexome profiling of mitochondrial extracts from patient cells showed impaired assembly of the mt-SSU, resulting in a lack of functional mitoribosomes, inhibition of mitochondrial translation, and multiple deficiencies of the oxidative phosphorylation enzymes (OXPHOS). Patient cells showed a decrease in the abundance of fully assembled complexes I and IV and aberrant assembly of complex V. The defects could be rescued by complementation with wildtype MRPS2. Gardeitchik et al. (2018) noted that the phenotype in these patients was relatively mild compared to other COXPDs, and suggested that this may result from a combination of different effects of the mutations on the stability or activity of the affected protein, the presumed role of MRPS2 late in mitoribosomal biogenesis, and different thresholds at which individual tissues are affected by diminished energy supply. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Face \- Dysmorphic features, mild (in some patients) Ears \- Hearing loss, sensorineural SKIN, NAILS, & HAIR Skin \- Wrinkly skin (1 patient) MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mildly delayed walking \- Intellectual disability \- Poor speech METABOLIC FEATURES \- Hypoglycemia, episodic LABORATORY ABNORMALITIES \- Increased lactate \- Increased alanine \- 2-oxoglutaric aciduria \- Increased excretion of Krebs cycle intermediates \- Variably decreased activities of mitochondrial respiratory complexes I, III, and IV in different tissues MISCELLANEOUS \- Onset in infancy \- Nonprogressive disorder \- Two unrelated patients have been reported (last curated April 2018) MOLECULAR BASIS \- Caused by mutation in the mitochondrial ribosomal protein S2 gene (MRPS2, 611971.0001 ) ▲ 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	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 36	c4693722	24,819	omim	https://www.omim.org/entry/617950	2019-09-22T15:44:22	{"omim": ["617950"]}
A number sign (#) is used with this entry because factor V deficiency, also known as parahemophilia, is caused by homozygous or compound heterozygous mutation in the gene encoding coagulation factor V (F5; 612309) on chromosome 1q24. Clinical Features Owren (1947) described a haemorrhagic diathesis, which he referred to as 'parahemophilia,' due to the absence of a previously unknown clotting factor. Kingsley (1954) and Seibert et al. (1958) reported familial factor V deficiency in a consanguineous kindreds, indicating autosomal recessive inheritance. Seibert et al. (1958) observed consistently prolonged bleeding and clotting times in affected individuals. Yoshioka et al. (1975) stated that 28 cases of factor V deficiency had been recorded in Japan. Mitterstieler et al. (1978) reported a 14-month-old girl with a tendency toward heavy bleeding caused by severe isolated congenital factor V deficiency. Ten of 56 examined family members had factor V levels ranging from 26 to 60% of normal; these were classified as heterozygotes. The case histories of the heterozygotes did not reveal a bleeding tendency. Mitterstieler et al. (1978) concluded that the inheritance of this factor V deficiency is autosomal recessive, with varying expressivity in heterozygotes. Chiu et al. (1983) identified 4 individuals with factor V deficiency and a variant form of the factor V molecule that reacted with a polyclonal rabbit antibody, but not with the naturally occurring antibody. In all, 14 patients with congenital factor V deficiency were studied. In 10, factor V antigen and coagulant activity were both decreased compared to controls. Fischer et al. (1984) found an inbred Brazilian kindred, located because 2 affected persons had the same surname, with multiple cases of isolated factor V deficiency. Ehrenforth et al. (1998) described severe factor V deficiency presenting as a subdural hematoma in the newborn. Guasch et al. (1998) reported a girl, born of consanguineous parents, who presented at age 3 years with prolonged bleeding from a cut in her upper lip after trauma. Routine clotting tests showed prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT). Essentially no plasma factor V activity or antigen could be detected in plasma. At age 7 years, she had never had a bleed that necessitated therapy, although minor injuries sometimes resulted in prolonged bleeding. Her only other symptom was easy bruising. The patient's father had undergone many surgical procedures without any bleeding complications, but her mother had excessive bleeding after tooth extractions and childbirth. aPTTs and PTs of the parents were within the normal range. Van Wijk et al. (2001) reported a 19-year-old Korean woman with severe factor V deficiency. She developed bleeding of the soft tissue of the mouth at the age of 19 months, experienced a large subdural hematoma at the age of 4 years, and suffered soft tissue bleeds of the mouth, epistaxis, and hematomas for which she received fresh frozen plasma once every 3 months. In recent years her bleeding pattern changed to spontaneous muscle bleedings. Van Wijk et al. (2001) also reported a 15-year-old girl from Morocco, the daughter of first-cousin parents, with severe factor V deficiency with F5 activity less than 1%. The patient was identified in the course of family screening. A 23-year-old brother, previously described by Tanis et al. (1998), also had severe factor V deficiency and prolonged bleeding after injuries. Both patients were homozygous for a mutation in the F5 gene (612309.0008) Molecular Genetics In a patient with factor V deficiency, Guasch et al. (1998) identified a homozygous mutation in the F5 gene (612309.0004). In a Korean woman with factor V deficiency, van Wijk et al. (2001) identified compound heterozygosity for 2 mutations in the F5 gene (612309.0006; 612309.0007). Population Genetics Zehnder et al. (1999) pointed out that homozygous factor V deficiency is rare, approximately 1 in a million. On this basis, heterozygotes should have a frequency of 1 in 1,000. Heterozygous deficiency states are generally unrecognized because of a lack of significant clotting time prolongation or bleeding risk. History Hurtubise et al. (1979) isolated an immunoglobulin with the characteristics of a monoclonal antibody against factor V from the serum of a patient with a fatal hemorrhagic diathesis. INHERITANCE \- Autosomal recessive HEMATOLOGY \- Bleeding episodes (epistaxis, menorrhagia, ecchymosis) \- Factor V deficiency \- Prolonged bleeding LABORATORY ABNORMALITIES \- Prolonged activated partial thromboplastin time (APTT) \- Prolonged prothrombin time (PT) MISCELLANEOUS \- Incidence of 1 in 1,000,000 \- Heterozygotes are usually asymptomatic MOLECULAR BASIS \- Caused by mutation in the coagulation factor V gene (F5, {612309.0004) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	FACTOR V DEFICIENCY	c0015499	24,820	omim	https://www.omim.org/entry/227400	2019-09-22T16:28:06	{"doid": ["2216"], "mesh": ["D005166"], "omim": ["227400"], "icd-10": ["D68.2"], "orphanet": ["326"], "synonyms": ["Alternative titles", "PARAHEMOPHILIA", "OWREN PARAHEMOPHILIA", "LABILE FACTOR DEFICIENCY"]}
Delleman and Oorthuys (1981) reported 2 presumably unrelated boys with orbital cyst, cerebral malformations, and focal dermal hypo- and aplasia. Despite some similarities to the Goltz (305600) and Goldenhar (164210) syndromes, a new entity was suspected. In neither case were the parents related. 'Punched out' lesions over the nasal alae and in other areas were found in both. In one case the maternal grandmother had unilateral congenital clinical anophthalmia. Moog et al. (1996) presented the long-term follow-up of a 19-year-old patient who was one of the first 2 patients described by Delleman and Oorthuys (1981). Delleman et al. (1984) added 2 new cases. Al-Gazali et al. (1988) reviewed 5 published cases and reported 4 new cases. They illustrated a dramatic example of unilateral orbital cyst as well as examples of periorbital skin appendages. All cases have been sporadic. Giorgi et al. (1989) described another case. Also see Wilson et al. (1985). Hoo et al. (1991) reported a case in which, as in most cases, involvement was mainly unilateral. Among reported cases, left involvement has dominated over right involvement by about 2 to 1. Moog et al. (1996) reported a new case of this disorder presenting with bilateral clinical anophthalmia and orbital cysts, typical skin lesions, a complex brain malformation, and cleft lip/palate. The infant died due to the severe cerebral malformations at the age of 10 months. Moog et al. (1996) considered the most important differential diagnostic entities to be encephalocraniocutaneous lipomatosis, focal dermal hypoplasia (FDH; 305600), and microphthalmia with linear skin defects (MCOPS7; 309801). Moog et al. (1997) reported 3 new cases and reviewed the clinical features of 23 previously reported cases. The 3 new cases were sporadic. They all had cystic microphthalmia, abnormalities of the ventricular system, and lipomatous skin tags. In addition, 2 of the 3 had Dandy-Walker malformation and focal dermal hypoplastic defects. The 2 children who survived the neonatal period had psychomotor retardation and epilepsy. Twenty-four of the 26 patients reviewed had a colobomatous ocular defect, and all 26 had at least 1 ocular feature. Twenty-four patients had skin appendages, and in 21 of these the appendages were mainly around the orbit. Twenty-one had focal dermal hypoplasia or aplasia. A great variety of cerebral malformations was seen, with 3 patients having a normal CT scan. Of the 17 patients greater than 6 months of age at the time of report, all showed psychomotor retardation, and 13 showed seizures or an abnormal EEG. Moog et al. (1997) concluded that the triad of ocular, cutaneous, and cerebral features were characteristic of the syndrome and that, in particular, the ocular features were typical and constant. They also noted the difficulty in differentiating oculocerebrocutaneous syndrome from encephalocraniocutaneous lipomatosis. Moog et al. (1997) reported that the most reliable discriminating features were orbital cysts and agenesis of the corpus callosum, which are unknown in encephalocraniocutaneous lipomatosis, and cerebral calcifications, which are unreported in oculocerebrocutaneous syndrome. Moog et al. (1997) reported an 18-to-7 preponderance of male infants. Family history was negative in all but 1 of the patients reported by Delleman and Oorthuys (1981) and in 1 of the cases reported by Al-Gazali et al. (1988), where a paternal cousin had an eye cyst and the mother of the proband had a bilateral coloboma. Happle (1987) suggested that oculocerebrocutaneous syndrome, like a number of other sporadically occurring disorders with an irregular distribution of skin involvement, may be the result of an autosomal dominant lethal gene that is compatible with survival only in the mosaic state. Moog et al. (1997) argued that a dominant lethal mutation with survival only in mosaic form (Happle, 1987) was an unlikely etiologic mechanism because there was little variation in the tissues involved and because the skin lesions were distributed in a known linear pattern without sharp midline delineation. Moog et al. (1997) suggested that the pathogenic mechanism is probably disruption of the anterior neuroectodermal plate leading to neurocristopathy with primary craniofacial dysmorphogenesis. Leichtman et al. (1994) and Angle and Hersh (1997) described children with what was suggested to be a more severe form of OCCS who also had anophthalmia, congenital hydrocephalus, and cleft lip and palate. McCandless and Robin (1998) described a third case of severe OCCS in an infant girl with a similar constellation of findings and additional anomalies including lateral facial cleft, vertebral anomaly, and ventricular septal defect. The additional findings pointed to phenotypic overlap of OCCS and the Goldenhar anomaly (164210), an overlap previously noted by Delleman and Oorthuys (1981) and Al-Gazali et al. (1988). McCandless and Robin (1998) suggested that the minimal diagnostic criteria for Delleman syndrome includes central nervous system cyst or hydrocephalus, orbital cysts or microphthalmia, and focal skin defects. Moog et al. (2005) reviewed brain imaging studies, clinical records, photographs, and pathology specimens of 2 new and 9 previously reported patients with OCCS. They found a consistent pattern of malformations in 8 of the 11 cases, consisting of frontal predominant polymicrogyria and periventricular nodular heterotopia, enlarged lateral ventricles or hydrocephalus, agenesis of the corpus callosum (sometimes associated with interhemispheric cysts), and a novel mid-hindbrain malformation consisting of an enlarged, dysplastic tectum, absent cerebellar vermis, small cerebellar hemispheres, and a large posterior fossa fluid collection. The 3 remaining patients had similar but less severe forebrain abnormalities and lacked the mid-hindbrain malformation. Moog et al. (2005) suggested that the mid-hindbrain malformation is pathognomonic for OCCS and may be used to distinguish OCCS from related syndromes with comparable forebrain anomalies. Nomenclature See 309800 for discussion of the misuse of the term 'anophthalmia' in the medical literature. INHERITANCE \- Isolated cases HEAD & NECK Face \- Facial asymmetry Eyes \- Orbital cysts \- Microphthalmia \- Anophthalmia, clinical \- Eyelid coloboma \- Nystagmus \- Dermoids Nose \- Notched nasal alae Mouth \- Cleft palate CHEST Ribs Sternum Clavicles & Scapulae \- Rib dysplasia GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKELETAL Pelvis \- Congenital hip dislocation SKIN, NAILS, & HAIR Skin \- Focal dermal aplasia/hypoplasia \- Skin appendages (periorbital, face, thorax, rarely on trunk) \- Punch-like skin defects \- Postauricular crescent-shaped hypoplastic skin lesion Hair \- Focal alopecia NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures \- Ventricular dilatation \- Dandy-Walker malformation \- Hypoplastic corpus callosum \- Agenesis of the corpus callosum \- Orbital encephalocele \- Heterotopia \- Cerebral cysts MISCELLANEOUS \- All cases sporadic (18 males, 7 females) \- Features may be bilateral (15/24) or left side (9/24) ▲ 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	OCULOCEREBROCUTANEOUS SYNDROME	c0796092	24,821	omim	https://www.omim.org/entry/164180	2019-09-22T16:37:20	{"mesh": ["C538088"], "omim": ["164180"], "orphanet": ["1647"], "synonyms": ["Alternative titles", "OCCS", "ORBITAL CYST WITH CEREBRAL AND FOCAL DERMAL MALFORMATIONS", "DELLEMAN SYNDROME"]}
Outdated diagnosis and treatment for patients with multiple symptoms of a neurological condition Female hysteria Women with hysteria under the effects of hypnosis SpecialtyPsychiatry Female hysteria was once a common medical diagnosis for women, which was described as exhibiting a wide array of symptoms, including anxiety, shortness of breath, fainting, nervousness, sexual desire, insomnia, fluid retention, heaviness in the abdomen, irritability, loss of appetite for food or sex, (paradoxically) sexually forward behaviour, and a "tendency to cause trouble for others".[1] It is no longer recognized by medical authorities as a medical disorder. Its diagnosis and treatment were routine for hundreds of years in Western Europe.[1] In Western medicine hysteria was considered both common and chronic among women. The American Psychiatric Association dropped the term hysteria in 1952. Even though it was categorized as a disease, hysteria's symptoms were synonymous with normal functioning female sexuality.[1] In extreme cases, the woman may have been forced to enter an insane asylum or to have undergone surgical hysterectomy.[2] ## Contents * 1 Early history * 2 Middle Ages, Renaissance, and the early modern period * 3 18th century * 4 19th century * 5 Freud and decline of diagnosis * 6 Relationship with women's rights and feminism * 7 See also * 8 References * 9 Further reading * 10 External links ## Early history[edit] Further information: Wandering womb Water massages as a treatment for hysteria (c. 1860) Female patient with sleep hysteria The history of hysteria can be traced to ancient times. Dating back to 1900 BC in ancient Egypt, the first descriptions of hysteria within the female body were found recorded on the Kahun Papyri.[3] In this culture, the womb was thought capable of affecting much of the rest of the body, but "there is no warrant for the fanciful view that the ancient Egyptians believed that a variety of bodily complaints were due to an animate, wandering womb".[4] Uterine prolapse was also known.[4] In ancient Greece, wandering womb was described in the gynecological treatise of the Hippocratic Corpus, "Diseases of Women",[5] which dates back to the 5th and 4th centuries BC. Plato's dialogue Timaeus compares a woman's uterus to a living creature that wanders throughout a woman's body, "blocking passages, obstructing breathing, and causing disease".[6] Aretaeus of Cappadocia described the uterus as "an animal within an animal" (less emotively, "a living thing inside a living thing"), which causes symptoms by wandering around a woman's body putting pressure on other organs.[5] The standard cure for this "hysterical suffocation" was scent therapy, in which good smells were placed under a woman's genitals and bad odors at the nose, while sneezing could be also induced to drive the uterus back to its correct place.[5] The concept of a pathological "wandering womb" was later viewed as the source of the term hysteria,[6] which stems from the Greek cognate of uterus, ὑστέρα (hystera), although the word hysteria does not feature in ancient Greek medicine: 'the noun is not used in this period'.[6] While in the Hippocratic texts a wide range of women were susceptible – including in particular the childless – Galen in the 2nd century omitted the childless and saw the most vulnerable group as "widows, and particularly those who previously menstruated regularly, had been pregnant and were eager to have intercourse, but were now deprived of all this" (On the Affected Parts, 6.5).[5] He also denied that the womb could "move from one place to another like a wandering animal".[5] His treatments included scent therapy and sexual intercourse, but also rubbing in ointments to the external genitalia; this was to be performed by midwives, not physicians.[5] While most Hippocratic writers saw the retention of menstrual blood in the womb as a key problem, for Galen even more serious was the retention of "female seed".[7] This was believed to be thinner than male seed and could be retained in the womb.[6] Hysteria was referred to as "the widow's disease", because the female semen was believed to turn venomous if not released through regular climax or intercourse.[8] If the patient was married, this could be completed by intercourse with their spouse. Other than participating in sexual intercourse, it was thought that fumigating the body with special fragrances would supposedly draw the uterus back to its natural spot in the female body. Foul smells applied to the nose would drive it down, and pleasant scents at the vulva would attract it.[6] ## Middle Ages, Renaissance, and the early modern period[edit] Through the Middle Ages, another cause of dramatic symptoms could be found: demonic possession. It was thought that demoniacal forces were attracted to those who were prone to melancholy, particularly to single women and the elderly. When a patient could not be diagnosed or cured of a disease, it was thought that the symptoms of what would now be diagnosed as mental illness, were actually those of someone possessed by the devil.[9] After the 17th century, the correlation of demonic possession and hysteria were gradually discarded and instead was described as behavioral deviance, a medical issue.[10] In the 16th and 17th centuries, hysteria was still believed to be due to the retention of humour or fluids in the uterus, sexual deprivation, or by the tendency of the uterus to wander around the female body causing irritability and suffocation. Self-treatment such as masturbation, was not recommended and was also considered taboo. Marriage, and regular sexual encounters with her husband, was still the most highly recommended long-term course of treatment for a woman suffering from hysteria.[9][11] It was thought to purge the uterus of any built-up fluid, and semen was thought to have healing properties, 'In this model ejaculation outside the vagina was conducive to uterine disease, since the female genitalia did not receive the health benefits of male emission. Some physicians regarded all contraceptive practices as injurious to women for this reason. Giovanni Matteo Ferrari da Gradi cited marriage and childbearing as a cure for the disease. If pleasure was obtained from them then hysteria could be cured.[11] If a woman was unmarried, or widowed, manual stimulation by a midwife involving certain oils and scents was recommended to purge the uterus of any fluid retention. Lack of marriage was also thought to be the cause of most melancholy in single women, such as nuns or widows. Studies of the causes and effects of hysteria were continued in the 16th and 17th century by medical professionals such as Ambroise Pare, Thomas Sydenham, and Abraham Zacuto who published their findings furthering medical knowledge of the disease, and informing treatment.[11][9] Physician Abraham Zacuto writes in his Praxis Medica Admiranda from 1637, > 'Because of retention of the sexual fluid, the heart and surrounding areas are enveloped in a morbid and moist exudation: this is especially true of the more lascivious females, inclined to venery, passionate women who are most eager to experience physical pleasure; if she is of this type she cannot ever be relieved by any aid except that of her parents who are advised to find her a husband. Having done so the man's strong and vigorous intercourse alleviated the frenzy.' > > — Maines, 29, [11] There was continued debate about whether it was morally acceptable for a physician to remove excess female seed through genital manipulation of the female patient; Pieter van Foreest (Forestus) and Giovanni Matteo da Grado (Gradus) insisted on using midwives as intermediaries, and regarded the treatment as the last resort.[12] ## 18th century[edit] In the 18th century, hysteria slowly became associated with mechanisms in the brain rather than the uterus. French physician Philippe Pinel freed hysteria patients detained in Paris' Salpêtrière sanatorium on the basis that kindness and sensitivity were needed to formulate good care. ## 19th century[edit] Jean-Martin Charcot argued that hysteria derived from a neurological disorder and showed that it was more common in men than women.[3] Charcot's theories of hysteria being a physical affliction of the mind and not of the body led to a more scientific and analytical approach to hysteria in the 19th century. He dispelled the beliefs that hysteria had anything to do with the supernatural and attempted to define it medically.[13] Charcot's use of photography,[14] and the resulting concretization of women's expressions of health and distress, continued to influence women's experiences of seeking healthcare.[15] Though older ideas persisted during this era, over time female hysteria began to be thought of less as a physical ailment and more of a psychological one.[16] George Beard, a physician who cataloged an incomplete list including 75 pages of possible symptoms of hysteria,[17] claimed that almost any ailment could fit the diagnosis. Physicians thought that the stress associated with the typical female life at the time caused civilized women to be both more susceptible to nervous disorders and to develop faulty reproductive tracts.[18] One American physician expressed pleasure in the fact that the country was "catching up" to Europe in the prevalence of hysteria.[17] According to Pierre Roussel and Jean-Jacques Rousseau, femininity was a natural and essential desire for women: "Femininity is for both authors an essential nature, with defined functions, and the disease is explained by the non-fulfillment of natural desire."[9] It was during the industrial revolution and the major development of cities and modern lifestyles that disruption of this natural appetite was thought to cause lethargy or melancholy, leading to hysteria.[9] At the time female patients sought medical practitioners for the massage treatment of hysteria. The rate of hysteria was so great in the socially restrictive industrial period that women were prone to carry smelling salts about their person in case they swooned, reminiscent of Hippocrates' theory of using odors to coerce the uterus back into place. For physicians, manual massage treatment was becoming laborious and time-consuming, and they were seeking a way to increase productivity.[11] Rachel Maines hypothesized that physicians from the classical era until the early 20th century commonly treated hysteria by manually stimulating the genitals of, i. e. masturbating, female patients to the point of orgasm, which was denominated "hysterical paroxysm", and that the inconvenience of this may have motivated the original development of and market for the vibrator.[1] Although Maines's theory that hysteria was treated by masturbating female patients to orgasm is widely repeated in the literature on female anatomy and sexuality,[19] some historians dispute Maines's claims regarding the prevalence of this treatment for hysteria and its relevance to the invention of the vibrator, describing them as a distortion of the evidence or that they are only relevant to a very small group.[20][21][22] In 2018, Hallie Lieberman and Eric Schatzberg of Georgia Institute of Technology challenged Maines's claims for the use of electromechanical vibrators to treat hysteria in the 19th century.[23] Maines stated that her theory of the prevalence of masturbation for hysteria and its relevance to the invention of the vibrator is a hypothesis and not proven fact.[19] Frederick Hollick was a firm believer that a main cause of hysteria was licentiousness present in women.[24] ## Freud and decline of diagnosis[edit] The number of French psychiatric theses on hysteria[25] During the early 20th century, the number of women diagnosed with female hysteria sharply declined. This decline has been attributed to many factors. Some medical authors claim that the decline was due to gaining a greater understanding of the psychology behind conversion disorders such as hysteria.[25] With so many possible symptoms, historically hysteria was considered a catchall diagnosis where any unidentifiable ailment could be assigned.[3] As diagnostic techniques improved, the number of ambiguous cases that might have been attributed to hysteria declined. For instance, before the introduction of electroencephalography, epilepsy was frequently confused with hysteria.[26] Sigmund Freud claimed that hysteria was not anything physical at all but an emotional, internal affliction that could affect both males and females, which was caused by previous trauma that led to the afflicted being unable to enjoy sex in the normal way.[11][13] This would later lead to Freud's development of the Oedipus complex, which connotes femininity as a failure, or lack of masculinity.[13] Though these earlier studies had shown that men were also prone to suffer from hysteria, including Freud himself,[5] over time, the condition was related mainly to issues of femininity as the continued study of hysteria took place only in women.[27] Many cases that had previously been labeled hysteria were reclassified by Freud as anxiety neuroses.[26] Sigmund Freud was fascinated by cases of hysteria. He thought that hysteria may have been related to the unconscious mind and separate from the conscious mind or the ego.[28] He was convinced that deep conflicts in the mind, some concerning instinctual drives for sex and aggression, were driving the behavior of those with hysteria. Freud developed psychoanalysis in order to help patients that had been diagnosed with hysteria reduce internal conflicts causing physical and emotional suffering. While hysteria was reframed with reference to new laws and was new in principle, its recommended treatment in psychoanalysis would remain what Bernheimer observes it had been for centuries: marrying and having babies and in this way regaining the "lost" phallus.[13] New theories relating to hysteria came from pure speculation; doctors and physicians could not connect symptoms to the disorder, causing it to decline rapidly as a diagnosis.[29] Today, female hysteria is no longer a recognized illness, but different manifestations of hysteria are recognized in other conditions such as schizophrenia, borderline personality disorder, conversion disorder, and anxiety attacks.[30] ## Relationship with women's rights and feminism[edit] The most vehement negative statements associating feminism with hysteria came during the militant suffrage campaign. > "One does not need to be against womens suffrage," the London Times editorialized in 1908, "to see that some of the more violent partisans of that cause are suffering from hysteria. We use the word not with any scientific precision, but because it is the name most commonly given to a kind of enthusiasm that has degenerated into habitual nervous excitement."' > > — Gilman, 320, [5] In the 1980s, feminists began to reclaim hysteria, using it as a symbol of the systematic oppression of women and reclaiming the term for themselves.[5] Especially among sex-positive feminists, who believe sexual repression and having it called hysteria is a form of oppression.[5] The idea stemmed from the belief that Hysteria was a kind of pre-feminist rebellion against the oppressive defined social roles placed upon women. Feminist writers such as Catherine Clément and Hélène Cixous wrote in The Newly Born Woman from a place of opposition to the theories proposed in psychoanalytical works, pushing against the notion that socially constructed femininities and hysteria are natural to being female.[5][13] Feminist social historians of both genders argue that hysteria is caused by women's oppressed social roles, rather than by their bodies or psyches, and they have sought its sources in cultural myths of femininity and in male domination.[5] ## See also[edit] * Hysterical contagion * Male hysteria * Mass hysteria * Mass psychogenic illness * Premenstrual dysphoric disorder * Vapours (disease) ## References[edit] 1. ^ a b c d Maines, Rachel P. (1999). The Technology of Orgasm: "Hysteria", the Vibrator, and Women's Sexual Satisfaction. Baltimore: The Johns Hopkins University Press. p. 23. ISBN 0-8018-6646-4. 2. ^ Mankiller, Wilma P. (1998). The Reader's Companion to U.S. Women's History. Boston, MA: Houghton Mifflin Co. pp. 26. ISBN 0-6180-0182-4. 3. ^ a b c Tasca C, Rapetti M, Carta MG, Fadda B (2012). "Women and hysteria in the history of mental health". Clinical Practice and Epidemiology in Mental Health. 8: 110–9. doi:10.2174/1745017901208010110. PMC 3480686. PMID 23115576. 4. ^ a b Merskey, Harold; Potter, Paul (1989). "The womb lay still in ancient Egypt". British Journal of Psychiatry. 154 (6): 751–53. doi:10.1192/bjp.154.6.751. PMID 2688786. 5. ^ a b c d e f g h i j k l Gilman, Sander L.; King, Helen; Porter, Roy; Rousseau, G.S.; Showalter, Elaine (1993). Hysteria Beyond Freud. Los Angeles: University of California Press. 6. ^ a b c d e King, Helen (1993). "Once upon a text: Hysteria from Hippocrates". In Gilman, Sander; King; Porter, Roy; Rousseau, G.S.; Showalter, Elaine (eds.). Hysteria beyond Freud. University of California Press. p. 25. ISBN 0-520-08064-5. 7. ^ Flemming, Rebecca (2000). Medicine and the Making of Roman Women. Oxford University Press. ISBN 0199240027. 8. ^ Roach, Mary (2009). Bonk: The Curious Coupling of Science and Sex. New York: W.W. Norton & Co. p. 214. ISBN 9780393334791. 9. ^ a b c d e Carta, Mauro Giovanni; Fadda, Bianca; Rappeti, Mariangela; Tasca, Cecilia (October 19, 2012). "Women and Hysteria In Mental Health". Clin Pract Epidemiol Ment Health. 8: 110–19. doi:10.2174/1745017901208010110. PMC 3480686. PMID 23115576. 10. ^ Spanos, Gottlieb, Nicholas, Jack (1979). "Demonic possession, mesmerism, and hysteria: A social psychological perspective on their historical interrelations". Journal of Abnormal Psychology. 88 (5): 527–546. doi:10.1037/0021-843X.88.5.527. 11. ^ a b c d e f Maines, Rachel (1999). The technology of Orgasm: 'Hysteria', the Vibrator, and Women's Sexual Satisfaction. Baltimore: The Johns Hopkins University Press. 12. ^ Schleiner, Winfried (1995). Medical Ethics in the Renaissance. Georgetown University Press. p. 115. 13. ^ a b c d e Devereux, Cecily (March 2014). "Hysteria, Feminism, and Gender Revisited: The Case of the Second Wave". eJournal. University of Alberta. Retrieved October 20, 2016. 14. ^ Goetz, C.G. (1991). "Visual art in the neurologic career of Jean-Martin Charcot". Archives of Neurology. 48 (4): 421–25. doi:10.1001/archneur.1991.00530160091020. PMID 2012518. 15. ^ Jones, A. (2010). The Feminism and Visual Culture Reader. New York: Routledge. pp. 248–58, 300–08. 16. ^ Simon, Matt (May 7, 2014). "Fantastically Wrong: The Theory of the Wandering Wombs That Drove Women to Madness". Wired. Retrieved November 28, 2014. 17. ^ a b Briggs L (2000). "The race of hysteria: "overcivilization" and the "savage" woman in late nineteenth-century obstetrics and gynecology". American Quarterly. 52 (2): 246–73. doi:10.1353/aq.2000.0013. PMID 16858900. S2CID 8047730. 18. ^ Morantz RM, Zschoche S (December 1980). "Professionalism, feminism, and gender roles: a comparative study of nineteenth-century medical therapeutics". Journal of American History. 67 (3): 568–88. doi:10.2307/1889868. JSTOR 1889868. PMID 11614687. 19. ^ a b Maines, Rachel. "Big Think Interview with Rachel Maines". bigthink.com. Retrieved 16 November 2016. 20. ^ King, Helen (2011). "Galen and the Widow: Towards a history of therapeutic masturbation in ancient gynaecology" (PDF). EuGeStA: Journal on Gender Studies in Antiquity. 1: 205–235. 21. ^ Hall, Lesley. "Doctors masturbating women as a cure for hysteria/'Victorian vibrators'". lesleyahall.net. Retrieved 29 October 2016. 22. ^ Riddell, Fern (10 November 2014). "No, no, no! Victorians didn't invent the vibrator". The Guardian. Retrieved 29 October 2016. 23. ^ Lieberman, Hallie; Schatzberg, Eric (2018). "A failure of academic quality control: The Technology of Orgasm" (PDF). Journal of Positive Sexuality. 4 (2): 24–47. 24. ^ Hollick, Frederick (1853). The diseases of woman: their causes and cure familiarly explained; with practical hints for their prevention and for the preservation of female health. 25. ^ a b Micale MS (September 1993). "On the "disappearance" of hysteria. A study in the clinical deconstruction of a diagnosis". Isis; an International Review Devoted to the History of Science and Its Cultural Influences. 84 (3): 496–526. doi:10.1086/356549. PMID 8282518. S2CID 37252994. 26. ^ a b Micale MS (July 2000). "The decline of hysteria". The Harvard Mental Health Letter. 17 (1): 4–6. PMID 10877868. 27. ^ "The History of Hysteria: Sexism in Diagnosis". 2017. 28. ^ Coon, Mitterer, Dennis, John (2013). Introduction to Psychology: Gateways to Mind and Behavior. Cengage Learning. pp. 512–513. 29. ^ Micale MS (1993). "On the "disappearance" of hysteria. A study in the clinical deconstruction of a diagnosis". Isis; an International Review Devoted to the History of Science and Its Cultural Influences. 84 (3): 496–526. doi:10.1086/356549. JSTOR 235644. PMID 8282518. S2CID 37252994. 30. ^ Costa, Dayse Santos; Lang, Charles Elias (2016). "Hysteria Today, Why?". Psicologia USP. 27 (1): 115–124. doi:10.1590/0103-656420140039. ## Further reading[edit] * Kapsalis, Terri (2008). The Hysterical Alphabet. WhiteWalls. ISBN 9780945323167. * Libbrecht, Katrien (1995). Hysterical Psychosis: A Historical Survey. London: Transaction Publishers. ISBN 1-56000-181-X. * Micale, Mark S. (1995). Approaching Hysteria: Disease and its Interpretations. Princeton University Press. ISBN 0-691-03717-5. * Micale, Mark S. (2009-06-30). Hysterical Men: The Hidden History of Male Nervous Illness. Harvard University Press. ISBN 9780674040984. * Micklem, Niel (1996). The Nature of Hysteria. Routledge. ISBN 0-415-12186-8. * Bronfen, Elisabeth (2014-07-14). The Knotted Subject: Hysteria and Its Discontents. Princeton University Press. ISBN 9781400864737. * Augsburg, Tanya (1996). Private Theatres Onstage (Hysteria and the Female Medical Subject). UMI. * Showalter, Elaine (1987). The Female Malady: Women, Madness and English Culture, 1830-1980. Virago. ISBN 978-0860688693. * Lewis Herman, Judith (1992). Trauma and Recovery: The Aftermath of Violence--From Domestic Abuse to Political Terror. Basic Books. ISBN 978-0-465-08730-3. ## External links[edit] * Erika Kinetz, "Is Hysteria Real? Brain Images Say Yes" (The New York Times) * Female Hysteria during Victorian Era [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Female hysteria	None	24,822	wikipedia	https://en.wikipedia.org/wiki/Female_hysteria	2021-01-18T18:56:43	{"wikidata": ["Q2709115"]}
A rare, slow-growing, epithelial thyroid carcinoma typically presenting as an asymptomatic thyroid mass and is classed as either papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) or Hurthle cell thyroid cancer (HCTC). ## Epidemiology The annual incidence of differentiated thyroid cancer (DTC) is about 1/10,000, and the incidence appears to be increasing. The female to male ratio is about 3:1. ## Clinical description PTC, FTC, and HCTC have similar presentations, and constitute about 75, 20, and 5 percent of cases, respectively. About 10 percent of PTC are classified as tall cell variant, the most aggressive from of PTC. HCTC is generally considered slightly more aggressive than PTC and FTC. The age at diagnosis is usually over 30 years. Presentation is typically with an asymptomatic thyroid nodule. Rare but worrisome presentations include hoarseness due to vocal cord paralysis and obstruction of the airway or esophagus, and may suggest an aggressive variant of DTC or anaplastic thyroid carcinoma. DTC grows slowly, and distant metastases are rare at the time of presentation. The most common metastatic site is the cervical lymph nodes. Distant metastasis to lungs or bones is rare (about 5%). Pediatric cases are rare. They are more frequently present with lymph node involvement. Despite this apparently more aggressive presentation, the prognosis is excellent. Pathologically, PTC are usually composed of a mixture of papillae and follicles, frequently with relatively large nuclei containing folds and a clear center. About 50% contain calcium deposits. Different histological PTC subtypes have been described. FTC are characterized by microfollicles and presence of capsular and vascular invasion. HCTC, pathologically similar to FTC, are distinguished by mitochondria-rich, eosinophilic cytoplasm. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described variant; it is currently unclear if it is a pre-malignant lesion or a DTC variant. ## Etiology DTC arise from the epithelial cells of the thyroid gland. Most DTCs are sporadic and without known cause. Ionizing radiation predisposes to PTC. Iodine deficiency is associated with an increased risk of FTC. The sporadic molecular pathogenesis of these three malignancies is partially understood. In PTC, the V600E BRAF mutation (7q34) as well as fusion genes involving RET (10q11.2) and NTRK1 (1q23.1) are common. Activating RAS mutations occur in both PTC and FTC as well as in benign thyroid lesions. The PAX8/PPAR gamma fusion gene (2q13) is more frequently observed in follicular thyroid cancer. About 5% of PTCs have a familial predisposition although the associated germline alterations are unknown. HCC has a unique and complex genetic profile that includes somatic mutations (including DAXX, TERT, TP53, NRAS, NF1, CDKN1A, ARHGAP35 and complex I mtDNA) and widespread chromosomal loss. ## Diagnostic methods DTC usually presents on physical examination or ultrasound as an asymptomatic nodule within the thyroid gland. Serum concentrations of thyroid hormone are usually normal. Thyroid fine needle aspiration biopsy cytology is frequently used to distinguish between the benign and malignant nodules. Additional diagnostic techniques include ultrasound characteristics and genetic analyses of the fine needle biopsy material. Diagnosis is confirmed on pathology review following surgical resection. ## Differential diagnosis Differential diagnosis of thyroid nodules includes benign thyroid nodules (nodular goiter, thyroid cyst, follicular adenoma), other thyroid malignancies, as well as Hashimoto's thyroiditis and thyroid lymphoma. ## Management and treatment The treatment of DTC is prioritized. First, complete surgical resection is essential for cure. Second, thyroid hormone administration to suppress TSH to appropriate concentrations helps prevent recurrence. Third, since most DTCs maintain the ability to take up iodine, 131-iodine therapy is useful in eradicating residual microscopic disease. For those few patients refractory to conventional therapy, external radiation and multikinase inhibitors are effective. Long-term follow-up is essential due to the cumulative risk of recurrence (about 20% at 20 years). Recurrences are detected by physical examination, neck ultrasound, iodine scans, and serum thyroglobulin measurements. ## Prognosis Prognosis is generally good in most patients, but about 5% of cases are fatal. Those below age 55 years with tumor size below 4 cm have a particularly good prognosis. Those with distant metastatic disease have a poorer prognosis. Occasionally, patients may progress to anaplastic thyroid cancer that uniformly has a very poor prognosis. Molecular markers help predict prognosis. Tumors that have both a TERT promoter mutation plus either an activating V600E BRAF mutation or activating RAS mutation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Differentiated thyroid carcinoma	c0238463	24,823	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=146	2021-01-23T18:38:45	{"gard": ["12027"], "mesh": ["D000077273"], "omim": ["188550", "607464"], "umls": ["C0238463"], "icd-10": ["C73"], "synonyms": ["Papillary or follicular thyroid carcinoma", "Well-differentiated thyroid carcinoma"]}
## Description Stuttering is a speech disorder characterized by the presence of syllable repetitions, syllable prolongations, and interruptions in the smooth flow of speech known as blocks (summary by Riaz et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of familial persistent stuttering, see 184450. Inheritance Riaz et al. (2005) stated that approximately half of stutterers have a family history of the disorder, and twin and adoption studies support a genetic contribution. Mapping In a linkage study of stuttering, Riaz et al. (2005) collected families in the city of Lahore, Pakistan, and surrounding areas. These families were highly inbred, with stuttering occurring in 2 or more generations, and were chosen with preference for a high number of affected individuals. A genomewide linkage scan was performed in 44 families. Initial nonparametric analysis gave evidence of linkage on chromosomes 1, 5, 7, and 12. Additional genotyping was performed on chromosome 12 to a 5-cM level of resolution, and 16 additional individuals were then included, bringing the number of families to 46. Analysis of the enlarged data set provided consistent evidence of linkage on chromosome 12 with a nonparametric lod score of 4.61 with PAH (612349), and a lod score of 3.51 by another approach. The results suggested that a locus on 12q may contain a gene with a large effect on stuttering in this population. In a large consanguineous Pakistani family with stuttering, Kang et al. (2010) refined the STUT2 locus to a 10-Mb region between D12S101 and D12S1597, on chromosome 12q24. Molecular Genetics ### Associations Pending Confirmation For discussion of a possible role of variation in the NAGPA gene in familial persistent stuttering-2, see 607985.0001-607985.0003. In affected members of a large consanguineous 6-generation Pakistani family with stuttering showing linkage to chromosome 12q (Riaz et al., 2005), Kang et al. (2010) identified a glu1200-to-lys (E1200K) variant in the GNPTAB gene (607840). Thirteen affected individuals were heterozygous, and 12 were homozygous. However, the variant did not completely segregate with the disorder: 3 noncarriers were affected, and 2 homozygous E1200K carriers and 9 heterozygous E1200K carriers were unaffected. Kang et al. (2010) suggested nonpenetrance in these individuals. The authors identified 3 additional variants in the GNPTAB gene in 4 additional individuals with stuttering. None of the individuals had features of mucolipidosis. By studying other genes in the lysosomal enzyme-targeting pathway, Kang et al. (2010) found 3 variants each in the GNPTG (607838) and NAGPA (607985) genes that were found in 11 of 270 patients with stuttering, but not in 276 controls. Kang et al. (2010) concluded that variations in genes governing lysosomal metabolism may be susceptibility factors for nonsyndromic stuttering. Kang et al. (2010) performed no functional studies on any of the identified mutations. By haplotype analysis of 8 unrelated individuals who were heterozygous or homozygous for the E1200K variant in the GNPTAB gene, Fedyna et al. (2011) determined that it arose as a founder allele 572 generations, or 14,300 years ago. Haplotype analysis identified a common 6.67-kb haplotype containing the variant. Animal Model Barnes et al. (2016) engineered mice to carry a homozygous glu1179-to-lys mutation in the Gnptab gene, which is homologous to the glu1200-to-lys mutation in human GNPTAB. Compared with wildtype pups, pups with the mutation emitted fewer vocalizations per unit time when separated from their dam. They also showed longer pauses between vocalizations and were more stereotyped in their vocalizations than wildtype littermates. Gnptab missense pups were similar to wildtype on an extensive battery of nonvocal behaviors. Speech from people who stutter showed similar abnormalities when compared with control speech. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	STUTTERING, FAMILIAL PERSISTENT, 2	c1836484	24,824	omim	https://www.omim.org/entry/609261	2019-09-22T16:06:21	{"mesh": ["C563756"], "omim": ["609261"]}
Head injuries in sports of any level (junior, amateur, professional) are the most dangerous and sickening kind of injuries that can occur in sport, and are becoming more common in Australian sport. Concussions are the most common side effect of a head injury and are defined as "temporary unconsciousness or confusion and other symptoms caused by a blow to the head." A concussion also falls under the category of Traumatic Brain Injury (TBI).[1] Especially in contact sports like Australian rules football and Rugby issues with concussions are prevalent, and methods to deal with, prevent and treat concussions are continuously being updated and researched to deal with the issue. Concussions pose a serious threat to the patients’ mental and physical health, as well as their playing career, and can result in lasting brain damage especially if left untreated. The signs that a player may have a concussion are: loss of consciousness or non-responsiveness, balance problems (unsteadiness on feet, poor co-ordination), a dazed, blank or vacant look and/or confusion and unawareness of their surroundings.[2] Of course the signs are relevant only after the player experiences a blow to the head. ## Contents * 1 Dangers of concussion * 2 AFL * 3 Cricket * 4 Rugby * 5 Concussions in children * 6 See also * 7 References ## Dangers of concussion[edit] In the short term, concussions do not pose a serious problem and a player suffering may experience: headache, dizziness, loss of memory, blurred vision, confusion, disorientation and /or sensitiveness to bright light and loud noises.[3] However, the real danger occurs after repeated concussions suffered by the same player, if the player returns to play immediately after contracting a concussion or too soon after suffering one. If the player returns to play immediately or too soon after, there is an increased risk of another concussion (which is much more serious) as well as to the rest of the body due to a slower reaction time. The player can also suffer from a number of psychological issues like depression, as well as permanent brain damage and severe brain swelling.[2] A player, regardless of age or level of competition, should not return to play or training following a concussion, without a medical clearance from a registered medical doctor. ## AFL[edit] One of the all-time great AFL players, Jonathon Brown's career was cut short after a series of life-threatening head knocks. In a high-impact game like Australian Rules Football, head injuries and concussions have always been common, but public awareness has risen over the last decade towards the dangers of continuing to play while suffering from a concussion. It is estimated that there are 5–6 players who suffer a concussion for every 1000 hours spent on the field, meaning there are 6–7 concussions per team during one season.[4] Previously, players at the elite level, either realised they would be pulled out of the game if they were identified as concussed hid the fact from coaches and continued to play, but recently the AFL released new concussion management guidelines to combat the issue. Now, only a medical officer with previous experience in the subject may declare the player fit to play, also the coaches are warned against rushing their players back into the team after suffering a concussion. The guidelines also dictate that immediately, or as soon as possible, after a player suffers a concussion, or is suspected of suffering from one, they must be subjected to a medical assessment after which they may or may not be allowed to return to the field depending on the results.[5] Introduced in 2013 in the AFL, the 'concussion sub' can be used when a player suffers a concussion or is suspected of having one, the player in question is substituted out of the game for at least 20 minutes, during which a test takes place to evaluate the players psychological well-being. The occurrence of concussions in amateur leagues are less common because of the lower impact intensity. However, concussions suffered at amateur levels can at times be more dangerous then those suffered in the AFL because of the inferior resources possessed and in some cases the coaches are not willing to pull a player out of the game, or rest them if they are suffering from a concussion.[6] A study conducted by the Australian Football Injury Prevention Project (AFIPP) in 2002 showed that out of 301 players (who play for amateur clubs in the Melbourne metropolitan area), 14 suffered from a form of head knock, 7 of which resulted in concussion.[7] 18.9% of players participating in the test suffered from concussion, bearing in mind that the sample size is also small. A separate study showed that out of 1015 Australian Rules Football players tested, 78 of them were concussed, 9 of which were concussed multiple times. The players mental functions were tested at controlled intervals with 38.6% of players still displaying symptoms at 48 hours after being concussed but after 96 hours, only 1.1% displayed any symptoms.[8] ## Cricket[edit] Cricket is classified differently to high intensity sports like Australian rules football and rugby, due to the stop-start nature of the game rather than continuous flowing play. However, due to the speed of fast bowlers and the hardness of cricket balls, cricket is still very much a high impact sport. Out of all Australian sporting codes, cricket requires the most protective gear to properly guard batsmen from a variety of injuries that can be afflicted all over the body. The most important piece of protective gear is the helmet, which includes a grill covering the face, to protect batsmen from head injuries. In the most recent Australian tour of the West Indies, now former Australian batsmen Chris Rogers suffered a concussion during training and was ruled out of the test series without playing a match. This has led Cricket Australia to plan out an updated concussion policy and guidelines[9] The principles are based on the International Consensus Conferences on Concussion in Sport (the Zurich Guidelines) and involve the player suspected of being concussed answering a set of questions to determine whether he has to leave the field. While concussion in cricket is considered quite rare due to increasingly safer helmets, the effects can be quite severe. NSW batsmen Ben Rohrer was struck in the head by a cricket ball during a Sheffield Shield match against Victoria in November last year, he recalls his legs feeling like jelly and falling over on the pitch.[10] The most widely known case is the death of NSW batsmen Phillip Hughes who died after being receiving a cricket ball to the head in 2014. A study conducted with 542 junior cricket players revealed only 13% of injuries were limited to the facial region, and none of them suffered a concussion.[11] ## Rugby[edit] High intensity, high impact and played by men with big bodies, rugby is an extremely physical game where concussions are common. Most popular in New South Wales and Queensland, rugby can be classified into two different codes, rugby union and rugby league. Both are played at a very high level of intensity with full contact allowed, and as such has one of the highest concussion rates in the world, let alone Australia. Studies conducted into the incidence of concussion in professional and amateur levels of rugby have revealed that approximately 3.9 concussions per 1000 hours of play occur in professional rugby (1 concussion in every 6 games). Playing at the amateur level, concussion rates are much lower measured at 1 in every 21 matches (1.2 per 1000 hours). This amounts to roughly 5–7 concussions per team per season.[12] The National Rugby League released a 4 step set of guidelines, in 2012, for all coaches to follow in the case one of their players suffering a concussion during a game. The guidelines detail that the player be given basic first aid before being assessed by a medical officer, they also stress heavily that if the player is determined to be concussed there is no way the player should return to the field. if the concussion is serious, the player should be sent as soon as possible to hospital for medical treatment.[2] Wearing protective gear, such as a helmet and mouthguard, can reduce the chances of sustaining a concussion. See also: Concussions in rugby union ## Concussions in children[edit] The occurrence of concussion in children during sport is significantly more likely compared to other levels of athletes. Roughly 20% of children playing sport are diagnosed with concussion. Despite the lower level of impact compared to the professional or amateur levels, children's neck muscles are quite weak and most lack the awareness and skill level to cushion or prepare themselves for a blow leading to a high concussion rate.[13] The guidelines and protocols for a child suffering a concussion are basically the same as if an adult received one. For a child diagnosed with a concussion, the real issue is returning to school rather than the sporting field, as a concussion can affect a child's learning ability. A medical clearance is required before a return to school is possible and parents are recommended to properly manage their child through the first 72 hours after experiencing a concussion.[14] ## See also[edit] Concussions in sport ## References[edit] 1. ^ Makdissi, Michael (2010). "Sports Related Concussion – Management in General Practice". Australian Family Physician. 2. ^ a b c "Management of Concussion in Rugby League". Cite journal requires `\|journal=` (help) 3. ^ "What is concussion?". www.concussioninsportproject.com.au. Archived from the original on 4 March 2016. Retrieved 1 September 2015. 4. ^ Khurana, Vini G.; Kaye, Andrew H. (1 January 2012). "An overview of concussion in sport". Journal of Clinical Neuroscience. 19 (1): 1–11. doi:10.1016/j.jocn.2011.08.002. PMID 22153800. 5. ^ "AFL Community: Concussion". www.aflcommunityclub.com.au. Retrieved 1 September 2015. 6. ^ Newton, Joshua D.; White, Peta E.; Ewing, Michael T.; Makdissi, Michael; Davis, Gavin A.; Donaldson, Alex; Sullivan, S. John; Seward, Hugh; Finch, Caroline F. (1 January 2014). "Intention to use sport concussion guidelines among community-level coaches and sports trainers". Journal of Science and Medicine in Sport. 17 (5): 469–473. doi:10.1016/j.jsams.2013.10.240. PMID 24252427. 7. ^ Braham, R; Finch, CF; McCrory, P (1 January 2004). "The incidence of head/neck/orofacial injuries in non-elite Australian Football". Journal of Science and Medicine in Sport. 7 (4): 451–453. doi:10.1016/s1440-2440(04)80263-9. PMID 15712501. 8. ^ Makdissi, Michael; Darby, David; Maruff, Paul; Ugoni, Antony; Brukner, Peter; McCrory, Paul R. (1 March 2010). "Natural History of Concussion in Sport Markers of Severity and Implications for Management". The American Journal of Sports Medicine. 38 (3): 464–471. doi:10.1177/0363546509349491. ISSN 0363-5465. PMID 20194953. 9. ^ "Cricket Australia to roll out new concussion policy across country this summer". Retrieved 2 September 2015. 10. ^ "Cricket Australia trialling 'very conservative' guidelines on concussion". Retrieved 2 September 2015. 11. ^ Finch, Caroline F.; White, Peta; Dennis, Rebecca; Twomey, Dara; Hayen, Andrew (1 January 2010). "Fielders and batters are injured too: A prospective cohort study of injuries in junior club cricket". Journal of Science and Medicine in Sport. 13 (5): 489–495. doi:10.1016/j.jsams.2009.10.489. PMID 20031485. 12. ^ Gardner, Andrew J.; Iverson, Grant L.; Williams, W. Huw; Baker, Stephanie; Stanwell, Peter (20 August 2014). "A Systematic Review and Meta-Analysis of Concussion in Rugby Union". Sports Medicine. 44 (12): 1717–1731. doi:10.1007/s40279-014-0233-3. ISSN 0112-1642. PMID 25138311. 13. ^ "Management of Concussion in Children". www.concussioninsportproject.com.au. Archived from the original on 4 March 2016. Retrieved 2 September 2015. 14. ^ McNamee, M.J.; Partridge, B. & Anderson, L (2015). "Concussion in Sport: Conceptual and Ethical Issues". Kinesiology Review (4 ed.). 2: 190–202. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Concussions in Australian sport	None	24,825	wikipedia	https://en.wikipedia.org/wiki/Concussions_in_Australian_sport	2021-01-18T19:00:11	{"wikidata": ["Q22090497"]}
Majeed syndrome is a rare genetic multisystemic disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, which may be accompanied by neutrophilic dermatosis. ## Epidemiology The syndrome is extremely rare. Fourteen cases born into consanguineous families, from the Middle East, India and Spain have been reported. ## Clinical description Onset is generally within the first two years of life although it may present later in childhood (range 1 month to 8 years) as bone pain. Chronic recurrent multifocal osteomyelitis (CRMO) associated with Majeed syndrome is typically more severe than that of non-syndromic CRMO, and is more persistent, with short remissions and more frequent exacerbations. It can be associated with fever, joint pain, delayed bone age, growth failure, short adult stature, and development of flexion contractures. Patients also have a hypochromic, microcytic anemia with dyserythropoiesis present on 11 of 11 bone marrow biopsies. In half of the cases, the anemia is mild with the remainder requiring one or more transfusions for anemia. The inflammatory neutrophilic dermatosis Sweet syndrome has been reported in two patients with Majeed syndrome. Other reported manifestations include failure to thrive, hepatomegaly, neutropenia, and transient cholestatic jaundice. The course is chronic and the syndrome may have a significant impact on quality of life. ## Etiology Majeed syndrome is caused by a mutation in LPIN2 (18p11.31), which encodes phosphatidate phosphatase LPIN2 (Lipin-2), important in lipid metabolism. Recent studies have shown that Lipin-2 is a negative regulator of the NLRP3 inflammasome. ## Diagnostic methods The diagnosis is based on the typical clinical manifestations and on molecular genetic testing of the causative gene mutation. Osteomyelitis can be diagnosed on skeletal radiographs but may require magnetic resonance imaging (MRI). Bone, bone marrow and skin biopsies may also be needed. ## Differential diagnosis Differential diagnoses include Caffey disease, SAPHO syndrome, non-syndromic CRMO, deficiency of the interleukin-1 receptor antagonist (DIRA) and immune deficiency. ## Antenatal diagnosis Prenatal diagnosis is possible in affected families when a disease causing mutation has been identified. ## Genetic counseling Majeed syndrome follows an autosomal recessive pattern of inheritance. Genetic counseling can inform parents with an affected child of their 25 % risk of having an affected child at each pregnancy. ## Management and treatment Treatment is empiric. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main treatment options for non-syndromic CRMO, but are not likely to control bone inflammation in Majeed syndrome patients. Corticosteroids may also be used to control CRMO and inflammatory dermatosis, but have a multitude of side effects that limit their use for long term treatment. Methotrexate with or without pamidronate has been utilized in a few cases with mild to moderate improvement reported. TNF inhibitors were used in 2 children without significant benefit. IL-1 beta inhibition looks more promising with resolution of clinical symptoms, normalization of blood inflammatory markers and normalization of radiologic bone lesions in 4 of 4 patients treated. ## Prognosis The prognosis has generally been poor because of progressive bone and hematological manifestations, however, outcomes have improved with more aggressive treatments. There is limited information on long-term outcomes in patients treated with IL-1 beta inhibitors but short-term follow-up has shown sustained clinical response to this biologic class. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Majeed syndrome	c1864997	24,826	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77297	2021-01-23T18:22:38	{"gard": ["10088"], "mesh": ["C537839"], "omim": ["609628"], "umls": ["C1864997"], "synonyms": ["Chronic recurrent multifocal osteomyelitis-congenital dyserythropoietic anemia-neutrophilic dermatosis syndrome"]}
## Clinical Features This disorder is characterized by well-localized pain when the patella is grated against the femoral condyles or when the knee is actively extended with the patella manually displaced distally. Rubacky (1963) described 5 families with multiple affected persons in multiple generations and male-to-male transmission. The association of patellar chondromalacia with recurrent dislocation of the patella (169000) is well known and the former is usually attributed to the latter. However, Rubacky (1963) suggested that the cause and effect relation may be the other way around in some cases. This condition is probably not a form of osteochondritis dissecans (165800), which can affect the patella. Limbs \- Patellar pain \- Patellar chondromalacia Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	PATELLA, CHONDROMALACIA OF	c0008475	24,827	omim	https://www.omim.org/entry/168900	2019-09-22T16:36:31	{"doid": ["13357"], "mesh": ["D046789"], "omim": ["168900"], "icd-9": ["717.7"], "icd-10": ["M22.4"], "orphanet": ["1428"], "synonyms": []}
Livedo racemosa SpecialtyDermatology Livedo racemosa is a skin condition with persistent red or violet discoloration, characterised by a broken, branched, discontinuous and irregular pattern. It can be restricted to the limbs or diffuse. It is usually the first sign of a systemic vascular disorder.[1] ## See also[edit] * Livedo reticularis * Livedoid dermatitis * List of cutaneous conditions ## References[edit] 1. ^ "Livedo racemosa: Clinical, laboratory and histopathological findings in 33 patients and literature review". Journal of the American Academy of Dermatology. 76 (6): AB425. June 2017. doi:10.1016/j.jaad.2017.06.143. ISSN 0190-9622. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Livedo racemosa	c0085642	24,828	wikipedia	https://en.wikipedia.org/wiki/Livedo_racemosa	2021-01-18T18:41:39	{"mesh": ["D054068"], "wikidata": ["Q1866422"]}
## Summary ### Clinical characteristics. Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is characterized by distinctive craniofacial features, genital anomalies, hypotonia, and mild-to-profound developmental delay / intellectual disability (DD/ID). Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short triangular nose, tented upper lip, and thick or everted lower lip with coarsening of the facial features over time. While all affected individuals have a normal 46,XY karyotype, genital anomalies comprise a range from hypospadias and undescended testicles, to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Alpha-thalassemia, observed in about 75% of affected individuals, is mild and typically does not require treatment. Osteosarcoma has been reported in a few males with germline pathogenic variants. ### Diagnosis/testing. The diagnosis of ATR-X syndrome is established in a proband with suggestive findings, a 46,XY karyotype, and a hemizygous pathogenic variant in ATRX identified by molecular genetic testing. ### Management. Treatment of manifestations: DD/ID, seizures, gastrointestinal manifestations and feeding difficulties, excessive drooling, and genital anomalies are managed per standard of care. Surveillance: Regular assessment of growth and developmental progress in infancy and childhood. ### Genetic counseling. ATR-X syndrome is inherited in an X-linked manner. The mother of a proband may be heterozygous (i.e., a carrier) or the affected individual may have a de novo pathogenic variant. If the mother of the proband has an ATRX pathogenic variant, the chance of transmitting it in each pregnancy is 50%: sibs with a 46,XY karyotype who inherit the pathogenic variant will be affected; sibs with a 46,XX karyotype who inherit the pathogenic variant will be heterozygous and will rarely show clinical manifestations. Affected males do not reproduce. Once the ATRX pathogenic variant in the family has been identified, carrier testing for at-risk females, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible. ## Diagnosis Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome should be suspected in individuals with the following clinical findings, hematologic findings, and family history. Clinical findings * A recognizable pattern of craniofacial findings including small head circumference, upsweep of the frontal hair, telecanthus or widely spaced eyes, short triangular nose, tented upper lip, thick or everted lower lip, and open mouth. Irregular anatomy of the pinnae, widely spaced teeth, and protruding tongue are supplemental findings, the latter two adding to a coarseness of the facial appearance, particularly after the first few years of life. * Growth impairment including microcephaly and short stature, usually present at birth * Genital anomalies (in an individual with a 46,XY karyotype) that can range from hypospadias and undescended testes to ambiguous genitalia to normal external female genitalia * Developmental delay / intellectual disability, typically in the severe-to-profound range Hematologic findings. Hematologic studies show evidence of alpha-thalassemia in approximately 75% of males with ATR-X syndrome [Gibbons et al 2008]. * HbH inclusions (β-globin tetramers) in erythrocytes can be demonstrated following incubation of fresh blood smears with 1% brilliant cresyl blue. The proportion of cells with HbH inclusions ranges from 0.01% to 30% [Gibbons et al 1995a]. HbH inclusions may be demonstrated readily in some individuals, found only in an occasional erythrocyte in some, or observed only after repeated testing in others. The absence of HbH inclusions in one fourth of affected individuals and the rarity of inclusions (≤1% of erythrocytes) in an additional 40% of affected individuals diminish the utility of this testing in most clinical settings. * Red blood cell indices. A microcytic hypochromic anemia characteristic of alpha-thalassemia may be seen in some affected individuals, but many have red cell indices in the normal range [Gibbons et al 1995b]. * Newborn screening. In rare instances, ATR-X syndrome has been identified through the detection of HgH on newborn screening for hemoglobinopathies. Family history consistent with X-linked inheritance (e.g., no male-to-male transmission). Absence of a known family history does not preclude the diagnosis. ### Establishing the Diagnosis The diagnosis of ATR-X syndrome is established in a male proband with suggestive findings and a hemizygous pathogenic variant in ATRX identified by molecular genetic testing (see Table 1). Note: Identification of a hemizygous ATRX variant of uncertain significance does not establish or rule out a diagnosis of this disorder. #### Molecular Genetic Testing Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and 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. Single-gene testing. Sequence analysis of ATRX is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. Multigene panel. An X-linked intellectual disability panel and other multigene panels that include ATRX and other genes of interest (see Differential Diagnosis) are 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. This approach does not require the clinician to determine which genes are likely involved. Exome sequencing is commonly used; genome sequencing is becoming possible in some laboratories. If exome sequencing is not diagnostic, exome array should 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 ATR-X Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ATRXSequence analysis 3, 4~95% 5 Gene-targeted deletion/duplication analysis 6~5% 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis. 5\. Based on data from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, of note: whole-gene duplications but not deletions have been reported. Breakpoints of large duplications and/or duplication of adjacent genes (e.g., those described by Honda et al [2012], Isrie et al [2012], and Lugtenberg et al [2009]) may not be detected by these methods. #### Other Testing Epigenetic signature analysis / methylation microarray. A characteristic methylation signature identified on epigenetic signature analysis of leukocytes in individuals with ATR-X syndrome [Schenkel et al 2017] may be useful as a first-tier screening test in an individual with an atypical phenotype or as a second-tier test when molecular genetic testing identifies an ATRX variant of uncertain significance. ## Clinical Characteristics ### Clinical Description A more or less distinctive phenotype is characteristic of alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome. Craniofacial, genital, and developmental manifestations are prominent among the most severely affected individuals [Gibbons et al 1995b, Badens et al 2006a, Stevenson et al 2012]. As additional individuals/families have been evaluated using molecular genetic testing, the range of phenotypic variability has broadened, particularly on the mild end of the spectrum. Affected males may have mild, moderate, or profound intellectual disability (ID), even within the same family. Adults in the family described by Yntema et al [2002] appeared to have nonsyndromic X-linked ID (XLID), although childhood photographs showed evidence of facial hypotonia. Basehore et al [2015] reported 25 affected males in five families with the p.Arg37Ter variant who had variable but overall milder phenotypes (see Genotype-Phenotype Correlations). ### Table 2. Selected Features of Alpha-thalassemia X-linked Intellectual Disability Syndrome View in own window Feature% of Persons with FeatureComments Developmental delay100%A minority never speak or have meaningful speech. Intellectual disability100%Variable severity, from mild to profound Characteristic facies * Hypertelorism/telecanthus * Small nose * Tented upper lip * Open mouth * Prominent lips 90%Usually present from birth, but may persist or become less distinctive in adult life. W/age, face may also coarsen w/open mouth, spaced teeth, & prominent lips. Microcephaly75%-85%Usually present at birth; head size of those w/out microcephaly usually in lower centiles Short stature60%-70%Usually present at birth Gastrointestinal dysfunction70%-80%A major morbidity; incl: early feeding difficulty, vomiting, reflux, abdominal distention, obstruction, pain, & constipation Genital anomalies70%-80%Wide range, from minimal hypospadias or undescended testes to normal-appearing female external genitalia NeurologicHypotonia80%-90%Contributes to facial phenotype Seizures30%-40% #### Developmental Impairment / Intellectual Disability Severe developmental impairment and intellectual disability are the most important clinical manifestations. From the outset, developmental milestones are globally and markedly delayed. Speech and ambulation occur late in childhood. Some affected individuals never walk independently or develop significant speech. #### Growth Impairment Growth impairment with microcephaly and short stature occurs in most individuals with ATR-X syndrome and is often present at birth. Stature is typically short (>2 SD below the mean in 67% of individuals using standard growth charts; syndrome-specific growth charts are not available). Growth above average is exceptional. #### Gastrointestinal Manifestations Gastrointestinal manifestations, present in the majority of individuals, contribute significantly to morbidity. Approximately three fourths have gastroesophageal reflux and one third have chronic constipation. Gastric pseudo-obstruction can result from abnormal suspension of the stomach and constipation can result from colon hypoganglionosis [Martucciello et al 2006]. Aspiration, presumably related to gastroesophageal reflux, has been a fatal complication in some. #### Genital Anomalies Genital anomalies are often minor, including first-degree hypospadias, undescended testes, and underdevelopment of the scrotum. Although all individuals with ATR-X syndrome have a normal 46,XY karyotype, gonadal dysgenesis resulting in inadequate testosterone production can cause more severe defects that can include second- and third-degree hypospadias, small penis, ambiguous genitalia, or even normal-appearing female external genitalia. Although all individuals with ATR-X syndrome have a normal 46,XY karyotype, occasionally gonadal dysgenesis results in inadequate testosterone production and ambiguous genitalia. Although the spectrum of possible genital anomalies in ATR-X syndrome is broad, the type of genital anomaly appears to be consistent within a family. #### Hypotonia Hypotonia, a hallmark of ATR-X syndrome, contributes to the facial manifestations, drooling, developmental delay, and possibly to the gastrointestinal manifestations. #### Seizures Seizures of various types occur in about one third of individuals with ATR-X syndrome but are not a defining manifestation of the syndrome [Gibbons et al 1995b, Stevenson et al 2012, Giacomini et al 2019]. Brain atrophy and white matter abnormalities have been found on MRI and CT imaging [Wada et al 2013]. #### Other The neurobehavioral phenotype has not been extensively delineated; however, most individuals appear affable, but some are emotionally labile with tantrums and bouts of prolonged crying or laughing. Minor skeletal anomalies (brachydactyly, clinodactyly, tapered digits, joint contractures, pectus carinatum, kyphosis, scoliosis, dimples over the lower spine, varus and valgus foot deformation, and pes planus) occur, but do not contribute significantly to morbidity. Major malformations are not common, but ocular coloboma, cleft palate, cardiac defects, inguinal hernia, heterotaxy, and asplenia [Leahy et al 2005] have been reported. Although predisposition to tumor development has not been confirmed in individuals with germline ATRX pathogenic variants, four children with ATR-X syndrome have developed osteosarcoma [Ji et al 2017, Masliah-Planchon et al 2018], a finding that contrasts with the well-recognized tumor association of somatic ATRX pathogenic variants (see Cancer and Benign Tumors). Masliah-Planchon et al [2018] provide clinical, histologic, and genetic data supporting the possibility of tumor predisposition associated with germline ATRX pathogenic variants in their report of three instances of osteosarcoma in two males: * One individual with two metachronous osteosarcomas, the first (of the tibia) diagnosed and successfully treated at age nine years, and the second (of the humerus) diagnosed and successfully treated ten years later at age 20 years * One child, diagnosed with osteosarcoma of the femur with pulmonary nodules at age four years, who succumbed 18 months later #### Heterozygous Females Heterozygous females rarely show clinical manifestations. Typically, carrier females have marked skewing of X-chromosome inactivation (>90:10) with preferential inactivation of the X chromosome with the ATRX pathogenic variant. Rare exceptions have been reported, including the following: * A five-generation pedigree in which three females had signs of ATR-X syndrome [Christensen et al 1999] * Moderate ID without other phenotypic features of ATR-X syndrome in a female carrier with random X-chromosome inactivation [Wada et al 2005] * A girl conceived by in vitro fertilization (IVF) who had craniofacial features, growth retardation, and developmental impairment typical of ATR-X syndrome [Badens et al 2006b]. Leukocyte studies showed marked skewing of X-chromosome inactivation with her pathogenic variant-bearing X chromosome being the active X chromosome. The role of IVF in this unique case of female expression is not known. ### Genotype-Phenotype Correlations Pathogenic variants that affect the ATRX zinc finger domain produce severe psychomotor impairment and urogenital anomalies, whereas pathogenic variants in the helicase domains cause milder phenotypes [Badens et al 2006a]. More severe genital anomalies occur with variants in the plant homeodomain-like domain. A nonsense variant in exon 2 (p.Arg37Ter) appears to be a common pathogenic variant that results in an overall milder phenotype [Basehore et al 2015] (see Table 7). ### Nomenclature "Alpha-thalassemia X-linked intellectual disability syndrome" and "ATR-X syndrome" are the preferred designations for this disorder. ATRX pathogenic variants have been found in several named XLID syndromes (Carpenter-Waziri syndrome, Holmes-Gang syndrome, Chudley-Lowry syndrome, XLID-arch fingerprints – hypotonia), in XLID with spastic paraplegia, in XLID with epilepsy, and in nonsyndromic XLID [Lossi et al 1999, Stevenson 2000, Stevenson et al 2000, Yntema et al 2002, Stevenson et al 2012]. These entities should be considered to be in the phenotypic spectrum of ATR-X syndrome; there are no compelling reasons to maintain the syndromic names. Note: A family considered to have Juberg-Marsidi syndrome was found to have an ATRX pathogenic variant [Villard et al 1996]. Subsequently, the original family reported with Juberg-Marsidi syndrome was found to have a HUWE1 pathogenic variant, indicating that the family studied by Villard et al [1996] represented a misdiagnosis [Friez et al 2016]. Although two families considered to have Smith-Fineman-Myers syndrome have ATRX pathogenic variants, the original family with Smith-Fineman-Myers has not been restudied. Hence, the relationship of ATR-X syndrome and Smith-Fineman-Myers syndrome is unclear [Villard et al 1999a, Li et al 2020]. ### Prevalence The prevalence is not known. More than 200 affected individuals are known to the laboratories conducting molecular genetic testing; substantial underascertainment, especially of those with milder phenotypes, is probable. No racial or ethnic concentration of individuals has been reported. ## Differential Diagnosis ### Table 3. Genes of Interest in the Differential Diagnosis of Alpha-Thalassemia X-Linked Intellectual Disability Syndrome View in own window Gene(s)DiffDx DisorderMOIClinical Features of DiffDx Disorder Overlapping w/ATR-X syndromeNot observed in ATR-X syndrome HBA1 HBA2Hemoglobin H (HbH) disease (See Alpha-Thalassemia.)AR 1Microcytic hypochromic hemolytic anemia, hepatosplenomegaly, mild jaundice, & sometimes thalassemia-like bone changes * Persons w/ATR-X syndrome have normal α-globin genotype (αα/αα); those w/HbH disease have deletion or dysfunction of 3 of 4 α-globin alleles. * ID is not a component of alpha-thalassemia involving α-globin production. MECP2 \+ adjacent genes in Xq28MECP2 duplication syndromeXL * Severe ID, spasticity, infantile hypotonia, absent or limited speech, seizures, & recurrent respiratory infections * Autistic behaviors & GI dysfunction observed in several affected boys * 50% of affected males die by early adulthood. * Face is not characteristically hypotonic as in ATR-X syndrome. * Microcephaly is less common. * Downslanted palpebral fissures RPS6KA3Coffin-Lowry syndromeXL * Severe-to-profound ID in males * Large open mouth & prominent lips * Short stature, microcephaly, & dental anomalies common * Childhood-onset kyphoscoliosis (often progressive) * Life span ↓ in some persons * Short, soft, fleshy hands, often w/hyperextensible & tapering fingers * Childhood-onset SIDAs in ~20% of persons 2 * Carrier females often have fullness of face & lips, fleshy & hyperextensible fingers, & learning difficulties. AR = autosomal recessive; DiffDx = differential diagnosis; GI = gastrointestinal; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked 1\. Alpha-thalassemia is usually inherited in an autosomal recessive manner. 2\. Childhood-onset SIDAs (stimulus-induced drop attacks) refers to a brief collapse (but no loss of consciousness) triggered by unexpected tactile or auditory stimuli or excitement. Alpha-thalassemia intellectual disability, chromosome 16-related (ATR-16 syndrome; OMIM 141750) is the association of alpha-thalassemia and intellectual disability in individuals with a contiguous gene deletion involving the distal short arm of chromosome 16. Such deletions produce alpha-thalassemia by deleting the two genes in cis configuration at 16p13 that encode α-globin chains. Because the chromosome deletions and rearrangements giving rise to ATR-16 are large and variable, no specific clinical phenotype is observed in ATR-16; this is in contrast to ATR-X syndrome, in which the phenotype is more predictable. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome, 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 ATR-X Syndrome View in own window System/ConcernEvaluationComment GrowthAssess height, weight, head circumferenceIn infants & children DevelopmentDevelopmental assessment * To incl motor, adaptive, cognitive, & speech/language eval * Eval for early intervention / speech therapy / PT / OT / special education NeurologicNeurologic eval * To assess muscle tone, evidence for spasticity (↑ reflexes, Babinski response) * To incl EEG & MRI if seizures a concern Gastrointestinal/ FeedingGastroenterology / nutrition / feeding team evalFor: * Nutritional status * Swallowing difficulties & aspiration risk * GERD &/or recurrent vomiting * Gastric pseudo-obstruction * Constipation Genital abnormalitiesPhysical exam for evidence of a disorder of genital development such as cryptorchidism, hypospadias, ambiguous genitalia, normal female external genitalia in 46,XY individualsConsultation w/pediatric urologist if surgical intervention required MusculoskeletalOrthopedics / physical medicine & rehabilitation / PT/OT evalTo incl assessment of: * Gross motor & fine motor skills * Contractures, clubfoot, & kyphoscoliosis * Mobility & need for adaptive devices * Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills) Congenital heart defectsPediatric cardiologistSeptal defects require eval re possible intervention. Ophthalmologic involvementOphthalmologic examAssess for strabismus, ↓ visual acuity, structural eye defects (e.g., coloboma). Genetic counselingBy genetics professionals 1To inform affected individuals & their families re nature, MOI, & implications of ATR-X syndrome in order to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent. * Need for social work involvement for parental support. GERD = gastroesophageal reflux disease; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations ### Table 5. Treatment of Manifestations in Individuals with ATR-X Syndrome View in own window Manifestation/ConcernTreatmentConsiderations/Other DD/IDSee Developmental Delay / Intellectual Disability Management Issues. SeizuresStandardized treatment w/AEDs by experienced neurologist * Many AEDs may be effective; none demonstrated effective specifically for this disorder * Education of parents/caregivers 1 Gastrointestinal/ FeedingFeeding therapy; calorie-dense formula; gastrostomy tube placement as needed for persistent feeding issues * Usual treatment for GERD, constipation * Treatment for gastric pseudo-obstruction per treating gastroenterologist/pediatric surgeon DroolingAnticholinergics, botulinum toxin type A injection of salivary glands &/or surgical redirecting of submandibular ductsOptions when drooling is a serious problem Genital abnormalitiesPer treating urologist MusculoskeletalOrthopedics / physical medicine & rehabilitation / PT / OTUse of durable medical equipment & positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers) Congenital heart defectsPer treating cardiologist Ophthalmologic involvementPer treating ophthalmologist AED = antiepileptic drug; DD = developmental delay; ID = intellectual disability; OT = occupational therapy; PT = physical therapy #### Developmental Disability / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider: * Individualized education plan (IEP) services: * An IEP provides specially designed instruction and related services to children who qualify. * IEP services will be reviewed annually to determine if any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, privatesupportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech and in many cases, can improve it. #### Social/Behavioral Concerns Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance ### Table 6. Recommended Surveillance for Individuals with ATR-X Syndrome View in own window System/ConcernEvaluationFrequency GrowthHeight, weight, head circumferenceAt each visit in infancy & childhood DevelopmentMonitor developmental progress & educational needs. Gastrointestinal/ Feeding * Measurement of growth parameters * Eval of nutritional status & safety of oral intake * Monitor for excessive vomiting, GERD, abdominal distention & pain, constipation. Genital abnormalitiesFollow up w/treating urologist as needed.At initial visit in infancy Neurologic * Monitor those w/seizures as clinically indicated. * Assess for new manifestations such as seizures, changes in tone, movement disorders. At each visit Congenital heart defectsPer treating cardiologistPer treating cardiologist Ophthalmologic involvementPer treating ophthalmologistPer treating ophthalmologist ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Alpha-Thalassemia X-Linked Intellectual Disability Syndrome	c1845055	24,829	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1449/	2021-01-18T20:46:40	{"mesh": ["C538258"], "synonyms": ["ATR-X Syndrome"]}
Paget disease of the nipple describes a rare presentation of breast cancer, seen most frequently in women aged 50-60, manifesting with nipple drainage and itching, erythema, crusty and excoriated nipple, thickened plaques, and hyperpigmentation (less frequently). It is due to tumor cells invading the nipple-areola complex and represents 1-3% of all new breast cancer diagnoses. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Paget disease of the nipple	c0030185	24,830	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=180275	2021-01-23T18:13:26	{"gard": ["7303"], "mesh": ["D010144"], "umls": ["C0030185", "C1704323"], "icd-10": ["C50.0"], "synonyms": ["Mammary Paget disease", "Paget disease of the breast", "Paget's disease of the nipple"]}
Gold and Hogenhuis (1968) observed this combination in 2 sisters and their brother of Hindu extraction. Spinal fluid protein was moderately elevated. Severe distal sensory and motor loss was present. Eyes \- Cataract Neuro \- Neuropathy, hypertrophic \- Severe distal sensory and motor loss Lab \- Spinal fluid protein elevated Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	HYPERTROPHIC NEUROPATHY AND CATARACT	c1855885	24,831	omim	https://www.omim.org/entry/239900	2019-09-22T16:26:46	{"mesh": ["C565490"], "omim": ["239900"]}
A number sign (#) is used with this entry because of evidence that periventricular nodular heterotopia-7 (PVNH7) is caused by heterozygous mutation in the NEDD4L gene (606384) on chromosome 18q21. Description Periventricular nodular heterotopia-7 is a neurologic disorder characterized by abnormal neuronal migration during brain development resulting in delayed psychomotor development and intellectual disability; some patients may develop seizures. Other features include cleft palate and 2-3 toe syndactyly (summary by Broix et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see 300049. Clinical Features Broix et al. (2016) reported 6 unrelated children with delayed psychomotor development apparent since infancy, intellectual disability, and poor or absent speech. One patient had a similarly affected sib. Most patients had truncal hypotonia, and 1 patient was unable to sit or walk at age 6 years. Five patients had cleft palate, 1 had a bifid uvula, and all but 1 had 2-3 toe syndactyly. Four patients had seizures, including 2 with onset at 4 to 5 months of age. Brain imaging showed periventricular nodular heterotopia in all patients; 1 patient also had frontal cortical dysplasia, another had polymicrogyria, and 2 had a dysmorphic corpus callosum. Some patients had inconsistent dysmorphic facial features, such as micrognathia, deep-set eyes, and small nose. Additional variable features found in 1 or 2 patients included hearing impairment, optic atrophy, strabismus, myopia, cryptorchidism, and contractures. Molecular Genetics In 6 probands with PVNH7, Broix et al. (2016) identified de novo heterozygous missense mutations in the NEDD4L gene (606384.0001-606384.0004). The mutations were found by whole-exome sequencing or by direct screening of the NEDD4L gene in a cohort of patients with a similar phenotype. One of the patients had a similarly affected sib who also carried the mutation; their mother was found to be somatic mosaic for the mutation. Cellular transfection of the mutations showed that they resulted in unstable proteins that underwent proteasomal degradation, although ubiquitination activity was preserved for at least 1 mutation studied. In utero electroporation of 2 of the mutations and overexpression of wildtype NEDD4L into embryonic mouse brains resulted in an arrest of neuronal cells within the ventricular and periventricular zone, depletion of neurons in the cortical plate, and other abnormal neuronal distribution patterns. Further investigations showed differential disruption of certain signaling pathways: excess wildtype NEDD4L led to disruption of DAB1 (603448) and mTOR (601231) signaling pathways, while expression of the mutations was associated with deregulation of mTOR, AKT (164730), and SMAD2/3 (601366/603109) activities. Broix et al. (2016) hypothesized that the mutations, all of which occurred in the HECT domain, resulted in conformational changes and constitutive activation of the catalytic function of NEDD4L, which could trigger both autoubiquitination and degradation of the mutant proteins, as well as aberrant ubiquitination of other NEDD4L substrates. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Micrognathia \- Dysmorphic facial features, variable (in some patients) Ears \- Hearing impairment (in some patients) Eyes \- Strabismus \- Optic atrophy (in some patients) Mouth \- Cleft palate GENITOURINARY External Genitalia (Male) \- Cryptorchidism SKELETAL \- Contractures (in some patients) Feet \- Toe syndactyly, 2-3 MUSCLE, SOFT TISSUES \- Truncal hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Poor or absent speech \- Delayed or absent walking \- Seizures (in some patients) \- Periventricular nodular heterotopia \- Cortical dysplasia (in some patients) \- Thin corpus callosum (in some patients) MISCELLANEOUS \- Onset at birth \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the ubiquitin protein ligase, NEDD4-like gene (NEDD4L, 606384.0001 ) ▲ 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	PERIVENTRICULAR NODULAR HETEROTOPIA 7	c1868720	24,832	omim	https://www.omim.org/entry/617201	2019-09-22T15:46:37	{"mesh": ["D054091"], "omim": ["617201"], "orphanet": ["98892", "2149"]}
Smith-Magenis syndrome is a developmental disorder that affects many parts of the body. The major features of this condition include mild to moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems. Most people with Smith-Magenis syndrome have a broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw. The middle of the face and the bridge of the nose often appear flattened. The mouth tends to turn downward with a full, outward-curving upper lip. These facial differences can be subtle in early childhood, but they usually become more distinctive in later childhood and adulthood. Dental abnormalities are also common in affected individuals. Disrupted sleep patterns are characteristic of Smith-Magenis syndrome, typically beginning early in life. Affected people may be very sleepy during the day, but they have trouble falling asleep at night and awaken several times during the night and early morning. People with Smith-Magenis syndrome typically have affectionate, engaging personalities, but most also have behavioral problems. These include frequent temper tantrums and outbursts, aggression, anxiety, impulsiveness, and difficulty paying attention. Self-injury, including biting, hitting, head banging, and skin picking, is very common. Repetitive self-hugging is a behavioral trait that may be unique to Smith-Magenis syndrome. Some people with this condition also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"). Other signs and symptoms of Smith-Magenis syndrome include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia) and other vision problems. Although less common, heart and kidney defects also have been reported in people with Smith-Magenis syndrome. ## Frequency Smith-Magenis syndrome affects at least 1 in 25,000 individuals worldwide. However, researchers believe that many people with this condition are not diagnosed, so the true prevalence may be closer to 1 in 15,000 individuals. ## Causes In most people with Smith-Magenis syndrome, the condition results from the deletion of a small piece of chromosome 17 in each cell. This deletion occurs on the short (p) arm of the chromosome at a position designated p11.2. The deleted segment most often includes approximately 3.7 million DNA building blocks (base pairs), also written as 3.7 megabases (Mb). (An extra copy of this segment causes a related condition called Potocki-Lupski syndrome.) Occasionally the deletion is larger or smaller. All of the deletions affect one of the two copies of chromosome 17 in each cell. Although the deleted region contains multiple genes, researchers believe that the loss of one particular gene, RAI1, underlies many of the characteristic features of Smith-Magenis syndrome. All of the deletions known to cause the condition contain this gene. The RAI1 gene provides instructions for making a protein that helps regulate the activity (expression) of other genes. Although most of the genes regulated by the RAI1 protein have not been identified, this protein appears to control the expression of several genes involved in daily (circadian) rhythms, such as the sleep-wake cycle. Studies suggest that the deletion leads to a reduced amount of RAI1 protein in cells, which disrupts the expression of genes that influence circadian rhythms. These changes may account for the sleep disturbances that occur with Smith-Magenis syndrome. It is unclear how a loss of one copy of the RAI1 gene leads to the other physical, mental, and behavioral problems associated with this condition. A small percentage of people with Smith-Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion. Although these individuals have many of the major features of the condition, they are less likely than people with a deletion to have short stature, hearing loss, and heart or kidney abnormalities. It is likely that, in people with a deletion, the loss of other genes in the deleted region accounts for these additional signs and symptoms; the role of these genes is under study. ### Learn more about the gene and chromosome associated with Smith-Magenis syndrome * RAI1 * chromosome 17 ## Inheritance Pattern Smith-Magenis syndrome is usually not inherited. This condition typically results from a chromosomal deletion or an RAI1 gene mutation that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development. Most people with Smith-Magenis syndrome have no history of the condition in their family. In a small number of cases, people with Smith-Magenis syndrome have inherited the deletion or mutation from an unaffected mother who had the genetic change only in her egg cells. This phenomenon is called germline mosaicism. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Smith-Magenis syndrome	c1866927	24,833	medlineplus	https://medlineplus.gov/genetics/condition/smith-magenis-syndrome/	2021-01-27T08:25:48	{"gard": ["8197"], "omim": ["182290"], "synonyms": []}
Myoclonus-dystonia is a movement disorder that typically affects the neck, torso, and arms. Individuals with this condition experience quick, involuntary muscle jerks or twitches (myoclonus). About half of individuals with myoclonus-dystonia develop dystonia, which is involuntary tensing of various muscles that causes unusual positioning. In myoclonus-dystonia, dystonia often affects one or both hands, causing writer's cramp, or the neck, causing the head to turn (torticollis). The movement problems usually first appear in childhood or early adolescence with the development of myoclonus. In most cases, the movement problems remain stable throughout life. In some adults, myoclonus improves with alcohol consumption, which can lead to affected individuals self-medicating and developing alcohol use disorder. People with myoclonus-dystonia often develop psychological disorders such as depression, anxiety, panic attacks, and obsessive-compulsive disorder (OCD). ## Frequency The prevalence of myoclonus-dystonia in Europe is estimated to be 1 in 500,000 individuals. Its prevalence elsewhere in the world is unknown. ## Causes Mutations in the SGCE gene cause 30 to 50 percent of cases of myoclonus-dystonia. The SGCE gene provides instructions for making a protein called epsilon (ε)-sarcoglycan, whose function is unknown. The ε-sarcoglycan protein is located within the outer membrane of cells in many tissues, but it is most abundant in nerve cells (neurons) in the brain and in muscle cells. SGCE gene mutations that cause myoclonus-dystonia result in a shortage (deficiency) of functional ε-sarcoglycan protein. This lack of functional protein seems to affect the regions of the brain involved in coordinating and controlling movements (the cerebellum and basal ganglia, respectively). It is unknown why SGCE gene mutations seem to affect only these areas of the brain. Mutations in multiple other genes are associated with myoclonus-dystonia. Mutations in each of these genes cause a small percentage of cases. These genes are primarily active (expressed) in the brain and mutations likely lead to impairment of normal movement. Some people with myoclonus-dystonia do not have an identified mutation in any of the known associated genes. The cause of the condition in these individuals is unknown. ### Learn more about the genes associated with Myoclonus-dystonia * RELN * SGCE Additional Information from NCBI Gene: * KCTD17 ## Inheritance Pattern In cases in which the genetic cause is known, myoclonus-dystonia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In cases in which the cause of the condition is unknown, the inheritance is unclear. When caused by SGCE gene mutations, myoclonus-dystonia occurs only when the mutation is inherited from a person's father. People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or "turned on," in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting. Because only the paternal copy of the SGCE gene is active, myoclonus-dystonia occurs when mutations affect the paternal copy of the SGCE gene. Mutations in the maternal copy of the gene typically do not cause any health problems. Rarely, individuals who inherit an SGCE gene mutation from their mothers will develop features of myoclonus-dystonia. It is unclear why a gene that is supposed to be turned off is active in these rare cases. Other genes associated with myoclonus-dystonia are not imprinted, and mutations that cause the condition can be inherited from either parent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Myoclonus-dystonia	c1834570	24,834	medlineplus	https://medlineplus.gov/genetics/condition/myoclonus-dystonia/	2021-01-27T08:24:46	{"gard": ["7139"], "mesh": ["C536096"], "omim": ["159900"], "synonyms": []}
HR syndrome Other namesAcute interstitial pneumonia or Hamman–Rich syndrome Micrograph of diffuse alveolar damage, the histologic correlate of acute interstitial pneumonitis. H&E stain. SpecialtyPulmonology Acute interstitial pneumonitis is a rare, severe lung disease that usually affects otherwise healthy individuals. There is no known cause or cure. Acute interstitial pneumonitis is often categorized as both an interstitial lung disease and a form of acute respiratory distress syndrome (ARDS) but it is distinguished from the chronic forms of interstitial pneumonia such as idiopathic pulmonary fibrosis.[1] ## Contents * 1 Symptoms and signs * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 Epidemiology * 6 History * 7 References * 8 External links ## Symptoms and signs[edit] The most common symptoms of acute interstitial pneumonitis are highly productive cough with expectoration of thick mucus, fever, and difficulties breathing. These often occur over a period of one to two weeks before medical attention is sought. The presence of fluid means the person experiences a feeling similar to 'drowning'. Difficulties breathing can quickly progress to an inability to breathe without support (respiratory failure).[citation needed] Acute interstitial pneumonitis typically progresses rapidly, with hospitalization and mechanical ventilation often required only days to weeks after initial symptoms of cough, fever, and difficulties breathing develop.[citation needed] ## Diagnosis[edit] Rapid progression from initial symptoms to respiratory failure is a key feature. An x-ray that shows ARDS is necessary for diagnosis (fluid in the small air sacs (alveoli) in both lungs). In addition, a biopsy of the lung that shows organizing diffuse alveolar damage is required for diagnosis. This type of alveolar damage can be attributed to nonconcentrated and nonlocalized alveoli damage, marked alveolar septal edema with inflammatory cell infiltration, fibroblast proliferation, occasional hyaline membranes, and thickening of the alveolar walls. The septa are lined with atypical, hyperplastic type II pneumocytes, thus leading to the collapse of airspaces. Other diagnostic tests are useful in excluding other similar conditions, but history, x-ray, and biopsy are essential. These other tests may include basic blood work, blood cultures, and bronchoalveolar lavage.[citation needed] The clinical picture is similar to ARDS, but AIP differs from ARDS in that the cause for AIP is not known. * Acute interstitial pneumonia showing a marked reduction in lung capacity * * * ## Treatment[edit] Treatment is primarily supportive. Management in an intensive care unit is required and the need for mechanical ventilation is common. Therapy with corticosteroids is generally attempted, though their usefulness has not been established. The only treatment that has met with success to date is a lung transplant.[citation needed] ## Prognosis[edit] Sixty percent of people with acute interstitial pneumonitis will die in the first six months of illness.[2] The median survival is 1½ months.However, most people who have one episode do not have a second. People who survive often recover lung function completely.[citation needed] ## Epidemiology[edit] Acute interstitial pneumonitis occurs most frequently among people older than forty years old. It affects men and women equally. There are no known risk factors; in particular, smoking is not associated with increased risk.[citation needed] ## History[edit] Acute interstitial pneumonitis was first described in 1935 by Louis Hamman and Arnold Rich, and given the name Hamman–Rich syndrome.[3] ## References[edit] 1. ^ Hamman L.; Rich A.R. (1944). "Acute diffuse interstitial fibrosis of the lungs". Bull. Johns Hopkins Hosp. 74: 177–212. 2. ^ Bouros, D; Nicholson AC; Polychronopoulos V; du Bois RM (2000). "Acute interstitial pneumonia". Eur. Respir. J. 15 (2): 412–8. doi:10.1034/j.1399-3003.2000.15b31.x. PMID 10706513. 3. ^ Hamman, L; Rich AR (1935). "Fulminating diffuse interstitial fibrosis of the lungs". Transactions of the American Clinical and Climatological Association. European Respiratory Society. 51: 154–163. PMID 21407504. ## External links[edit] Classification D * ICD-10: J84.1 * ICD-10-CM: J84.114 * ICD-9-CM: 516.3 * OMIM: 178500 * MeSH: D011658 * DiseasesDB: 4815 * synd/3010 at Who Named It? * 00181 at CHORUS * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Acute interstitial pneumonitis	c1279945	24,835	wikipedia	https://en.wikipedia.org/wiki/Acute_interstitial_pneumonitis	2021-01-18T18:57:18	{"gard": ["12835"], "umls": ["C1279945"], "orphanet": ["79126"], "wikidata": ["Q424258"]}
Emanuel syndrome is a constitutional genomic disorder due to the presence of a supernumerary derivative 22 chromosome and characterized by severe intellectual disability, characteristic facial dysmorphism (micrognathia, hooded eyelids, upslanting downslanting parebral fissures, deep set eyes, low hanging columnella and long philtrum), congenital heart defects and kidney abnormalities. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Emanuel syndrome	c1836929	24,836	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96170	2021-01-23T18:51:21	{"gard": ["9835"], "mesh": ["C535733"], "omim": ["609029"], "umls": ["C1836929"], "icd-10": ["Q92.6"], "synonyms": ["Der(22)t(11;22) syndrome", "Supernumerary der(22) syndrome"]}
A number sign (#) is used with this entry because autosomal recessive megalencephalic leukoencephalopathy with subcortical cysts-2A (MLC2A) is caused by homozygous or compound heterozygous mutation in the HEPACAM gene (611642) on chromosome 11q24. For a discussion of genetic heterogeneity of megalencephalic leukoencephalopathy with subcortical cysts, see MLC1 (604004). Description Megalencephalic leukoencephalopathy with subcortical cysts-2A is an autosomal recessive neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. Brain MRI shows typical white matter abnormalities, including swelling of the cerebral white matter and subcortical cysts, in all stages of the disease (summary by Lopez-Hernandez et al., 2011). Heterozygous mutations in the HEPACAM gene can cause a similar, but less severe disorder that shows improvement of MRI changes with age (MLC2B; 613926). Clinical Features Lopez-Hernandez et al. (2011) reported 10 patients from 8 families with MLC2A. All had onset of macrocephaly in the first year of life, and most showed mildly delayed motor development. Neurologic deterioration occurred between age 1 and 6 years, with slowly progressive ataxia, spasticity, dysarthria, and cognitive decline. Eight patients developed seizures, and 4 became wheelchair-bound in late childhood. Brain MRI showed diffuse cerebral white matter signal abnormalities and white matter swelling. There was involvement of the internal and external capsules and corpus callosum. All had subcortical cysts, primarily in the frontal and temporal regions. Many had cavum septi pellucidi and cavum vergae, and most had brainstem and cerebellar involvement (van der Knaap et al., 2010). At follow-up, all patients had the same brain MRI anomalies with mild progression in some, and all had mental retardation except 1 patient, who had normal intelligence at age 18 years. Inheritance The transmission pattern of megalencephalic leukoencephalopathy with subcortical cysts-2A in the families reported by Lopez-Hernandez et al. (2011) was consistent with autosomal recessive inheritance. Molecular Genetics In 10 patients from 8 families with megalencephalic leukoencephalopathy with subcortical cysts-2A, Lopez-Hernandez et al. (2011) identified homozygous or compound heterozygous mutations in the HEPACAM gene (see, e.g., 611642.0001-611642.0005). INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly NEUROLOGIC Central Nervous System \- Megalencephaly \- Delayed motor development \- Neurologic deterioration \- Ataxia \- Spasticity \- Hypertonia \- Seizures \- Cognitive decline \- Mental retardation \- Dysarthria \- Diffuse white matter abnormalities on brain MRI \- Diffuse swelling of cerebral white matter \- Cavum septi pellucidi \- Cavum Vergae \- Subcortical cysts in frontal and temporal lobes \- Subcortical cysts may occur elsewhere \- Cerebral atrophy \- Cerebellar atrophy \- Enlarged ventricles MISCELLANEOUS \- Brainstem, cerebellum, internal and external capsule, inner rim of the corpus callosum may show disease involvement on MRI \- Onset of macrocephaly in the first year of life \- Slowly progressive \- Most patients become wheelchair-bound in later childhood MOLECULAR BASIS \- Caused by mutation in the hepatocyte cell adhesion molecule gene (HEPACAM, 611642.0001 ) ▲ 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	MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 2A	c1858854	24,837	omim	https://www.omim.org/entry/613925	2019-09-22T15:57:02	{"doid": ["0080318"], "mesh": ["C536141"], "omim": ["613925"], "orphanet": ["2478"], "genereviews": ["NBK1535"]}
A hereditary disease that develops in adulthood and is characterized by chronic liver disorders (cirrhosis), respiratory disorders (emphysema), and rarely panniculitis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Alpha-1-antitrypsin deficiency	c0221757	24,838	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=60	2021-01-23T17:51:24	{"gard": ["5784"], "mesh": ["D019896", "C531610"], "omim": ["613490"], "umls": ["C0221757", "C3501835"], "icd-10": ["E88.0"]}
Erythropoietic protoporphyria (EPP) is a type of porphyria. Porphyrias are caused by an abnormality in the heme production process. Heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. Erythropoietic protoporphyria is caused by pathogenic variants (mutations) in the FECH gene which lead to an impaired activity of ferrocheletase (FECH), an important enzyme in heme production. This results in the build-up of protoporphyrin in the bone marrow, red blood cells, blood plasma, skin, and eventually liver. Build up of protoporphyrin can cause extreme sensitivity to sunlight, liver damage, abdominal pain, gallstones, and enlargement of the spleen. Inheritance is autosomal recessive. Treatment includes avoiding sun and UV light exposure, vitamin D supplements, creams for tanning, and using protective clothing. A medication known as Afamelanotide (Scenesse®), a synthetic α-melanocyte stimulating hormone (a melanocyte is a skin cell that produces melanin, a skin-darkening pigment) analog was approved for treatment of EPP by the European Medicines Agency in 2014 and is awaiting approval in United States by the FDA. This medication increases pain-free sun exposure and has improved quality of life in those with EPP. Liver complications may be treated with cholestyramine and other porphyrin absorbents , plasmapheresis, a procedure where the liquid part of the blood, or plasma, is separated from the blood cells, and intravenous heme are sometimes beneficial. Liver transplantation may be required. Another type of porphyria, known as X-linked protoporphyria, is caused by a variation in the ALAS2 gene and have similar symptoms to erythropoietic protoporphyria when males are affected by EPP. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Autosomal erythropoietic protoporphyria	c0162568	24,839	gard	https://rarediseases.info.nih.gov/diseases/4527/autosomal-erythropoietic-protoporphyria	2021-01-18T18:01:56	{"mesh": ["D046351"], "omim": ["177000"], "orphanet": ["79278"], "synonyms": ["Erythrohepatic protoporphyria", "EPP", "Heme synthetase deficiency", "Ferrochelatase deficiency"]}
Congenital myopathy with myasthenic-like onset is a rare, genetic, non-dystrophic myopathy characterized by fatigable muscle weakness associated with congenital myopathy. Patients present with axial hypotonia, myopathic facies with fatigable ptosis, feeding difficulties, delayed gross motor development and proximal limb weakness with a RYR1-related typical pattern of muscle involvement (i.e. severe involvement of the soleus muscle and sparring of the rectus femoris, sartorius, gracilis and semitendinous muscles). Scoliosis and frequent respiratory tract infections are additional observed features. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Congenital myopathy with myasthenic-like onset	c4706390	24,840	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424107	2021-01-23T17:02:39	{"icd-10": ["G71.2"]}
Microalbuminuria SpecialtyNephrology Microalbuminuria is a term to describe a moderate increase in the level of urine albumin. It occurs when the kidney leaks small amounts of albumin into the urine, in other words, when an abnormally high permeability for albumin in the glomerulus of the kidney occurs. Normally, the kidneys filter albumin, so if albumin is found in the urine, then it is a marker of kidney disease. The term microalbuminuria is now discouraged by Kidney Disease Improving Global Outcomes[1] and has been replaced by moderately increased albuminuria. ## Contents * 1 Causes * 1.1 Associations * 2 Diagnosis & Treatment * 3 References * 4 Footnotes * 5 External links ## Causes[edit] Higher dietary intake of animal protein, animal fat, and cholesterol may increase risk for microalbuminuria,[2] and generally, diets higher in fruits, vegetables, and whole grains but lower in meat and sweets may be protective against kidney function decline.[3][4][5] ### Associations[edit] * Marker of vascular endothelial dysfunction * An important prognostic marker for kidney disease * in diabetes mellitus * in hypertension * in post-streptococcal glomerulonephritis * Increasing microalbuminuria during the first 48 hours after admission to an intensive care unit predicts elevated risk for acute respiratory failure, multiple organ failure, and overall mortality * A risk factor for venous thromboembolism[6] Microalbuminuria is an important adverse predictor of glycemic outcomes in prediabetes. Prediabetes individuals with increased microalbuminuria even in the so-called normal range is associated with increased progression to diabetes and decreased reversal to normoglycemia. Hence, prediabetes individuals with microalbuminuria warrant more aggressive intervention to prevent diabetes in them.[7] ## Diagnosis & Treatment[edit] The level of albumin protein produced by microalbuminuria can be detected by special albumin-specific urine dipsticks, which have a lower detection threshold than standard urine dipsticks. A microalbumin urine test determines the presence of the albumin in urine. In a properly functioning body, albumin is not normally present in urine because it is retained in the bloodstream by the kidneys. Microalbuminuria can be diagnosed from a 24-hour urine collection (between 30–300 mg/24 hours) or, more commonly, from elevated concentration in a spot sample (20 to 200 mg/l). Both must be measured on at least two of three measurements over a two- to three-month period.[8] An albumin level above the upper limit values is called "macroalbuminuria", or sometimes just albuminuria. Sometimes, the upper limit value is given as one less (such as 300 being given as 299) to mark that the higher value (here 300) is defined as macroalbuminuria.[9] Taurine in combination with N-acetylcysteine (Nefrosave Tablet) was useful in attenuating UACR in microalbuminuric type 2 diabetic patient as per Indian Journal of Nephrology 2008 To compensate for variations in urine concentration in spot-check samples, comparing the amount of albumin in the sample against its concentration of creatinine is helpful. This is termed the albumin/creatinine ratio (ACR)[10] and microalbuminuria is defined as ACR ≥3.5 mg/mmol (female) or ≥2.5 mg/mmol (male),[11] or with both substances measured by mass, as an ACR between 30 and 300 µg albumin/mg creatinine.[12] For the diagnosis of microalbuminuria, care must be taken when collecting sample for the urine ACR. An early-morning sample is preferred. The patient should refrain from heavy exercises 24 hours before the test. A repeat test should be done 3 to 6 months after the first positive test for microalbuminuria. Lastly, the test is inaccurate in a person with too much or too little muscle mass. This is due to the variation in creatinine level which is produced by the muscle.[13] Definitions of microalbuminuria Individual Lower limit Upper limit Unit 24h urine collection 30[9] 300[9] mg/24h (milligram albumin per 24 hours) Short-time urine collection 20[9] 200[9] µg/min (microgram albumin per minute) Spot urine albumin sample 30[14] 300[14] mg/L (milligram albumin per liter of urine) Spot urine albumin/creatinine ratio Women 3.5[15] 25[15] or 35[15] mg/mmol (milligram albumin per millimole creatinine) 30[15] 400[15] μg/mg (microgram albumin per milligram creatinine) Men 2.5[15] or 3.5[15] 25[15] or 35[15] mg/mmol 30[15] 300[15] μg/mg ## References[edit] * Abid O, Sun Q, Sugimoto K, Mercan D, Vincent JL (2001). "Predictive value of microalbuminuria in medical ICU patients: results of a pilot study". Chest. 120 (6): 1984–8. doi:10.1378/chest.120.6.1984. PMID 11742932. * Andersen S, Blouch K, Bialek J, Deckert M, Parving HH, Myers BD (2000). "Glomerular permselectivity in early stages of overt diabetic nephropathy". Kidney Int. 58 (5): 2129–37. doi:10.1111/j.1523-1755.2000.00386.x. PMID 11044234. * Heart Outcomes Prevention Evaluation Study Investigators (2000). "Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy". Lancet. 355 (9200): 253–9. doi:10.1016/S0140-6736(99)12323-7. PMID 10675071. * Lemley KV, Abdullah I, Myers BD, et al. (2000). "Evolution of incipient nephropathy in type 2 diabetes mellitus". Kidney Int. 58 (3): 1228–37. doi:10.1046/j.1523-1755.2000.00223.x. PMID 10972685. * Lièvre M, Marre M, Chatellier G, et al. (2000). "The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group". Controlled Clinical Trials. 21 (4): 383–96. doi:10.1016/S0197-2456(00)00060-X. PMID 10913814. * Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P (2001). "The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes". N. Engl. J. Med. 345 (12): 870–8. doi:10.1056/NEJMoa011489. PMID 11565519. * Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150. ## Footnotes[edit] 1. ^ "KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease" (PDF). 2. ^ Lin, Julie; Hu, Frank B.; Curhan, Gary C. (2010-05-01). "Associations of diet with albuminuria and kidney function decline". Clinical Journal of the American Society of Nephrology. 5 (5): 836–843. doi:10.2215/CJN.08001109. ISSN 1555-905X. PMC 2863979. PMID 20299364. 3. ^ Lin, Julie; Fung, Teresa T.; Hu, Frank B.; Curhan, Gary C. (2011-02-01). "Association of dietary patterns with albuminuria and kidney function decline in older white women: a subgroup analysis from the Nurses' Health Study". American Journal of Kidney Diseases. 57 (2): 245–254. doi:10.1053/j.ajkd.2010.09.027. ISSN 1523-6838. PMC 3026604. PMID 21251540. 4. ^ Wiseman, M. J.; Hunt, R.; Goodwin, A.; Gross, J. L.; Keen, H.; Viberti, G. C. (1987-01-01). "Dietary composition and renal function in healthy subjects". Nephron. 46 (1): 37–42. doi:10.1159/000184293. ISSN 1660-8151. PMID 3600911. 5. ^ Barsotti, G.; Morelli, E.; Cupisti, A.; Meola, M.; Dani, L.; Giovannetti, S. (1996-01-01). "A low-nitrogen low-phosphorus Vegan diet for patients with chronic renal failure". Nephron. 74 (2): 390–394. doi:10.1159/000189341. hdl:11382/374104. ISSN 1660-8151. PMID 8893161. 6. ^ Mahmoodi, BK; Gansevoort, RT; Veeger, NJ; Matthews, AG; Navis, G; Hillege, HL; Van Der Meer, J; Prevention of Renal Vascular End-stage Disease (PREVEND) Study Group (2009). "Microalbuminuria and risk of venous thromboembolism". JAMA: The Journal of the American Medical Association. 301 (17): 1790–7. doi:10.1001/jama.2009.565. PMID 19417196. 7. ^ Dutta D, Choudhuri S, Mondal SA, Mukherjee S, Chowdhury S (2014). "Urinary albumin : creatinine ratio predicts prediabetes progression to diabetes and reversal to normoglycemia: role of associated insulin resistance, inflammatory cytokines and low vitamin D". Journal of Diabetes. 6 (4): 316–22. doi:10.1111/1753-0407.12112. PMID 24251376. 8. ^ "Person—microalbumin level (measured), total micrograms per minute N[NNN].N". Retrieved 2007-07-05. 9. ^ a b c d e Mary Lee (2009-02-26). Basic Skills in Interpreting Laboratory Data. ASHP. pp. 291–. ISBN 978-1-58528-274-6. 10. ^ Bakker AJ (February 1999). "Detection of microalbuminuria. Receiver operating characteristic curve analysis favors albumin-to-creatinine ratio over albumin concentration". Diabetes Care. 22 (2): 307–13. doi:10.2337/diacare.22.2.307. PMID 10333950. 11. ^ "Proteinuria". UK Renal Association. December 15, 2005. Archived from the original on August 14, 2007. 12. ^ clinlabnavigator.com > Test Interpretations Last Updated on Saturday, 19 June 2010 13. ^ Microalbuminura in diabetes 14. ^ a b Person—microalbumin level (measured) at Australian Institute of Health and Welfare. 01/03/2005 15. ^ a b c d e f g h i j k [1] Justesen, T.; Petersen, J.; Ekbom, P.; Damm, P.; Mathiesen, E. (2006). "Albumin-to-creatinine ratio in random urine samples might replace 24-h urine collections in screening for micro- and macroalbuminuria in pregnant woman with type 1 diabetes". Diabetes Care. 29 (4): 924–925. doi:10.2337/diacare.29.04.06.dc06-1555. PMID 16567839. ## External links[edit] Classification D * ICD-9-CM: 791.0 External resources * MedlinePlus: 003591 * Patient UK: Microalbuminuria * Microalbumin and Urine Albumin/Creatinine Ratio – Lab Tests Online * v * t * e Components and results of urine tests Components * Albumin * Myoglobin * hCG * Leukocyte esterase * Urine pregnancy test * Ketone bodies * Glucose * Urobilinogen * Bilirubin * Creatinine * RBC * WBC * Urinary casts Chemical properties * Urine specific gravity * Isosthenuria * Urine osmolality * Hypersthenuria * Urine pH * Urine anion gap Abnormal findings Red blood cells * Hematuria (Microscopic hematuria) White blood cells * Eosinophiluria Proteinuria * Albuminuria/Microalbuminuria * Albumin/creatinine ratio * Urine protein/creatinine ratio * Myoglobinuria * Hemoglobinuria * Bence Jones protein Small molecules * Glycosuria * Ketonuria * Bilirubinuria * Hyperuricosuria * Aminoaciduria Other * Bacteriuria * Chyluria * Crystalluria [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Microalbuminuria	c0730345	24,841	wikipedia	https://en.wikipedia.org/wiki/Microalbuminuria	2021-01-18T18:33:46	{"icd-9": ["791.0"], "wikidata": ["Q1676817"]}
Febrile neutropenia SpecialtyHematology Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia (bacteria in the bloodstream) is present in approximately 20% of all patients with this condition.[1] ## Contents * 1 Causes * 2 Diagnosis * 2.1 MASCC and CISNE risk indexes * 3 Treatment * 4 See also * 5 References * 6 External links ## Causes[edit] Febrile neutropenia can develop in any form of neutropenia, but is most generally recognized as a complication of chemotherapy when it is myelosuppressive (suppresses the bone marrow from producing blood cells).[citation needed] ## Diagnosis[edit] ### MASCC and CISNE risk indexes[edit] The Multinational Association for Supportive Care in Cancer (MASCC) risk index can be used to identify low-risk patients (score ≥21 points) for serious complications of febrile neutropenia (including death, intensive care unit admission, confusion, cardiac complications, respiratory failure, kidney failure, low blood pressure, bleeding, and other serious medical complications).[2] The score was developed to select patients for therapeutic strategies that could potentially be more convenient or cost-effective. A prospective trial demonstrated that a modified MASCC score can identify patients with febrile neutropenia at low risk of complications, as well.[3] In contrast, the Clinical Index of Stable Febrile Neutropenia (CISNE) score is specific of patients with solid tumors and seemingly stable episodes. CISNE is able to discriminate groups of patients who are at low, intermediate, and high risk of complications in this population. With the CISNE, the complication rate was determined to be 1.1% for low-risk patients, 6.2% for intermediate-risk patients, and 36.0% for high-risk patients.[4] The prime purpose of this model was to avoid complications from an early hospital release. On the contrary, CISNE should not be used so much to select low-risk patients for outpatient treatment.[5] ## Treatment[edit] Generally, patients with febrile neutropenia are treated with empirical antibiotics until the neutrophil count has recovered (absolute neutrophil counts greater than 500/mm3) and the fever has abated; if the neutrophil count does not improve, treatment may need to continue for two weeks or occasionally more. In cases of recurrent or persistent fever, an antifungal agent should be added.[citation needed] Guidelines issued in 2002 by the Infectious Diseases Society of America recommend the use of particular combinations of antibiotics in specific settings; mild low-risk cases may be treated with a combination of oral amoxicillin-clavulanic acid and ciprofloxacin, while more severe cases require cephalosporins with activity against Pseudomonas aeruginosa (e.g. cefepime), or carbapenems (imipenem or meropenem).[1] A subsequent meta-analysis published in 2006 found cefepime to be associated with more negative outcomes, and carbapenems (while causing a higher rate of pseudomembranous colitis) were the most straightforward in use.[6] In 2010, updated guidelines were issued by the Infectious Diseases Society of America, recommending use of cefepime, carbapenems (meropenem and imipenem/cilastatin), or piperacillin/tazobactam for high-risk patients and amoxicillin-clavulanic acid and ciprofloxacin for low-risk patients. Patients who do not strictly fulfill the criteria of low-risk patients should be admitted to the hospital and treated as high-risk patients.[citation needed] Research to compare antibiotic treatments currently recommended in consensus guidelines [7]identified 44 studies comparing different antibiotics. Significantly higher mortality was reported for Cefepime compared to all other antibiotics combined. Piperacillin‐tazobactam resulted in lower mortality than other antibiotics. Piperacillin‐tazobactam might be the preferred antibiotic for the treatment of cancer patients with fever and neutropenia, while cefepime should not be used. Empiric treatment should be started within 60 minutes of being admitted. Periodic monitoring should be done to see if the empiric treatment is working, or if a more target therapy should be initiated.[8][9] In people with cancer who have febrile neutropoenia (excluding patients with acute leukaemia), oral treatment is an acceptable alternative to intravenous antibiotic treatment if they are haemodynamically stable, without organ failure, without pneumonia and with no infection of a central line or severe soft-tissue infection.[10] Furthermore, outpatient treatment for low‐risk febrile neutropaenia in people with cancer probably makes little or no difference to treatment failure and mortality compared with the standard hospital (inpatient) treatment and may reduce time that patients need to be treated in hospital.[11] ## See also[edit] * Neutropenia * Leukocytopenia * Myelosuppression * Chemotherapy ## References[edit] 1. ^ a b Hughes WT, Armstrong D, Bodey GP, et al. (March 2002). "2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer". Clin. Infect. Dis. 34 (6): 730–51. doi:10.1086/339215. ISSN 1058-4838. PMID 11850858. 2. ^ Klastersky J, Paesmans M, Rubenstein EB, et al. (16 August 2000). "The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients". J Clin Oncol. 18 (16): 3038–51. doi:10.1200/JCO.2000.18.16.3038. ISSN 0732-183X. PMID 10944139. 3. ^ de Souza Viana L, Serufo JC, da Costa Rocha MO, Costa RN, Duarte RC (July 2008). "Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients". Supportive Care in Cancer. 16 (7): 841–6. doi:10.1007/s00520-007-0347-3. ISSN 0941-4355. PMID 17960431. S2CID 22805397. 4. ^ Carmona-Bayonas, Alberto, et al. "Prediction of Serious Complications in Patients With Seemingly Stable Febrile Neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a Prospective Cohort of Patients From the FINITE Study." Journal of Clinical Oncology (2015): JCO-2014. 5. ^ Fonseca, Paula Jiménez, et al. "A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia." British Journal of Cancer (2016): 1191-1198. 6. ^ Paul M, Yahav D, Fraser A, Leibovici L (February 2006). "Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials". J. Antimicrob. Chemother. 57 (2): 176–89. doi:10.1093/jac/dki448. ISSN 0305-7453. PMID 16344285. 7. ^ Paul, Mical; Yahav, Dafna; Bivas, Assaf; Fraser, Abigail; Leibovici, Leonard (2010-11-10). "Anti-pseudomonal beta-lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta-lactams". Cochrane Database of Systematic Reviews (11): CD005197. doi:10.1002/14651858.cd005197.pub3. ISSN 1465-1858. PMID 21069685. 8. ^ Flowers, Christopher R.; Seidenfeld, Jerome; Bow, Eric J.; Karten, Clare; Gleason, Charise; Hawley, Douglas K.; Kuderer, Nicole M.; Langston, Amelia A.; Marr, Kieren A. (2013-02-20). "Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline". Journal of Clinical Oncology. 31 (6): 794–810. doi:10.1200/JCO.2012.45.8661. ISSN 1527-7755. PMID 23319691. 9. ^ Dellinger, R. Phillip; Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian (January 2008). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008". Critical Care Medicine. 36 (1): 296–327. doi:10.1097/01.CCM.0000298158.12101.41. ISSN 1530-0293. PMC 4969965. PMID 18158437. 10. ^ Vidal, Liat; Ben dor, Itsik; Paul, Mical; Eliakim-Raz, Noa; Pokroy, Ellisheva; Soares-Weiser, Karla; Leibovici, Leonard (2013-10-09). "Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients". Cochrane Database of Systematic Reviews (10): CD003992. doi:10.1002/14651858.cd003992.pub3. ISSN 1465-1858. PMC 6457615. PMID 24105485. 11. ^ Rivas-Ruiz, Rodolfo; Villasis-Keever, Miguel; Miranda-Novales, Guadalupe; Castelán-Martínez, Osvaldo D; Rivas-Contreras, Silvia (2019-03-19). "Outpatient treatment for people with cancer who develop a low-risk febrile neutropaenic event". Cochrane Database of Systematic Reviews. 3: CD009031. doi:10.1002/14651858.cd009031.pub2. ISSN 1465-1858. PMC 6423292. PMID 30887505. ## External links[edit] * Febrile neutropenia entry in the public domain NCI 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Febrile neutropenia	c0746883	24,842	wikipedia	https://en.wikipedia.org/wiki/Febrile_neutropenia	2021-01-18T18:41:07	{"mesh": ["D064147"], "icd-9": ["288.0288.0"], "icd-10": ["D7070."], "wikidata": ["Q3775974"]}
Ostium primum atrial septal defect Other namesEndocardial cushion defect Schemating drawing showing the location of different types of ASD, the view is into an opened right atrium. HV: right ventricle; VCS: superior caval vein; VCI: inferior caval vein; 1: upper sinus venosus defect; 2: lower sinus venosus defect; 3: secundum defect; 4: defect involving coronary sinus; 5; primum defect. SpecialtyMedical genetics The ostium primum atrial septal defect is a defect in the atrial septum at the level of the tricuspid and mitral valves. This is sometimes known as an endocardial cushion defect because it often involves the endocardial cushion, which is the portion of the heart where the atrial septum meets the ventricular septum and the mitral valve meets the tricuspid valve. Endocardial cushion defects are associated with abnormalities of the atrioventricular valves (the mitral valve and the tricuspid valve). These include the cleft mitral valve, and the single atrioventricular valve (a single large, deformed valve that flows into both the right ventricle and the left ventricle). Endocardial cushion defects are the most common congenital heart defect that is associated with Down syndrome. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Classification * 3 Treatment * 4 References * 5 External links ## Signs and symptoms[edit] On ECG a left axis deviation is generally found in ostium primum ASD, but an RSR pattern (M pattern) in V1 is characteristic. Fixed splitting of the second heart sound (S2) occurs because of equal filling of the left and right atria during all phases of the respiratory cycle. ECG of a patient with Ostium primum ASD Patients with atrial Septal Defects may have atrial fibrillation, atrial tachycardia, or atrial flutter, but these abnormal heart rhythms are not usually seen until the affected individual grows older. Features also seen on the ECG include right atrial enlargement and varying degrees of atrioventricular block. When a person is suspected of having an ASD based on the findings of an incomplete right bundle branch block with a rSr' or rSR', the frontal plane QRS should be examined. The frontal plane QRS is the most helpful clue to distinguish between an ostium secundum ASD and an ostium primum ASD. In primum defects left axis deviation is seen in most patients with an axis of > -30 degrees and very few patients have right axis deviation. In contrast ostium secundum defects have an axis between 0 degrees and 180 degrees with most cases to the right of 100 degrees. In the ECG above, you can see an example of the rSR' pattern in V1 with a R' greater than S with T wave inversion which is commonly seen in volume overload right ventricular hypertrophy. ## Diagnosis[edit] ### Classification[edit] A defect in the ostium primum is occasionally classified as an atrial septal defect,[1] but it is more commonly classified as an atrioventricular septal defect.[2][3] ## Treatment[edit] Hemodynamically significant ASDs (flow ratio 1.5:1) are large enough to be closed surgically. The long term prognosis is excellent. Pulmonary hypertension with shunt reversal is a contraindication for surgery, however the pulmonary hypertension can frequently be treated with medicines. The hole can then be closed safely with a good long term prognosis. ## References[edit] Notes 1. ^ "Atrial Septal Defect Types - Mayo Clinic". Retrieved 2007-10-14. 2. ^ Fix, James D.; Dudek, Ronald W. (1998). Embryology. Baltimore: Williams & Wilkins. pp. 52. ISBN 978-0-683-30272-1. 3. ^ Q21.2 Sources * Pryor R, Woodwork MB, Blount SG: Electrocardiographic Changes in Atrial Septal Defects:Ostium Secundum versus Ostium Primum defect. Am Heart J 58:689, 1959. ## External links[edit] Classification D * ICD-10: Q21.2 * ICD-9-CM: 745.6 * DiseasesDB: 1090 External resources * eMedicine: ped/1685 This article incorporates text available under the CC BY-SA 3.0 license. * v * t * e Congenital heart defects Heart septal defect Aortopulmonary septal defect * Double outlet right ventricle * Taussig–Bing syndrome * Transposition of the great vessels * dextro * levo * Persistent truncus arteriosus * Aortopulmonary window Atrial septal defect * Sinus venosus atrial septal defect * Lutembacher's syndrome Ventricular septal defect * Tetralogy of Fallot Atrioventricular septal defect * Ostium primum Consequences * Cardiac shunt * Cyanotic heart disease * Eisenmenger syndrome Valvular heart disease Right * pulmonary valves * stenosis * insufficiency * absence * tricuspid valves * stenosis * atresia * Ebstein's anomaly Left * aortic valves * stenosis * insufficiency * bicuspid * mitral valves * stenosis * regurgitation Other * Underdeveloped heart chambers * right * left * Uhl anomaly * Dextrocardia * Levocardia * Cor triatriatum * Crisscross heart * Brugada syndrome * Coronary artery anomaly * Anomalous aortic origin of a coronary artery * Ventricular inversion [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Ostium primum atrial septal defect	c0031192	24,843	wikipedia	https://en.wikipedia.org/wiki/Ostium_primum_atrial_septal_defect	2021-01-18T18:39:34	{"mesh": ["D006344"], "umls": ["C0031192"], "icd-9": ["745.6"], "icd-10": ["Q21.2"], "wikidata": ["Q7107685"]}
Tandan et al. (1990) described an apparently 'new' disorder combining neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and mild dementia. The propositus, a 72-year-old man, had pes cavus, peripheral neuropathy, ptosis, parkinsonism, hyperreflexia, orthostatic hypotension, central hypoventilation, and mild dementia. Several family members in 3 generations, with at least 1 instance of male-to-male transmission, had pes cavus, neuropathy, ptosis, parkinsonism, and dementia, although not all of the features were consistently present. Survival past the seventh decade was common. Autopsy in 2 affected members showed that the neuropathy was axonal; mild to moderate loss of anterior horn cells in the spinal cord and pigmentary loss with gliosis in the substantia nigra were other findings. Limbs \- Pes cavus \- Trophic limb changes Neuro \- Ptosis \- Parkinsonism \- Dementia \- Hyperreflexia \- Orthostatic hypotension \- Central hypoventilation \- Weak or absent deep tendon reflexes \- Sensory defect \- Chronic sensorineural polyneuropathy Lab \- Mild to moderate loss of anterior horn cells in the spinal cord and substantia nigral pigmentary loss with gliosis \- Normal or slightly reduced nerve conduction velocity \- Axonal loss with little evidence of demyelination or hypertrophic changes in nerve biopsies Inheritance \- Autosomal dominant, also other autosomal dominant forms, as well as autosomal recessive, and X-linked forms Skin \- Hyperhidrosis \- Penetrating foot ulcers Cardiac \- Heart block Muscle \- Peroneal muscle atrophy and weakness \- Distal arm and leg muscle atrophy and weakness Misc \- More severe in homozygotes Oncology \- Enhanced neurotoxicity of vincristine GI \- Chronic diarrhea \- Nausea \- Vomiting ▲ 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	CHARCOT-MARIE-TOOTH DISEASE WITH PTOSIS AND PARKINSONISM	c1861668	24,844	omim	https://www.omim.org/entry/118301	2019-09-22T16:43:23	{"mesh": ["C538079"], "omim": ["118301"]}
## Summary ### Clinical characteristics. PACS1 neurodevelopmental disorder (PACS1-NDD) is characterized by mild-to-severe neurodevelopmental delays. Language skills are more severely affected than motor skills. Hypotonia is reported in about a third of individuals and is noted to improve over time. Approximately 60% of individuals are ambulatory. Feeding difficulty is common, with 25% requiring gastrostomy tube to maintain appropriate caloric intake. Other common features include constipation, seizures, behavioral issues, congenital heart anomalies, short stature, and microcephaly. Common facial features include hypertelorism, downslanting palpebral fissures, bulbous nasal tip, low-set and simple ears, smooth philtrum, wide mouth with downturned corners, thin upper vermilion, and wide-spaced teeth. To date approximately 35 individuals with PACS1-NDD have been reported. ### Diagnosis/testing. The diagnosis of PACS1-NDD is established in a proband with a heterozygous pathogenic variant in PACS1 identified by molecular genetic testing. ### Management. Treatment: Standard treatment for feeding issues, constipation, seizures, behavioral issues, cardiac anomalies, vision issues, and renal anomalies. Surveillance: Monitor for growth and nutrition issues, constipation, seizures, and behavioral issues. Monitor closure of septal defects as per cardiologist; monitor renal function if renal malformation is present as per nephrologist. Agents/circumstances to avoid: Known seizure triggers. ### Genetic counseling. PACS1-NDD is an autosomal dominant disorder. All individuals reported to date have the disorder as the result of a de novo pathogenic variant. If the PACS1 pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings PACS1-NDD should be considered in individuals with the following clinical findings: * Developmental delay and/or intellectual disability that are typically moderate, although range includes mild to severe delays * Hypotonia * Feeding difficulties * Epilepsy (partial and tonic seizures reported, often with early or infantile onset; well-controlled by medication) * Behavioral features (e.g., autism spectrum disorder, temper tantrums, aggression); overall friendly disposition in individuals of all ages * Characteristic facial features (e.g., hypertelorism, downslanting palpebral fissures, bulbous nasal tip, low-set and simple ears, smooth philtrum, wide mouth with downturned corners, thin upper vermilion, and wide-spaced teeth) * Congenital heart anomalies (e.g., atrial septal defect, ventral septal defect, patent ductus arteriosus) ### Establishing the Diagnosis The diagnosis of PACS1-NDD is established in a proband with a heterozygous pathogenic variant in PACS1 by molecular genetic testing (see Table 1). Note: Identification of a heterozygous PACS1 variant of uncertain significance does not establish or rule out a diagnosis of PACS1-NDD. Molecular genetic testing in a child with developmental delay or an older individual with intellectual disability typically begins with chromosomal microarray analysis (CMA). If CMA is not diagnostic, the next step is typically either a multigene panel or exome sequencing. Note: (1) Single-gene testing (sequence analysis of PACS1) is rarely useful and typically NOT recommended. (2) Since PACS1-NDD likely occurs through a gain-of-abnormal-function or dominant-negative mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplications is unlikely to identify a disease-causing variant. An intellectual disability (ID) multigene panel that includes PACS1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition in a person with a nondiagnostic CMA 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. Of note, given the rarity of PACS1-NDD, some panels for ID may not include this gene. (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(s) are likely involved. Exome sequencing is most commonly used and yields results similar to an ID multigene panel with the additional advantage that exome sequencing includes genes recently identified as causing ID whereas some multigene panels may not. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by exome sequencing. Note: To date, such variants have not been identified as a cause of PACS1-NDD. Genome sequencing is also possible. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in PACS1 Neurodevelopmental Disorder View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method PACS1Sequence analysis 3~35/35 4 Gene-targeted deletion/duplication analysis 5None reported 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Since PACS1-NDD likely occurs through a gain-of-abnormal-function or dominant-negative mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant. ## Clinical Characteristics ### Clinical Description To date, approximately 35 individuals with PACS1 neurodevelopmental disorder (PACS1-NDD) have been described in the literature [Schuurs-Hoeijmakers et al 2012, Chad et al 2015, Gadzicki et al 2015, Schuurs-Hoeijmakers et al 2016, Stern et al 2017, Martinez-Monseny et al 2018, Miyake et al 2018, Pefkianaki et al 2018, Dutta 2019, Hoshino et al 2019]. The following description of the phenotypic features associated with this condition is based on these reports. ### Table 2. Select Features of PACS1 Neurodevelopmental Disorder View in own window FeatureProportion of Persons w/FeatureComment DD/ID35/35 * Moderate impairment in most * Language skills more severely affected than motor skills Feeding/ GI issues20-22/35Gastroesophageal reflux & constipation are most common manifestations. Seizures20/35 * Partial & tonic seizures * Infantile seizures reported Characteristic behavioral features18/35Autism spectrum disorder present in ~25%-30% Dysmorphic facial features35/35Hypertelorism, downslanting palpebral fissures, bulbous nasal tip, low-set & simple ears, smooth philtrum, wide mouth w/downturned corners, thin upper vermilion (w/a "wavy" profile), wide-spaced teeth Congenital heart anomalies15/35Atrial septal defects &/or ventricular septal defects in ~40% Brain MRI findings13/20Hypoplasia or partial agenesis of the cerebellar vermis is most common finding Ocular anomalies11/35Coloboma of the iris, retina, &/or optic nerve, myopia, strabismus, nystagmus DD = developmental delay; GI = gastrointestinal; ID = intellectual disability Developmental delay and/or intellectual disability was reported in all individuals [Chad et al 2015, Schuurs-Hoeijmakers et al 2016, Stern et al 2017, Martinez-Monseny et al 2018, Miyake et al 2018, Pefkianaki et al 2018, Dutta 2019, Hoshino et al 2019]. Most had moderate delays, with a range of mild-to-severe delay and/or disability reported. Hypotonia was reported in about a third of individuals and was noted to improve over time. Approximately 60% of individuals are ambulatory, with onset of walking between age two and four years [Schuurs-Hoeijmakers et al 2016, Martinez-Monseny et al 2018, Pefkianaki et al 2018, Hoshino et al 2019]. Clumsiness and unsteady gait are reported. Regression in walking with frequent falls was noted in one individual. Two individuals use ambulatory assistive devices; one individual occasionally used a wheelchair from age ten years, and one individual required a walker from age 11 years, due to ataxia and a crouching gait [Schuurs-Hoeijmakers et al 2016]. Development of contractures has not been reported. Language skills are universally affected, and more severely affected than motor skills. Most individuals develop verbal language, with several beginning to speak in their second year of life [Schuurs-Hoeijmakers et al 2016]. Two reported individuals started speaking in their third year of life [Schuurs-Hoeijmakers et al 2012, Gadzicki et al 2015]; one had meaningful words at age one year eight months and two-word sentences at age five years [Hoshino et al 2019], and one started using sentences at age eight years and was reading at age 11 years [Schuurs-Hoeijmakers et al 2016]. Seven out of 32 individuals were nonverbal at the time of evaluation, at ages two, three, four, six, ten, 11, and 20 years, respectively [Schuurs-Hoeijmakers et al 2016, Pefkianaki et al 2018, Hoshino et al 2019]. Stern et al [2017] reported that four of eight individuals were unable to speak more than a few words within the first three years of life. Three individuals were reported to have dysarthria [Stern et al 2017]. Of the individuals reported to be nonverbal, one was able to use sign language, picture exchange cards, and an iPad communication application [Schuurs-Hoeijmakers et al 2016], and one was unable to use sign language but able to use a communication board and demonstrated good receptive language skills [Pefkianaki et al 2018]. No individuals were reported to lose verbal skills. Feeding difficulties / gastrointestinal issues. Poor weight gain and poor suck have been reported; oral aversion and a preference for soft foods were also reported. Difficulty with eating solid foods and poor weight gain may continue into adolescence and adulthood. Six of 27 individuals required a gastrostomy tube to maintain appropriate caloric intake [Schuurs-Hoeijmakers et al 2016, Stern et al 2017]. Constipation and reflux have been reported in several individuals. Delayed stomach emptying was reported in one individual. Epilepsy. Seizures are present in about 50%-60% of reported individuals [Schuurs-Hoeijmakers et al 2016, Stern et al 2017, Martinez-Monseny et al 2018, Miyake et al 2018, Pefkianaki et al 2018, Dutta 2019, Hoshino et al 2019]. Seizure types have included partial and tonic seizures. Seizure onset has been reported as young as day two of life [Schuurs-Hoeijmakers et al 2012]. Seizures in individuals with PACS1-NDD have been well controlled by antiepileptic medications [Schuurs-Hoeijmakers et al 2016]. Behavior. Autism spectrum disorder occurs in about 25% to 30% of individuals. Temper tantrums and aggression are frequently reported, as is oral aversion and a preference for soft foods. Many individuals with PACS1-NDD, of all ages, are noted to have a happy, friendly disposition. Facial features. All reported individuals have dysmorphic facial features [Chad et al 2015, Gadzicki et al 2015, Schuurs-Hoeijmakers et al 2016, Stern et al 2017, Martinez-Monseny et al 2018, Miyake et al 2018, Pefkianaki et al 2018, Dutta 2019, Hoshino et al 2019]. The most common features include: hypertelorism, downslanting palpebral fissures, bulbous nasal tip, low-set and simple ears, smooth philtrum, wide mouth with downturned corners, thin upper vermilion (with a "wavy" profile), and wide-spaced teeth. Congenital heart anomalies were reported in about 45% of individuals [Schuurs-Hoeijmakers et al 2016, Stern et al 2017, Martinez-Monseny et al 2018, Hoshino et al 2019]. About 40% of individuals have an atrial septal defect and/or ventral septal defect. Additional cardiac defects include bicuspid aortic valve in two individuals [Schuurs-Hoeijmakers et al 2016, Martinez-Monseny et al 2018], dysplastic aortic and pulmonary valves [Schuurs-Hoeijmakers et al 2016], and dilation of pulmonary artery in one individual each [Stern et al 2017]. Additional cardiac findings have included patent ductus arteriosus and patent foramen ovale. Growth. Abnormal height and weight measurements have been reported in 50%-60% of individuals. Approximately 40% of individuals have short stature and/or low weight [Schuurs-Hoeijmakers et al 2012, Chad et al 2015, Gadzicki et al 2015, Schuurs-Hoeijmakers et al 2016, Stern et al 2017, Pefkianaki et al 2018, Martinez-Monseny et al 2018, Miyake et al 2018, Hoshino et al 2019]; 5%-10% of these individuals are affected from birth, while 20% develop growth deficiency during childhood. Frequently, both weight and height are below average, although weight is more frequently affected than height. One individual with birth weight and length below the 10th centile had normal growth by age five years [Stern et al 2017]. Approximately 20% of individuals have microcephaly (7/33) [Schuurs-Hoeijmakers et al 2016, Miyake et al 2018, Dutta 2019]. Limited information is available regarding the onset of microcephaly, but Stern et al [2017] reported one individual with small head circumference (defined as <10th centile) at birth and also at age five years, one individual with small head circumference at birth and normal head circumference at age five years, and one individual with a normal head circumference at birth but a small head circumference at age 19 months. Two individuals were greater than the 90th percentile for weight and/or length at birth, but had normal growth parameters at age three years and age 17 years [Stern et al 2017]. One individual with PACS1-NDD had sustained overgrowth and macrocephaly [Martinez-Monseny et al 2018]. Neuroimaging. Brain abnormalities have been identified in about 65% of individuals who have had imaging. The most frequent findings involve the cerebellar vermis (hypoplasia and partial agenesis). Additional findings include mild colpocephaly, ventriculomegaly/hydrocephalus ex vacuo, thin corpus callosum, frontal cortical dysplasia, paucity of cerebral white matter, mild delay in myelination, and hyperintensity of periventricular white matter. Ocular anomalies. Coloboma of the iris, retina, and/or optic nerve was reported in 5/35 individuals, with three of five individuals reported to have bilateral coloboma [Schuurs-Hoeijmakers et al 2016, Pefkianaki et al 2018, Dutta 2019, Hoshino et al 2019]. Other ocular abnormalities reported include myopia, strabismus, and nystagmus. Other * Genitourinary abnormalities. Cryptorchidism has been reported in several males. Duplex kidney and hydronephrosis were reported in two individuals. Incontinence, renal agenesis, end-stage renal disease, urinary reflux, testicular microlithiasis, hypospadias and chordee, and bicornate uterus were each reported in one individual. * Musculoskeletal features. Minor skeletal differences of the hands and feet are frequently reported, including clinodactyly or camptodactyly of the fifth fingers, tapered fingers, syndactyly, high plantar arch, pes planus, and broad great toe. Scoliosis occurred in three individuals [Author, personal communication]. Vertebral anomalies and pectus excavatum were each identified in one individual. * Immunologic abnormalities have included frequent infections (3/33), leukopenia (1/33), neutropenia (1/33), and low immunoglobin levels (1/33) [Schuurs-Hoeijmakers et al 2016]. * Hearing loss. One individual had mild-to-moderate hearing loss of unknown type [Schuurs-Hoeijmakers et al 2016]. * Prognosis. It is unknown whether life span in individuals with PACS1-NDD is normal. One reported individual was alive at age 21 years [Schuurs-Hoeijmakers et al 2016], demonstrating that survival into adulthood is possible. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been identified. ### Penetrance To date, penetrance appears to be 100%. ### Prevalence Prevalence is currently unknown. Approximately 35 individuals with PACS1-NDD have been reported in the literature. ## Differential Diagnosis Because the phenotypic features associated with PACS1 neurodevelopmental disorder are not sufficient to diagnose this condition, all disorders with intellectual disability (ID) without other distinctive findings should be considered in the differential diagnosis. To date more than 180 such disorders with ID have been identified. See OMIM Phenotypic Series: Autosomal dominant ID; Autosomal recessive ID; Nonsyndromic X-linked ID; and Syndromic X-linked ID. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with PACS1 neurodevelopmental disorder (PACS1-NDD), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with PACS1 Neurodevelopmental Disorder View in own window System/ConcernEvaluationComment DevelopmentDevelopmental assessment * To incl motor, adaptive, cognitive, & speech/language eval * Eval for early intervention / special education Feeding issues / Gastrointestinal manifestationsGastroenterology / nutrition / feeding team eval * To incl eval of aspiration risk & nutritional status * Consider eval for gastric tube placement in those w/severe feeding/growth issues or aspiration risk. * Additional eval may be needed for constipation symptoms. NeurologicNeurologic evalConsider EEG if seizures are a concern. Psychiatric / BehavioralNeuropsychiatric evalIndividuals age >12 mos: screen for behavior concerns incl features of autism spectrum disorder CardiovascularEchocardiogramTo evaluate for structural heart defects EyesOphthalmologic evalTo assess for ↓ vision, abnormal ocular movement, strabismus, or other anomalies GenitourinaryRenal ultrasoundTo evaluate for renal anomalies Genetic counselingBy genetics professionals 1To inform patients & families re nature, MOI, & implications of PACS1-NDD to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support; * Need for home nursing referral. MOI = mode of inheritance 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with PACS1 Neurodevelopmental Disorder View in own window Manifestation/ ConcernTreatmentConsiderations/Other DD/IDSee Developmental Delay / Intellectual Disability Management Issues. Poor weight gain * Feeding therapy * Gastrostomy tube placement may be required for persistent feeding issues. Feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia Bowel dysfunctionStool softeners, prokinetics, osmotic agents, or laxatives as needed for constipation EpilepsyStandardized treatment w/AEDs by experienced child neurologist * Many AEDs may be effective; none has been demonstrated effective specifically for this disorder * Education of parents/caregivers 1 BehaviorSee Social/Behavioral Concerns. Cardiac anomaliesTreatment per cardiologist Abnormal vision &/or strabismusStandard treatment(s) per ophthalmologist Renal anomaliesTreatment per nephrologist &/or urologist Family/ Community * Ensure appropriate social work involvement to connect families w/local resources, respite, & support. * Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies. Consider involvement in adaptive sports or Special Olympics. AED = antiepileptic drug; DD = developmental delay; ID = intellectual disability 1\. Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider: * Individualized education plan (IEP) services: * An IEP provides specially designed instruction and related services to children who qualify. * IEP services will be reviewed annually to determine whether any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * Vision consultants should be a part of the child's IEP team to support access to academic material. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Motor Dysfunction Gross motor dysfunction * Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation). * Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers). Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing. Oral motor dysfunction. Assessment should be carried out at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically by an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary. Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairment to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech and in many cases, can improve it. #### Social/Behavioral Concerns Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst. Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance ### Table 5. Recommended Surveillance for Individuals with PACS1 Neurodevelopmental Disorder View in own window System/ConcernEvaluationFrequency DevelopmentMonitor developmental progress & educational needs.At each visit Feeding * Measurement of growth parameters * Eval of nutritional status & safety of oral intake GastrointestinalMonitor for constipation. RespiratoryMonitor for evidence of aspiration, respiratory insufficiency. Neurologic * Monitor those w/seizures as clinically indicated. * Assess for new manifestations incl seizures, changes in tone, movement disorders Psychiatric/ BehavioralBehavioral assessment for anxiety, attention, & aggressive or self-injurious behavior CardiovascularMonitor closure of septal defects by echo if present & not repaired.Annually or per cardiologist GenitourinaryMonitor renal function if renal malformation is present.Annually or per nephrologist Miscellaneous/ OtherAssess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.At each visit ### Agents/Circumstances to Avoid Individuals with PACS1-NDD should avoid any known seizure triggers (e.g., sleep deprivation, alcohol use, missed medications). ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	PACS1 Neurodevelopmental Disorder	c3554343	24,845	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK559434/	2021-01-18T21:06:26	{"synonyms": ["Schuurs-Hoeijmakers Syndrome"]}
A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-9 (ECTD9) can be caused by homozygous mutation in the HOXC13 gene (142976) on chromosome 12q13. Description Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia) (summary by Lin et al., 2012). Clinical Features Lin et al. (2012) described a 5-generation consanguineous Chinese Hui family segregating ectodermal dysplasia-9. The 3 affected individuals showed congenital atrichia and severe nail dystrophy. All vellus, lanugo, and terminal hairs were absent on the scalp and body, and axillary and pubic hairs never developed during puberty. Soft and small keratinized structures developed later on all digits and presented as micronychia. The affected individuals described that they never need their nails trimmed. The 2 male affected individuals underwent surgical management for unilateral cryptorchidism and inguinal hernia, and urologists suspected a diagnosis of persistent Mullerian duct syndrome (261550). No genital anomalies were observed in the affected female individual. No abnormalities of the nervous system, skeleton, sweat glands, sebaceous glands, eyes, or teeth were observed. Histopathological examination of scalp skin of the index individual showed an apparently reduced number of hair follicles with disorganized hair shafts lacking the normal layered structure. Lin et al. (2012) also described a 21-year-old Afghan female who presented with severe congenital hypotrichosis and nail dystrophy. She had her nails trimmed once a month and had never cut her hair. Inheritance Lin et al. (2012) reported 2 unrelated families segregating ectodermal dysplasia-9 in which affected children were born to healthy first-cousin parents, which is consistent with an autosomal recessive mode of inheritance. Mapping By haplotype analysis using microsatellite markers on chromosome 12p11.1-q21.1 in a consanguineous Syrian family with autosomal recessive ectodermal dysplasia of the hair/nail type, Farooq et al. (2013) showed linkage to a 17-Mb region on chromosome 12q13.13-12q14.3, between markers D12S390 and D12S43, within which the entire HOXC13 gene is located. Molecular Genetics Lin et al. (2012) performed whole-exome sequencing in a consanguineous Chinese family segregating ectodermal dysplasia-9 and identified a homozygous nonsense mutation (Y130X; 142976.0001) in the HOXC13 gene in all 3 affected individuals. In a female with hypotrichosis and nail dystrophy from a consanguineous Afghan family, they identified a homozygous 27.6-kb deletion involving the first exon of the HOXC13 gene (142976.0002). In a 7-month-old girl with autosomal recessive ectodermal dysplasia of the hair/nail type, who was born to consanguineous Syrian parents, Farooq et al. (2013) identified homozygosity for a single nucleotide deletion in the HOXC13 gene (c.355delC; 142976.0003). Expression studies in cultured cells showed that the mutant HOXC13 protein mislocalized within the cytoplasm and failed to upregulate the promoter activities of its target genes. INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Nails \- Nail dystrophy \- Koilonychia (spoon nails) \- Micronychia Hair \- Hypotrichosis \- Atrichia MOLECULAR BASIS \- Caused by mutation in the homeo box C13 gene (HOXC13, 142976.0001 ) ▲ 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	ECTODERMAL DYSPLASIA 9, HAIR/NAIL TYPE	c1865951	24,846	omim	https://www.omim.org/entry/614931	2019-09-22T15:53:48	{"mesh": ["C566592"], "omim": ["614931"], "orphanet": ["69084"]}
Gallbladder cancer SpecialtyGastroenterology Hepatology Oncology SymptomsAbdominal pain, Bloating, Fever, Unexplained weight loss, Nausea, Yellowing of the skin, although some people may have no symptoms[1] ComplicationsCancer spreading to other parts of the body Usual onsetAbove 65 years old[2] TypesAdenocarcinoma (most common), Squamous cell carcinoma (more rare)[3] CausesUnknown[4] Risk factorsHistory of Gallstones and other Gallbladder diseases Diagnostic methodBlood tests, medical imaging, examination of the Bile duct Differential diagnosisOther types of cancer in the Digestive system TreatmentSurgery, Radiation therapy, Chemotherapy[5] PrognosisFive-year survival rate ~19% (USA) (January, 2020)[6] Frequency~3,700 cases per year (USA)[7] Deaths~2,000 deaths per year (USA)[8] Gallbladder cancer is a relatively uncommon cancer, with an incidence of fewer than 2 cases per 100,000 people per year in the United States.[9] It is particularly common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics.[10] If it is diagnosed early enough, it can be cured by removing the gallbladder, part of the liver and associated lymph nodes. Most often it is found after symptoms such as abdominal pain, jaundice and vomiting occur, and it has spread to other organs such as the liver. It is a rare cancer that is thought to be related to gallstones building up, which also can lead to calcification of the gallbladder, a condition known as porcelain gallbladder. Porcelain gallbladder is also rare. Some studies indicate that people with porcelain gallbladder have a high risk of developing gallbladder cancer, but other studies question this. The outlook is poor for recovery if the cancer is found after symptoms have started to occur, with a 5-year survival rate close to 3%. ## Contents * 1 Signs and symptoms * 2 Risk factors * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 5 Epidemiology * 6 Prognosis * 7 References * 8 External links ## Signs and symptoms[edit] * Steady pain in the upper right abdomen * Indigestion * Dyspepsia (gas) * Bilious vomit * Weakness * Loss of appetite * Weight loss * Jaundice and vomiting due to obstruction Early symptoms mimic gallbladder inflammation due to gallstones. Later, the symptoms may be that of biliary and stomach obstruction. Of note, Courvoisier's law states that in the presence of a palpably enlarged gallbladder which is nontender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones. This implicates possible malignancy of the gallbladder or pancreas, and the swelling is unlikely due to gallstones due to the chronic inflammation association with gallstones leading to a shrunken, non-distensible gallbladder. However, Ludwig Georg Courvoisier's original observations, published in Germany in 1890, were not originally cited as a law, and no mention of malignancy or pain (tenderness) was made. These points are commonly misquoted or confused in the medical literature.[11] ## Risk factors[edit] * Gender— approximately twice as common in women than men, usually in seventh and eighth decades * Obesity * Chronic cholecystitis and cholelithiasis * Primary sclerosing cholangitis[12] * Chronic typhoid infection of gallbladder; chronic Salmonella typhi carriers have 3 to 200 times higher risk of gallbladder cancer than non-carriers and 1–6% lifetime risk of development of cancer[13] * Various single nucleotide polymorphisms (SNPs) have been shown to be associated with gallbladder cancer; however, existing genetic studies in GBC susceptibility have so far been insufficient to confirm any association[14] * Gall bladder polyps[15] * Calcified gallbladder wall (porcelain gallbladder)[15] * Congenital abnormalities of the bile duct such as choledochal cyst[15] ## Diagnosis[edit] Early diagnosis is not generally possible. People at high risk, such as women or Native Americans with gallstones, are evaluated closely. Transabdominal ultrasound, CT scan, endoscopic ultrasound, MRI, and MR cholangio-pancreatography (MRCP) can be used for diagnosis. A large number of gallbladder cancers are found incidentally in patients being evaluated for cholelithiasis, or gallstone formation, which is far more common.[16] A biopsy is the only certain way to tell whether or not the tumorous growth is malignant.[17] * Gallbladder adenocarcinoma lymphatic invasion histopathology * Incidentally discovered gallbladder cancer (adenocarcinoma) following a cholecystectomy. * Gallbladder adenocarcinoma histopathology ### Differential diagnosis[edit] Xanthogranulomatous cholecystitis (XGC) is a rare form of gallbladder disease which mimics gallbladder cancer although it is not cancerous.[18][19] It was first discovered and reported in the medical literature in 1976 by J.J. McCoy, Jr., and colleagues.[18][20] ## Treatment[edit] If detected early in a stage where it has not spread, gall bladder cancer can be treated by surgery. Surgery for gallbladder cancer is called radical cholecystectomy or extended cholecystectomy. It entails the removal of gall bladder along with adequate removal of its liver bed to the healthy tissue. The lymph nodes in the vicinity are also removed. Sometimes removal of a large part of the liver called hepatectomy is required to completely remove the tumor. The bile duct if involved also needs to be removed.[15] However, with gallbladder cancer's extremely poor prognosis, most patients will die within a year of surgery. If surgery is not possible, endoscopic stenting or percutaneous transhepatic biliary drainage (PTBD) of the biliary tree can reduce jaundice and a stent in stomach may relieve vomiting. Chemotherapy and radiation may also be used with surgery. If gallbladder cancer is diagnosed after cholecystectomy for stone disease (incidental cancer), re-operation to remove part of liver and lymph nodes is required in most cases. When it is done as early as possible, patients have the best chance of long-term survival and even cure.[21] ## Epidemiology[edit] Most tumors are adenocarcinomas, with a small percent being squamous cell carcinomas. * Gallbladder cancer is relatively rare, affecting fewer than 5000 people in the United States per year[22] * Gallbladder cancer is more common in South American countries, Japan, and Israel; in Chile, gallbladder cancer is the fourth most common cause of cancer deaths. * 5th most common gastrointestinal cancer * Up to 5 times more common in women than men depending on population (e.g. 73% female in China[23] * The age adjusted incidence rates of gall bladder cancer is highest in Chile, followed by in the state of Assam in India[24] ## Prognosis[edit] This section needs expansion. You can help by adding to it. (January 2019) The prognosis still remains poor. The cancer commonly spreads to the liver, bile duct, stomach, and duodenum.[citation needed] ## References[edit] 1. ^ https://www.mayoclinic.org/diseases-conditions/gallbladder-cancer/symptoms-causes/syc-20353370 2. ^ https://www.cancer.org/cancer/gallbladder-cancer/causes-risks-prevention/risk-factors.html 3. ^ https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/types 4. ^ https://www.mayoclinic.org/diseases-conditions/gallbladder-cancer/symptoms-causes/syc-20353370 5. ^ https://www.mayoclinic.org/diseases-conditions/gallbladder-cancer/diagnosis-treatment/drc-20353374 6. ^ https://www.cancer.net/cancer-types/gallbladder-cancer/statistics 7. ^ https://cebp.aacrjournals.org/content/24/9/1319 8. ^ https://cebp.aacrjournals.org/content/24/9/1319 9. ^ "CDC - Gallbladder Cancer Incidence and Death Rates". www.cdc.gov. 2018-09-27. Retrieved 2018-12-10. 10. ^ Kapoor VK, McMichael AJ (2003). "Gallbladder cancer: an 'Indian' disease". Natl Med J India. 16 (4): 209–13. PMID 14606770. 11. ^ Fitzgerald, J Edward F; White Matthew J; Lobo Dileep N (Apr 2009). "Courvoisier's gallbladder: law or sign?". World Journal of Surgery. United States. 33 (4): 886–91. doi:10.1007/s00268-008-9908-y. ISSN 0364-2313. PMID 19190960. S2CID 21799234. 12. ^ Folseraas, T; Boberg, KM (February 2016). "Cancer Risk and Surveillance in Primary Sclerosing Cholangitis". Clinics in Liver Disease. 20 (1): 79–98. doi:10.1016/j.cld.2015.08.014. PMID 26593292. 13. ^ Ferreccio, C. (2012). "Salmonella typhi and Gallbladder Cancer". Bacteria and Cancer. pp. 117–137. doi:10.1007/978-94-007-2585-0_5. ISBN 978-94-007-2584-3. 14. ^ Srivastava K, Srivastava A, Sharma KL, Mittal B. Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis. Mutat Res. 2011 Jul–Oct;728(1–2):67–79. 15. ^ a b c d "Gallbladder Cancer: Symptoms, Causes & Treatment \| Dr. Nikhil Agrawal". Dr.Nikhil Agrawal. Retrieved 2020-10-11. 16. ^ Duffy, A.; Capanu, M.; Abou-Alfa, G. K.; Huitzil, D.; Jarnagin, W.; Fong, Y.; D'Angelica, M.; Dematteo, R. P.; Blumgart, L. H. (2008-12-01). "Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC)". Journal of Surgical Oncology. 98 (7): 485–489. doi:10.1002/jso.21141. ISSN 1096-9098. PMID 18802958. 17. ^ "Tests for gallbladder cancer". Cancer Research UK. Archived from the original on 10 October 2011. Retrieved 17 September 2012. 18. ^ a b Makino I, Yamaguchi T, Sato N, Yasui T, Kita I (August 2009). "Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma with a false-positive result on fluorodeoxyglucose PET". World J. Gastroenterol. 15 (29): 3691–3. doi:10.3748/wjg.15.3691. PMC 2721248. PMID 19653352. 19. ^ Rao RV, Kumar A, Sikora SS, Saxena R, Kapoor VK (2005). "Xanthogranulomatous cholecystitis: differentiation from associated gall bladder carcinoma". Trop Gastroenterol. 26 (1): 31–3. PMID 15974235. 20. ^ McCoy JJ, Vila R, Petrossian G, McCall RA, Reddy KS (March 1976). "Xanthogranulomatous cholecystitis. Report of two cases". J S C Med Assoc. 72 (3): 78–9. PMID 1063276. 21. ^ Kapoor VK (March 2001). "Incidental gallbladder cancer". Am. J. Gastroenterol. 96 (3): 627–9. PMID 11280526.[dead link] 22. ^ Carriaga, M. T.; Henson, D. E. (1995-01-01). "Liver, gallbladder, extrahepatic bile ducts, and pancreas". Cancer. 75 (1 Suppl): 171–190. doi:10.1002/1097-0142(19950101)75:1+<171::AID-CNCR2820751306>3.0.CO;2-2. ISSN 0008-543X. PMID 8000995.[dead link] 23. ^ Hsing AW, Gao YT, Han TQ, et al. (December 2007). "Gallstones and the risk of biliary tract cancer: a population-based study in China". Br. J. Cancer. 97 (11): 1577–82. doi:10.1038/sj.bjc.6604047. PMC 2360257. PMID 18000509. 24. ^ National Cancer Registry Programme (2013).Three-year report of population based cancer registries:2009-2011. NCDIR-ICMR, Bangalore. ## External links[edit] * U.S. National Cancer Institute Gallbladder Cancer Treatment (www.cancer.gov) Classification D * ICD-10: C23–C24 * ICD-9-CM: 156 * MeSH: D005706 * DiseasesDB: 30714 * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Gallbladder cancer	c0153452	24,847	wikipedia	https://en.wikipedia.org/wiki/Gallbladder_cancer	2021-01-18T18:42:57	{"gard": ["9328"], "mesh": ["D005706"], "umls": ["C0016978", "C0278806", "C0153452"], "icd-10": ["C24", "C23"], "wikidata": ["Q977787"]}
The term 'mydriasis' is used in at least two senses: a state of dilatation of the pupils (see 159420) and the process by which the pupils become dilated, as in response to a pharmacologic agent. Goldsmith et al. (1977) used the term in the latter sense in connection with their study of pupillary response to mydriatics in Chile. Among 673 persons tested they found 42 whose irides failed to dilate 'to a clinically useful degree' after a standard administration of a mydriatic. The frequency of nondilators differed among ethnic groups and the distribution within groups suggested that the trait is inherited. Mydriasis has been known to be more sluggish in persons with dark-colored irides than in those with light-colored irides. Bertler and Smith (1971) found concordance in pupillary responses in monozygotic but not in dizygotic twins. Hyperreactive mydriasis to atropine is a feature of Down syndrome (Harris and Goodman, 1968). (Paskind (1921) concluded that atropine had little effect in African American subjects, whereas in white subjects it produced an average slowing of 10 beats per minute.) In the rabbit, failure of the iris to respond to atropine is hereditary and reflects the presence or absence of atropinesterase (Sawin and Glich, 1943; Szorady, 1973). One of the earliest studies of racial differences in mydriatic response to pharmacologic agents was that of Chen and Poth (1929). They found that Caucasians were most susceptible and African Americans least susceptible to the mydriatic action of cocaine, euphthalmine, and ephedrine; Chinese showed an intermediate response. Eyes \- Irides fail to dilate after a standard dose of a mydriatic Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MYDRIATIC RESPONSE TO PHARMACOLOGIC AGENTS	c1834634	24,848	omim	https://www.omim.org/entry/159410	2019-09-22T16:37:52	{"omim": ["159410"]}
Juvenile glycerol kinase deficiency (GKD) is an uncommon form of GKD (see this term) characterized by Reye-like clinical manifestations including episodic vomiting, acidemia, and disorders of consciousness. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Glycerol kinase deficiency, juvenile form	c0268418	24,849	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284411	2021-01-23T18:31:44	{"omim": ["307030"], "icd-10": ["E74.8"]}
An intermediate form of lichen myxedematosus (LM) (a form of mucin dermal deposit) which does not meet the criteria for either scleromyxedema or the localized form. Three clinical subtypes have been described and include scleromyxedema without monoclonal gammopathy; localized forms with monoclonal gammopathy and/or systemic symptoms; localized forms with mixed features of the 5 subtypes of localized LM (discrete form, acral persistent papular mucinosis, self-healing papular mucinosis, papular mucinosis of infancy, and a pure nodular form). The course of atypical LM is unpredictable because only a few cases have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Atypical lichen myxedematosus	c4510874	24,850	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86797	2021-01-23T17:37:23	{"icd-10": ["L98.5"], "synonyms": ["Intermediate lichen myxedematosus"]}
A number sign (#) is used with this entry because of evidence that the disorder represents a contiguous gene syndrome due to a deletion in chromosome 16p that involves the alpha-1 (HBA1; 141800) and alpha-2 (HBA2; 141850) genes, among others. X-linked alpha-thalassemia/mental retardation syndrome (ATR-X; 301040) is a similar phenotypic disorder caused by mutation in the ATRX gene (300032). Clinical Features Weatherall et al. (1981) reported the association of hemoglobin H disease (Hb H; see alpha-thalassemias, 141800) and mental retardation in 3 unrelated patients of northern European descent. Hjelle et al. (1982) described a somewhat similar case in a male of northern European extraction. Hb H was associated with multiple congenital anomalies: spina bifida from T6 to the sacrum with a T10-L4 myelomeningocele, congenital cataracts, bilateral inguinal hernias, bilateral deformities of the femoral necks, and subluxation of the left hip. One of his 2 sibs also had congenital cataracts, but there was no family history of other congenital anomalies or of fetal wastage. According to restriction enzyme analyses, the father had 2 alpha-globin genes on one chromosome and only 1 gene on the homolog (i.e., was a silent alpha-thalassemia carrier), whereas the mother had cis alpha-thalassemia trait (i.e., 2 alpha genes on 1 chromosome and none on the homolog). The proband had the thalassemia chromosome of each parent. The restriction patterns were typical of Asian alpha-thalassemia. The brother with congenital cataracts carried the father's thalassemic chromosome. Higgs et al. (1989) stated that they were aware of 13 individuals, 10 males and 3 females from a variety of racial groups, with this association. Nine of the patients had Hb H disease, with hypochromic microcytic anemia and 1 to 11% of Hb H in the peripheral blood. The other 4 had alpha-thalassemia trait with only occasional Hb H-containing cells. In all cases, family studies showed that alpha-thalassemia in the proband resulted entirely or in part from a de novo mutation affecting alpha-globin production. Wilkie et al. (1990) reported 8 unrelated patients with mental retardation and alpha-thalassemia due to deletions of chromosome 16p, including patients previously reported by Weatherall et al. (1981), Borochovitz et al. (1970) and Bowcock et al. (1984), Hutz et al. (1986), and Buckle et al. (1988). Molecular genetic analysis of all 8 patients showed that each failed to inherit an alpha-globin allele from 1 of the parents and had deletions of variable size in band 16p13.3. In at least 4 cases, the deletion resulted from unbalanced chromosome translocation; hence aneuploidy of a second chromosome was also present. The clinical features varied widely and were relatively nonspecific. Lindor et al. (1997) described a female infant of mixed northern European ancestry in which alpha-thalassemia was ascertained by newborn screening. Evaluation at 9 months of age showed minor anomalies and developmental delay. Chromosomal analysis demonstrated a de novo deletion of the most distal portion of 16p. By fluorescence in situ hybridization it was established that the anomaly was a terminal deletion with a breakpoint at 16p13.3, and not a translocation. This was said to have been only the fifth reported case of the ATR-16 chromosome that was not complicated by duplication or deletion in other chromosomes. They suggested that ATR-16 is underdiagnosed, since making the diagnosis is confounded by the mildness of the phenotype, the high frequency of alpha-thalassemia trait in many populations, the subtlety of cytogenetic findings, and the lack of altered Southern blot band sizes. Holinski-Feder et al. (2000) reported a 5-generation family in which 10 individuals of both sexes had mild to moderate mental retardation and mild nonspecific dysmorphic features. The disorder was inherited in a seemingly autosomal dominant fashion with reduced penetrance. Standard clinical and laboratory screening protocols and extended cytogenetic analysis, including the use of high-resolution karyotyping and multiplex FISH, did not reveal the cause of the mental retardation. However, a genomewide scan showed linkage to chromosome 16p13.3, and a deletion of part of 16pter was demonstrated in patients, similar to the deletion observed in patients with ATR-16 syndrome. Subsequent FISH analysis demonstrated that the patients in this family inherited a duplication of terminal 3q in addition to the deletion of 16p. FISH analysis of obligate carriers revealed that a balanced translocation between the terminal parts of 16p and 3q segregated in this family. Affected individuals had hematologic parameters consistent with mild alpha-thalassemia. Holinski-Feder et al. (2000) emphasized the role of cryptic, cytogenetically invisible subtelomeric translocations in mental retardation, which has been estimated to be implicated in 5 to 10% of cases (Flint et al., 1995; Giraudeau et al., 1997; Slavotinek et al., 1999). Gallego et al. (2005) described a child with ATR-16 syndrome who had been referred for genetic evaluation because of minor anomalies and developmental delay. Cytogenetic analysis showed a de novo complex rearrangement of chromosome 16. FISH analysis, using chromosome 16 subtelomeric probes, showed that the patient had a deletion of the distal short arm of chromosome 16 that contains the alpha-globin genes and a duplication of 16q. Southern blot analysis of the alpha-globin locus showed a half-normal dose of the alpha-globin genes. Microsatellite marker studies showed that the duplicated chromosome 16q region was maternal in origin. Hematologic studies showed anemia, hypochromia, and occasional cells with Hb H inclusion bodies. Gallego et al. (2005) concluded that a hematologic screening for alpha-thalassemia should be considered in patients with mild developmental delay and a suggestive phenotype of ATR-16 with microcytic hypochromic anemia and normal iron status. They suggested that the finding in this patient of a stellate pattern of the iris may be useful in the clinical delineation of ATR-16 and/or duplication of 16qter. Gallego et al. (2005) stated that approximately 15 cases of ATR-16 had been described and that 'only a handful of cases involving duplication of 16q22-qter' had been reported among liveborns. Molecular Genetics Pfeifer et al. (2000) stated that the SOX8 gene (605923) was found to be deleted in a patient with ATR-16 syndrome who carried a 2-Mb deletion on chromosome 16p13.3. Based on the high expression of SOX8 in the brain, they suggested that haploinsufficiency for the SOX8 protein could contribute to the mental retardation found in ATR-16 syndrome. Lamb et al. (1993) restudied a South African Dutch patient with mental retardation who was originally reported by Borochovitz et al. (1970) to have a normal karyotype and was later found by Wilkie et al. (1990) to have a subtle shortening of band 16p13.3 of one chromosome 16 homolog. Lamb et al. (1993) showed that the patient had a truncation of the terminal 2 Mb of chromosome 16p and that the telomeric sequence (TTAGGG)n had been added at the site of breakage. The chromosomal break, which was paternal in origin and had probably arisen at meiosis, had apparently been stabilized in vivo by the direct addition of the telomeric sequence. Harteveld et al. (2007) used multiplex ligation-dependent probe amplification (MLPA) to fine map deletions of chromosome 16p in 3 patients with ATR-16 and 1 patient with alpha-thalassemia without mental retardation. The region for which haploinsufficiency resulted in dysmorphic features and mental retardation was narrowed down to 800-kb on 16p between 0.9 and 1.7 Mb from the telomere. Gibson et al. (2008) reported an 8-year-old Caucasian girl with ATR-16 syndrome associated with a do novo submicroscopic terminal deletion at chromosome 16p encompassing at least 1 Mb and including the SOX8 gene. Gibson et al. (2008) noted that isolated monosomy for chromosome 16p is rarely described, as most patients with this disorder have complex translocations or karyotypic abnormalities. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Weight \- Obesity, mild (less common) HEAD & NECK Head \- Microcephaly Face \- Wide, flat, broad forehead \- Long philtrum \- Retrognathia, mild Ears \- Small ears Eyes \- Epicanthal folds \- Hypertelorism \- Downslanting palpebral fissures \- Ptosis Nose \- Flat, broad nasal bridge \- Triangular nasal tip \- Anteverted nostrils Mouth \- High-arched palate \- Protruding tongue Teeth \- Crowded teeth Neck \- Short neck \- Webbed neck CARDIOVASCULAR Vascular \- Patent ductus arteriosus (in 1 reported case) CHEST External Features \- Asymmetric chest Breasts \- Abnormally placed nipples \- Accessory nipple GENITOURINARY External Genitalia (Male) \- Micropenis \- Hypospadias Internal Genitalia (Male) \- Cryptorchidism SKELETAL Hands \- Clinodactyly of isolated digits Feet \- Talipes equinovarus NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate \- Seizures (less common) HEMATOLOGY \- Alpha-thalassemia \- Microcytic, hypochromic anemia \- Hb H inclusions in red blood cells LABORATORY ABNORMALITIES \- Subtelomeric deletion of chromosome 16p \- Normal serum ferritin MISCELLANEOUS \- Highly variable phenotype \- See also X-linked alpha-thalassemia/mental retardation syndrome ( 301040 ) \- Contiguous gene syndrome MOLECULAR BASIS \- A contiguous gene syndrome caused by deletion of the alpha-1 hemoglobin ( 141800 ) and alpha-2 hemoglobin ( 141850 ) genes ▲ 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	ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, CHROMOSOME 16-RELATED	c0795917	24,851	omim	https://www.omim.org/entry/141750	2019-09-22T16:40:20	{"doid": ["0110029"], "mesh": ["C563050"], "omim": ["141750"], "orphanet": ["98791"], "synonyms": ["Alternative titles", "ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, DELETION-TYPE", "ATR-16 SYNDROME", "ATR, DELETION-TYPE", "HEMOGLOBIN H-RELATED MENTAL RETARDATION", "MENTAL RETARDATION WITH HEMOGLOBIN H", "CHROMOSOME 16p DELETION SYNDROME"]}
Otofaciocervical syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit. Vertebral defects and short stature may also be associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Otofaciocervical syndrome	c1833691	24,852	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2792	2021-01-23T18:39:19	{"gard": ["2273", "4169"], "mesh": ["C563481"], "omim": ["166780", "615560"], "umls": ["C1833691", "C2931416"], "icd-10": ["Q87.0"], "synonyms": ["Fara-Chlupackova syndrome", "OFC syndrome"]}
A rare neurologic disease characterized by progressive sensorineural deafness, progressive sensory neuropathy and gastrointestinal abnormalities, including progressive loss of gastric motility and small bowel diverticulosis and ulcerations, resulting in cachexia. Additonal neurological manifestations may include dysarthria and absent tendon reflexes, as well as ptosis and external ophthalmoplegia. There have been no further descriptions in the literature since 1985. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Deafness-small bowel diverticulosis-neuropathy syndrome	c1857338	24,853	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3217	2021-01-23T18:58:09	{"gard": ["2568"], "mesh": ["C537305"], "omim": ["221400"], "umls": ["C1857338"], "synonyms": ["Groll-Hirschowitz syndrome", "Hearing loss-small bowel diverticulosis-neuropathy syndrome"]}
A number sign (#) is used with this entry because multiple sulfatase deficiency (MSD) is caused by homozygous or compound heterozygous mutation in the sulfatase-modifying factor-1 gene (SUMF1; 607939) on chromosome 3p26. Description Multiple sulfatase deficiency is an autosomal recessive inborn error of metabolism resulting in tissue accumulation of sulfatides, sulfated glycosaminoglycans, sphingolipids, and steroid sulfates. The enzymatic defect affects the whole family of sulfatase enzymes; thus, the disorder combines features of metachromatic leukodystrophy (250100) and of various mucopolysaccharidoses (see, e.g., MPS6; 253200). Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and ichthyosis. Different types of MSD can be distinguished according to the age of onset: neonatal, late infantile (0 to 2 years), and juvenile (2 to 4 years). Neonatal MSD is the most severe form with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. Late-infantile MSD, which includes the majority of cases, resembles late-infantile metachromatic leukodystrophy with progressive loss of mental and motor abilities and skeletal changes. There is also an attenuated form of late-infantile MSD with onset beyond the second year of life. Rare cases of juvenile-onset MSD have been reported with onset of symptoms in late childhood and slower progression (Blanco-Aguirre et al., 2001) (summary by Schlotawa et al., 2011). Clinical Features The clinical features of multiple sulfatase deficiency are an interesting composite of those seen with deficiency of the individual sulfatases. Kihara (1982) pointed out that multiple sulfatase deficiency combines the enzyme deficiency and phenotypic features of at least six entities: metachromatic leukodystrophy (250100), Maroteaux-Lamy syndrome (253200), X-linked ichthyosis (308100), Hunter syndrome (309900), Sanfilippo A syndrome (252900), and Morquio syndrome (253000). Mossakowski et al. (1961) reported 3 affected sibs, and Austin (1965) reported 2 affected sibs. Rampini et al. (1970) reported 3 cases. Some patients initially suspected of having Hunter syndrome may have multiple sulfatase deficiency in which deficiency of iduronate sulfatase dominates. Burk et al. (1981, 1984) reported 2 cases that had been mistakenly diagnosed as Hunter syndrome. In both, developmental delay dated from birth. Increased urinary mucopolysaccharides had a pattern different from that in mucopolysaccharidosis (heparan sulfate 39%, dermatan sulfate 21%, chondroitin sulfate C 40%). Abnormally broad great toes were found in both, and ichthyosis developed at an early age. Limitation in extension at the elbows and radiologic changes of dysostosis multiplex were suggestive of a mucopolysaccharidosis. The defect in this disorder may be similar to that in combined beta-galactosidase/neuraminidase deficiency; the defect may reside in a molecule necessary to protect the multiple sulfatases against excessive intralysosomal degradation and to assure their full hydrolytic capacity. If this is the explanation, then the activity of the molecule must not be limited to the intralysosomal site: 6 of the enzymes are lysosomal, whereas steroid sulfatase is microsomal. Burch et al. (1986) described a neonatal case of multiple sulfatase deficiency. In most reported cases the clinical phenotype resembles late infantile metachromatic leukodystrophy at presentation, but patients later develop ichthyosis and features of a mucopolysaccharidosis. The patient reported by Burch et al. (1986) had dysmorphic features and hydrocephalus present at birth and also had mild chondrodysplasia calcificans, heart abnormalities, and an abnormal fold of tissue between the laryngeal inlet and the esophagus. Excessive mucopolysacchariduria was present. Soong et al. (1988) described an affected 9.75-year-old girl. They stated that only 20 cases had been described. Blanco-Aguirre et al. (2001) reported 2 Mexican brothers with childhood onset of MSD at around age 3 years. After normal development in the first 2 years, both showed neurodegeneration with delayed speech and motor difficulties, including ataxia. Both developed ichthyosis, retinal degeneration, dysmetria, and hyperreflexia of the lower limbs. Examination at ages 22 and 17 years, respectively, showed coarse facies, nystagmus, high-arched palate, mental retardation, and broad thumbs and index fingers, but no organomegaly. Brain imaging showed cerebral and cerebellar atrophy, enlarged ventricles, and periventricular white matter abnormalities. Skeletal survey showed dysostosis multiplex. Laboratory studies showed some residual sulfatase activities, which Blanco-Aguirre et al. (2001) postulated was responsible for the slow progression and attenuated phenotype. Other Features Steinmann et al. (1981) reported on a woman who during pregnancy excreted consistently low amounts of urinary estriols for which no apparent reason was found. After birth, the girl was diagnosed as having classic multiple sulfatase deficiency based on the clinical and biochemical features. The authors concluded that absent steroid sulfatase activity was responsible for the low urinary estriol excretion during pregnancy, reported for the first time in this condition, and for ichthyosis appearing soon after birth. Ikeda et al. (1998) described a 3-year-old boy with multiple sulfatase deficiency who had the complication of hemophagocytic syndrome but recovered with conventional therapy. Hemophagocytic syndrome is characterized by fever, pancytopenia, coagulopathy, liver dysfunction, and proliferation of mature histiocytes. Ikeda et al. (1998) referred to the occurrence of hemophagocytic syndrome in methylmalonic aciduria (251000) and in lysinuric protein intolerance (222700). Biochemical Features Murphy et al. (1971) described a case in which the mucopolysaccharides in the liver were thought to consist of both heparan sulfate and dermatan sulfate, as well as showing accumulated cholesterol sulfate. Fluharty et al. (1978) demonstrated apparently normal arylsulfatase A in cultured fibroblasts under some conditions, indicating that this disorder may be one of regulation. Horwitz (1979) concluded that the defect probably concerns either a regulatory process for production of sulfatases or a posttranslational modification common to sulfatases. At least 9 sulfatases are known to be deficient (Basner et al., 1979); some are lysosomal, some microsomal. Fedde and Horwitz (1984) listed 7 sulfatases as deficient in MSD. In addition, they identified 2-deoxyglucoside 2-sulfamate sulfatase (heparin-N sulfatase; EC 3.1.10.10), for which an isolated genetically determined deficiency has not been identified. Rommerskirch and von Figura (1992) provided strong evidence that the defect in this disorder indeed involves a posttranslational process common to 7 or more sulfatases. In accordance with this concept, they detected RNAs of normal size and amount in MSD fibroblasts for 3 sulfatases tested. When they introduced cDNAs encoding arylsulfatase A, arylsulfatase B, or steroid sulfatase into MSD fibroblasts and fibroblasts with a single sulfatase deficiency by retroviral gene transfer, they found that infected fibroblasts overexpressed the respective sulfatase polypeptides. Whereas a concomitant increase of sulfatase activities was observed in single sulfatase deficiency fibroblasts, MSD fibroblasts expressed sulfatase polypeptides with a severely diminished catalytic activity. From these results, Rommerskirch and von Figura (1992) concluded that the mutation in MSD severely decreases the capacity of a posttranslational, or cotranslational, process that renders sulfatases enzymatically active or prevents their premature inactivation. Schmidt et al. (1995) found from structural analysis of 2 catalytically active sulfatases that a cysteine residue that is predicted from the cDNA sequence and conserved among all known sulfatases is replaced by a 2-amino-3-oxopropionic acid residue, while in sulfatases derived from MSD cells, the cysteine residue is retained. Schmidt et al. (1995) proposed that the co- or posttranslational conversion of a cysteine to 2-amino-3-oxopropionic acid is required for generating catalytically active sulfatases and that deficiency of this protein modification is the cause of MSD. The 2 sulfatases that they studied were arylsulfatase A (ARSA; 607574) and arylsulfatase B (ARSB; 611542). Inheritance Multiple sulfatase deficiency is an autosomal recessive disorder. Mossakowski et al. (1961) observed 3 affected sibs, 2 female and 1 male, in a French Canadian family. The 2 patients reported by Austin (1965) were sibs (in the M family). Molecular Genetics Dierks et al. (2003) and Cosma et al. (2003) identified homozygous or compound heterozygous mutations in the SUMF1 gene in patients with MSD (see, e.g., 607939.0001-607939.0010). Genotype/Phenotype Correlations Schlotawa et al. (2011) observed clear genotype/phenotype correlations among 10 patients with MSD, including 1 with neonatal onset, 7 with severe late-infantile onset, and 2 with mild late-infantile onset. The most severely affected patient with neonatal onset had marked impairments in both SUMF1 stability and enzyme activity and was compound heterozygous for a splice site and a nonsense mutation (607939.0001 and 607939.0003, respectively). Sulfatase activities in this patient were almost undetectable. In contrast, 2 patients with mild late-infantile onset were homozygous for a missense mutation (G263V; 607939.0018), which showed the highest residual enzymatic activity among the studied variants. Patients with the intermediate severe late-infantile form had mutations that compromised stability and caused low levels of residual activity (see, e.g., S155P; 607939.0010). Animal Model Settembre et al. (2007) found that Sumf1-null mice displayed early mortality, congenital growth retardation, skeletal abnormalities, and neurologic deficits, similar to human patients with MSD. Massive lysosomal storage of glycosaminoglycans was observed in all tissues examined and was associated with systemic inflammation, apoptosis, and neurodegeneration. Sumf1-null mice completely lacked all sulfatase activities, indicating that mammals have a single sulfatase modification system. In brain tissue of MSD mice, Settembre et al. (2008) observed increased autophagosomes resulting from impaired autophagosome-lysosome fusion. Cells showed impaired ability to degrade aggregation-prone proteins. There was also an accumulation of ubiquitin-positive inclusions and increased numbers of dysfunctional mitochondria. Similar findings were observed in a mouse model of another lysosomal storage disorder, MPS IIIA (252900). The findings were consistent with these diseases being disorders of autophagy, which may be a common mechanism in neurodegenerative lysosomal storage diseases. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Large forehead \- Prominent forehead \- Periorbital edema \- Flat face \- Coarse facies Ears \- Deafness (variable) Eyes \- Corneal clouding (variable) \- Retinal degeneration Nose \- Upturned nose ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Dysostosis multiplex Spine \- Hypoplastic vertebral bodies Hands \- Broad thumbs \- Broad index fingers SKIN, NAILS, & HAIR Skin \- Ichthyosis MUSCLE, SOFT TISSUES \- Neonatal hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Neurologic deterioration \- Mental retardation \- Hydrocephalus \- Ataxia \- Hyperreflexia of the lower limbs \- Spasticity \- Demyelination \- Cerebral atrophy \- Cerebellar atrophy \- Dilated ventricles \- Periventricular white matter abnormalities LABORATORY ABNORMALITIES \- Decreased activities of multiple sulfatases \- Urinary excretion of mucopolysaccharides \- Accumulation of sulfatides, glycosaminoglycans, sphingolipids, and steroid sulfates in tissues and body fluids MISCELLANEOUS \- Onset usually in the first 4 years of life \- Neonatal and late-infantile onset \- Later onset is associated with slower progression and lesser severity MOLECULAR BASIS \- Caused by mutation in the sulfatase-modifying factor 1 gene (SUMF1, 607939.0001 ) ▲ 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	MULTIPLE SULFATASE DEFICIENCY	c0268263	24,854	omim	https://www.omim.org/entry/272200	2019-09-22T16:22:00	{"doid": ["0050441"], "mesh": ["D052517"], "omim": ["272200"], "icd-10": ["E75.26"], "orphanet": ["585"], "synonyms": ["Alternative titles", "MUCOSULFATIDOSIS", "SULFATIDOSIS, JUVENILE, AUSTIN TYPE"], "genereviews": ["NBK538937"]}
Saul-Wilson syndrome is characterized by short stature (dwarfism) and other skeletal abnormalities. The growth problems in Saul-Wilson syndrome are called primordial, which means they begin before birth; affected individuals show slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate, with the average adult height being 3 feet, 6 inches (107 centimeters). Individuals with Saul-Wilson syndrome have distinctive facial features that often include a prominent forehead, sparse scalp hair and eyebrows, prominent scalp veins, a narrow nasal bridge, a beaked nose, a wide area separating the nostrils (broad columella), a thin upper lip, and a small lower jaw (micrognathia). This combination of facial features can give affected individuals an appearance of premature aging, particularly in infancy, that is sometimes described as progeroid. Additional skeletal abnormalities in Saul-Wilson syndrome include abnormalities in the structure of the long bones, short fingers and toes, an inward- and downward-turning foot (clubfoot), an abnormality of the hip joint that causes a decreased angle between the head and shaft of the upper leg bones (coxa vara), or flattened bones of the spine (platyspondyly) and other spinal abnormalities. Some affected individuals have bones that are unusually fragile, resulting in bone fractures that occur with little or no trauma. Adults with Saul-Wilson syndrome may experience joint pain (osteoarthritis) due to breakdown (degeneration) of the joints. Children with Saul-Wilson syndrome often have hearing loss, clouding of the lenses of the eyes (cataracts), or a blue tint to the whites of the eyes (blue sclerae). They may also have retinitis pigmentosa, in which breakdown of the light-sensitive layer (retina) at the back of the eye can cause vision loss. Individuals with Saul-Wilson syndrome may have early delay of speech and motor development, but they usually have normal intelligence. In Saul-Wilson syndrome, levels of white blood cells can vary from normal to low (intermittent neutropenia). Neutropenia makes it more difficult for the body to fight off foreign invaders such as bacteria and viruses, and may contribute to recurrent respiratory infections that occur in childhood in some individuals with Saul-Wilson syndrome. ## Frequency Saul-Wilson syndrome is a very rare disorder. At least 16 affected individuals have been reported in the scientific literature. ## Causes Saul-Wilson syndrome is caused by mutations in the COG4 gene. This gene provides instructions for making one piece of a group of proteins known as the conserved oligomeric Golgi (COG) complex. This complex functions in the Golgi apparatus, which is a cellular structure in which newly produced proteins are modified so they can carry out their functions. The COG complex plays an important role in the transport of proteins from the Golgi apparatus to another cellular structure called the endoplasmic reticulum. The endoplasmic reticulum processes proteins and helps move them to other structures in the cell. Transporting proteins from the Golgi apparatus to the endoplasmic reticulum (known as retrograde transport) is important for recycling proteins and relocating misplaced proteins. The COG4 gene mutations that cause Saul-Wilson syndrome result in production of an abnormal COG4 protein. Although the protein is altered, it is still able to be a part of the COG complex. When the abnormal COG4 protein is part of the COG complex, the transport of proteins between the Golgi apparatus and the endoplasmic reticulum is increased. It is unclear how this change in retrograde transport impairs bone growth and leads to the signs and symptoms of Saul-Wilson syndrome. ### Learn more about the gene associated with Saul-Wilson syndrome * COG4 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Saul-Wilson syndrome	None	24,855	medlineplus	https://medlineplus.gov/genetics/condition/saul-wilson-syndrome/	2021-01-27T08:24:39	{"omim": ["618150"], "synonyms": []}
## Description Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002). For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750. Mapping To determine the localization of genetic risk factors for celiac disease in addition to 6p21.3 (212750), Greco et al. (1998) performed a systematic screening of the genome in 110 affected sib pairs and their parents. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of celiac disease. Replication of the regions of interest was then carried out on 71 pairs in which 1 sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci on 6p21.3, this study suggested that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiated the 2 forms. Using the maximum lod score method applied to a dense set of markers, Greco et al. (2001) analyzed 6 regions to which potential linkage of celiac disease had previously been proposed. In a new sample of 89 Italian sib pairs, they found evidence for linkage only for chromosome 5q. Their data from this study as well as the data from their previous report (Greco et al., 1998) were compatible with the presence of a risk factor for CD with a moderate effect, operating in addition to the well-known HLA risk factors. Using pooled data from the European Genetics Cluster on Coeliac Disease, Babron et al. (2003) performed meta- and megaanalyses of genotype data from 2,025 individuals, 1,056 of whom had celiac disease. They confirmed the association to the HLA region, and also found a strong suggestion of a genetic risk factor in the 5q31-q33 region, with a maximum Zlr of 4.39, p = 6 x 10(-6). Linkage of celiac disease to this region had also been found by Naluai et al. (2001) and Liu et al. (2002). Amundsen et al. (2007) performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families with celiac disease who demonstrated linkage to the 5q31-q33 region. They failed to identify an association signal of any of the markers that could account for the linkage signal in their cohort. They suggested that collective effects of multiple risk genes within the region, incomplete genetic coverage, or effects related to copy number are possible explanations for their findings. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	CELIAC DISEASE, SUSCEPTIBILITY TO, 2	c1857846	24,856	omim	https://www.omim.org/entry/609754	2019-09-22T16:05:36	{"omim": ["609754"], "synonyms": ["Alternative titles", "GLUTEN-SENSITIVE ENTEROPATHY, SUSCEPTIBILITY TO, 2"]}
A number sign (#) is used with this entry because this form of peroxisomal biogenesis disorder (PBD9B) is caused by homozygous or compound heterozygous mutation in the PEX7 gene (601757) on chromosome 6q23. Description While most patients of PBD complementation group 11 manifest rhizomelic chondrodysplasia punctata (RCDP1; 215100), a few have been reported with unusually mild phenotypes with longer survival, less neurologic involvement, normal or near-normal growth, and absence of rhizomelia (Braverman et al., 2002). In some cases this phenotype was indistinguishable from that of classic Refsum disease (266500) and patients carried this diagnosis. Individuals with PBDs of complementation group 11 (CG11, equivalent to CGR) have mutations in the PEX7 gene. For information on the history of PBD complementation groups, see 214100. Clinical Features Moser et al. (1995) reported 3 patients with PBD CG11 who had unusually mild clinical and biochemical manifestations. Two sisters had congenital cataracts but no dysmorphic features and normal limbs. The older sister had normal cognitive function, and the younger was mentally retarded, functioning at 5 years of age at an 18-month to 2-year-old level. A moderate elevation of levels of phytanic acid in plasma and intermediate reductions in erythrocyte plasmalogen levels and fibroblast plasmalogen synthesis pointed to peroxisome dysfunction. In fibroblasts, the reduced capacity to oxidize phytanic acid and the moderate reduction in plasmalogen synthesis, in combination with normal VLCFA levels, suggested a relationship to RCDP that was confirmed by complementation studies. The third patient, a 55-year-old Norwegian man, had retinitis pigmentosa, polyneuropathy, ichthyosis, hearing loss, and normal cognitive function at age 9 years. He was diagnosed with classic Refsum disease (266500) by Professor Sigvald Refsum. When he was 26 years of age, his plasma phytanic acid levels were elevated and he was given a phytanic acid-restricted diet. At age 53 his neurologic disability had worsened and he had also developed cardiomyopathy. He had not adhered to the diet, but plasma phytanic acid levels were only slightly increased. Except for a reduction in the capacity to oxidize phytanic acid, peroxisomal functions in fibroblasts were normal. Barth et al. (1996) studied a 9-year-old girl with cataracts and atypical bone dysplasia. Neurologic findings were mild compared to classic RCDP. Plasma phytanic acid was normal. Results of de novo plasmalogen synthesis and phytanic acid oxidation studied in cultured skin fibroblasts were intermediate between normal controls and classic RCDP. Peroxisomal thiolase was present only in the unprocessed 44-kD protein. That this was a mild variant of classic RCDP was supported further by complementation studies. Earlier studies had shown that fibroblasts from all RCDP patients belong to a single complementation group. Fibroblasts from this patient likewise fell into this complementation group. The patient had been considered normal until 3 months of age when her mother noticed that her legs could not be straightened. Flexion contractures of the hips, elbows, and knees were found at 1 year. Bilateral cataracts necessitated lens extraction at 2 years. She did not walk independently until 8 years of age. Speech development and adaptive behavior at 8 years represented a mental age between 1 and 2 years. Review of x-ray findings of the knees at the age of 10 months showed irregular calcific stippling outlining the patellas. This stippling had disappeared on repeat examination at 5 years. The length of the humeri and femora were very short with the shortness of the femora not explained by the dysplasia of the hips. Braverman et al. (2002) reported 5 patients with PEX7 mutations and atypically mild phenotypes. One, aged 58 years (PBD147), had a phenotype indistinguishable from that of classic Refsum disease. The second had bilateral cataracts but otherwise normal exams. The third presented in infancy with moderate developmental delay, epiphyseal irregularities on skeletal x-rays, and poor growth. He developed features of adult Refsum disease at age 12 years. The fourth patient at the age of 3 years had moderate mental impairment, cataracts, and chondrodysplasia punctata but is without rhizomelia or growth failure. The fifth patient, age 9 years, had cataracts, chondrodysplasia, and severe mental deficiency but no rhizomelia or growth failure. Horn et al. (2007) reported follow-up of a man with Refsum disease (PBD147 in the report of Braverman et al. (2002)) originally diagnosed by Dr. Refsum in 1948 and reported again by Eldjarn et al. (1966). He presented at age 7 years with all of the classic clinical features, including progressive retinopathy with loss of night vision and concentric narrowing of the visual fields. Pupils were small and irregular in shape and showed impaired response to light stimulation. He had neurogenic hearing loss and anosmia. A chronic sensorimotor neuropathy manifest as lower limb atrophy, lack of distal reflexes, and impaired distal sensation. Subcutaneous nerves were thickened and palpable. There was a history of ichthyosis, and he had hammertoe deformity. Long-term dietary restriction of phytanic acid intake stabilized his progressive loss of vision and hearing. However, at age 40, he developed progressive cardiac disease with arrhythmias and heart failure necessitating cardiac transplant at age 58. Van den Brink et al. (2003) reported 2 probands with Refsum disease. The first proband originated from a family comprising 8 sibs and was 1 of 3 affected. He became ataxic at age 12 years and on examination at age 19 years had retinitis pigmentosa, with limited ocular fields, absence of night blindness, and normal ERG. Other features included anosmia, short fifth metacarpal and palmar ichthyosis, pes cavus, musculature weakness, and nerve hypertrophy, which was confirmed by sural nerve biopsy. His sister presented at age 20 years with postpartum ataxia and numbness in her fingers and toes. She had profound retinitis pigmentosa, abnormal ERG, anosmia, sensory and motor dysfunction with nerve hypertrophy, and mild pes cavus. The third affected sib, a brother, had mild retinitis pigmentosa and anosmia, but no other signs on screening at age 24 years. The second proband originated from a family comprising 8 sibs with 2 living affected members. Although born with bilateral cataracts, she presented to a neurology clinic at age 20 years with polyneuritis and onset of ataxia at age 19 years. She had bilateral short fifth metacarpals and metatarsals, and mild retinitis pigmentosa. Her brother presented at age 34 years with mild ataxia and mild retinitis pigmentosa but no night blindness, obvious anosmia, or deafness. Neither patient had any episodes of ichthyosis or signs of deafness. One other male sib died of supposed poliomyelitis with symptoms of weakness and ataxia at age 12 years. Yu et al. (2013) reported 3 children from a consanguineous Pakistani family who were diagnosed with autism spectrum disorder and intellectual disability and who carried a homozygous mutation in the PEX7 gene. These children were not dysmorphic and did not exhibit skeletal dysplasia, but 2 had cataracts, and 2 had epilepsy. Yu et al. (2013) recontacted 2 sibs reported by Braverman et al. (2002) with mild peroxisome biogenesis disorder 9B; one was originally described as intellectually disabled and the other as neurotypical. Both had cataracts and the intellectually disabled sib had seizures. Review of clinical records and reexamination revealed that the first child had been diagnosed with autism spectrum disorder and the second with severe ADHD, providing additional examples of the range of clinical expressivity of mild mutations in PEX7. Biochemical Features All of the patients studied by van den Brink et al. (2003) with a clinical diagnosis of Refsum disease had elevated plasma phytanic acid (range 142-1,950 micromol/l). Extended biochemical analysis revealed normal pristanic acid beta-oxidation and normal punctate pattern of catalase immunofluorescence but plasmalogen synthesis was deficient. This last finding had not been observed in classic Refsum disease but is characteristic of patients with RCDP1, who carry mutations in the PEX7 gene. Mapping In a linkage study of 8 genetically informative families including 17 living patients with Refsum disease, Wierzbicki et al. (2000) excluded linkage to the region of chromosome 10 containing the PAHX gene (602026), mutant in classic Refsum disease, in 3 families with 9 affected individuals. Van den Brink et al. (2003) performed multipoint linkage analysis in 2 families with probands clinically diagnosed with Refsum disease but in whom no mutations were identified in the PHYH (PAHX) gene. They found linkage to a region of chromosome 6 that extended D6S292 to D6S441, with a peak lod score of 1.92 between D6S314 and D6S308 close to the locus for PEX7. Molecular Genetics In a 58-year-old patient with a phenotype indistinguishable from that of classic Refsum disease, Braverman et al. (2002) detected compound heterozygosity for a premature termination mutation (601757.0007) and a splice site mutation (601757.0008) in the PEX7 gene. A patient with bilateral cataracts but with otherwise normal exams was compound heterozygous for 2 missense mutations (e.g., 601757.0002). Horn et al. (2007) provided follow-up of this patient. In 3 affected sibs with a clinical diagnosis of Refsum disease, van den Brink et al. (2003) found compound heterozygosity for 2 mutations in the PEX7 gene: Y40X (601757.0009) and a 7-bp duplication (601757.0010). Another unrelated patient was compound heterozygous for Y40X and a missense mutation (T14P; 601757.0011). History Vallat et al. (1996) described an otherwise normal 44-year-old man with very high, isolated L-hyperpipecolatemia (220-250 micromoles/liter; normal less than 2.5) but none of the clinical features seen in peroxisomal diseases. Urinary excretion of pipecolic acid was very low (0.8 mmol/mol creatinine; normal less than 1.5). Liver pipecolic acid oxidase was not measured in liver. The authors suggested that isolated L-hyperpipecolatemia may be a benign trait. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Neurogenic hearing loss (in some patients) Eyes \- Cataract (in some patients) \- Retinitis pigmentosa Nose \- Anosmia CARDIOVASCULAR Heart \- Cardiomyopathy (in some patients) SKELETAL Hands \- Short 5th metacarpals (in some patients) Feet \- Short 5th metatarsals (in some patients) \- Pes cavus SKIN, NAILS, & HAIR Skin \- Ichthyosis MUSCLE, SOFT TISSUES \- Muscle weakness NEUROLOGIC Central Nervous System \- Ataxia Peripheral Nervous System \- Sensorimotor polyneuropathy \- Nerve hypertrophy LABORATORY ABNORMALITIES \- PBD complementation group 11 \- PBD complementation group R \- Elevated plasma phytanic acid levels MISCELLANEOUS \- Variable age of onset (range 7-24 years) \- Dietary restriction of phytanic acid intake can stabilize hearing and vision loss MOLECULAR BASIS \- Caused by mutation in the peroxisome biogenesis factor 7 gene (PEX7, 601757.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	PEROXISOME BIOGENESIS DISORDER 9B	c0034960	24,857	omim	https://www.omim.org/entry/614879	2019-09-22T15:53:50	{"mesh": ["D012035"], "omim": ["614879"], "orphanet": ["773"], "synonyms": ["Alternative titles", "REFSUM DISEASE, ADULT, 2", "PEROXISOME BIOGENESIS DISORDER, PEX7-RELATED, ATYPICAL"], "genereviews": ["NBK1353"]}
## Clinical Features Sugarman et al. (1971) reported a new form of oral-facial-digital syndrome in 2 sisters. Features were mental retardation, eye abnormalities, lobulated hamartomatous tongue, dental abnormalities, bifid uvula, postaxial hexadactyly of hands and feet, pectus excavatum, short sternum, and kyphosis. One of the sibs showed ceaseless 'see-saw winking' of the eyes. The parents were not related. We have observed a family in which 3 of 4 sibs (2 males, 1 female) were affected. None had 'see-saw' winking. However, all had myoclonic jerks, affected lids, extraocular muscles, arms, etc. Hypertelorism, exotropia, irregular teeth, hamartomatous tongue, postaxial polydactyly, and profound mental retardation were features strikingly like those in Sugarman's cases. The sibs showed severe spasticity. One had a macular red spot, leading some to classify the disorder as cerebromacular degeneration (Ford, 1960). Others had suggested Biedl-Bardet syndrome (209900) as the diagnosis, as often happens when the combination of mental retardation and polydactyly is encountered. Smith and Gardner-Medwin (1993) described a brother and sister with mental retardation, malformations of the cerebellar vermis, characteristic 'metronome eye movements,' lingual hamartomas, and postaxial polydactyly. Some of the features overlapped with those of OFD syndrome VI (277170) and Joubert syndrome (213300). Inheritance Munke et al. (1990) considered the mode of inheritance to be autosomal recessive. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Low-set ears Eyes \- Macular red spot \- See-saw eye winking \- Hypertelorism Nose \- Bulbous nose Mouth \- Cleft uvula \- Tongue nodules \- Cleft tongue Teeth \- Extra teeth \- Small teeth CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum \- Short sternum SKELETAL Spine \- Kyphosis Hands \- Postaxial polydactyly Feet \- Postaxial polydactyly SKIN, NAILS, & HAIR Nails \- Hyperconvex nails NEUROLOGIC Central Nervous System \- Myoclonic jerks \- Mental retardation ▲ 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	OROFACIODIGITAL SYNDROME III	c0406726	24,858	omim	https://www.omim.org/entry/258850	2019-09-22T16:24:05	{"doid": ["0060373"], "mesh": ["C557817"], "omim": ["258850"], "orphanet": ["2752"], "synonyms": ["Alternative titles", "OFDS III", "ORAL-FACIAL-DIGITAL SYNDROME, TYPE III", "SUGARMAN SYNDROME"]}
A rare genetic disease characterized by juvenile-onset insulin-dependent diabetes mellitus associated with central and peripheral nervous system abnormalities with variable onset between infancy and adolescence. Neurological manifestations include combined cerebellar and afferent ataxia, sensorineural hearing loss, pyramidal tract signs, and demyelinating sensorimotor peripheral neuropathy. Hypothyroidism has been reported in some patients. Brain imaging may show generalized cerebral atrophy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	c4015436	24,859	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=445062	2021-01-23T18:18:09	{"omim": ["616192"], "synonyms": ["Combined cerebellar and peripheral ataxia-deafness-diabetes mellitus syndrome", "Combined cerebellar and peripheral ataxia-hearing loss-diabetes mellitus syndrome"]}
Stargardt macular degeneration is a genetic eye disorder that causes progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, Stargardt macular degeneration affects a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In most people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. In addition to central vision loss, people with Stargardt macular degeneration have problems with night vision that can make it difficult to navigate in low light. Some affected individuals also have impaired color vision. The signs and symptoms of Stargardt macular degeneration typically appear in late childhood to early adulthood and worsen over time. ## Frequency Stargardt macular degeneration is the most common form of juvenile macular degeneration, the signs and symptoms of which begin in childhood. The estimated prevalence of Stargardt macular degeneration is 1 in 8,000 to 10,000 individuals. ## Causes In most cases, Stargardt macular degeneration is caused by mutations in the ABCA4 gene. Less often, mutations in the ELOVL4 gene cause this condition. The ABCA4 and ELOVL4 genes provide instructions for making proteins that are found in light-sensing (photoreceptor) cells in the retina. The ABCA4 protein transports potentially toxic substances out of photoreceptor cells. These substances form after phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. Mutations in the ABCA4 gene prevent the ABCA4 protein from removing toxic byproducts from photoreceptor cells. These toxic substances build up and form lipofuscin in the photoreceptor cells and the surrounding cells of the retina, eventually causing cell death. Loss of cells in the retina causes the progressive vision loss characteristic of Stargardt macular degeneration. The ELOVL4 protein plays a role in making a group of fats called very long-chain fatty acids. The ELOVL4 protein is primarily active (expressed) in the retina, but is also expressed in the brain and skin. The function of very long-chain fatty acids within the retina is unknown. Mutations in the ELOVL4 gene lead to the formation of ELOVL4 protein clumps (aggregates) that build up and may interfere with retinal cell functions, ultimately leading to cell death. ### Learn more about the genes associated with Stargardt macular degeneration * ABCA4 * ELOVL4 ## Inheritance Pattern Stargardt macular degeneration can have different inheritance patterns. When mutations in the ABCA4 gene cause this condition, it 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. When this condition is caused by mutations in the ELOVL4 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Stargardt macular degeneration	c1855465	24,860	medlineplus	https://medlineplus.gov/genetics/condition/stargardt-macular-degeneration/	2021-01-27T08:25:12	{"gard": ["181"], "mesh": ["C535804"], "omim": ["248200", "600110"], "synonyms": []}
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure (cardiovascular and/or urinary), parkinsonism, cerebellar impairment and corticospinal signs with a median survival of 6-9 years. ## Epidemiology Prevalence ranges from 1/50,000-1/20,000. MSA-parkinsonian type (MSA-p) predominates in the Western Hemisphere and MSA-cerebellar type (MSA-c) predominates in the Eastern Hemisphere. Genders are equally distributed. ## Clinical description MSA is an adult-onset disorder (>30 years, mean age 55-60 years). Clinical manifestations include autonomic failure (orthostatic hypotension, syncope, respiratory disturbances (sleep apnea, stridor and inspiratory sighs), constipation, bladder dysfunction (early urinary incontinence), erectile dysfunction in males and Raynaud syndrome). In some cases, pyramidal signs (generalized hyperreflexia and positive Babinski sign) are observed. MSA-p, a form of MSA with predominant parkinsonian features, comprises bradykinesia, rigidity, irregular jerky postural tremor and abnormal postures (camptocormia, Pisa syndrome and disproportionate antecollis). Patients with MSA-p may develop levodopa-induced orofacial and craniocervical dystonia. Classic pill-rolling rest tremor is uncommon. MSA-c is a form of MSA with predominant cerebellar features such as gait and limb ataxia, oculomotor dysfunction and dysarthria. The predominant motor feature can change with time and patients with cerebellar ataxia can develop increasingly severe parkinsonian features which dominate the clinical presentation. Neuropsychiatric features, oculomotor dysfunction and sleep disturbances are also observed in MSA and include apathy, anxiety, depression, rapid eye movement sleep behavior disorder and periodic limb movements in sleep. ## Etiology Etiology of MSA is unknown but presence of cytoplasmic aggregates of α-synuclein, primarily in oligodendroglia, in combination with neurodegeneration in striatonigral and olivopontocerebellar structures are the pathological hallmark features. Mutations in COQ2 (4q21.23) (encoding an enzyme involved in biosynthesis of coenzyme Q10) have been shown in multiplex families with MSA, while some variants were associated with an increased risk for sporadic MSA. ## Diagnostic methods Diagnosis of ''probable'' MSA requires presence of parkinsonism with poor levodopa response or cerebellar signs together with severe autonomic failure (otherwise unexplained urinary incontinence or an orthostatic decrease of blood pressure within 3 min of standing by at least 30 mm Hg systolic or 15 mm Hg diastolic). MRI findings include atrophy of putamen and middle cerebellar peduncles, as well as putaminal and cerebellar hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography. ''Definite'' MSA requires post-mortem demonstration of α-synuclein positive glial cytoplasmic inclusions with neurodegeneration of striatonigral and olivopontocerebellar structures. ## Differential diagnosis Differential diagnosis of MSA-p includes Parkinson's disease and other atypical parkinsonian disorders (progressive supranuclear palsy, corticobasal syndrome). Differential diagnosis of MSA-c includes dominantly inherited spinocerebellar ataxias (SCAs 1, 2, 3, 6, and 7), fragile X-associated tremor/ataxia syndrome (FXTAS) and mitochondriopathies (POLG1 gene mutations). ## Genetic counseling MSA occurs sporadically. However, some familial cases have been described. ## Management and treatment Therapy mainly targets parkinsonism and autonomic failure. Levodopa may transiently improve parkinsonism (20-30% of patients). No effective neuroprotective therapy is available. ## Prognosis MSA is rapidly progressive and is associated with wheelchair dependence, unintelligible speech, intermittent urinary catheterization, disabling orthostatic hypotension, and cognitive impairment (executive dysfunction). Disease progression is assessed using the unified MSA rating scale (UMSARS), which rates activities of daily life, autonomic and motor impairment, as well as overall disability. Prognosis is poor with a median survival of 6-9 years. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Multiple system atrophy	c0393571	24,861	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=102	2021-01-23T17:06:23	{"gard": ["7079"], "mesh": ["D019578"], "omim": ["146500"], "umls": ["C0393571"], "icd-10": ["G23.2", "G23.3"], "synonyms": ["MSA", "Multisystem atrophy"]}
Multiminicore disease is a disorder that primarily affects muscles used for movement (skeletal muscles). This condition causes muscle weakness and related health problems that range from mild to life-threatening. Researchers have identified at least four forms of multiminicore disease, which can be distinguished by their characteristic signs and symptoms. The forms of multiminicore disease are the classic form, the progressive form with hand involvement, the antenatal form with arthrogryposis, and the ophthalmoplegic form. The classic form accounts for about 75 percent of cases of multiminicore disease. This form causes muscle weakness beginning in infancy or early childhood. The muscles of the torso and neck (axial muscles) are most affected with arm and leg muscles less so. Muscle weakness causes affected infants to appear "floppy" (hypotonic) and they may have feeding problems early in life. Muscle weakness can delay the development of motor skills such as sitting, standing, and walking. In this form, the muscles of the ribcage and spine become stiff. In addition, the muscles needed for breathing are weak. This combination of muscle weakness and stiffness leads to severe or life-threatening respiratory problems. Almost all children with the classic form develop an abnormal curvature of the spine (scoliosis), which appears during childhood and steadily worsens over time. The progressive form with hand involvement causes muscle weakness and looseness of the joints (joint laxity) in the arms and hands. Individuals with this form may experience muscle pain (myalgia) or extreme fatigue in response to physical activity (exercise intolerance). This form accounts for about 10 percent of cases of multiminicore disease. The antenatal form with arthrogryposis is characterized by stiff, rigid joints throughout the body (arthrogryposis) and distinctive facial features. Weakness in the muscles needed for breathing can result in breathing problems for affected individuals. This form also accounts for about 10 percent of cases of multiminicore disease. The ophthalmoplegic form of multiminicore disease is characterized by paralysis of the eye muscles (external ophthalmoplegia). This can lead to abnormal eye movements and droopy eyelids (ptosis). This form of the condition can also cause weakness in the muscles close to the center of the body (proximal muscles), such as those of the upper arms and legs. The ophthalmoplegic form accounts for 5 to 10 percent of cases of multiminicore disease. Many people with multiminicore disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate (tachycardia) and body temperature (hyperthermia), abnormally fast breathing (tachypnea), muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). The complications of malignant hyperthermia can be life-threatening unless they are treated promptly. Multiminicore disease gets its name from small, disorganized areas called minicores, which are found in skeletal muscle cells of many affected individuals. These abnormal regions can only been seen when muscle tissue is viewed under a microscope. Minicores are often present in cells with few or no mitochondria, which are the energy-producing centers within cells. Although the presence of minicores can help doctors diagnose multiminicore disease, it is unclear how they are related to muscle weakness and the other features of this condition. ## Frequency Multiminicore disease is thought to be a rare disorder, although its incidence is unknown. ## Causes Mutations in the SELENON and RYR1 genes have been found to cause about half of all cases of multiminicore disease. About 30 percent of cases of multiminicore disease, primarily the classic form, are caused by mutations in the SELENON gene. This gene provides instructions for making a protein called selenoprotein N. This protein is highly active in many tissues before birth and may be involved in the formation of muscle tissue (myogenesis). The protein may also be important for normal muscle function after birth, although it is active at much lower levels in adult tissues. This protein is thought to play a role in maintaining an appropriate balance of calcium (calcium homeostasis) in cells. Calcium plays an important role in muscle movement. It is unclear, however, how mutations in the SELENON gene lead to muscle weakness and the other features of multiminicore disease. An estimated 20 percent of multiminicore disease, primarily the non-classic forms, are caused by mutations in the RYR1 gene. The RYR1 gene provides instructions for making a protein called ryanodine receptor 1. This protein plays an essential role in skeletal muscles. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of charged atoms (ions) into muscle cells. The ryanodine receptor 1 protein forms a channel that releases calcium ions stored within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract, allowing the body to move. Mutations in the RYR1 gene change the structure and function of the ryanodine receptor 1 protein and the calcium channel that it forms. The abnormal calcium channel alters the normal flow of stored calcium ions within muscle cells. A disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of multiminicore disease. RYR1 gene mutations are also associated with an increased risk of malignant hyperthermia. It is likely that individuals with multiminicore disease who do not have a known mutation in either of these two genes have mutations in other genes that underlie the condition. ### Learn more about the genes associated with Multiminicore disease * RYR1 * SELENON ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Multiminicore disease	c1850674	24,862	medlineplus	https://medlineplus.gov/genetics/condition/multiminicore-disease/	2021-01-27T08:24:39	{"gard": ["10316", "9129", "9130"], "mesh": ["C564969"], "omim": ["255320", "602771"], "synonyms": []}
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (January 2017) (Learn how and when to remove this template message) A microgyrus is an area of the cerebral cortex that includes only four cortical layers instead of six. Microgyria are believed by some to be part of the genetic lack of prenatal development which is a cause of, or one of the causes of, dyslexia. Albert Galaburda of Harvard Medical School noticed that language centers in dyslexic brains showed microscopic flaws known as ectopias and microgyria (Galaburda et al., 2006, Nature Neuroscience 9(10): 1213-1217). Both affect the normal six-layer structure of the cortex. These flaws affect connectivity and functionality of the cortex in critical areas related to sound and visual processing. These and similar structural abnormalities may be the basis of the inevitable and hard to overcome difficulty in reading. ## External links[edit] * The neurological basis of developmental dyslexia[permanent dead link] * Another article on the subject * Birthdates of neurons in induced microgyria This neuroanatomy 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	Microgyrus	c2362742	24,863	wikipedia	https://en.wikipedia.org/wiki/Microgyrus	2021-01-18T18:52:15	{"umls": ["C2362742"], "wikidata": ["Q16999912"]}
Referred itch Other namesMitempfindung A diagram showing the connected points between stimulus and itch. Referred itch is the phenomenon in which a stimulus applied in one region of the body is felt as an itch or irritation in a different part of the body. The syndrome is relatively harmless, though it can be irritating, and healthy individuals can express symptoms. Stimuli range from a firm pressure applied to the skin – a scratch – to irritation or pulling on a hair follicle on the skin.[1] The referred sensation itself should not be painful; it is more of an irritating prickle leading to the compulsion to scratch the area. The stimulus and referred itch are ipsilateral (the stimulus and the referred itch occur on the same side of the body). Also, because scratching or putting pressure on the referred itch does not cause the stimulus area to itch, the relationship between the stimulus and the referred itch is unidirectional.[2] The itching sensation is spontaneous and can cease with continued stimulation. There are two types of referred itch: normal and acquired (pathological). Normal mitempfindung is usually detected in early childhood and persists for the majority, if not the rest, of the individual’s life. Acquired or pathological mitempfindung is the effect of damage to the central nervous system and only lasts for a short period of time.[1] Symptoms are variable among affected individuals, but it is widely accepted that the soles of the feet, palms, and the face are never affected by mitempfindung[citation needed]. There is no evidence of genetic influence on referred itch.[1] There is a published study, however, that mentions an affected man whose children were also affected. Much is still unknown about the physiological mechanisms of the phenomenon, and no single theory is accepted. Research and information regarding mitempfindung is limited and dated. Most research on the topic was conducted in the late 19th century, and the most recent publications occurred in the late 1970s. A handful of studies were done in the early 1990s, but further data must be collected and interpreted before a thorough understanding of mitempfindung is reached. ## Contents * 1 Signs and symptoms * 1.1 Location of original itch and referred itch * 1.2 Synesthesia and mitempfindung * 1.3 Normal and pathological referred itch * 2 Causes * 3 Mechanisms * 4 Management * 5 Epidemiology * 6 History * 7 Current research * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] ### Location of original itch and referred itch[edit] The location of the reference point for each individual that experiences referred itch is well conserved and specific to each person, in that a certain location will elicit the phenomenon repeatedly for a given person while itches elsewhere may not. However, frequent and repetitive stimulation of the same original itch location can weaken the phenomenon, making the referred itch increasingly more discrete with each repeated trial.[1] There is also no evidence of a relationship between the site of the original stimulus and that of the referred itch.[1] Though the location of the referred itch may remain fairly constant and precise for a particular stimulus location on a single individual, there is no substantial evidence linking any two locations in a definite origin/referred location relationship. Thus, referral patterns are extremely variable and offer little to no indication of where a referred itch will occur if the location of the original itch is known. The phenomenon is unidirectional.[1] Consequently, scratching an itch in a location that has previously served as the point of a referred itch does not induce an itch in the person’s typical origination site. ### Synesthesia and mitempfindung[edit] Mitempfindung has been thought to be related to synesthesia in some individuals, specifically digit-color synesthesia.[3] Digit-color synesthesia is a phenomenon in which affected individuals associate individual numbers with certain colors; individuals have been said to "count in colors."[3][4] Both synesthesia and mitempfindung develop in early childhood and are highly variable among individuals.[3] Furthermore, synesthesia and mitempfindung are both unidirectional. A scratch on the trigger zone creates a referred sensation in a distant body part but not vice versa. Likewise, in synesthesia, a person's association of a number with a color does not mean that that color aways evokes that number for them. ### Normal and pathological referred itch[edit] Referred itch is the class of referred sensation that focuses on the situation in which an itch in one place on the body simultaneously triggers an itch in a different location. Other examples of referred sensation include sensations of temperature, pain, and pressure.[1] Referred itch is commonly observed in completely healthy individuals and can often go unnoticed depending upon the particular person’s self-awareness of their itches and the causes of those itches. The ephemeral nature of referred itch and its restriction to a very small area on one’s body (the itch is precisely located, it does not induce widespread itching) make it difficult to document or even notice.[1] The majority of the cases of referred itch studied by experimenters occur in healthy individuals. Furthermore, referred itch itself does not confer any adverse effects on the health of those experiencing it. With the exception of the annoyance of feeling multiple itches and a potentially minuscule feeling of pain, it is an innocuous condition. The cause of referred itch in healthy individuals is still not known for certain, but there are a multiple recorded cases of referred itch being triggered by certain pathological stimuli.[1] Two men developed temporary referred sensation after suffering from shingles. Here, the referred sensation occurred in the areas previously affected by the shingles.[1] Another man who suffered from hyperpathia and reduced nerve functioning later experienced referred itch in conjunction with his pathology.[1] This evidence suggests that although referred itch occurs spontaneously in healthy individuals, certain pathologies make it possible to acquire the condition, even if only temporarily. ## Causes[edit] Itch (pruritus) has many causes. Allergies and inflammatory skin disease all produce itch as a symptom.[5][6] Pathophysiologically, the sensation of the itch is poorly understood. Nevertheless, there are many known inducers of itch. Histamine is wildly known as an inducer of the itch sensation. Other substances known to induce itch are substance P, cytokines, and proteases. Temperature also has an effect. It is conventional opinion that applied cold temperature inhibits itch by inhibiting C-fiber activity.[7][8][9][10][11] However, studies have also described paradoxical phenomena associated with temperature and itch, where applied short-term moderate cold temperature stimulus enhanced the itch.[12] Such a phenomenon might be explained by "paradoxical heat", which is when one has the perception of heat when, in fact, the skin is innocuously cooled.[13] Thus, the exact effect of temperature on itch remains unclear, with different levels of heat and cold proven to both enhance and inhibit itch.[14] Alcohol is known to have close interactions with histamine release. Alcohol both stimulates the release of histamine from mast cells and inhibits its degradations by inhibiting diamine oxidase. Though histamine is used by the body to mediate alcohol-induced gastric and intestinal damage as well as alcohol flushing, it is possible that elevated levels of histamine might have a correlation with referred itch (or even itch in general).[15] ## Mechanisms[edit] An itch, also known as pruritus, is classified as a sensory stimulation to scratch a certain area of the skin. An itch can be a fleeting sensation, as with a random tickle or prick, or persistent, as with a rash such as eczema or other skin irritant such as an allergen. Itch has been demonstrated to be closely related to pain and to share many of its physiological mechanisms. The relationship between pain and itch is evident in the fact that itch sensations occur along a similar neurological and sensory pathway as sensations of pain, and the fact that individuals who are insensitive to pain are also insensitive to itch.[16] Itch is induced by mechanical, chemical, thermal, or electrical stimuli of sensory receptors in the peripheral nervous system, or by psychological prompts. The receptors that are responsible for the sensation of itch caused by environmental stimuli are found within the upper layers of the skin.[17] Once stimulated, usually by histamine within the body, a signal is sent through the peripheral nervous system to the brain (thalamus), where the information is processed and the command for the bodily response is issued.[16] Itch can also originate as a result of damage to the nervous system (central or peripheral) or in response to the presence of excess opioids.[16] Because of the scarcity of research available on mitempfindung, there is no widely accepted theory on how the referral of sensation is manifested. There are, however, a wide range of hypotheses which carry traction within the scientific community. One proposed mechanism implicates the nerve and its branches. At the cellular level, this hypothesis postulates that abnormal branching of neurons occurs during embryogenesis.[18] During development, the branch of an afferent article may travel unusually far in the nervous system. Thus, in an individual with a fully developed nervous system, the stimulus at the end of one branch may be interpreted as coming from a point of ending in another, distant, part of the body. Again, research has not been done to prove this hypothesis as valid or invalid.[2] There is an untested hypothesis that claims that referred itch uses the spinocervical tract pathway.[2] The cells in this tract lie in the dorsal horn of the spinal cord, and its axons run in the ipsilateral and dorsolateral quadrant, which is consistent with observations that stimuli in the trigger points are ipsilateral to the sites of referred sensations. These axons project to the thalamus and midbrain, suggesting that the thalamus is involved in the phenomenon. The cells in this tract are also excited by mechanical stimuli, lending support that this pathway can explain the mechanism of referred itch. Central neuronal damage to this area – either direct or secondary to peripheral nerve damage – makes it an area of focal hyperexcitability or reduced inhibition. This hypothesis has been found to be unlikely because there would be an expected progression of itches (i.e., from legs to trunk, and from trunk to neck).[2] However, there is no symmetrical distribution found between trigger zones and sites of referred sensation. There is great support behind the idea of the thalamus affecting mitempfindung.[2] Because of the arrangement of sensory regions in the thalamus, there may be a spread of excitation in this brain region. Studies have shown that the thalamic region dedicated to the trunk is found between the regions supporting sensation from the arms and legs. This supports the finding that trigger zones in the chest area lead to referred sensation in the legs. And since the thalamic region for the face lies in a separate area called the arcuate nucleus, this explains why the face remains unaffected by referred itch. Some spread in association within the cerebral cortex may also explain the large distances between trigger points and referred sensation sites.[2] In the precentral area where the homunculus rests, it is known that hand and shoulder areas overlap the trunk area. And the area of the thumb overlaps that of the upper part of the tongue. There is a published case in which stimulation in the thumb led to a referred sensation in the upper part of the tongue. ## Management[edit] The origin of referred itch is unknown, whether it be neuropathic (originating in the brain), pruritoceptic (originating at the skin), or disease related, so treatment for it specifically still remains unclear. Nevertheless, treatment for different kinds of itch, some of which may be applicable to referred itch, are available. Note that people with this symptom should seek medical care and consult appropriate medications with a doctor. Aspirin taken orally has minimal effect on itch.[19] Therapeutic options for itch that originates in the central nervous system are limited, and need further confirmation, but are in general based on the counteracting interaction between itch and pain via the spine.[20] Treatments of low dosage lidocaine and gabapentin might be effective in relieving itch that is thought to originate in the central nervous system.[21] ## Epidemiology[edit] The prevalence of mitempfindung is difficult to determine exactly, because many individuals would not be aware of having referred itch until the phenomenon is explained to them. Consequently, variability exists within the scientific literature as to the actual prevalence of referred itch in humans.[1] Mittelmann (1920) has reported that 8 out of 9 people questioned experienced referred sensations. In 1973, Sterling reported that about half of 20 healthy individuals questioned had mitempfindung.[1] The variability and heterogeneous characteristic of mitempfindung among individuals makes it difficult to determine a precise set of identifying symptoms of the disease, or a set of risk factors. Nevertheless, mitempfindung is thought to be extremely common. ## History[edit] The term mitempfindungen (literally "associated sensations") was first used in 1844 by the German scientist Johannes Müller.[22] "Referred itch" was only used after 1884, in context to Kowalewsky’s research. The phenomenon of referred itch was documented as early as 1733. Around that time, the English scientist Stephen Hales observed that when an area of the body was scratched by the nails, an itching sensation could be triggered on a distant part of the body. He had called the phenomenon the many "Instances of the Sympathy of the Nerves."[23] More extensive observations on the referral of sensation were documented by Kowalewsky, who observed referred sensations on himself. Kowalewsky published his findings in 1884. ## Current research[edit] Although referred itch was first observed nearly 280 years ago, its cause and mechanism between stimulus and referred itch still remain vague and unproven. Up to this point, the most convincing evidence points toward the thalamus, sympathetic nervous system, and chemical signals (like histamine) as the major aspects of our physiology responsible for the phenomenon, as explained above. Increasing knowledge of itching in general and its similarities with pain in the future could help to reveal some of what is unknown about referred itch, as could a better understanding of histamine and the C-fibers' involvement with itch sensations. Without question, there is a need for further experimentation and study to be directed at referred itch, particularly as the body of evidence pertaining to it is scattered and often inconclusive. ## References[edit] 1. ^ a b c d e f g h i j k l m Schott GD. "Distant referral of cutaneous sensation (Mitempfindung). Observations on its normal and pathological occurrence." Brain. 1988 Oct., Vol. 111, Issue 5: 1187-1198. 2. ^ a b c d e f Evans PR (1976). "Referred itch (Mitempfindungen)". Br Med J. 2 (6040): 839–41. doi:10.1136/bmj.2.6040.839. PMC 1688972. PMID 990713. 3. ^ a b c Burrack A.; Knoch D.; Brugger P. (2006). "Mitempfindung in Synaesthetes: Co-incidence or Meaningful Association?". Cortex. 42 (2): 151–54. doi:10.1016/s0010-9452(08)70339-3. PMID 16683488. 4. ^ Cytowic, Richard E. (2002). Synesthesia : a union of the senses (2nd ed.). Cambridge, MA: MIT Press. ISBN 9780262271073. OCLC 51959282. 5. ^ Behrendt H, Krämer U, Schäfer T, Kasche A, Eberlein-König B, Darsow U, et al. (2001). "Allergotoxicology – a research concept to study the role of environmental pollutants in allergy". ACI Int. 13: 122–128. 6. ^ Charlesworth EN, Beltrani VS (2002). "Pruritic dermatoses: overview of etiology and therapy". Am J Med. 113 (9): 25S–33S. doi:10.1016/S0002-9343(02)01434-1. PMID 12517579. 7. ^ Greaves MW (1993) Pathophysiology and clinical aspects of pruritus. In: Dermatology in General Medicine. (Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds), 4th ed., Vol. 1, New York: McGraw-Hill, 416 8. ^ Bromm B, Scharein E, Darsow U, Ring J (1995). "Effects of menthol and cold on histamine-induced itch and skin reactions in man". Neurosci Lett. 187 (3): 157–160. doi:10.1016/0304-3940(95)11362-Z. PMID 7624016. 9. ^ Carstens E, Jinks SL (1998). "Skin cooling attenuates rat dorsal horn neuronal responses to intracutaneous histamine". NeuroReport. 9 (18): 4145–4149. doi:10.1097/00001756-199812210-00027. PMID 9926864. 10. ^ Craig AD (2002). "How do you feel? Interoception: the sense of the physiological condition of the body". Nature Reviews Neuroscience. 3 (8): 655–666. doi:10.1038/nrn894. PMID 12154366. 11. ^ Mochizuki H, Tashiro M, Kano M, Sakurada Y, Itoh M, Yanai K (2003). "Imaging of central itch modulation in the human brain using positron emission tomography". Pain. 105 (1–2): 339–346. doi:10.1016/S0304-3959(03)00249-5. PMID 14499452. 12. ^ Florian et. al, 2006, Short-term alternating temperature enhances histamine-induced itch: a biphasic stimulus model 13. ^ Davis KD, Pope GE, Crawley AP, Mikulis DJ (2004). "Perceptual illusion of "paradoxical heat" engages the insular cortex". J Neurophysiol. 92 (2): 1248–1251. doi:10.1152/jn.00084.2004. PMID 15277602. 14. ^ Yosipovitch G, Fast K, Bernhard JD (2005). "Noxious heat and scratching decrease histamine-induced itch and skin blood flow". J Invest Dermatol. 125 (6): 1268–1272. doi:10.1111/j.0022-202X.2005.23942.x. PMID 16354198. 15. ^ Alcohol-Histamine interactions, Sergey M. Zimatkin and Oleg V. Antichtchik, Institute of Biochemistry, National Academy of Science of Belarus, Grodno, Belarus, and Department of Biology, Abo Akademi University, Finland. 16. ^ a b c Davidson Steve; Giesler Glenn J (2010). "The Multiple Pathways for Itch and their Interactions with Pain". Trends in Neurosciences. 33 (12): 550–558. doi:10.1016/j.tins.2010.09.002. PMC 2991051. PMID 21056479. 17. ^ Ikoma A, Steinhoff M, Ständer S, Yosipovitch G, Schmelz M (Jul 2006). "The Neurobiology of Itch". Nature Reviews Neuroscience. 7 (7): 535–47. doi:10.1038/nrn1950. PMID 16791143. 18. ^ Pearce JM (2006). "Referred Itch (Mitempfindung)". Eur. Neurol. 55 (4): 233–234. doi:10.1159/000093877. 19. ^ Daly BM, Shuster S (1986). "Effect of aspirin on pruritus". BMJ. 293 (6552): 907. doi:10.1136/bmj.293.6552.907. PMC 1341706. PMID 3094711. 20. ^ Department of Dermatology, Wake forest, et al. 2003 Itch 21. ^ Fishman SM, Caneris OA, Stojanovic MP, Borsook D (1997). "Intravenous lidocaine". Am J Med. 102 (6): 584–585. doi:10.1016/s0002-9343(97)00057-0. PMID 9217675. 22. ^ Müller J (1844) Handbuch der Physiologie des Menschen für Vorlesungen, Volume 1. Fourth edition. Coblenz; J. Holscher, p. 603. 23. ^ Hales S (1733) Statical Essays, Volume 2. London: W. Innys, R. Manby and T. Woodmward, pp. 59-60. ## Further reading[edit] * Pearce JM (June 2006). "Referred Itch (Mitempfindung)". Eur. Neurol. 55 (4): 233–234. doi:10.1159/000093877. * Richter CP (October 1977). "Mysterious form of referred sensation in man". Proc. Natl. Acad. Sci. U.S.A. 74 (10): 4702–5. Bibcode:1977PNAS...74.4702R. doi:10.1073/pnas.74.10.4702. PMC 432016. PMID 270709. ## External links[edit] Classification D * ICD-10: Xxx.x * ICD-9-CM: xxx [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Referred itch	c3662133	24,864	wikipedia	https://en.wikipedia.org/wiki/Referred_itch	2021-01-18T18:51:08	{"umls": ["C3662133"], "wikidata": ["Q7307181"]}
Charcot-Marie-Tooth disease type 4E (CMT4E) is a congenital, hypomyelinating subtype of Charcot-Marie-Tooth disease type 4 characterized by a Dejerine-Sottas syndrome-like phenotype (incl. hypotonia and/or delayed motor development in infancy), extremely slow nerve conduction velocities, potential respiratory dysfunction, cranial nerve involvement, and the typical CMT phenotype, i.e. distal muscle weakness and atrophy, sensory loss, and foot deformity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Charcot-Marie-Tooth disease type 4E	c0393818	24,865	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99951	2021-01-23T18:07:27	{"gard": ["9203"], "mesh": ["C535301"], "omim": ["605253"], "icd-10": ["G60.0"], "synonyms": ["Autosomal recessive congenital hypomyelinating neuropathy", "CMT4E"]}
A number sign (#) is used with this entry because of evidence that susceptibility to the development of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is conferred by homozygous or compound heterozygous mutation in the HAVCR2 gene (606652) on chromosome 5q33. Description Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon form of T-cell non-Hodgkin lymphoma in which cytotoxic CD8 (see 186910)+ T cells infiltrate adipose tissue forming subcutaneous nodules. Both children and adults can be affected, with a median age at diagnosis of 36 years and a female gender bias. Most patients have accompanying systemic features such as fever or flank pain. A subset (about 20%) of patients develop hemophagocytic lymphohistiocytosis (HLH), usually associated with CD8+ T cells rimming adipocytes in the bone marrow. An infectious agent is not identified, and the disorder is believed to result from improperly activated inflammation. Immunosuppressive therapy may be helpful; hematopoietic bone marrow transplantation is usually curative (summary by Gayden et al., 2018). For a general discussion of genetic heterogeneity of HLH, see HLH1 (267700). Clinical Features Gayden et al. (2018) reported 16 patients, including 2 pairs of sibs, with SPTCL. Twelve patients were of East Asian origin, including Polynesia, 3 were Caucasian of European origin, and 1 was of North African descent. Most patients presented in the first or second decades (usually late childhood) with variable symptoms of an inflammatory condition, including fever, facial swelling, fatigue, painful flank, pancytopenia or anemia, and subcutaneous nodules consistent with panniculitis. However, several patients presented as adults. Skin biopsies confirmed panniculitis with cytotoxic CD8+ T-cell infiltrations with adipocyte rimming and necrosis, consistent with a diagnosis of SPTCL. Molecular studies of the skin lesions, when performed, showed T-cell receptor beta-chain rearrangements, most often monoclonal. Bone marrow examination in 14 of 16 patients showed hemophagocytic lymphohistiocytosis (HLH), and often showed adipocyte rimming by CD8+ T cells. Laboratory findings from 1 patient (P4) during active disease showed evidence of inflammation with increased serum levels of inflammatory cytokines. Patient-derived T cells and macrophages produced increased levels of inflammatory cytokines in vitro, including TNFA (191160), IL2 (147680), and IL1B (147720). Additional variable laboratory findings included abnormal liver enzymes, autoantibodies, and features associated with HLH, such as increased triglycerides, hyperferritinemia, and hypofibrinogenemia. Polprasert et al. (2019) reported 11 unrelated patients of East Asian descent with SPTCL. The median age at diagnosis was 32 years (range 5 to 59). Multiple SPTCL lesions were commonly observed on the trunk, eyelids, extremities, and buccal mucosa. Pathologic analysis showed atypical CD8+ cytotoxic T cells infiltrating subcutaneous adipose tissue and lining adipocytes. Two (18.2%) of the 11 patients developed HLH. Most patients showed monoclonal T-cell receptor (TCR; see 186880) gene rearrangement. All patients responded to immunosuppressive therapy. Clinical Management Among 16 patients with SPTCL, Gayden et al. (2018) found that immunosuppressive and chemotherapeutic treatment was effective, but some patients achieved complete remission only after hematopoietic stem cell transplantation. One patient (P4) treated with anakinra, an IL1 inhibitor, obtained symptom resolution and sustained improvement in overall state. Inheritance The transmission pattern of SPTCL in the families reported by Gayden et al. (2018) was consistent with autosomal recessive inheritance with some evidence of incomplete penetrance. Molecular Genetics In 9 patients from 7 unrelated families of East Asian origin with SPTCL, Gayden et al. (2018) identified a germline homozygous missense variant in the HAVCR2 gene (Y82C; 606652.0001). Homozygosity for Y82C was found in tumor tissue from the patients for whom tumor tissue was available. A homozygous Y82C variant was found in tumor tissue from 3 additional patients of East Asian descent, but germline DNA was not available for study. A germline homozygous I97M variant (606652.0002) was found in 2 unrelated patients of European descent (patients P13 and P14), one of whom was shown to carry the I97M variant in homozygosity in tumor tissue. A heterozygous I97M variant was found in the germline and tumor tissue of a third patient (P15) of European descent. One patient of North African descent (P16) was compound heterozygous for these 2 mutations in her tumor; additional DNA was not available for germline analysis. The variants, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in 5 families from whom DNA was available. In patient panniculitis biopsies, mutant HAVCR2 showed abnormal intracellular aggregate staining in the peri-Golgi apparatus with limited plasma expression compared to wildtype. Peripheral monocytes from several patients showed absent HAVCR2 expression, and there was absent protein expression on activated CD4 (186940)+ and CD8+ lymphocytes. Heterozygous carriers had an intermediate level of membrane protein expression. Decreased membrane expression of the mutant proteins was confirmed after transfection of the mutations in HEK293 cells. In vitro functional expression studies indicated that the mutant proteins were improperly folded and had disrupted posttranslational glycosylation, resulting in decreased or absent expression at the cell surface. In vitro studies of T lymphocytes and macrophages derived from 3 patients (P3, P4, and P11) with the Y82C mutation showed increased secretion of the inflammatory cytokines TNFA (191160), IL2 (147680), and IL1B (147720) compared to controls, and this response was increased with stimulation by lipopolysaccharide (LPS) and an NLRP3 (606416) agonist. There was also a decrease in FOXP3 (300292)+ CD4+ regulatory T cells. The findings suggested that misfolding of HAVCR2 promotes secretion of inflammatory cytokines and activation of the NLRP3 inflammasome, and that the disorder results from uncontrolled immune activation. These mutations were found in 16 (60%) of 27 patients with the disorder who were studied. Polprasert et al. (2019) identified a homozygous Y82C mutation in 10 unrelated patients from Thailand or Japan with SPTCL. Another patient was compound heterozygous for Y82C and T101I (606652.0003). The mutations were found by whole-exome sequencing and confirmed by deep sequencing. The Y82C variant had a mean allele frequency of 3.6 x 10(-3) in the gnomAD database, with enrichment among East Asians (2.1 x 10(-2)). The T101I variant had a mean allele frequency of 6.6 x 10(-3) in gnomAD, and was enriched among South Asians (1.8 x 10(-3)). Functional studies of the variants and studies of the effects of the mutation on HAVCR2 in patient cells were not performed. Analysis of patient SPTCL cells identified somatic mutations in genes associated with epigenetic regulation and signal transduction. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial swelling (in some patients) ABDOMEN Spleen \- Splenomegaly (in some patients) SKIN, NAILS, & HAIR Skin \- Subcutaneous nodules, diffuse \- Erythematous plaques \- Panniculitis \- Atypical cytotoxic CD8+ T cells rimming adipocytes \- Hemophagocytosis (in some patients) METABOLIC FEATURES \- Fever HEMATOLOGY \- Anemia (in some patients) \- Pancytopenia (in some patients) IMMUNOLOGY \- Increased levels of inflammatory cytokines, including TNF-alpha, IL2, and IL1B \- Hemophagocytic lymphohistiocytosis (HLH) (in some patients) \- Atypical cytotoxic CD8+ T cells rimming adipocytes in bone marrow (in some patients) \- Autoimmunity (in some patients) NEOPLASIA \- T-cell non-Hodgkin lymphoma, subcutaneous LABORATORY ABNORMALITIES \- Increased triglycerides (in patients with HLH) \- Hypofibrinogenemia (in patients with HLH) \- Hyperferritinemia (in patients with HLH) MISCELLANEOUS \- Variable age at onset (median 36 years) \- Variable severity \- Immunosuppressive drugs and hematopoietic bone marrow transplant are effective treatments MOLECULAR BASIS \- Caused by mutation in the hepatitis A virus cellular receptor 2 gene (HAVCR2, 606652.0001 ) ▲ 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	T-CELL LYMPHOMA, SUBCUTANEOUS PANNICULITIS-LIKE	c0522624	24,866	omim	https://www.omim.org/entry/618398	2019-09-22T15:42:09	{"mesh": ["C537503"], "omim": ["618398"], "orphanet": ["86884"]}
A rare paraneoplastic syndrome characterized by renal phosphate wasting and bone demineralization due to a phosphaturic mesenchymal tumor of the mixed connective tissue variant. It causes osteomalacia in adults with bone pain and pathological fractures, and rickets in children. ## Epidemiology The prevalence of the disease is not known. Since the association between phosphate reabsorption and tumor was first made, approximately 400 cases of oncogenic osteomalacia have been reported in the literature. ## Clinical description Disease onset typically is in adulthood, with mean age of 45 years of age, although a few pediatric cases have been reported. Typical features are chiefly related to chronic hypophosphatemia caused by hyperphosphaturia. The causative tumors are typically small and benign, occur in either bone or soft tissue, and cause no local symptoms. Patients usually present with symptoms of isolated hypophosphatemia. This means that the diagnosis is usually made late, and even when it is, the tumors are often not found. Typically, both calcium and parathyroid hormone levels are normal, as is the serum 25 hydroxyvitamin D (25OH vitamin D) concentration. Osteomalacia causes bone pain and can lead to pathological fractures or rickets in young patients where the epiphyses have not matured. Severe hypophosphatemia can cause muscle weakness. ## Etiology This syndrome is caused by phosphatonin secretion by the causative tumor. Classically the phosphatonin is FGF-23 (Fibroblast Growth Factor 23), other phosphatonins (Matrix Extracellular Phosphoglycoprotein - MEPE and secreted frizzled-related protein 4 - sFRP4) appear to have the same biochemical effect, and were, in fact discovered by examination of patients with these tumors. FGF-23 causes urinary phosphate wasting by downregulating the main renal phosphate reabsorption transporter, the type 2 sodium-phosphate cotransporter (NaPi2a), localized in the proximal tubule. FGF-23 overexpression may also affect bone mineralization by suppressing osteoblast differentiation. ## Diagnostic methods The finding of isolated hypophosphatemia, urinary phosphate wasting in the absence of the renal Fanconi syndrome and without hereditary hypophosphatemic rickets, should prompt the search for a causative tumor. As these mesenchymal tumors generally express somatostatin receptors, they can be demonstrated by somatostatin/octreotide scanning. All imaging should be whole body (vertex to toes). ## Differential diagnosis Differential diagnosis may include other forms of hypophosphatemic osteomalacia (X-linked, autosomal dominant or recessive hypophosphatemic rickets) as well as primary or acquired renal Fanconi syndrome. ## Management and treatment Definitive treatment is with surgical resection of the tumor. If the tumor cannot be found or removed, medical treatment involves the supplementation of phosphate and active vitamin D (e.g. alfacalcidol). Radiotherapy may be helpful if the tumor is located but is non-resectable for anatomical reasons. A new anti-FGF23 monoclonal antibody has been promising in the treatment of X-linked hypophosphatemic rickets, and may therefore be effective in FGF-23 mediated oncogenic osteomalacia; however, this remains to be proven. ## Prognosis Excellent recovery after complete tumor excision with complete resolution of symptoms and biochemical abnormalities. Long term monitoring is required as local recurrence and metastases have been reported, even if rarely. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Oncogenic osteomalacia	c1274103	24,867	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=352540	2021-01-23T18:12:52	{"gard": ["9652"], "mesh": ["C537751"], "umls": ["C1274103"], "icd-10": ["M83.8"], "synonyms": ["Oncogenic hypophosphatemic osteomalacia", "TIO", "Tumor-induced osteomalacia"]}
PGM1-CDG is one of the many subtypes of congenital disorders of glycosylation (CDG), which are inherited diseases that affect the body's process of adding sugar building blocks to proteins (glycosylation). There are many steps in glycosylation, each of which is controlled by a different gene. The type of CDG a person has depends on which gene is involved. The signs and symptoms of PGM1-CDG can be different from person to person. They may include cleft palate or bifid uvula; low blood sugar (hypoglycemia); endocrine disorders; muscle disease, leading to muscle weakness or death of muscle fibers (rhabdomyolysis); liver disease; blood clotting problems; and a weak and enlarged heart chamber (dilated cardiomyopathy). Some people with PGM1-CDG have central nervous system involvement such as seizures, development delay, or intellectual disability. PGM1-CDG is caused by mutations in the PGM1 gene and inheritance is autosomal recessive. The diagnosis may be suspected based on symptoms and specific blood test results, and it is confirmed with genetic testing. Treatment depends on the symptoms and severity in each person and may include oral D-galactose supplementation, standard treatment of hypoglycemia, and/or heart medications or heart transplantation for cardiomyopathy. The course of the disorder and whether symptoms or complications may affect the lifespan are difficult to predict and vary among people with PGM1-CDG. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	PGM1-CDG	c2752015	24,868	gard	https://rarediseases.info.nih.gov/diseases/4329/pgm1-cdg	2021-01-18T17:58:21	{"mesh": ["C567859"], "omim": ["614921"], "orphanet": ["319646"], "synonyms": ["GSD type 14", "GSDXIV", "Phosphoglucomutase deficiency type 1", "Type 14 glycogenosis", "Congenital disorder of glycosylation, type It ", "CDG syndrome type It", "CDG-It", "CDG1T", "Congenital disorder of glycosylation type 1t", "Congenital disorder of glycosylation type It", "Phosphoglucomutase-1 deficiency", "PGM1-related congenital disorder of glycosylation", "Glycogen storage disease due to phosphoglucomutase deficiency"]}
A rare inflammatory optic neuropathy characterized by severe and persistent pain followed by subacute visual loss, a relapsing-remitting course, and steroid-dependence. Involvement of both optic nerves is common and is usually sequential. Serum antibodies against aquaporin 4 are absent in most cases. Magnetic resonance imaging shows contrast enhancement of the acutely inflamed optic nerves. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Chronic relapsing inflammatory optic neuropathy	None	24,869	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=499085	2021-01-23T17:47:52	{"icd-10": ["G60.8"], "synonyms": ["CRION", "Chronic recurrent isolated optic neuritis"]}
For other uses, see Rosacea (disambiguation). Rosacea Other namesAcne rosacea Rosacea over the cheeks and nose[1] Pronunciation * /roʊˈzeɪʃiə/ SpecialtyDermatology SymptomsFacial redness, pimples, swelling, and small and superficial dilated blood vessels[2][3] ComplicationsRhinophyma[3] Usual onset30–50 years old[2] DurationLong term[2] TypesErythematotelengiectatic, papulopustular, phymatous, ocular[2] CausesUnknown[2] Risk factorsFamily history[3] Diagnostic methodBased on symptoms[2] Differential diagnosisAcne, perioral dermatitis, seborrhoeic dermatitis, dermatomyositis, lupus[2] MedicationAntibiotics either by mouth or applied to the skin[3] Frequency~5%[2] Rosacea is a long-term skin condition that typically affects the face.[2][3] It results in redness, pimples, swelling, and small and superficial dilated blood vessels.[2] Often, the nose, cheeks, forehead, and chin are most involved.[3] A red, enlarged nose may occur in severe disease, a condition known as rhinophyma.[3] The cause of rosacea is unknown.[2] Risk factors are believed to include a family history of the condition.[3] Factors that may potentially worsen the condition include heat, exercise, sunlight, cold, spicy food, alcohol, menopause, psychological stress, or steroid cream on the face.[3] Diagnosis is based on symptoms.[2] While not curable, treatment usually improves symptoms.[3] Treatment is typically with metronidazole, doxycycline, minocycline, or tetracycline.[4] When the eyes are affected, azithromycin eye drops may help.[5] Other treatments with tentative benefit include brimonidine cream, ivermectin cream, and isotretinoin.[4] Dermabrasion or laser surgery may also be used.[3] The use of sunscreen is typically recommended.[3] Rosacea affects between 1 and 10% of people.[2] Those affected are most often 30 to 50 years old and female.[2] Caucasians are more frequently affected.[2] The condition was described in The Canterbury Tales in the 1300s, and possibly as early as the 200s BC by Theocritus.[6][7] ## Contents * 1 Signs and symptoms * 1.1 Erythematotelangiectatic rosacea * 1.2 Glandular rosacea * 2 Cause * 2.1 Cathelicidins * 2.2 Demodex mites * 2.3 Intestinal bacteria * 3 Diagnosis * 3.1 Classification * 3.2 Variants * 4 Treatments * 4.1 Behavior * 4.2 Medications * 4.3 Laser * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Rosacea on the face Signs include facial redness, small and superficial dilated blood vessels on facial skin, papules, pustules, and swelling.[2] ### Erythematotelangiectatic rosacea[edit] Erythematotelangiectatic rosacea[8] rosacea (also known as "vascular rosacea"[8]) is characterized by prominent history of prolonged (over 10 minutes) flushing reaction to various stimuli, such as emotional stress, hot drinks, alcohol, spicy foods, exercise, cold or hot weather, or hot baths and showers.[9] ### Glandular rosacea[edit] In glandular rosacea, men with thick sebaceous skin predominate, a disease in which the papules are edematous, and the pustules are often 0.5 to 1.0 cm in size, with nodulocystic lesions often present.[9] ## Cause[edit] Topical steroid-induced rosacea (left); after steroid withdrawal and photobiomodulation therapy (right) The exact cause of rosacea is unknown.[2] Triggers that cause episodes of flushing and blushing play a part in its development. Exposure to temperature extremes, strenuous exercise, heat from sunlight, severe sunburn, stress, anxiety, cold wind, and moving to a warm or hot environment from a cold one, such as heated shops and offices during the winter, can each cause the face to become flushed.[2] Certain foods and drinks can also trigger flushing, such as alcohol, foods and beverages containing caffeine (especially hot tea and coffee), foods high in histamines, and spicy foods.[10] Medications and topical irritants have also been known to trigger rosacea flares. Some acne and wrinkle treatments reported to cause rosacea include microdermabrasion and chemical peels, as well as high dosages of isotretinoin, benzoyl peroxide, and tretinoin. Steroid-induced rosacea is caused by the use of topical steroids.[11] These steroids are often prescribed for seborrheic dermatitis. Dosage should be slowly decreased and not immediately stopped to avoid a flare-up. ### Cathelicidins[edit] In 2007, Richard Gallo and colleagues noticed that patients with rosacea had high levels of the antimicrobial peptide cathelicidin[12] and elevated levels of stratum corneum tryptic enzymes (SCTEs). Antibiotics have been used in the past to treat rosacea, but they may only work because they inhibit some SCTEs.[12] ### Demodex mites[edit] Studies of rosacea and Demodex mites have revealed that some people with rosacea have increased numbers of the mite,[10] especially those with steroid-induced rosacea. On other occasions, demodicidosis (commonly known as "mange") is a separate condition that may have "rosacea-like" appearances.[13] A 2007, National Rosacea Society-funded study demonstrated that Demodex folliculorum mites may be a cause or exacerbating factor in rosacea.[14] The researchers identified Bacillus oleronius as distinct bacteria associated with Demodex mites. When analyzing blood samples using a peripheral blood mononuclear cell proliferation assay, they discovered that B. oleronius stimulated an immune system response in 79 percent of 22 patients with subtype 2 (papulopustular) rosacea, compared with only 29% of 17 subjects without the disorder. They concluded, "The immune response results in inflammation, as evident in the papules (bumps) and pustules (pimples) of subtype 2 rosacea. This suggests that the B. oleronius bacteria found in the mites could be responsible for the inflammation associated with the condition."[14] ### Intestinal bacteria[edit] Small intestinal bacterial overgrowth (SIBO) was demonstrated to have greater prevalence in rosacea patients and treating it with locally acting antibiotics led to rosacea lesion improvement in two studies. Conversely in rosacea patients who were SIBO negative, antibiotic therapy had no effect.[15] The effectiveness of treating SIBO in rosacea patients may suggest that gut bacteria play a role in the pathogenesis of rosacea lesions. ## Diagnosis[edit] Most people with rosacea have only mild redness and are never formally diagnosed or treated. No test for rosacea is known. In many cases, simple visual inspection by a trained health-care professional is sufficient for diagnosis. In other cases, particularly when pimples or redness on less-common parts of the face is present, a trial of common treatments is useful for confirming a suspected diagnosis. The disorder can be confused or co-exist with acne vulgaris or seborrheic dermatitis. The presence of a rash on the scalp or ears suggests a different or co-existing diagnosis because rosacea is primarily a facial diagnosis, although it may occasionally appear in these other areas. ### Classification[edit] Commonly affected zones[16] Micrograph showing rosacea as enlarged, dilated capillaries and venules located in the upper dermis, angulated telangiectasias, perivascular and perifollicular lymphocytic infiltration, and superficial dermal edema.[17] Four rosacea subtypes exist,[18] and a patient may have more than one subtype:[19]:176 1. Erythematotelangiectatic rosacea exhibits permanent redness (erythema) with a tendency to flush and blush easily.[10] Also small, widened blood vessels visible near the surface of the skin (telangiectasias) and possibly intense burning, stinging, and itching are common.[10] People with this type often have sensitive skin. Skin can also become very dry and flaky. In addition to the face, signs can also appear on the ears, neck, chest, upper back, and scalp.[20] 2. Papulopustular rosacea presents with some permanent redness with red bumps (papules); some pus-filled pustules can last 1–4 days or longer. This subtype is often confused with acne. 3. Phymatous rosacea is most commonly associated with rhinophyma, an enlargement of the nose. Signs include thickening skin, irregular surface nodularities, and enlargement. Phymatous rosacea can also affect the chin (gnathophyma), forehead (metophyma), cheeks, eyelids (blepharophyma), and ears (otophyma).[21] Telangiectasias may be present. 4. In ocular rosacea, affected eyes and eyelids may appear red due to telangiectasias and inflammation, and may feel dry, irritated, or gritty. Other symptoms include foreign-body sensations, itching, burning, stinging, and sensitivity to light.[22] Eyes can become more susceptible to infection. About half of the people with subtypes 1–3 also have eye symptoms. Blurry vision and vision loss can occur if the cornea is affected.[22] ### Variants[edit] Variants of rosacea include:[23]:689 * Pyoderma faciale, also known as rosacea fulminans,[23] is a conglobate, nodular disease that arises abruptly on the face.[8][23] * Rosacea conglobata is a severe rosacea that can mimic acne conglobata, with hemorrhagic nodular abscesses and indurated plaques.[23] * Phymatous rosacea is a cutaneous condition characterized by overgrowth of sebaceous glands.[8] Phyma is Greek for swelling, mass, or bulb, and these can occur on the face and ears.[23]:693 ## Treatments[edit] Treatment of depends on the types present.[24] Mild cases are often not treated at all, or are simply covered up with normal cosmetics. Therapy for the treatment of rosacea is not curative, and is best measured in terms of reduction in the amount of facial redness and inflammatory lesions, a decrease in the number, duration, and intensity of flares, and concomitant symptoms of itching, burning, and tenderness. The two primary modalities of rosacea treatment are topical and oral antibiotic agents.[25] Laser therapy has also been classified as a form of treatment.[25] While medications often produce a temporary remission of redness within a few weeks, the redness typically returns shortly after treatment is suspended. Long-term treatment, usually 1–2 years, may result in permanent control of the condition for some patients.[25][26] Lifelong treatment is often necessary, although some cases resolve after a while and go into a permanent remission.[26] Other cases, if left untreated, worsen over time.[citation needed] ### Behavior[edit] Avoiding triggers that worsen the condition can help reduce the onset of rosacea, but alone will not normally lead to remission except in mild cases. Keeping a journal is sometimes recommended to help identify and reduce food and beverage triggers. Because sunlight is a common trigger, avoiding excessive exposure to the sun is widely recommended. Some people with rosacea benefit from daily use of a sunscreen; others opt for wearing hats with broad brims. Like sunlight, emotional stress can also trigger rosacea. People who develop infections of the eyelids must practice frequent eyelid hygiene. Managing pretrigger events such as prolonged exposure to cool environments can directly influence warm-room flushing.[27] ### Medications[edit] Medications with good evidence include topical ivermectin and azelaic acid creams and brimonidine, and doxycycline and isotretinoin by mouth.[28] Lesser evidence supports topical metronidazole cream and tetracycline by mouth.[28] Metronidazole is thought to act through anti-inflammatory mechanisms, while azelaic acid is thought to decrease cathelicidin production. Oral antibiotics of the tetracycline class such as doxycycline, minocycline, and oxytetracycline are also commonly used and thought to reduce papulopustular lesions through anti-inflammatory actions rather than through their antibacterial capabilities.[10] Using alpha-hydroxy acid peels may help relieve redness caused by irritation, and reduce papules and pustules associated with rosacea.[29] Oral antibiotics may help to relieve symptoms of ocular rosacea. If papules and pustules persist, then sometimes isotretinoin can be prescribed.[30] The flushing and blushing that typically accompany rosacea are typically treated with the topical application of alpha agonists such as brimonidine and less commonly oxymetazoline or xylometazoline.[10] ### Laser[edit] Evidence for the use of laser and intense pulsed-light therapy in rosacea is poor.[31] ## Epidemiology[edit] Women, especially those who are menopausal, are more likely than men to develop rosacea.[32] Those of Caucasian descent, especially those of Northern or Eastern European descent with highly pale skin, appear more affected.[33] ## See also[edit] * Medicine portal * Seborrheic dermatitis * Keratosis pilaris ## References[edit] 1. ^ Sand, M; Sand, D; Thrandorf, C; Paech, V; Altmeyer, P; Bechara, FG (4 June 2010). "Cutaneous lesions of the nose". Head & Face Medicine. 6: 7. doi:10.1186/1746-160X-6-7. PMC 2903548. PMID 20525327. 2. ^ a b c d e f g h i j k l m n o p q r Tüzün Y, Wolf R, Kutlubay Z, Karakuş O, Engin B (February 2014). "Rosacea and rhinophyma". Clinics in Dermatology. 32 (1): 35–46. doi:10.1016/j.clindermatol.2013.05.024. PMID 24314376. 3. ^ a b c d e f g h i j k l "Questions and Answers about Rosacea". www.niams.nih.gov. April 2016. Archived from the original on 13 May 2017. Retrieved 5 June 2017. 4. ^ a b van Zuuren, EJ; Fedorowicz, Z (September 2015). "Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments". The British Journal of Dermatology. 173 (3): 651–62. doi:10.1111/bjd.13956. PMID 26099423. S2CID 41303286. 5. ^ "Rosacea First choice treatments". Prescrire International. 182: 126–128. May 2017. Archived from the original on 10 September 2017. 6. ^ Zouboulis, Christos C.; Katsambas, Andreas D.; Kligman, Albert M. (2014). Pathogenesis and Treatment of Acne and Rosacea. Springer. p. XXV. ISBN 978-3-540-69375-8. Archived from the original on 10 September 2017. 7. ^ Schachner, Lawrence A.; Hansen, Ronald C. (2011). Pediatric Dermatology E-Book. Elsevier Health Sciences. p. 827. ISBN 978-0-7234-3665-2. Archived from the original on 10 September 2017. 8. ^ a b c d Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 9. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 245. ISBN 0-7216-2921-0. 10. ^ a b c d e f Del Rosso JQ (October 2014). "Management of cutaneous rosacea: emphasis on new medical therapies". Expert Opin Pharmacother. 15 (14): 2029–38. doi:10.1517/14656566.2014.945423. PMID 25186025. 11. ^ "Rosacea". DermNet, New Zealand Dermatological Society. Archived from the original on 7 December 2010. Retrieved 3 February 2011. 12. ^ a b Kenshi Yamasaki; Anna Di Nardo; Antonella Bardan; Masamoto Murakami; Takaaki Ohtake; Alvin Coda; Robert A Dorschner; Chrystelle Bonnart; Pascal Descargues; Alain Hovnanian; Vera B Morhenn; Richard L Gallo (August 2007). "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea". Nature Medicine. 13 (8): 975–80. doi:10.1038/nm1616. PMID 17676051. S2CID 23470611. 13. ^ Baima B, Sticherling M (2002). "Demodicidosis revisited". Acta Dermato-Venereologica. 82 (1): 3–6. doi:10.1080/000155502753600795. PMID 12013194. 14. ^ a b Lacey N, Delaney S, Kavanagh K, Powell FC (2007). "Mite-related bacterial antigens stimulate inflammatory cells in rosacea" (PDF). British Journal of Dermatology. 157 (3): 474–481. doi:10.1111/j.1365-2133.2007.08028.x. PMID 17596156. S2CID 8057780. 15. ^ Elizabeth Lazaridou; Christina Giannopoulou; Christina Fotiadou; Eustratios Vakirlis; Anastasia Trigoni; Demetris Ioannides (November 2010). "The potential role of microorganisms in the development of rosacea". JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 9 (1): 21–25. doi:10.1111/j.1610-0387.2010.07513.x. PMID 21059171. S2CID 23494211. 16. ^ name="JAmAcadDermatol2004-Wilkin">Wilkin J, Dahl M, Detmar M, Drake L, Liang MH, Odom R, Powell F (2004). "Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea" (PDF). J Am Acad Dermatol. 50 (6): 907–12. doi:10.1016/j.jaad.2004.01.048. PMID 15153893. Archived from the original (PDF reprint) on 27 February 2007. 17. ^ Celiker, Hande; Toker, Ebru; Ergun, Tulin; Cinel, Leyla (2017). "An unusual presentation of ocular rosacea". Arquivos Brasileiros de Oftalmologia. 80 (6): 396–398. doi:10.5935/0004-2749.20170097. ISSN 0004-2749. PMID 29267579. 18. ^ Wilkin J, Dahl M, Detmar M, Drake L, Liang MH, Odom R, Powell F (2004). "Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea" (PDF). J Am Acad Dermatol. 50 (6): 907–12. doi:10.1016/j.jaad.2004.01.048. PMID 15153893. Archived from the original (PDF reprint) on 27 February 2007. 19. ^ Marks, James G; Miller, Jeffery (2006). Lookingbill and Marks' Principles of Dermatology (4th ed.). Elsevier Inc. ISBN 1-4160-3185-5. 20. ^ "What Rosacea Looks Like". Archived from the original on 4 February 2013. Retrieved 30 January 2013. 21. ^ Jansen T, Plewig G (1998). "Clinical and histological variants of rhinophyma, including nonsurgical treatment modalities". Facial Plast Surg. 14 (4): 241–53. doi:10.1055/s-2008-1064456. PMID 11816064. 22. ^ a b Vieira AC, Mannis MJ (December 2013). "Ocular rosacea: common and commonly missed". J Am Acad Dermatol. 69 (6 (Suppl 1)): S36–41. doi:10.1016/j.jaad.2013.04.042. PMID 24229635. 23. ^ a b c d e Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 24. ^ van Zuuren, EJ; Fedorowicz, Z; Tan, J; van der Linden, MMD; Arents, BWM; Carter, B; Charland, L (July 2019). "Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments". The British Journal of Dermatology. 181 (1): 65–79. doi:10.1111/bjd.17590. PMC 6850438. PMID 30585305. 25. ^ a b c Noah Scheinfeld; Thomas Berk (January 2010). "A Review of the Diagnosis and Treatment of Rosacea". Postgraduate Medicine. 122 (1): 139–43. doi:10.3810/pgm.2010.01.2107. PMID 20107297. S2CID 22914205. Archived from the original on 5 January 2011. 26. ^ a b Culp B, Scheinfeld N (January 2009). "Rosacea: a review". P&T. 34 (1): 38–45. PMC 2700634. PMID 19562004. 27. ^ Dahl, Colin (2008). A Practical Understanding of Rosacea – part one. Australian Sciences. Archived from the original on 21 March 2008. Retrieved 27 August 2008. 28. ^ a b van Zuuren, EJ; Fedorowicz, Z; Carter, B; van der Linden, MM; Charland, L (28 April 2015). "Interventions for rosacea". The Cochrane Database of Systematic Reviews. 4 (4): CD003262. doi:10.1002/14651858.CD003262.pub5. PMC 6481562. PMID 25919144. 29. ^ Tung, RC; Bergfeld, WF; Vidimos, AT; Remzi, BK (2000). "alpha-Hydroxy acid-based cosmetic procedures. Guidelines for patient management". American Journal of Clinical Dermatology. 1 (2): 81–8. doi:10.2165/00128071-200001020-00002. PMID 11702315. S2CID 58337540. 30. ^ Hoting E, Paul E, Plewig G (December 1986). "Treatment of rosacea with isotretinoin". Int J Dermatol. 25 (10): 660–3. doi:10.1111/j.1365-4362.1986.tb04533.x. PMID 2948928. S2CID 22421145. 31. ^ van Zuuren, EJ; Fedorowicz, Z; Carter, B; van der Linden, MM; Charland, L (28 April 2015). "Interventions for rosacea". The Cochrane Database of Systematic Reviews (4): CD003262. doi:10.1002/14651858.CD003262.pub5. PMC 6481562. PMID 25919144. 32. ^ Tamparo, Carol (2011). Fifth Edition: Diseases of the Human Body. Philadelphia: F. A. Davis Company. p. 184. ISBN 978-0-8036-2505-1. 33. ^ "Understanding Rosacea". Rosacea.org. 21 August 2012. ## External links[edit] Classification D * ICD-10: L71 * ICD-9-CM: 695.3 * MeSH: D012393 * DiseasesDB: 96 External resources * MedlinePlus: 000879 * eMedicine: derm/377 Wikibooks has a book on the topic of: Rosacea Wikimedia Commons has media related to Rosacea (disease). * Rosacea at Curlie * Rosacea photo library at Dermnet * Questions and Answers about Rosacea, from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases * 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 Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Rosacea	c0035854	24,870	wikipedia	https://en.wikipedia.org/wiki/Rosacea	2021-01-18T18:35:20	{"mesh": ["D012393"], "umls": ["C0035854"], "wikidata": ["Q831530"]}
A rare ependymal tumor characterized by the presence of a RELA fusion gene. This supratentorial grade II or III ependymoma most often occurs in children and young adults. Histopathological features are variable, but a distinctive vascular pattern of branching capillaries or clear-cell change are common. Patients may present with focal neurological deficits, seizures, or features of raised intracranial pressure. Prognosis is worse than in other supratentorial ependymomas. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	RELA fusion-positive ependymoma	c4289581	24,871	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=530792	2021-01-23T17:18:12	{"synonyms": ["Supratentorial C11ORF95-RELA fused ependymoma"]}
Infantile mercury poisoning is a rare intoxication affecting children, most commonly characterized by erythema of the hands, feet and nose, edematous, painful, pink to red, desquamating fingers and toes, bluish, cold and wet extremities, excessive sweating, irritability, photophobia, muscle weakness, diffuse hypotonia, paresthesia, hypertension and tachycardia, due to elemental, organic or inorganic mercury exposure. Additional manifestations include alopecia, loss of appetite, excessive salivation with red and swollen gums, tooth and nail loss and insomnia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Infantile mercury poisoning	c4553710	24,872	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247165	2021-01-23T18:37:51	{"icd-10": ["T56.1"], "synonyms": ["Erythroedema polyneuritis", "Feer disease", "Infantile acrodynia", "Infantile mercury intoxication", "Pink disease", "Swift disease", "Swift-Feer disease"]}
Congenital erythropoietic porphyria, or Günther disease, is a form of erythropoietic porphyria characterized by very severe and mutilating photodermatosis. ## Epidemiology Since its description at the end of the 19th century, about 200 cases have been reported in the literature. ## Clinical description The disease most often manifests at birth with extreme cutaneous photosensitivity that is severe and mutilating. The principle signs include cutaneous lesions that are bullous and rapidly erosive on the surface of skin exposed to the sun and light (hands, face, feet). Urine is often very red/brown and colors the diaper of affected infants. In very severe forms, patients present with hemolysis of differing severity. Significant splenomegaly can appear, linked with hemolytic anemia. Bone involvement is constant, with rarefaction of bony architecture and a risk of multiple fractures. ## Etiology Congenital erythropoietic porphyria is caused by a deficiency of uroporphyrinogen- synthase (URO-S; the fourth enzyme in the heme biosynthesis pathway) leading to a massive accumulation of isomeric I porphyrins (uro and coproporphyrins) in the bone marrow. The enzyme deficiency is caused by mutations of the UROS gene, coding for URO-S. Transmission is autosomal recessive. It should be noted that there is a certain degree of genotype-phenotype correlation by the identification of ``severe'' or ``moderate'' mutations. In 50% of cases the ``severe'' mutation C73R is present. ## Diagnostic methods Diagnosis is based on the evidence of a massive accumulation of isomeric I porphyrins in the urine and blood. The evidence of a deficiency of URO-S in red blood cells and the identification of causal mutations of the UROS gene allow a confirmed diagnosis. ## Differential diagnosis Differential diagnosis can include hepatoerythropioetic porphyria (see this term). ## Antenatal diagnosis Antenatal diagnosis is possible, in families at risk, by analysis of amniotic fluid, measurement of URO-S and/or molecular genetic analysis of the amniotic cells. ## Management and treatment Management of the disease is often difficult becausehemolytic anemia, splenic sequestration and thrombocytopenia often necessitate repeated transfusions, which in turn can lead to iron overload. Splenectomy is often indicated. Intense photoprotection is required to prevent the appearance and aggravation of cutaneous lesions. There is a constant risk of the lesions becoming infected but generally this is controlled by antibiotic therapy. ## Prognosis In severe forms hemolytic anemia and, in particular, thrombocytopenia dominate the prognosis and greatly diminish the life expectancy of patients. The multiple fractures often cause mobility disabilities. Bone marrow transplantation has recently spectacularly improved the prognosis of congenital erythropoietic porphyria (particularly if the patient is young) by healing cutaneous lesions and hemolytic anemia and causing them to disappear. A project exploring ex-vivo genetic treatment of bone marrow cells is currently in progress. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Congenital erythropoietic porphyria	c0162530	24,873	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79277	2021-01-23T18:21:58	{"gard": ["4446"], "mesh": ["D017092"], "omim": ["263700"], "icd-10": ["E80.0"], "synonyms": ["CEP", "Günther disease"]}
A number sign (#) is used with this entry because of evidence that Joubert syndrome-1 (JBTS1) is caused by homozygous mutation in the INPP5E gene (613037) on chromosome 9q34. Description Joubert syndrome is a clinically and genetically heterogeneous group of disorders characterized by hypoplasia of the cerebellar vermis with the characteristic neuroradiologic 'molar tooth sign,' and accompanying neurologic symptoms, including dysregulation of breathing pattern and developmental delay. Other variable features include retinal dystrophy and renal anomalies (Saraiva and Baraitser, 1992; Valente et al., 2005). ### Genetic Heterogeneity of Joubert Syndrome See also JBTS2 (608091), caused by mutation in the TMEM216 gene (613277) on chromosome 11q13; JBTS3 (608629), caused by mutation in the AHI1 gene (608894) on chromosome 6q23; JBTS4 (609583), caused by mutation in the NPHP1 gene (607100) on chromosome 2q13; JBTS5 (610188), caused by mutation in the CEP290 gene, also called NPHP6 (610142), on chromosome 12q21.32; JBTS6 (610688), caused by mutation in the TMEM67 gene (609884) on chromosome 8q21; JBTS7 (611560), caused by mutation in the RPGRIP1L gene (610937) on chromosome 16q12.2; JBTS8 (612291), caused by mutation in the ARL13B (608922) on chromosome 3q11.2; JBTS9 (612285), caused by mutation in the CC2D2A gene (612013) on chromosome 4p15.3; JBTS10 (300804), caused by mutation in the CXORF5 gene (300170) on chromosome Xp22.3; JBTS11 (see 613820), caused by mutation in the TTC21B gene (612014) on chromosome 2q24; JBTS12 (see 200990), caused by mutation in the KIF7 gene (611254) on chromosome 15q26; JBTS13 (614173), caused by mutation in the TCTN1 gene (609863) on chromosome 12q24; JBTS14 (614424), caused by mutation in the TMEM237 gene (614423) on chromosome 2q33; JBTS15 (614464), caused by mutation in the CEP41 gene (610523) on chromosome 7q32; JBTS16 (614465), caused by mutation in the TMEM138 gene (614459) on chromosome 11q; JBTS17 (614615), caused by mutation in the C5ORF42 gene (614571) on chromosome 5p13; JBTS18 (614815), caused by mutation in the TCTN3 gene (613847) on chromosome 10q24; JBTS19 (see 614844), caused by mutation in the ZNF423 gene (604577) on chromosome 16q12; JBTS20 (614970), caused by mutation in the TMEM231 gene (614949) on chromosome 16q23; JBTS21 (615636), caused by mutation in the CSPP1 gene (611654) on chromosome 8q13; JBTS22 (615665), caused by mutation in the PDE6D gene (602676) on chromosome 2q37; JBTS23 (616490), caused by mutation in the KIAA0586 gene (610178) on chromosome 14q23; JBTS24 (616654), caused by mutation in the TCTN2 gene (613846) on chromosome 12q24; JBTS25 (616781), caused by mutation in the CEP104 gene (616690) on chromosome 1p36; JBTS26 (616784), caused by mutation in the KIAA0556 gene (616650) on chromosome 16p12; JBTS27 (617120), caused by mutation in the B9D1 gene (614144) on chromosome 17p11; JBTS28 (617121), caused by mutation in the MKS1 gene (609883) on chromosome 17q23; JBTS29 (see 617562), caused by mutation in the TMEM107 gene (616183) on chromosome 17p13; JBTS30 (617622), caused by mutation in the ARMC9 gene (617612) on chromosome 2q37; JBTS31 (617761), caused by mutation in the CEP120 gene (613446) on chromosome 5q23; JBTS32 (617757), caused by mutation in the SUFU gene (607035) on chromosome 10q24; JBTS33 (617767), caused by mutation in the PIBF1 gene (607532) on chromosome 13q21; JBTS34 (see 614175), caused by mutation in the B9D2 gene (611951) on chromosome 19q13; and JBTS35 (618161), caused by mutation in the ARL3 gene (604695) on chromosome 10q24. Clinical Features De Haene (1955) collected from the literature 4 cases of total and 7 cases of partial agenesis of the vermis of the cerebellum, and added the only familial example: 3 brothers (1 autopsy) died at ages 4 to 8 years, the illness being characterized by tremor and hypotonia. Boltshauser and Isler (1977), who suggested the designation Joubert syndrome based on the article by Joubert et al. (1969) (see JBTS17, 614615), described 3 cases, 2 of them sibs. Detailed neuropathologic findings on 1 of these patients were reported by Friede and Boltshauser (1978). Boltshauser et al. (1981) reported 2 affected sisters whose parents were consanguineous. Egger and Baraitser (1984) suggested that the sibs reported by Gustavson et al. (1971) and by Haumont and Pelc (1983) had the Joubert syndrome, not the Mohr syndrome (252100). Kendall et al. (1990) reviewed the radiologic findings in 16 consecutive cases. Cantani et al. (1990) reviewed 53 published cases. In the children of healthy, consanguineous Turkish parents, van Dorp et al. (1991) observed a severely retarded male child with neurologic anomalies including Dandy-Walker malformation, hypoplasia of the corpus callosum, occipital meningoencephalocele, and bilateral coloboma of the optic nerve with retrobulbar cystic mass. The detailed findings at autopsy in an affected female fetus from the mother's second pregnancy were presented. The fetus showed hypognathia, occipital meningoencephalocele, and empty posterior fossa. Squires et al. (1991) described an affected infant, born to nonconsanguineous parents, who had episodic tachypnea, agenesis of the cerebellar vermis, a complex cardiac malformation, cutaneous dimples over the wrists and elbows, telecanthus, and micrognathia. Lindhout et al. (1980) and Laverda et al. (1984) described associated chorioretinal coloboma (see 243910). Saraiva and Baraitser (1992) reviewed 72 previously reported patients and 29 new patients with the possible diagnosis of Joubert syndrome. They presented data on 94 patients that fulfilled their criteria and proposed a classification into 2 groups: those with retinal dystrophy and those without. Retinal dystrophy ran true in families and was never absent when renal cysts were reported. Maria et al. (1999) reviewed the clinical features of Joubert syndrome and provided revised diagnostic criteria. They pointed out that careful examination of the face shows a characteristic appearance: large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis (occasionally), upturned nose with evident nostrils, open mouth (the mouth tends to have an oval shape early on, a 'rhomboid' appearance later, and finally can appear triangular with downturned mouth angles), tongue protrusion and rhythmic tongue motions, and occasionally low-set and tilted ears. Neuroophthalmologic examination shows oculomotor apraxia. Most children with this disorder have hyperpnea intermixed with central apnea in the neonatal period. Neuroimaging of the head in the axial plane demonstrates the 'molar tooth sign,' that is, deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis. See their Table 1 for the proposed revised diagnostic criteria. Fennell et al. (1999) reported on cognitive, behavioral, and developmental findings of follow-up studies of Joubert syndrome. The parents' reports of behaviors showed problems with temperament, hyperactivity, aggressiveness, and dependency, as well as problems in physical development and care that were thought to be related to the neurologic handicaps. Parents' reports of developmental attainments revealed that only 3 of 40 children were functioning in the borderline range, with the rest scoring in the severely impaired range. The studies reported by Yachnis and Rorke (1999) suggested that, in addition to vermal agenesis, Joubert syndrome is characterized by malformation of multiple brainstem structures. The latter could explain certain clinical features of the syndrome, including episodic hyperpnea and oculomotor apraxia. Brainstem malformation is represented by the 'molar tooth sign' on magnetic resonance imaging (Maria et al., 1999). Raynes et al. (1999) described 3 sisters with Joubert syndrome, 2 of whom were monozygotic twins with highly discordant phenotypes. The twins were born at 34 weeks' gestation with discordant birth weights. Their anatomic, neurologic, and developmental status also differed greatly: twin B was able to walk and run, and was verbal, unlike twin A who was wheelchair-bound, severely retarded, nonverbal, and autistic. Abnormal eye movements and retinal dysplasia were features in all 3 girls, but none had renal cysts demonstrable by ultrasonography. Magnetic resonance images showed the 'molar tooth sign,' the radiologic hallmark of Joubert syndrome, although only 1 twin, the more severely handicapped, had severe hypoplasia of the cerebellar hemispheres. Raynes et al. (1999) discussed the basis for the phenotypic discordance in the twins. Valente et al. (2005) reported 2 families with Joubert syndrome linked to chromosome 9q (JBTS1). In a family of Italian origin, 2 sibs had hypotonia that evolved into ataxia, marked oculomotor apraxia, and moderate visual reduction with mild pigmentary changes. Intelligence and kidney function were normal in both patients. In the second family, originating from Oman, an affected child had a typical neurologic phenotype with mental retardation, but no breathing dysregulation. Fundus exam and kidney function were normal. All of these patients had the molar tooth sign on MRI. In a retrospective review of midsagittal T1-weighted brain MRI studies of 20 patients with Joubert syndrome ranging in age from 18 days to 23 years, Spampinato et al. (2008) found absence of decussation of the superior cerebellar peduncles in all 6 patients over 30 months of age. Decussation was well seen on brain scans of 16 healthy controls over 30 months of age, but could not be visualized in any individuals, healthy or patients, under 30 months of age. Spampinato et al. (2008) concluded that the lack of superior cerebellar commissural fibers in Joubert syndrome accounted in part for the classic molar tooth sign observed in patients with the disorder. Braddock et al. (2007) analyzed the dysmorphic facial features of 34 children and young adults with Joubert syndrome who were not classified by molecular analysis. Findings included long face, frontal prominence, bitemporal narrowing, ptosis, prominent nasal bridge and tip, prognathism, eyebrow abnormalities, trapezoid-shaped mouth, lower lip eversion, and thick ear lobes. Anthropometric analysis showed several significant differences in measurements including bizygomatic, frontal, nasal, and mandibular dimensions. Facial characteristics appeared to become more distinct with age. Despite these findings, Braddock et al. (2007) noted that there was extreme variability likely resulting from genetic heterogeneity. Mapping To localize the region responsible for Joubert syndrome, Saar et al. (1999) performed a whole-genome scan in 2 consanguineous families of Arabian-Iranian origins with multiple affected members. In 1 family of Omani origin (Sztriha et al., 1999), Saar et al. (1999) detected linkage to the telomeric region of 9q, close to marker D9S158, with a multipoint lod score of Z = 3.7. The second family did not show linkage to this region, giving the first indication of genetic heterogeneity underlying Joubert syndrome. These findings were supported by subsequent analysis of 2 smaller families, one compatible with linkage to 9q34.3 and the other unlinked. The locus on 9q34.3 is referred to as JBTS1. Valente et al. (2005) reported 2 additional affected female twins from 1 of the families reported by Saar et al. (1999). ### Heterogeneity Blair et al. (2002) investigated a cohort of apparently unrelated North American Joubert syndrome pedigrees for association with the 9q34 and 17p11.2 loci that had previously been implicated and excluded these 2 loci in all cases where data were informative. Analysis of an additional 21 unrelated JBTS patients showed no evidence of homozygosity at the 9q34 and 17p11.2 loci that would suggest inheritance of founder JBTS mutations or unreported consanguinity. Together, these data suggested that one or more major loci for JBTS remained to be identified. Cytogenetics Natacci et al. (2000) reported a 22-year-old woman with a deletion in the short arm of chromosome 17 who presented with the clinical manifestations of both Smith-Magenis syndrome (SMS; 182290) and Joubert syndrome. Facial anomalies, brachydactyly, severe mental retardation, and self-injuring behavior were attributed to SMS, whereas the cerebellar vermis hypoplasia, hypotonia, ataxic gait, developmental delay, and abnormal respiratory pattern suggested Joubert syndrome. By fluorescence in situ hybridization analyses with YAC mapping to the 17p11.2 region, as well as locus-specific probes generated through a novel procedure, they established that the deletion encompasses a 4-Mb interval. The deletion differed from that commonly found in SMS in its telomeric boundary, and was more distal than usually observed. The presence of the Joubert syndrome phenotype in this patient and the detection of an unusual SMS deletion suggested the presence of a Joubert syndrome gene in close proximity to the SMS locus. Although Joubert syndrome has been linked to 9q34.3 in some families, no linkage to this area has been demonstrated in other families. Molecular Genetics In affected members of 7 families with Joubert syndrome, Bielas et al. (2009) identified 5 different homozygous mutations in the INPP5E gene (see, e.g., 613037.0002-613037.0005). Three families were from the United Arab Emirates, 1 from Turkey, 1 from Egypt, and 2 from Italy. All of the mutations were in the catalytic domain of the protein, and all mutant proteins showed decreased phosphatase activity. The findings implied a link between PtdIns signaling and ciliopathies. ### Associations Pending Confirmation For discussion of a possible association between Joubert syndrome and mutation in the PDPR gene, see 617835.0001. ### Exclusion Studies Because of its expression in the developing cerebellum and because of an associated mutation of Wnt1 in the 'swaying' mouse, Pellegrino et al. (1997) evaluated the WNT1 gene (164820) as a candidate gene for Joubert syndrome. The investigators ascertained a cohort of 50 patients with Joubert syndrome to evaluate the presence of associated malformations and to initiate studies leading to the identification of the responsible gene. Only 8% of patients had polydactyly, 4% had colobomas, 2% had renal cysts, and 2% had soft tissue tumors of the tongue. No mutations of the WNT1 gene were found in the patients of the cohort. Blair et al. (2002) undertook mutation analysis of several functional candidate genes in a total of 26 unrelated JBTS patients and excluded EN1 (131290), EN2 (131310), and FGF8 (600483) from a direct pathogenic role in JBTS. The BARHL1 gene (605211), which localizes to 9q34 and had previously been proposed as a strong positional candidate gene for JBTS, was also investigated and excluded from involvement in JBTS that is linked to 9q34. In 2 sibs and 1 unrelated patient with Joubert syndrome, Gould and Walter (2004) demonstrated no abnormality of the BARHL1 gene or the BARX1 gene (603260) on 9q12. ### Modifier Genes Khanna et al. (2009) presented evidence that a common allele in the RPGRIP1L gene (A229T; 610937.0013) may be a modifier of retinal degeneration in patients with ciliopathies due to other mutations, including JBTS. Nomenclature Valente et al. (2003) used the designation cerebellooculorenal syndromes (CORSs) for the clinically and genetically heterogeneous autosomal recessive syndromes, including Joubert syndrome, that share a complex neuroradiologic malformation resembling a molar tooth on brain axial images. They described a consanguineous Sicilian family showing linkage of a cerebellooculorenal syndrome (without ocular involvement except nystagmus), showing linkage to the pericentromeric region of chromosome 11. Valente et al. (2003) and Keeler et al. (2003) proposed that the locus be called CORS2 (608091), with CORS1 suggested as an alternative designation for the JBTS1 locus on 9q34. History The classic article by Joubert et al. (1969) was reprinted with a cluster of papers on this disorder. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly Face \- Prominent forehead \- High rounded eyebrows \- Hemifacial spasms Ears \- Low-set ears \- Tilted ears Eyes \- Abnormal jerky eye movements \- Impaired smooth pursuit \- Impaired saccades \- Oculomotor apraxia \- Coloboma of optic nerve \- Chorioretinal coloboma \- Retinal dysplasia (less common) \- Retinal dystrophy (less common) \- Epicanthal folds \- Ptosis Nose \- Upturned nose \- Anteverted nostrils Mouth \- Triangular-shaped open mouth \- Protruding tongue \- Rhythmic tongue movements \- Soft tissue tumors of the tongue (less common) RESPIRATORY \- Neonatal breathing dysregulation \- Hyperpnea, episodic \- Tachypnea, episodic \- Central apnea ABDOMEN Liver \- Hepatic fibrosis (less common) GENITOURINARY Kidneys \- Renal cysts (less common) SKELETAL Hands \- Missing digital phalanges (less common) Feet \- Polydactyly, postaxial (less common) NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation \- Ataxia \- Hypotonia \- Occipital meningocele (less common) \- Occipital myelomeningocele (less common) \- Hypoplasia of the brainstem \- Malformation of brainstem structures \- Molar tooth sign seen on MRI \- Cerebellar vermis hypoplasia \- Dysgenesis or agenesis of the cerebellar vermis \- Deep posterior interpeduncular fossa \- Thick and elongated superior cerebellar peduncles Behavioral Psychiatric Manifestations \- Hyperactivity \- Aggressiveness \- Self-mutilation MISCELLANEOUS \- Variable phenotype \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the inositol polyphosphate-5-phosphatase, 72-kd gene (INPP5E, 613037.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	JOUBERT SYNDROME 1	c4551568	24,874	omim	https://www.omim.org/entry/213300	2019-09-22T16:30:01	{"doid": ["0110980"], "mesh": ["C536293"], "omim": ["213300"], "orphanet": ["475"], "synonyms": ["Joubert-Boltshauser syndrome", "Joubert syndrome type A", "CPD IV", "CEREBELLOOCULORENAL SYNDROME 1", "Alternative titles", "CEREBELLOPARENCHYMAL DISORDER IV", "JOUBERT SYNDROME", "Cerebelloparenchymal disorder IV", "Classic Joubert syndrome", "Pure Joubert syndrome", "JOUBERT-BOLTSHAUSER SYNDROME"], "genereviews": ["NBK1325"]}
A number sign (#) is used with this entry because deutan colorblindness is caused by mutation in the OPN1MW gene (300821), which encodes green cone pigment. Description Normal color vision in humans is trichromatic, being based on 3 classes of cone that are maximally sensitive to light at approximately 420 nm (blue cones; 613522), 530 nm (green cones; 300821), and 560 nm (red cones; 300822). Comparison by neural circuits of light absorption by the 3 classes of cone photoreceptors allows perception of red, yellow, green, and blue colors individually or in various combinations. Dichromatic color vision is severely defective color vision based on the use of only 2 types of photoreceptors, blue plus green (protanopia; see 303900) or blue plus red (deuteranopia). Anomalous trichromacy is trichromatic color vision based on a blue, green, and an anomalous red-like photoreceptor (protanomaly), or a blue, red, and an anomalous green-like photoreceptor (deuteranomaly). The color vision defect is generally mild but may in certain cases be severe. Common variation in red-green color vision exists among both normal and color-deficient individuals (review by Deeb, 2005). Clinical Features Studies using reflection densitometry and retinal microbeam experiments showed that 2 different pigments mediate red and green sensitivity. These are located in the cones, each cone containing only 1 type of pigment (Waaler, 1968). Simunovic et al. (2001) examined red-green color-deficient subjects, a small sample of monochromats, and age-matched color-normal control subjects to determine whether color vision deficiency confers a selective advantage under scotopic conditions. They found no evidence that red-green color deficiency or monochromatism confers a selective advantage under scotopic conditions, including dark adaptation, scotopic visual field sensitivity, or performance on a scotopic perceptual task. Mapping Combining their own with published data, Arias and Rodriguez (1972) concluded that the recombination fraction for the deutan and protan loci may be higher than originally thought, perhaps 0.095. Emmerson et al. (1974) excluded close linkage of the HGPRT and deutan loci. Race and Sanger (1975) pointed out that when the 3-generation linkage data for deutan, protan, G6PD and classic hemophilia (on the one hand) versus Xg (on the other) are pooled, the score is 236 nonrecombinants and 193 recombinants: a recombination fraction of 45% (chi square 4.3, expecting 50% recombination). In Sardinia, studying G6PD, protan, deutan and Xg, Filippi et al. (1977) found linkage disequilibrium between G6PD and protan colorblindness but not between other pairs of these X-linked loci. From this they concluded that G6PD and protan are nearer one another than are G6PD and deutan. Purrello et al. (1984) followed up on the Sardinian kindred reported by Siniscalco et al. (1964). The kindred had an instance of recombination between the protan and deutan loci and was segregating also for G6PD, leading to the conclusion that the G6PD locus is between the 2 colorblindness loci. In a study of 4 common X-linked DNA polymorphisms, Brennand et al. (1982) found that only 1, a BamHI polymorphism identified with a cDNA probe of the HPRT gene, was segregating. Analysis of the chromosome haplotypes in the sons of the phase-known penta-heterozygous mother suggested the probable order HPRT--deutan--G6PD--protan--Xqter. The colorblindness genes lie proximal to the F8C and EMD loci. Population Genetics The frequency of red-green color vision defects among populations of northern European origin is around 8% of males and 0.5% of females, as determined by anomaloscopy in many studies. The frequency is lower in non-European populations (review by Deeb, 2005). Drummond-Borg et al. (1989) found abnormalities of color vision pigment genes in 15.7% of Caucasian men, a higher frequency than is shown by color vision testing. This may indicate that some color vision gene arrays associated with hybrid genes mediate normal color vision. Inheritance Colorblindness genes were the first to be mapped to a specific chromosome in any mammal. Wilson (1911), a noted cytologist, pointed out that the pedigree pattern described by Horner was explicable if the gene is X-linked recessive, if man has an XX-XY sex chromosome constitution, and if the colorblindness gene is on the X chromosome. Jorgensen et al. (1992) studied 2 female monozygotic twins who were obligatory heterozygotes for X-linked deuteranomaly associated with a green-red fusion gene derived from their deuteranomalous father. On anomaloscopy, however, one of the twins was phenotypically deuteranomalous while the other had normal color vision. The color vision-defective twin had 2 sons with normal color vision and 1 deuteranomalous son. Using a methylation-sensitive probe, M27-beta, for differentiating the active and the inactive X chromosomes, Jorgensen et al. (1992) showed that the skin cells of the color vision-defective twin had almost all paternal X chromosomes with the abnormal color vision gene as the active one, thereby explaining her color-vision defect. In contrast, a different pattern was observed in the skin cells from the woman with normal color vision; her maternal X chromosome was for the most part the active one. However, in blood lymphocytes, both twins showed identical methylation patterns with mixtures of inactivated maternal and paternal X chromosomes. Deuteranomaly in one of the twins was explained by extremely skewed X inactivation, as shown in skin cells. Failure to find this skewed pattern in blood cells was explained by the sharing of fetal circulation and exchange of hematopoietic precursor cells between twins. They reviewed other cases of monozygotic twins in which only one was affected by this particular disorder and cited an example of female MZ triplets in which only one had deuteranomaly (Yokota et al., 1990). Evolution Squirrel monkeys have a striking color-vision polymorphism; each animal has 1 of 6 different types of color vision. These arise from individual variation in the presence of 3 different middle- to long-wavelength cone pigments. Jacobs and Neitz (1987) presented evidence indicating that the 3 cone pigments are specified by 3 alleles on a single locus on the X chromosome of this species. Females, having 2 X chromosomes, have the possibility of inheriting alleles that code for 2 different pigments; this provides the basis for trichromatic color vision, by functioning in conjunction with the presence of a short-wavelength pigment coded by an autosome, as is the case in man (190900). That Old World monkeys appear to show no color-vision polymorphism, while humans do, may reflect differences in the selection pressures against color-vision variations in the 2 lines. Deeb et al. (1994) determined the coding sequences of the red and green visual pigment genes of the chimpanzee, gorilla, and orangutan. The deduced amino acid sequences were highly homologous to the equivalent human pigments. None of the amino acid differences occurred at sites previously shown to influence pigment absorption characteristics. Therefore, Deeb et al. (1994) predicted that the spectra of red and green pigments of the apes have wavelengths of maximum absorption differing very little from the equivalent human pigments and that color vision in these nonhuman primates is very similar, if not identical, to that in humans. Fourteen within-species polymorphisms (6 involving silent substitutions) were observed in the coding sequences of the red and green pigment genes of the great apes. Remarkably, the polymorphisms at 6 of these sites had been observed in human populations, suggesting that they predated the evolution of higher primates. Alleles at polymorphic sites were often shared between the red and green pigment genes. The average synonymous rate of divergence of red from green sequences was approximately one-tenth of that estimated for other proteins of higher primates, indicating the involvement of gene conversion in generating these polymorphisms. The high degree of homology and the juxtaposition of these 2 genes on the X chromosome has promoted unequal recombination and/or gene conversion, leading to sequence homogenization. However, natural selection operated to maintain the degree of separation in peak absorbance between the red and green pigments that resulted in optimal chromatic discrimination. Color vision represents, therefore, a unique case of molecular coevolution between 2 homologous genes that functionally interact at the behavioral level. It has been suggested that the colorblindness polymorphism is a heritage from frugivorous arboreal ancestors (Crossman, 1974). New World monkeys have only a single pigment encoded on the X chromosome. Old World monkeys have the same green and red pigments as man. The split between these 2 monkey classes occurred some 30 to 40 million years ago. The duplication of the X-linked genes presumably occurred thereafter. From the sequence homology figures, it appears that the short wavelength (blue), long wavelength (red and green), and rod pigments all diverged from a common ancestor about the same time, perhaps 500 million years ago. Nathans (1999) reviewed the evolution and physiology of human color vision. He quoted at the outset Theodosius Dobzhansky: 'Nothing in biology makes sense except in light of evolution.' Molecular Genetics Nathans et al. (1986) determined that whereas there is a single red pigment gene, green pigment genes vary in number among persons with normal color vision. The multiple green pigment genes are arranged in a head-to-tail tandem array. The existence of multiple green pigment genes in tandem array may explain why deutan colorblindness is more frequent than protan colorblindness. Furthermore, nonhomologous pairing and unequal crossing-over can explain the development of colorblindness. Gene conversion may also be involved. The green pigment genes vary in restriction pattern. Although there are 15 amino acid differences between the MW (green) and LW (red) opsins, the greater part of the spectral shift in sensitivity is the result of substitutions at sites 180, 277, and 285, with 5 other sites having smaller effects. Site 180 (see 300822.0002) is polymorphic in both MW and LW opsin genes. The middlewave opsin is missing or defective in deuteranopia and the longwave opsin in protanopia. Using refined methods, Neitz and Neitz (1995) reexamined the numbers and ratios of genes in the Xq28 cluster in men with normal color vision. Results indicated that many men have more pigment genes on the X chromosome than had previously been suggested and that many have more than 1 longwave pigment gene. Deeb (2005) noted that the high homology between the red and green pigment genes has predisposed the locus to relatively common unequal recombination events that give rise to red/green hybrid genes and to deletion of the green pigment genes. Such events constitute the most common cause of red-green color vision defects. Only the first 2 pigment genes of the red/green array are expressed in the retina and therefore contribute to the color vision phenotype. The severity of the red-green color vision defects is inversely proportional to the difference between the wavelengths of maximal absorption of the photopigments encoded by the first 2 genes in the array. Winderickx et al. (1992) found that only a single green pigment gene is expressed in persons with normal color vision. They suggested that a locus control-like element (300824), already known to be located 3.8 kb upstream of the transcription initiation site of the red pigment gene (300822), allows transcription of only a single copy of the green pigment genes, probably the most proximal copy. This finding provided an explanation for the not infrequent presence of 5-prime green-red hybrid genes in individuals with normal color vision. Although such hybrid genes are usually associated with defective color vision, this may not occur when their position in the gene array does not allow expression in retinal cone cells. The defect of color vision in deuteranomaly (found in 5% of males of European descent) is associated with a 5-prime--green-red--3-prime visual pigment hybrid gene, which may also exist in males with normal color vision. To explain why males with a normal red, a normal green, and a green-red hybrid gene may have either normal or deutan color vision, Winderickx et al. (1992) and Yamaguchi et al. (1997) hypothesized that only the first 2 genes are expressed and deuteranomaly results only if the green-red hybrid gene occupies the second position and is expressed preferentially over normal green-pigment genes occupying more distal positions. Hayashi et al. (1999) used long-range PCR amplification and studied 10 deutan males (8 deuteranomalous and 2 deuteranopic) with 3 visual pigment genes (red, green, and green-red hybrid) to investigate whether position of the hybrid gene in the array determined gene expression. The green-red hybrid gene was always at the second position (and the first position was always occupied by the red gene) in men with the deutan defect. Conversely, in 2 men with red, green, and green-red hybrid genes and normal color vision, the hybrid gene occupied the third position. When pigment gene mRNA expression was assessed in postmortem retinas of 3 men with the red, green, and green-red genotype, the green-red hybrid gene was expressed only when located in the second position. Since only the first 2 genes are expressed, the retinas of deuteranomals are presumably composed of cones containing red-sensitive pigment and cones containing a red-like--sensitive pigment. The findings of Hayashi et al. (1999) were consistent with the presence of a locus control region (LCR) at the 5-prime end of the X-linked visual pigment gene. This LCR was postulated to form a stable transcriptionally active complex in a stochastic manner with either the red-gene promoter to form red-sensitive pigment, or with the green-gene promoter to form green-sensitive pigment. The LCR is presumably too far removed from the third gene to affect its expression. Another explanation would be that distal gene expression is silenced by elements in the 3-prime-flanking region of the locus. Although the data came from individuals with 3 pigment genes, these findings presumably apply also to lack of expression of visual pigment genes in the fourth or even more distal positions. Jagla et al. (2002) investigated the genotypic variation in 50 red-green color vision-deficient males (27 deuteranopes and 23 protanopes) of middle European ancestry who possessed multiple genes in the X-linked photopigment gene array. Spectral sensitivities of the encoded pigments were inferred from published in vitro and in vivo data, and color vision phenotype was assessed by standard anomaloscopy. Most genotypes included hybrid genes whose sequence and position and whose encoded pigment correlated exactly with the phenotype. However, a few of the protanopes had gene arrays consistent with protanomaly rather than protanopia, since spectrally different pigments may be encoded by their arrays. Two of the deuteranopes had only R- and G-photopigment genes, without any detectable G/R-hybrid genes or identified mutations. About half of the protanopes possessed an upstream R/G-hybrid gene with different exon 2 coding sequences than their downstream G-pigment gene(s), which is inconsistent with published data implying that a single amino acid substitution in exon 2 can confer red-green color discrimination capacity on multigene protans by altering the optical density of the cones. Up to the time of the report by Winderickx et al. (1992), all red-green color vision defects had been associated with gross rearrangements within the red/green opsin gene array on Xq28. In a male with severe deuteranomaly without a rearrangement of the red/green pigment genes, Winderickx et al. (1992) found that substitution of a highly conserved cysteine by arginine at position 203 (C203R; 300821.0001) in the green pigment opsins accounted for his defect in color vision. Surprisingly, this mutation was found to be fairly common (2%) in the population but apparently was not always expressed. Ueyama et al. (2003) studied 247 Japanese males with congenital deutan color vision deficiency and found that 37 subjects (15%) had a normal genotype of a single red gene followed by 1 or more green genes. Two of the patients had previously been found to have a missense mutation in 1 or more green pigment genes (300821.0003 and 300821.0004) (Ueyama et al., 2002), but the other 35 had no mutations in either the exons or their flanking introns. However, 32 of the 35 subjects, including all 8 subjects with pigment color defect (a special category of deuteranomaly), had a -71A-C transversion (300821.0005) in the promoter of a green pigment gene at the second position in the red/green visual pigment gene array. Although the -71C substitution was also present in color-normal Japanese males at a frequency of 24.3%, it was never at the second position but always found farther downstream. The substitution was found in 19.4% of Chinese males and 7.7% of Thai males, but rarely in Caucasians or African Americans. These results suggested that the -71A-C substitution is closely associated with deutan color vision deficiency. In Japanese and presumably other Asian populations, farther downstream genes with -71C comprise a reservoir of the visual pigment genes that cause deutan color vision deficiency by unequal crossing-over between the intergenic regions. ### Reviews Nathans (1987) reviewed the molecular biology of colorblindness. Deeb (2005) reviewed the molecular basis of variation in human color vision. History Emery (1988) gave a delightful account of the history of early observations on colorblindness with particular reference to those made by John Dalton (born 1766, died 1844). He pointed out that Dalton's first scientific paper (Dalton, 1798) was concerned with his own affliction of colorblindness, although his reputation rests, of course, on his enunciation of the atomic theory. The Young-Helmholtz theory, which dates from the beginning of the 19th century (Young, 1802), assumed 3 elemental mechanisms for color vision: one with maximal sensitivity for red, a second for green, and a third for blue-violet. It was the genes for these 3 elemental mechanisms that were cloned and characterized by Nathans et al. (1986). As reviewed by Hunt et al. (1995), Dalton judged red sealing wax to be a good match for the outer face of a laurel leaf, and a crimson ribbon matched the color others called 'mud.' In the solar spectrum, he saw only 2 main hues, one of which corresponded to the normal observer's red, orange, yellow, and green, whereas the second corresponded to blue and violet. His brother had the same colorblindness. Dalton supposed that the vitreous humor of his eyes was tinted blue, selectively absorbing longer wavelengths. He instructed that his eyes should be examined after his death, but the examination revealed that the humors were perfectly clear. Hunt et al. (1995) presented the results of analyses on DNA extracted from Dalton's preserved eye tissue, showing that Dalton was a deuteranope, lacking the middlewave photopigment of the retina. Hunt et al. (1995) showed that this diagnosis is compatible with the historical record of Dalton's phenotype, although it contradicts the belief of Thomas Young (1807) that Dalton was a protanope. The characteristic X-linked recessive pedigree pattern of colorblindness was probably first pointed out by Swiss ophthalmologist Horner in the 1870s (see Thompson, 1986 for a biographic sketch of Horner). Horner's paper on Daltonism appeared in an obscure publication, the annual report of the Canton Zurich, which contained statistics of mortality and morbidity in all hospitals, institutions, etc., and economic aspects for the whole Canton (Horner, 1876). As pointed out by Steinmann (1990), Horner made several perceptive observations on hereditary traits and the advantageous position of the family doctor in observing them. Horner noted: 'I find Luxatio lentis over 3 generations, keratoconus over 2.' In regard to Daltonism, he wrote: 'Its heritability is long since known; Ribot and Darwin mention it, and also that it is more frequent in men. Since I have been able to find very accurate pedigrees which allow the illustration of a certain law, I present here the results of this genealogic study...The table (pedigree)...clearly demonstrates: (1) that there is no colorblind girl; (2) that the colorblind fathers have color-seeing daughters; (3) that the colorblind sons are always descended from color-seeing mothers; (4) that the apparent exception in generation F, where a colorblind father has a colorblind son, is readily explained by the general law, as soon as one takes into account that the mother--color-seeing--is the daughter of a colorblind father, and thus that there is a combination of 2 Daltonian descendents; (5) hence, the general law says: the sons of daughters whose fathers were colorblind, have the greatest chance of being colorblind...that is to say, Daltonism is inherited according to an atavism ('Rueckfalltypus') from grandfather to grandson.' Horner compared the mode of inheritance of Daltonism to that of hemophilia. He concluded by saying, 'If only family doctors, who occasionally know families of successive generations over many decades in great detail, would pay attention to such problems of inheritance, many precious little pearls would be found.' See Kalmus (1965; p. 62) and Bell (1926) for reproduction of Horner's original pedigree of deuteranopia. Rushton (1994) called attention to the fact that Pliny Earle, a Philadelphia physician born in 1809, described the inheritance of colorblindness on the basis of observations in his own family (Earle, 1845). Earle collected information on 5 generations to produce the most extensive family history of colorblindness that had been published up to that time (Sanborn, 1898). The evolutionary and other significance of the elegant piece of work of Nathans et al. (1986, 1986) was outlined by Botstein (1986). Eyes \- Colorblindness, partial, deutan series \- Green series defect Inheritance \- X-linked ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	COLORBLINDNESS, PARTIAL, DEUTAN SERIES	c3887938	24,875	omim	https://www.omim.org/entry/303800	2019-09-22T16:18:30	{"doid": ["13909"], "omim": ["303800"], "icd-9": ["368.52"], "icd-10": ["H53.53"], "synonyms": ["Alternative titles", "DEUTAN COLORBLINDNESS", "DEUTERANOPIA", "GREEN COLORBLINDNESS"]}
## Clinical Features Bhatti et al. (2008) studied a 6-generation consanguineous Pakistani family ('pedigree 4053') in which all affected members had prelingual profound nonsyndromic hearing impairment (NSHI) and used sign language for communication. There was no apparent vestibular involvement. Mapping Bhatti et al. (2008) performed a whole genome scan in 4 affected and 6 unaffected members of a 6-generation Pakistani family segregating autosomal recessive NSHI and obtained a maximum multipoint lod score of 5.2 at marker D1S404. A region of homozygosity in affected individuals mapped the locus to a 5.1-Mb interval on chromosome 1q43-q44 between markers D1S1547 and D1S2836. The authors noted that this region overlaps with 2.7 Mb of the autosomal dominant NSHI locus DFNA34 (617772), which is located between markers D1S102 and D1S3739. Molecular Genetics ### Exclusion Studies In a 6-generation consanguineous Pakistani family with nonsyndromic hearing impairment mapping to a region containing 15 known genes on chromosome 1q43-q44, Bhatti et al. (2008) sequenced the promoters and exons of 3 candidate genes, CHML (118825), OPN3 (606695) and MAP1LC3C (609605), but found no potentially functional variants. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, prelingual profound MISCELLANEOUS \- Based on the description of one 6-generation Pakistani family (last curated November 2008) ▲ 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	DEAFNESS, AUTOSOMAL RECESSIVE 45	c3888030	24,876	omim	https://www.omim.org/entry/612433	2019-09-22T16:01:31	{"doid": ["0110502"], "omim": ["612433"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
A rare organic aciduria characterized by neonatal onset of hypotonia, recurrent apneic episodes, lack of psychomotor development, feeding difficulties, extrapyramidal signs, and seizures. Other reported features include microcephaly, sensorineural deafness, bradycardia, and neutropenia. Laboratory studies show increased serum lactate and urinary excretion of 3-methylglutaconic acid. Brain imaging may reveal progressive cerebral atrophy. The disease is lethal in infancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	3-methylglutaconic aciduria type 8	None	24,877	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=505208	2021-01-23T19:09:17	{"synonyms": ["MGA8"]}
Hereditary mucoepithelial dysplasia (HMD) is a very rare condition that affects the skin, hair, mucosa (areas of the body that are lined with mucus), gums (gingiva), eyes, nose and lungs. Symptoms begin in infancy and vary in severity from person to person. The most common symptoms of this condition include hair loss (alopecia), patchy red skin around the perineum (the area between the anus and external genitalia); and red gums. Small, skin-colored bumps (keratosis pilaris) and early development of cloudy lens (cataracts) are also common. Other symptoms may include eye disease that gets worse over time, lung disease and a rough, red tongue. Intelligence is normal. The exact cause of HMD is still unknown, but it is thought to be an abnormality in desmosomes and gap junctions, which are cell structures involved in cell-to-cell contact. HMD appears to be inherited in an autosomal dominant pattern, but has occurred in individuals with no family history of the condition. The diagnosis of HMD is based on the symptoms and other skin and eye disorders need to be excluded. HMD is very rare and has been reported in less than 30 people in the literature. Treatment typically focuses on individual symptoms of the condition. The long-term outlook for people with HMD is unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Hereditary mucoepithelial dysplasia	c1274795	24,878	gard	https://rarediseases.info.nih.gov/diseases/5427/hereditary-mucoepithelial-dysplasia	2021-01-18T18:00:02	{"mesh": ["C536476"], "omim": ["158310"], "umls": ["C1274795"], "orphanet": ["1839"], "synonyms": ["Mucoepithelial dysplasia, hereditary", "Urban-Schosser-Spohn syndrome"]}
A number sign (#) is used with this entry because of evidence that congenital stationary night blindness type 1H (CSNB1H) is caused by homozygous or compound heterozygous mutation in the GNB3 gene (139130) on chromosome 12p13. Description Congenital stationary night blindness type 1H (CSNB1H) is an unusual and unique stationary retinal disorder with a dual anomaly in visual processing, characterized by a partial or severe degree of ON bipolar dysfunction and variably reduced cone sensitivity. Patients present with childhood-onset night blindness and middle age-onset photophobia, but have near-normal vision and do not exhibit nystagmus or high myopia (Vincent et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500). Clinical Features Vincent et al. (2016) studied a 3-generation Lebanese-Armenian kindred in which 2 brothers and their maternal aunt exhibited mildly reduced vision and normal fundus appearance; the 11-year-old younger brother and the 48-year-old aunt also had childhood-onset night blindness. The authors also studied a 65-year-old French woman with childhood-onset night blindness. Photophobia and color vision deficits were noted only in the 2 middle-aged patients. None of the patients had nystagmus, and all had a best-corrected visual acuity of 20/30 or better. Mild myopia was observed in 1, and 2 had hyperopia; all had normal fundus and visual fields. Visual parameters remained stable on follow-up in all cases, including 47 years of follow-up in the French woman. Vincent et al. (2016) considered these findings consistent with a diagnosis of CSNB. Electroretinography suggested partial rod ON bipolar dysfunction in the brothers, with severe dysfunction in the 2 older patients. Reduced cone sensitivity was also observed in the 2 older patients, which the authors noted was atypical in CSNB. Long-duration stimulus testing in the Lebanese-Armenian family confirmed cone OFF-pathway preservation. Molecular Genetics In a 3-generation Lebanese-Armenian kindred with congenital stationary night blindness in which the proband was known to be negative for mutation in 17 CSNB-associated genes and in 114 retinal dystrophy-associated genes, Vincent et al. (2016) performed whole-exome sequencing and identified homozygosity or compound heterozygosity for mutations in the GNB3 gene: 2 affected Lebanese-Armenian brothers were compound heterozygous for a nonsense mutation (W339X; 139130.0002) inherited from their unaffected Armenian mother, and an in-frame 3-bp deletion (K57del; 139130.0003) inherited from their unaffected Lebanese father. Their affected maternal aunt was homozygous for the nonsense mutation, which was present in heterozygosity in the unaffected maternal grandparents and an unaffected maternal uncle. Analysis of the GNB3 gene in 58 additional CSNB cases revealed a 65-year-old French woman from a consanguineous family who was negative for mutation in known CSNB genes but carried a missense mutation in GNB3 (S67F; 139130.0004) that was believed to be homozygous; family members were unavailable for testing. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Night blindness (childhood onset) \- Photophobia (in older patients) \- Color vision deficits (in older patients) \- Hyperopia (in some patients) \- Mild myopia (in 1 patient) \- Partial to severe rod ON bipolar dysfunction on electroretinography \- Reduced cone sensitivity (in older patients) MISCELLANEOUS \- Stable visual parameters over long follow-up MOLECULAR BASIS \- Caused by mutation in the guanine nucleotide-binding protein, beta-3 gene (GNB3, 139130.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1H	c0339535	24,879	omim	https://www.omim.org/entry/617024	2019-09-22T15:47:13	{"doid": ["0110866"], "mesh": ["C536122"], "omim": ["617024"], "orphanet": ["215"]}
Granuloma annulare (GA) is skin disorder that most often causes a rash with red bumps (erythematous papules) arranged in a circle or ring pattern (annular). GA is not contagious and is not cancerous. The rash may be localized or generalized. Localized GA is the most common form of GA (75% of the cases) and usually affects the forearms, hands, or feet. The generalized form of GA (15% of cases) presents with numerous erythematous papules that form larger, slightly raised patches (plaques) anywhere on the body, including the palms of hands and soles of feet. The plaques may or may not be in the ring pattern and can vary in color. Less common forms of GA include subcutaneous, perforating, and patch variants. The underlying cause of GA is unknown, but there are several factors that may trigger the disorder, including injury to the skin, viral infections, and certain medications and medical diseases. However, most cases of GA develop in healthy people. Some researchers propose unknown genetic factors may increase a person's risk to develop GA. Diagnosis of GA is made by the appearance of skin lesions and lack of other physical findings or symptoms. GA may be confirmed by a biopsy and tests may be performed to rule out other associated diseases. GA usually goes away without treatment within a few weeks to several years. However GA can sometimes last for decades, especially the generalized form. Steroids creams or injections and other therapies may be used to clear the rash more quickly, but are not successful in all cases, especially for those with the generalized form. Even after GA completely goes away, it may develop again. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Granuloma annulare	c0085074	24,880	gard	https://rarediseases.info.nih.gov/diseases/6546/granuloma-annulare	2021-01-18T18:00:13	{"mesh": ["D016460"], "umls": ["C0085074"], "synonyms": []}
Musicogenic seizure, also known as music-induced seizure, is a rare type of seizure, with an estimated prevalence of 1 in 10,000,000 individuals, that arises from disorganized or abnormal brain electrical activity when a person hears or is exposed to a specific type of sound or musical stimuli.[1][2] There are challenges when diagnosing a music-induced seizure due to the broad scope of triggers, and time delay between a stimulus and seizure.[3][4] In addition, the causes of musicogenic seizures are not well-established as solely limited cases and research have been discovered and conducted respectively.[1] Nevertheless, the current understanding of the mechanism behind musicogenic seizure is that music triggers the part of the brain that is responsible for evoking an emotion associated with that music.[1] Dysfunction in this system leads to an abnormal release of dopamine, eventually inducing seizure.[5] Currently, there are diverse intervention strategies that patients can choose from depending on their situations. They can have surgery to remove the region of the brain that generates a seizure.[6] Behavioral therapy is also available; patients are trained to gain emotional control to reduce the frequency of seizure.[1] Medications like carbamazepine and phenytoin (medication for general seizure) also suggest effectiveness to mitigate music-induced seizures.[7] ## Contents * 1 Signs & symptoms * 2 Causes * 3 Mechanism * 3.1 Emotional associations of music * 4 Diagnosis * 5 Treatment * 5.1 Surgery * 5.2 Behavioral therapy * 5.3 Medicine * 6 Epidemiology * 7 References ## Signs & symptoms[edit] While the signs and symptoms of musicogenic seizures are similar to that of other focal seizures, one unique distinction is the variation in the time interval between the stimulus and seizure among different patients.[4] Unlike most focal seizures, the duration between the triggering musical stimulus and seizure varies among patients; some patients encounter the seizure imminently after the trigger, while some experience a wide time gap between the stimulus and seizure.[4] During this latent prolonged time lapse, the symptoms experienced are autonomic responses.[8] Patients may encounter changes in respiratory rate, blood pressure, and heart rate such as tachycardia, leading them to feel distressed and agitated.[9][8] Furthermore, hallucinations are often experienced when encountering a seizure triggered by a musical stimulus.[8] For example, musical release hallucinations and synesthetic experiences are the most common hallucinations associated with music-induced seizures.[8] Musical auditory hallucinations may also develop due to epilepsy in the temporal lobe, which is found to be affected in 75% cases of musicogenic seizures.[4] ## Causes[edit] Musicogenic seizures are generally defined as a focal seizure, as the lateral and mesial temporal, and orbitofrontal areas of the brain are affected.[10] Musicogenic seizures have complex stimuli due to the broad scope of possibilities of triggers.[3] A wide spectrum of triggers has been noted to stimulate musicogenic seizures and musicogenic epilepsy as the type of music and method of perceiving music varies from one patient to another.[4] It has been reported that 17% of music-evoked seizures are induced solely by music, while 53% are induced by miscellaneous musical stimuli.[4] Examples of musical triggers not only include listening to noise, sound, volume, pure words, genre, singer, song, and anthem, but also playing, thinking and dreaming of music.[3][8][11] Among these triggers, most patients tend to be triggered by a specific tune, song or singer.[12] Musical characteristics such as cadence, frequency, and timbre are possible reasoning behind the musical stimuli.[3] Hence, this proposes that a particular rhythmic activity or pattern induces a seizure.[12] ## Mechanism[edit] An electroencephalogram (EEG) of the mesial temporal lobe of a patient in seizure. Although the understanding of the exact causes of musicogenic seizures is currently not fully known, a commonly understood mechanism is that this epilepsy is associated with emotional responses to music rather than the music itself.[1] Specifically, music creates an emotional response that is activated by the limbic areas.[1] This emotional effect of the music then triggers the increase of dopamine in the different parts of the brain, eventually leading to hyperexcitation, which is an abnormal excitation of neurons, and generation of seizures in those areas when there is a dysfunction in this system.[5] This notion is supported by many functional imaging studies like fMRI, PET scan, and clinical studies which suggested that patients of the musicogenic seizure often express emotional feelings before the onset of the seizure.[13] Fig.1 A diagram that shows the process involved in the auditory sensory relay from air vibrations from music to the primary auditory cortex ### Emotional associations of music[edit] The general relationship of the association between emotion and music is that after the auditory sensory relay of the musical information to the primary auditory cortex (shown in figure 1), the hippocampal connection in the brain encodes the association of positive/negative emotions with certain music in the memory.[1] Given this memory, when a person receives musical information from the environment, the hippocampus relays the emotional information related to that music to the mesolimbic system, which regulates the association of emotion and dopamine release.[14] These connections between the hippocampus, mesolimbic system, and auditory cortex provide a possible mechanism of music-induced seizure by helping the brain to relate music to emotion and dopamine release.[1] Dysfunction in this sensory relay network leads to an abnormal release of dopamine, eventually inducing hyperexcitability of neurons and seizure when certain music is heard.[5] Moreover, scientists discovered that there are other parts of the brain like basolateral amygdala involved in this connection between music, emotion, and seizure.[15] Hence, this suggests that the mechanism behind musicogenic seizure still remains obscure and more research is required to fully understand it.[1] ## Diagnosis[edit] The diagnoses of music-induced seizures are complicated as the nature of stimulus is relatively unique in the ambit of seizure triggers.[3] The usual diagnosis of seizures is routinely carried out through electroencephalography (EEG), physical examination and a review of patient history. However, an EEG may not be appropriate to diagnose and test a person with music-evoked seizures since EEG is used to test photosensitive epilepsy, a form of epilepsy where seizures are stimulated by light.[11] While an EEG typically tests varied frequencies of a light stimulus, musicogenic seizures are stimulated differently by music.[11] Moreover, there may be a time period delay between the music or sound stimulus received and seizure triggered.[11] The time gap between the stimulus and the response heightens the challenge of diagnoses. Recent hypotheses recommended testing routine electroencephalography (REEG) or amplitude-integrated electroencephalography (AEEG) to test music-evoked seizures. However, further obstacles arise in deducing the type of sound, song, and style of music which affects the patients suffering from musicogenic seizures.[4] There is a large range of possible sounds that may trigger musicogenic seizures, such as church bells, a song associated with nostalgia, dissonant sounds, and classical music. ## Treatment[edit] Illustration of deep brain stimulation Once the patient is diagnosed with the disease, there are diverse interventions that patients can choose from including surgical, behavioral, and medicinal treatments.[1] ### Surgery[edit] Surgical intervention is suitable for patients with refractory epilepsy.[6] Specifically, the patients undergo partial resectioning of the part of the brain that generates a seizure.[6] This region is identified by imaging techniques like EEG.[6] For patients who are not suitable to undergo a resectioning treatment, deep brain stimulation and vagus nerve stimulation may be effective alternatives; however, results suggest that it is often difficult for both deep brain and vagus nerve stimulation to completely stop seizures.[16] ### Behavioral therapy[edit] Behavioral or psychotherapeutic interventions may be effective in treating musicogenic epilepsy.[17] These therapies work by helping patients gain emotional control and thereby reducing the frequency of seizure. In fact, many patients often assert that their seizures are stopped after this behavioral therapy.[17] Structural formula of carbamazepine, a commonly used medication for epilepsy treatment.[6] ### Medicine[edit] Many pharmacological interventions have shown positive results. Often carbamazepine, phenytoin, and lamotrigine, commonly used for general epilepsy treatment, are prescribed to patients with music-induced seizure.[6] In some patients, these medications show better results when combined with oxcarbazepine, sodium valproate, or levetiracetam, which are also other medications for general epilepsy treatment.[6] ## Epidemiology[edit] Globally, epilepsy and seizures are among the most severe of the common neurological disorders .[18] Active epilepsy, defined as people who have continuing seizures or require treatment, can be found in 4-10 individuals per 1000 worldwide. A higher prevalence has been reported in low-income and middle-income countries at 7 to 15 cases of active epilepsy per 1000 individuals.[19] Musicogenic epilepsy is a rare subtype of these, with an estimated prevalence of 1 in 10,000,000 individuals.[1] The actual prevalence is perceived to be greater than reported. Due to the limited number of reported cases, insufficient research has been conducted on musicogenic seizures and musicogenic epilepsy.[1] It has been suggested that the disorder has a higher tendency to affect females, while the average age of onset is 28.[9] Nonetheless, the age of presentation is usually at 39, therefore suggesting an underestimated prevalence.[4] Moreover, the underestimated prevalence of musicogenic seizures could also be due to challenges in diagnosis such as deducing music as a seizure trigger.[4] ## References[edit] 1. ^ a b c d e f g h i j k l Ellis, Liddy (2017-03-01). "The potential mechanism of musicogenic epilepsy and future research avenues". Bioscience Horizons. 10. doi:10.1093/biohorizons/hzx004. ISSN 1754-7431. 2. ^ Sugerman, Deborah Tolmach (2013-09-18). "Seizures". The Journal of the American Medical Association. 310 (11): 1195. doi:10.1001/jama.2013.277840. ISSN 0098-7484. PMID 24045753. 3. ^ a b c d e Kaplan, Peter W.; Stoker, Guy (2010). "2. Musicogenic epilepsy – From sound to seizure". Epilepsy & Behavior. 17 (4): 579. doi:10.1016/j.yebeh.2010.01.027. ISSN 1525-5050. 4. ^ a b c d e f g h i Wieser, Heinz Gregor; Hungerbohler, Hansjorg; Siegel, Adrian M.; Buck, Alfred (1997). "Musicogenic Epilepsy: Review of the Literature and Case Report with Ictal Single Photon Emission Computed Tomography". Epilepsia. 38 (2): 200–207. doi:10.1111/j.1528-1157.1997.tb01098.x. ISSN 0013-9580. PMID 9048673. 5. ^ a b c Salimpoor, Valorie N; Benovoy, Mitchel; Larcher, Kevin; Dagher, Alain; Zatorre, Robert J (2011). "Anatomically distinct dopamine release during anticipation and experience of peak emotion to music". Nature Neuroscience. 14 (2): 257–262. doi:10.1038/nn.2726. ISSN 1097-6256. PMID 21217764. 6. ^ a b c d e f g Rohan, Deirdre; Cunningham, Anthony J. (2002). "A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy". Survey of Anesthesiology. 46 (3): 142–143. doi:10.1097/00132586-200206000-00024. ISSN 0039-6206. 7. ^ Nevitt, Sarah J.; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G. (15 December 2017). "Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data". The Cochrane Database of Systematic Reviews. 12: CD011412. doi:10.1002/14651858.CD011412.pub3. ISSN 1469-493X. PMC 6486134. PMID 29243813. 8. ^ a b c d e Kaplan, Peter W (2003). "Musicogenic epilepsy and epileptic music: a seizure's song". Epilepsy & Behavior. 4 (5): 464–473. doi:10.1016/s1525-5050(03)00172-0. ISSN 1525-5050. PMID 14527486. 9. ^ a b Maguire, Melissa Jane (2012-05-21). "Music and epilepsy: A critical review". Epilepsia. 53 (6): 947–961. doi:10.1111/j.1528-1167.2012.03523.x. ISSN 0013-9580. PMID 22612325. 10. ^ AVANZINI, GIULIANO (2003). "Musicogenic Seizures". Annals of the New York Academy of Sciences. 999 (1): 95–102. Bibcode:2003NYASA.999...95A. doi:10.1196/annals.1284.008. ISSN 0077-8923. PMID 14681120. 11. ^ a b c d "Music and epilepsy". Epilepsy Society. 2015-08-10. Retrieved 2019-04-10. 12. ^ a b Hix, H. L. (2009). "What Is Your Favorite Song?, and: When Did You First Learn about Your Father?, and: What Have You Kept Secret for Years?". Colorado Review. 36 (3): 86–88. doi:10.1353/col.2009.0110. ISSN 2325-730X. 13. ^ Morocz, I.A.; Karni, A.; Haut, S.; Lantos, G.; Liu, G. (2003-02-25). "fMRI of triggerable aurae in musicogenic epilepsy". Neurology. 60 (4): 705–709. doi:10.1212/01.WNL.0000047346.96206.A9. ISSN 0028-3878. PMID 12601117. 14. ^ Koelsch, Stefan; Skouras, Stavros (2014). "Functional centrality of amygdala, striatum and hypothalamus in a "small-world" network underlying joy: An fMRI study with music: A Neural Network Underlying Joy". Human Brain Mapping. 35 (7): 3485–3498. doi:10.1002/hbm.22416. PMC 6869778. PMID 25050430. 15. ^ Koelsch, Stefan (2010). "Towards a neural basis of music-evoked emotions". Trends in Cognitive Sciences. 14 (3): 131–137. doi:10.1016/j.tics.2010.01.002. PMID 20153242. 16. ^ Ryvlin, Philippe; Gilliam, Frank G.; Nguyen, Dang K.; Colicchio, Gabriella; Iudice, Alfonso; Tinuper, Paolo; Zamponi, Nelia; Aguglia, Umberto; Wagner, Louis (2015). "The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial". Epilepsy & Behavior. 46 (6): 893–900. doi:10.1016/j.yebeh.2015.02.056. PMC 4283995. PMID 24754318. 17. ^ a b Okudan, Zeynep Vildan; Ozkara, Cigdem (2018). "Reflex epilepsy: triggers and management strategies". Neuropsychiatric Disease and Treatment. 14: 327–337. doi:10.2147/ndt.s107669. ISSN 1178-2021. PMC 5779309. PMID 29403278. 18. ^ Hirtz, D.; Thurman, D. J.; Gwinn-Hardy, K.; Mohamed, M.; Chaudhuri, A. R.; Zalutsky, R. (2007-01-29). "How common are the "common" neurologic disorders?". Neurology. 68 (5): 326–337. doi:10.1212/01.wnl.0000252807.38124.a3. ISSN 0028-3878. PMID 17261678. 19. ^ "Epilepsy". www.who.int. Retrieved 2019-04-10. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Musicogenic seizure	c0278198	24,881	wikipedia	https://en.wikipedia.org/wiki/Musicogenic_seizure	2021-01-18T18:42:51	{"mesh": ["D020195"], "umls": ["C0278198"], "wikidata": ["Q85787208"]}
A number sign (#) is used with this entry because of evidence that episodic mitochondrial myopathy with or without optic atrophy and reversible leukoencephalopathy (MEOAL) is caused by homozygous mutation in the FDX2 gene (614585) on chromosome 19p13. Description Episodic mitochondrial myopathy with or without optic atrophy and reversible leukoencephalopathy (MEOAL) is an autosomal recessive neuromuscular disorder characterized mainly by childhood onset of progressive muscle weakness and exercise intolerance. Patients have episodic exacerbation, which may be associated with increased serum creatine kinase or lactic acid. Additional more variable features may include optic atrophy, reversible leukoencephalopathy, and later onset of a sensorimotor polyneuropathy. The disorder results from impaired formation of Fe-S clusters, which are essential cofactors for proper mitochondrial function (summary by Gurgel-Giannetti et al., 2018) Clinical Features Spiegel et al. (2014) reported a 15-year-old girl, born of consanguineous Jewish Moroccan parents, with myopathy with lactic acidosis. She had normal psychomotor development until age 12 years when she began to have recurrent episodes of proximal muscle weakness and myoglobinuria associated with lactic acidosis and increased serum creatine kinase. Muscle biopsy was histologically normal, but mitochondrial respiratory chain complexes I, II, and III were markedly decreased to 6 to 36% of normal, with complex II being most affected. Aconitase (ACO2; 100850) activity was also decreased to 25%. These findings indicated impairment of Fe-S-dependent enzymes. Optic atrophy was not noted. Gurgel-Giannetti et al. (2018) reported 6 patients from 2 apparently unrelated Brazilian families from the same geographic region with a complex neurologic phenotype. One of the families was known to be consanguineous. Three patients were in their first decade and 3 were adults at the time of the report, and the features evolved with age. The features were highly variable, even within a family. Patients presented in the first years of life with nystagmus and visual impairment due to nonprogressive optic atrophy. Four patients had delayed motor development, but 1 had normal development. One patient (patient 1) had global developmental delay and dysmorphic features, which were attributed to an additional coincidental tetrasomy for chromosome 9. In childhood, the patients had recurrent episodes of muscle weakness, cramps, and myalgia, often associated with exercise, infection, or low temperature, and sometimes causing transient loss of ambulation. One patient had rhabdomyolysis with increased serum creatine kinase. Motor features included a combination of myopathy, upper motor neuron signs, and a sensorimotor axonal polyneuropathy that was apparent in patients older than 10 years. Additional variable features included abnormal gait, hyporeflexia, mild spasticity, proximal and distal weakness, pes cavus, and ptosis. One patient had progressive weakness and was wheelchair-bound at age 33 years. Brain imaging in childhood showed hypoplastic optic nerves and chiasm, as well as mildly progressive T2-weighted hyperintensities in the subcortical white matter and sometimes in the pons. However, between 7 and 9 years of age, the white matter MRI abnormalities tended to resolve, showing remarkable improvement. Three patients who were clinically evaluated at the time of the abnormal brain findings had no corresponding pyramidal or extrapyramidal signs. The authors suggested that the reversible leukoencephalopathy may be related to resolving intramyelinic edema. Muscle biopsy, performed in 4 patients, showed ragged-red fibers and SDH- and COX-negative fibers, consistent with a mitochondrial abnormality. Other features included mitochondrial proliferation, paracrystalline inclusions, iron accumulation, and decreased expression of complexes II and IV, although mitochondrial respiratory chain enzyme activity was normal in the 1 patient tested. Several patients in family 1 also had microcytic anemia, neutropenia, and subclinical hypothyroidism. Inheritance The transmission pattern of MEOAL in the families reported by Gurgel-Giannetti et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In a 15-year-old girl, born of consanguineous Jewish Moroccan parents, with MEOAL, Spiegel et al. (2014) identified a homozygous missense mutation in the initiation codon of the the FDX2 gene (M1L; 614585.0001). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Patient muscle and fibroblasts showed almost undetectable levels of the FDX2 protein, consistent with a loss of function. In 6 affected individuals with MEOAL from 2 apparently unrelated Brazilian families from the same geographic region, Gurgel-Giannetti et al. (2018) identified a homozygous missense mutation in the FDX2 gene (P144L; 614585.0002). The mutation, which was found in the first family by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The same mutation was found in affected individuals from the second family who underwent whole-exome sequencing. Skeletal muscle samples from 1 patient in each family showed severely decreased protein levels compared to controls, whereas mRNA levels were similar to controls, suggesting that the mutant protein was unstable. The findings were consistent with impaired formation of Fe-S clusters that are essential for proper mitochondrial function. History Coleman et al. (1967) described 2 patients with progressive proximal and subsequently distal muscle fatigability and weakness at ages 5 to 10 years. Unusually large mitochondria, with high activities of oxidative enzymes and abnormal accumulation of neutral fat, were demonstrated by muscle biopsy. The muscle mitochondria contained anomalous quadrilaminar structures (Price et al., 1967). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus (in some patients) \- Visual impairment (in some patients) \- Optic atrophy (in some patients) \- Ptosis SKELETAL Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Mitochondrial myopathy, progressive \- Muscle weakness, episodic \- Muscle cramps \- Myalgia \- Muscle weakness may affect proximal or distal muscles \- Muscle weakness mainly affects lower limbs \- Abnormal accumulation of mitochondria seen on muscle biopsy \- Mitochondria contain abnormal paracrystalline inclusions \- Ragged red fibers \- COX-negative fibers \- Iron accumulation \- Decreased expression of some mitochondrial complex enzymes \- Rhabdomyolysis (in some patients) NEUROLOGIC Central Nervous System \- Delayed motor development, mild \- Difficulty walking \- Upper motor neuron signs (in some patients) \- Spasticity (in some patients) \- Hyperreflexia (in some patients) \- Leukoencephalopathy in subcortical white matter (in some patients) Peripheral Nervous System \- Hyporeflexia (in some patients) \- Sensorimotor peripheral neuropathy ENDOCRINE FEATURES \- Hypothyroidism (in some patients) HEMATOLOGY \- Microcytic anemia (in some patients) \- Neutropenia (in some patients) LABORATORY ABNORMALITIES \- Increased serum creatine kinase (in some patients) \- Increased serum lactate (in some patients) MISCELLANEOUS \- Onset in first decade \- Highly variable phenotype \- Leukoencephalopathy tends to resolve later in childhood \- Episodic myopathy may be triggered by infection or low temperature \- Peripheral neuropathy has onset in the second decade MOLECULAR BASIS \- Caused by mutation in the ferredoxin 2 gene (FDX2, 614585.0001 ) ▲ 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	MITOCHONDRIAL MYOPATHY, EPISODIC, WITH OR WITHOUT OPTIC ATROPHY AND REVERSIBLE LEUKOENCEPHALOPATHY	c0162670	24,882	omim	https://www.omim.org/entry/251900	2019-09-22T16:25:10	{"doid": ["699"], "mesh": ["D017240"], "omim": ["251900"], "genereviews": ["NBK1224"]}
Acute beryllium poisoning Beryllium SpecialtyOccupational medicine Acute beryllium poisoning is acute chemical pneumonia resulting from the toxic effect of beryllium in its elemental form or in various chemical compounds, and is distinct from berylliosis (also called chronic beryllium disease). After occupational safety procedures were put into place following the realization that the metal caused berylliosis around 1950, acute beryllium poisoning became extremely rare.[1] ## Contents * 1 Signs and symptoms * 2 Risk factors * 3 Diagnosis * 4 Management * 5 Prognosis * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] Generally associated with exposure to beryllium levels at or above 100 μg/m3,[1] it produces severe cough, sore nose and throat, weight loss, labored breathing, anorexia, and increased fatigue.[2]:46 In addition to beryllium's toxicity when inhaled, when brought into contact with skin at relatively low doses, beryllium can cause local irritation and contact dermatitis, and contact with skin that has been scraped or cut may cause rashes or ulcers.[3] Beryllium dust or powder can irritate the eyes.[4] ## Risk factors[edit] Beryllium ore Acute beryllium poisoning is an occupational disease.[1] Relevant occupations are those where beryllium is mined, processed or converted into metal alloys, or where machining of metals containing beryllium or recycling of scrap alloys occurs.[5] Metallographic preparation equipment and laboratory work surfaces must be damp-wiped occasionally to inhibit buildup of particles. Cutting, grinding, and polishing procedures that generate dust or fumes must be handled within sufficiently vented coverings supplied with particulate filters.[6] ## Diagnosis[edit] This section is empty. You can help by adding to it. (November 2017) ## Management[edit] Therapy is supportive and includes removal from further beryllium exposure.[1] For very severe cases mechanical ventilation may be required.[7] ## Prognosis[edit] The signs and symptoms of acute beryllium pneumonitis usually resolve over several weeks to months, but may be fatal in 10 percent of cases,[1] and about 15–20% of cases may progress to chronic beryllium disease.[8] Acute beryllium poisoning approximately doubles the risk of lung cancer.[9] The mechanism by which beryllium is carcinogenic is unclear, but may be due to ionic beryllium binding to nucleic acids; it is not mutagenic.[9] ## History[edit] Acute beryllium disease was first reported in Europe in 1933 and in the United States in 1943.[10] ## References[edit] 1. ^ a b c d e OSHA Beryllium Health Effects Page accessed March 29, 2016 2. ^ Agency for Toxic Substances and Disease Registry. September 2002 Toxicological Profile: Beryllium. See also 2009 Addendum 3. ^ Agency for Toxic Substances and Disease Registry via the CDC. TOX FAQs: Beryllium Page last reviewed: March 3, 2011. Page last updated: June 3, 2015 4. ^ NIOSH International Chemical Safety Cards: Beryllium Page last reviewed: July 22, 2015. Page last updated: July 1, 2014 5. ^ ATSDR. ToxGuide for Beryllium September 2002 6. ^ Batich, Ray and James M. Marder. (1985) Beryllium In (Ed. 9), Metals Handbook: Metallography and Microstructures (pp. 389-391). Metals Park, Ohio: American Society for Metals. 7. ^ Newman, LS for the Merck Manual. Beryllium Disease Last full review/revision May 2014 8. ^ Hardy, HL (1965). "Beryllium poisoning--lessons in control of man-made disease". The New England Journal of Medicine. 273 (22): 1188–99. doi:10.1056/NEJM196511252732205. PMID 5847559. 9. ^ a b National Toxicology Program, Department of Health and Human Services. Report on Carcinogens, Thirteenth Edition Beryllium and Beryllium Compounds 10. ^ Lang, Leslie (June–July 1994). "Beryllium: A Chronic Problem". Environmental Health Perspectives. 102 (6–7): 526–31. doi:10.1289/ehp.94102526. PMC 1569745. PMID 9679108. This article incorporates public domain material from the Occupational Safety and Health Administration document: "Beryllium". Retrieved 28 March 2016. This article incorporates public domain material from the United States Department of Health and Human Services website http://www.atsdr.cdc.gov/toxguides/toxguide-4.pdf. ## External links[edit] Classification D * ICD-10: T56.7 * ICD-9-CM: 985.3 * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Acute beryllium poisoning	None	24,883	wikipedia	https://en.wikipedia.org/wiki/Acute_beryllium_poisoning	2021-01-18T18:47:32	{"icd-9": ["985.3"], "icd-10": ["T56.7"], "wikidata": ["Q4896104"]}
Kufor-Rakeb syndrome (KRS) is a rare genetic neurodegenerative disorder characterized by juvenile Parkinsonism, pyramidal degeneration (dystonia), supranuclear palsy, and cognitive impairment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Kufor-Rakeb syndrome	c1847640	24,884	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=306674	2021-01-23T18:23:18	{"gard": ["9174"], "mesh": ["C537177"], "omim": ["606693"], "umls": ["C1847640"], "icd-10": ["G23.0"], "synonyms": ["PARK9"]}
Dysostosis SpecialtyMedical genetics A dysostosis is a disorder of the development of bone, in particular affecting ossification.[1]Examples include craniofacial dysostosis, Klippel–Feil syndrome, and Rubinstein–Taybi syndrome. It is one of the two categories of constitutional disorders of bone (the other being osteochondrodysplasia).[2]When the disorder involves the joint between two bones, the term synostosis is often used. ## References[edit] 1. ^ "dysostosis" at Dorland's Medical Dictionary[dead link] 2. ^ Offiah AC, Hall CM (March 2003). "Radiological diagnosis of the constitutional disorders of bone. As easy as A, B, C?". Pediatr Radiol. 33 (3): 153–61. doi:10.1007/s00247-002-0855-8. PMID 12612812. ## External links[edit] Classification D * MeSH: D004413 * DiseasesDB: 31424 * SNOMED CT: 109420003 External resources * Orphanet: 364559 * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum This article about a disease of musculoskeletal and connective tissue 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	Dysostosis	c0013393	24,885	wikipedia	https://en.wikipedia.org/wiki/Dysostosis	2021-01-18T18:51:47	{"mesh": ["D004413"], "umls": ["C0013393"], "orphanet": ["364559"], "wikidata": ["Q1269307"]}
Primary spontaneous pneumothorax is an abnormal accumulation of air in the pleural space (the space between the lungs and the chest cavity) that can result in the partial or complete collapse of a lung. It is called primary because it occurs in the absence of lung disease such as emphysema and spontaneous because the pneumothhorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely caused by the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. This air creates pressure on the lung and can lead to its collapse. Symptoms may include chest pain on the side of the collapsed lung and shortness of breath. The blebs that lead to primary spontaneous pneumothorax may be present in an individual's lung (or lungs) for a long time before they rupture. A change in air pressure or a very sudden deep breath may cause a rupture to occur. In most cases, there are no prior signs of illness. Once a bleb ruptures and causes a pneumothorax, rates for recurrence may be as high as 13 to 60 percent. Many researchers believe that genetic factors may play a role in the development of primary spontaneous pneumothorax. In rare cases, the condition can be caused by mutations in the FLCN gene. In these cases, the condition follows an autosomal dominant pattern of inheritance. In addition, several genetic disorders have been linked to primary spontaneous pneumothorax, including Marfan syndrome, homocystinuria, and Birt-Hogg-Dube syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Primary spontaneous pneumothorax	c1868193	24,886	gard	https://rarediseases.info.nih.gov/diseases/4997/primary-spontaneous-pneumothorax	2021-01-18T17:58:10	{"mesh": ["C566795"], "omim": ["173600"], "synonyms": ["Familial spontaneous pneumothorax", "Spontaneous pneumothorax"]}
A rare rapidly progressive and histologically distinct form of idiopathic interstitial pneumonia. ## Epidemiology Prevalence of Acute interstitial pneumonia (AIP) is estimated at 1 in 25,000. ## Clinical description AIP occurs over a wide age range, with a mean age of approximately 50 years. There is no sex predominance or association with smoking. The onset is acute/subacute (1±3 weeks), with dyspnoea and cough followed by rapid development of respiratory failure and the need for mechanical ventilation in the vast majority of the patients. Fever is present in almost half of the patients on presentation and a history of viral-like symptomatology exists in most cases but extensive investigations for bacterial and viral agents are negative. ## Diagnostic methods The chest radiograph and high-resolution computed tomography (HRCT) scan manifestations of AIP are bilateral and sometimes patchy, and there are alveolar densities associated with areas of ground glass attenuation. Consolidation is seen in the majority of cases, but is not as common as ground glass attenuation. Lung biopsies from patients with AIP show histologic features of the acute and/or organising phases of diffuse alveolar damage (DAD). The exudative phase shows oedema, hyaline membranes, and microvascular thrombi. The organising phase shows loose organising fibrosis, mostly within alveolar septa, and type II pneumocyte hyperplasia. The diagnosis of AIP is made in the appropriate clinical setting in a patient who has a clinical presentation compatible with acute respiratory distress syndrome (ARDS; see this term) but without a clear etiology. ## Differential diagnosis The differential diagnosis, histologically and clinically, includes acute exacerbation of pulmonary fibrosis, DAD in patients with collagen vascular diseases, DAD of known cause (ARDS), infection (especially Pneumocystis Jiroveci pneumonia and legionellosis) and drug-induced pneumonitis, as well as hypersensitivity pneumonitis and acute eosinophilic pneumonia(see these terms). ## Management and treatment There is no proven treatment, however high-dose corticosteroids and cyclophosphamide are the drugs usually used. ## Prognosis The prognosis is severe and early mortality is high. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Acute interstitial pneumonia	c1279945	24,887	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79126	2021-01-23T18:36:52	{"gard": ["12835"], "omim": ["178500"], "umls": ["C0085786", "C1279945"], "icd-10": ["J84.1"], "synonyms": ["Acute interstitial pneumonitis", "Hamman-Rich syndrome"]}
A pure form of hereditary spastic paraplegia characterized by onset in adolescence or early adulthood of slowly progressive spastic paraplegia, proximal muscle weakness of the lower extremities and small hand muscles, hyperreflexia, spastic gait and mild urinary compromise. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Autosomal dominant spastic paraplegia type 41	c3888208	24,888	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=320355	2021-01-23T17:03:27	{"omim": ["613364"], "icd-10": ["G11.4"], "synonyms": ["SPG41"]}
A rare X-linked syndromic intellectual disability which in symptomatic, female carriers is characterized by a highly variable phenotype including facial dysmorphisms (prominent forehead, hypertelorism, down-slanting palpebral fissures, epicanthic folds, thick lips with everted lower vermilion, thick nasal alae, and septum), short hands with tapering fingers, short stature and skeletal findings (progressive kyphoscoliosis). Intellectual disability is mild to moderate, but intellect can also be normal. A high rate of psychiatric disorders has also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Symptomatic form of Coffin-Lowry syndrome in female carriers	None	24,889	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276630	2021-01-23T16:54:40	{"icd-10": ["Q87.0"]}
Mondini dysplasia is a type of inner ear malformation that is present at birth (congenital). Individuals with Mondini dysplasia have one and a half coils of the cochlea instead of the normal two coils. It may occur in one ear (unilateral) or both ears (bilateral) and can cause varying degrees of sensorineural hearing loss, although most individuals have profound hearing loss. The condition can also predispose affected individuals to recurrent meningitis. It is caused by disruption in the embryonic development of the inner ear during the seventh week of gestation. The condition may be isolated (occurring with no other conditions or malformations) or may occur with other ear malformations or a number of syndromes. Treatment options may include surgical repair of the defect to prevent recurrent meningitis; amplification aids for those with residual hearing; and cochlear implantation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Mondini dysplasia	c4230309	24,890	gard	https://rarediseases.info.nih.gov/diseases/8215/mondini-dysplasia	2021-01-18T17:59:00	{"synonyms": ["Familial nonsyndromal Mondini dysplasia (subtype)"]}
Atresia is a condition in which an orifice or passage in the body is (usually abnormally) closed or absent.[1] Examples of atresia include: * Aural atresia, a congenital deformity where the ear canal is underdeveloped.[2] * Biliary atresia, a condition in newborns in which the common bile duct between the liver and the small intestine is blocked or absent.[3] * Choanal atresia, blockage of the back of the nasal passage, usually by abnormal bony or soft tissue.[4] * Esophageal atresia, which affects the alimentary tract and causes the esophagus to end before connecting normally to the stomach.[5] * Follicular atresia, degeneration and resorption of the ovarian follicles.[1] * Imperforate anus, malformation of the opening between the rectum and anus.[6] * Intestinal atresia, malformation of the intestine, usually resulting from a vascular accident in utero.[7] * Microtia, absence of the ear canal or failure of the canal to be tubular or fully formed[8] (can be related to Microtia, a congenital deformity of the pinna, or outer ear). * Ovarian follicle atresia, the degeneration and subsequent resorption of one or more immature ovarian follicles.[9] * Potter sequence, congenital decreased size of the kidney leading to absolutely no functionality of the kidney, usually related to a single kidney. * Pulmonary atresia, malformation of the pulmonary valve in which the valve orifice fails to develop.[10] * Renal agenesis, only having one kidney. * Tricuspid atresia, a form of congenital heart disease whereby there is a complete absence of the tricuspid valve, and consequently an absence of the right atrioventricular connection.[11] * Vaginal atresia, a congenital occlusion of the vagina or subsequent adhesion of the walls of the vagina, resulting in its occlusion. ## References[edit] 1. ^ a b Dorland's illustrated medical dictionary. Dorland, W. A. Newman (William Alexander Newman), 1864-1956. (32nd ed.). Philadelphia, PA: Saunders/Elsevier. 2012. p. 174. ISBN 978-1-4160-6257-8. OCLC 706780870.CS1 maint: others (link) 2. ^ Christensen, L. "Understanding Atresia, Microtia, and the Baha System". audiologyonline. Retrieved 14 April 2020. 3. ^ Zieve, David. "Biliary atresia". PubMed Health. Retrieved 11 September 2012. 4. ^ Zieve, David. "Choanal atresia". Pubmed Health. Retrieved 11 September 2012. 5. ^ Dugdale, David. "Esophageal atresia". PubMed Health. Retrieved 11 September 2012. 6. ^ Kaneshiro, Neil. "Imperforate Anus". PubMed Health. Retrieved 11 September 2012. 7. ^ "Intestinal atresia". Pedisurg. Retrieved 11 September 2012. 8. ^ Bonilla, Arthuro. "Microtia: Congenital ear deformity Institute". Congenital ear deformity Institute. Retrieved 11 September 2012. 9. ^ Kaipia, A.; Hsueh, A. J. W. (1997). "Regulation of Ovarian Follicle Atresia". Annual Review of Physiology. 59: 349–363. doi:10.1146/annurev.physiol.59.1.349. PMID 9074768. 10. ^ Schumacher, Kurt. "Pulmonary atresia". PubMed Health. Retrieved 11 September 2012. 11. ^ "Tricuspid atresia". PubMed Health. Retrieved 11 September 2012. This medical 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	Atresia	c0243066	24,891	wikipedia	https://en.wikipedia.org/wiki/Atresia	2021-01-18T18:49:28	{"mesh": ["Q000002"], "umls": ["C0243066"], "wikidata": ["Q757722"]}
A rare genetic isolated inherited retinal disorder characterized by primary cone degeneration with significant secondary rod involvement, with a variable fundus appearance. Typical presentation includes decreased visual acuity, central scotoma, photophobia, color vision alteration, followed by night blindness and loss of peripheral visual field. ## Epidemiology The prevalence is estimated at 1 in 40,000 in Europe. ## Clinical description Cone rod dystrophy (CRD) is characterized by primary cone involvement or, occasionally, by concomitant loss of both cones and rods, explaining the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The fundus appearance is varaible ranging from normal in the early stages, with only subtle temporal optic nerve pallor, macular pigment migration and atrophy or a bull's-eye maculopathy, to peripheral retinal pigment epithelium atrophy, intra retinal pigmentation migration, arteriolar attenuation, and optic disc pallor as disease progresses. Cone-rod dystrophy (CRD) should be distinguished from rod-cone dystrophy (RCD), also known as retinitis pigmentosa. Unlike RCD, which typically start with night blindness and progressive visual field constriction while central vision is preserved until late stages, CRD is characterized by a primary decrease in central vision leading to earlier legal blindness. At end stage, however, CRDs do not differ from end stage RCDs. CRDs are most frequently nonsyndromic, however they may also be part of several syndromes, such as Alström syndrome, Bardet-Biedl syndrome and Spinocerebellar Ataxia Type 7. ## Etiology Nonsyndromic CRDs are genetically heterogeneous (28 genes have been identified). The four most commonly mutated genes are ABCA4 (1p22.1) responsible for 30 to 60% of autosomal recessive CRDs, CRX (19q13.33) and GUCY2D (17p13.1) responsible for many reported cases of autosomal dominant CRDs, and RPGR (Xp11.4) responsible for X-linked CRDs. ## Diagnostic methods The diagnosis of CRD is based on clinical history, fundus examination, autofluorescence imaging, optical coherence tomography and full field electroretinogram. Molecular diagnosis can be made for some genes. Fundus examination can be normal at the early stages with only subtle temporal optic disc pallor or may show macular pigment migrations and atrophy or a bull's-eye maculopathy. Late stage findings include peripheral retinal pigment epithelium atrophy, intraretinal pigment migration, arteriolar attenuation, and optic disc pallor. ## Differential diagnosis Differential diagnosis includes other hereditary cone disorders (including achrompatopsia and allied cone dysfunction syndromes, cone dystrophy and Stargardt disease) and the rod-cone dystrophy, also known asretinitis pigmentosa, which is distinguished by the sequence of photoreceptor involvement (rod photoreceptors followed by cone photoreceptors). ## Genetic counseling Inheritance patterns depend on the gene involved and can be autosomal dominant, autosomal recessive or X-linked recessive. Genetic counseling is always advised. ## Management and treatment Currently, there is no therapy that stops evolution of the disease or that restores vision. Management aims at slowing down the degenerative process, treating the complications, visual rehabilitation and helping patients to cope with the social and psychological impact of blindness. ## Prognosis Visual prognosis is variable, with early central vision loss and progressive visual dysfunction leading to legal blindness before 40 years of age in most cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	Cone rod dystrophy	c3489532	24,892	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1872	2021-01-23T17:12:33	{"gard": ["10790"], "mesh": ["D000071700"], "omim": ["120970", "300476", "300834", "303700", "304020", "600624", "600977", "601777", "602093", "603649", "604116", "604393", "605549", "608194", "610283", "610381", "610478", "612657", "612775", "613660", "614500", "615163", "615374", "615860", "615973", "616502", "618555"], "icd-10": ["H35.5"]}
A number sign (#) is used with this entry because of evidence that infantile sialic acid storage disease (ISSD) is caused by homozygous or compound heterozygous mutation in the SLC17A5 gene (604322) on chromosome 6q13. Salla disease (604369) is an allelic disorder. Description Sialic acid storage diseases are autosomal recessive neurodegenerative disorders that may present as a severe infantile form (ISSD) or as a slowly progressive adult form that is prevalent in Finland (Salla disease). The main symptoms are hypotonia, cerebellar ataxia, and mental retardation; visceromegaly and coarse features are also present in the infantile cases. Progressive cerebellar atrophy and dysmyelination have been documented by MRI. Enlarged lysosomes are seen on electron microscopic studies, and patients excrete large amounts of free sialic acid in the urine (Verheijen et al., 1999). Clinical Features Infantile sialic storage disease was described by Tondeur et al. (1982) and studied by Thomas et al. (1983). The infant son and daughter of unrelated Yugoslav parents reported by Tondeur et al. (1982) had a much more severe clinical course than that in Salla disease (604369). The sibs showed coarse facies, hepatosplenomegaly, prominent psychomotor retardation, and unexpectedly fair complexion. Electron microscopy showed generalized lysosomal storage of a polysaccharide-like material. Biochemical analyses of urine and cultured fibroblasts showed increased levels of unbound (free) sialic acid. Although both sibs were alive at the time of report, the eldest was said to be in a terminal stage at age 4.5 years. Aneurysmal dilatation of capillaries in the bulbar conjunctiva had appeared at age 3. He had been normal at birth except for an inguinal hernia which was repaired at age 1 week; developmental abnormality was first noted at age 5 months and was progressive thereafter. Thomas et al. (1983) found that unstained and unfixed, cultured fibroblasts showed, by phase microscopy, many vacuolated structures resembling a honeycomb. Electron microscopy, following fixation, showed that the honeycombing resulted from numerous, closely packed, cytoplasmic membrane-bound vacuoles. Biochemical studies of crude sonicate showed the presence at levels 4 to 7 times normal of an acid-soluble substance with the characteristics of sialic acid. Quantitative studies showed 39.8 nmoles of free sialic acid per mg protein as compared with the normal of 1 to 2 nmoles per mg. Bound sialic acid levels were at the upper limit of normal. After incubation of the fibroblasts with tritiated N-acetyl-mannosamine there was a 7-fold increase (over the normal) in radioactivity of free sialic acid with no increase in labeled, bound sialic acid. Stevenson et al. (1982) reported a case of sialuria with infantile onset and severe manifestations. Free sialic acid was elevated in urine, serum and cellular cytosol. Hancock et al. (1982) reported a patient with extensive accumulation of free NeuAc in tissues and abnormal storage lysosomes who pursued a fulminant clinical course ending in death at 5 months. The amount of free sialic acid in the urine was about 20 times higher than the 15- to 30-fold increase in patients with Salla disease. Baumkotter et al. (1985) reported a patient with early-onset sialic acid storage disease whose early clinical course was similar to that of Salla disease but who had clinical and skeletal abnormalities not mentioned in that disorder. In 3 patients with different forms of N-acetylneuraminic acid (NANA) storage disease, accumulation of free NANA in the lysosomes was found in cultured fibroblasts, suggesting a transport defect (Mancini et al., 1986). One of the samples came from a patient with Salla disease, a second came from an infant with the severe form of NSD, and the third came from a child with a milder infantile form. Thomas et al. (1989) demonstrated striking cellular differences between the original French patient with sialuria (269921) and patients such as those reported by Hancock et al. (1983), Stevenson et al. (1983), and Tondeur et al. (1982) with infantile sialic acid storage disease. Whereas phase microscopy and immunochemical studies showed abnormal storage within intracellular inclusions in ISSD cells, Thomas et al. (1989) found no morphologic evidence of storage within any subcellular organelle in the French sialuria cells. Moreover, comparative subcellular fractionation studies on gradients of colloidal silica showed the excess sialic acid in ISSD cells to be located within the light (buoyant) lysosomal fraction, whereas the excessive, free sialic acid in the sialuria cells was found in the cytoplasmic fraction with no increased storage within the lysosomal fractions. Salla disease, which occurs predominantly in the Finnish population, is also a form of sialuria. Thomas (1989) suggested that Salla disease and ISSD may both be caused by a defect in transmembrane transport in the lysosome, leading to lysosomal storage of free sialic acid. Unlike Salla disease, ISSD has no particular ethnic prevalence; it presents with severe visceral involvement, dysostosis multiplex, psychomotor retardation, and early death. Mancini et al. (1991) demonstrated a proton-driven carrier for sialic acid in human lysosomal membranes. This transporter had similar properties to those previously identified in rat liver. By measuring the uptake kinetics of labeled glucuronic acid, they excluded the existence of more than 1 acidic monosaccharide carrier. Uptake studies with labeled sialic acid and glucuronic acid in lysosomal membrane vesicles from cultured fibroblasts from patients with different clinical forms of sialic acid storage disease showed defective carrier-mediated transport for both sugars. Further evidence that the defective transport of acidic sugars represents the primary genetic defect in sialic acid storage diseases was provided by the observation of reduced, half-normal transport rates in lymphoblast-derived lysosomal membrane vesicles from 5 unrelated obligate heterozygotes. This was the first observation of a human lysosomal transport defect for multiple physiologic compounds. Blom et al. (1990) also demonstrated a defect in the egress of glucuronic acid and other acidic monosaccharides from lysosomes in these disorders. Mancini et al. (1992) described a 10-year-old boy with free sialic acid storage disease. An unusual feature was slight corneal clouding. They noted that the patient's polymorphonuclear leukocytes showed a 10- to 30-fold increase in sialic acid content and that the values were slightly increased in the parents; they suggested that this was a means of identifying heterozygotes. Studies of tissues from a 3-month-old baby who died with the diagnosis of ISSD permitted Berra et al. (1995) to confirm the lysosomal nature of the disease by electron microscopy. They showed that the amount of free and total sialic acid was markedly increased and confirmed that only acid monosaccharide transport from the lysosome compartment is involved in the pathogenesis of ISSD. Lemyre et al. (1999) reported 3 new cases of ISSD and reviewed the literature regarding 24 additional cases. Each of the 3 new cases presented differently: the first with nephrotic syndrome, the second with fetal and neonatal ascites, and the third with fetal ascites and esophageal atresia type III. Coarse facies, fair complexion, hepatosplenomegaly, and severe psychomotor retardation were constant findings. Nephrotic syndrome occurred in 4 of 7 cases in which renal studies were performed. Fetal/neonatal ascites was the mode of presentation in 13 of 21 (60%) cases; Lemyre et al. (1999) suggested that ISSD should enter the differential diagnosis of hydrops fetalis with storage disease phenotype. Cardiomegaly was seen in 9 of 12 cases. Corneas were always clear, and 5 of 7 cases had albinoid fundi. Dysostosis multiplex was not prominent. Bone marrow aspiration was negative in 3 of 9 cases. Death usually occurred in infancy (range 1 month to 3.3 years, n = 20, mean 13.1 months); all reported deaths were caused by respiratory infection. Diagnosis ### Prenatal Diagnosis In a twin pregnancy of a mother who had had a previous child who died at the age of 17 months of infantile sialic acid storage disease, Lake et al. (1989) found by microscopic and biochemical analysis of chorionic villus sampling from both twins that 1 was affected. Selective feticide was performed. The unaffected twin completed the pregnancy uneventfully. Recurrent nonimmune hydrops fetalis as a presentation of sialic acid storage disease was documented by Lefebvre et al. (1999). Hydrops fetalis was diagnosed in 2 fetuses on second-trimester ultrasonography. The diagnosis of sialic acid storage disorder was based on high levels of free sialic acid in amniotic fluid and fetal cell cultures and by specific histologic features on fetopathologic examination. Sections through placental villi showing numerous empty vacuoles in the cytoplasm of both trophoblastic and Hofbauer cells were illustrated, as well as liver sections showing cytoplasmic vacuoles in the hepatocytes, and sections showing changes in the cytoplasm of the podocytes of the renal glomeruli. Mapping Haataja et al. (1994) localized the Salla disease locus to chromosome 6q. Similarities in biochemical findings suggested to Schleutker et al. (1995) that Salla disease and ISSD represent allelic disorders despite their drastically different clinical phenotypes. Schleutker et al. (1995) reported linkage studies to support this suggestion in 50 Finnish Salla disease families and 26 non-Finnish families with no genealogic connections to Finns affected with the Finnish type of Salla disease, the 'intermediate' form of the disease, or the infantile form of sialic acid storage disease. Linkage to the same locus on 6q14-q15 was found. The highest lod score of 17.30 was obtained with a microsatellite marker of locus D6S280. When linkage disequilibrium was adopted in the linkage analyses, they could further assign the locus to the immediate vicinity of marker locus D6S406. Linkage disequilibrium facilitated restriction of a critical chromosomal region to approximately 80 kb, well within limits of positional cloning techniques. Haplotype analysis of Finnish Salla disease chromosomes revealed 1 common haplotype which was also seen in most of the non-Finnish patients with the Finnish type of Salla disease. This ancestral haplotype differed from those observed in ISSD patients, who had a different common haplotype. The intermediate cases presumably represent compound heterozygotes. They lack the fetal and neonatal manifestations typical of ISSD but are more severely affected than the patients with Salla disease. Schleutker et al. (1995) studied 3 such families, each of which carried the Finnish Salla disease haplotype on 1 chromosome. Molecular Genetics Verheijen et al. (1999) used a positional candidate gene approach to identify a gene, SLC17A5, encoding a protein, sialin, with a predicted transport function that belongs to a family of anion/cation symporters (ACS). They found a homozygous SLC17A5 mutation (R39C; 604322.0001) in 5 Finnish patients with Salla disease and 6 different SLC17A5 mutations in 6 ISSD patients of different non-Finnish ethnic origins. History Using DNA polymorphisms (RFLPs) of 2 genes encoding lysosomal membrane proteins, LAMPA (153330) and LAMPB (309060), Schleutker et al. (1991) could demonstrate no linkage with the Salla disease phenotype, thus excluding these as candidate genes. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Face \- Coarse facial features Eyes \- Clear cornea \- Albinoid fundi \- Epicanthal folds \- Ptosis \- Nystagmus Nose \- Anteverted nose Mouth \- Gum hypertrophy \- High-arched palate CARDIOVASCULAR Heart \- Cardiomegaly \- Heart failure CHEST Ribs Sternum Clavicles & Scapulae \- Mild rib widening ABDOMEN \- Ascites Liver \- Hepatomegaly Spleen \- Splenomegaly GENITOURINARY Kidneys \- Nephrotic syndrome SKELETAL \- Osteopenia Skull \- J-shaped sella Limbs \- Metaphyseal irregularities Feet \- Calcaneal calcifications SKIN, NAILS, & HAIR Skin \- Hypopigmented skin Hair \- Fair hair NEUROLOGIC Central Nervous System \- Developmental delay \- Hypotonia \- Seizures \- Hydrocephalus \- Cerebral atrophy PRENATAL MANIFESTATIONS \- Hydrops fetalis Delivery \- Premature birth LABORATORY ABNORMALITIES \- Increased urinary free sialic acid (N-acetylneuraminic acid, 20-200x normal) \- Increased fibroblast free sialic acid \- Enlarged lysosomal vacuoles in lymphocytes \- Conjugated hyperbilirubinemia MISCELLANEOUS \- Allelic to Sialuria, Finnish type ( 604369 ) \- Early death (mean age 13 months) MOLECULAR BASIS \- Caused by mutations in the solute carrier family 17 (sodium phosphate), member 5 gene (SLC17A5, 604322.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	INFANTILE SIALIC ACID STORAGE DISEASE	c0342853	24,893	omim	https://www.omim.org/entry/269920	2019-09-22T16:22:19	{"mesh": ["D029461"], "omim": ["269920"], "orphanet": ["834", "309324"], "synonyms": ["Alternative titles", "SIALURIA, INFANTILE FORM", "N-ACETYLNEURAMINIC ACID STORAGE DISEASE", "NANA STORAGE DISEASE"], "genereviews": ["NBK1470"]}
A disorder that represents the ultimate dedifferentiation step of thyroid tumorigenesis and is one of the most severe cancers in humans. ## Epidemiology It accounts for less than 2% of thyroid cancers and affects older patients in their sixth to eighth decade. ## Clinical description Usual clinical presentation is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. Cervical lymph nodes enlargement and distant metastases occur frequently. ## Diagnostic methods Though cytological results obtained by fine needle aspiration may be suggestive of diagnosis, tissue biopsy for immunohistochemichal study can be necessary to exclude lymphoma and to validate aggressive therapies. ## Management and treatment Patients developing anaplastic thyroid cancer must be referred urgently in cancer centers to plan multimodality therapeutic approach depending on their performance status. The treatment regimen combines surgery when feasible, hyperfractionated and accelerated external beam radiotherapy and doxorubicin based chemotherapy. Such treatment can provide control of locoregional disease but does not impact on overall survival in patients with distant metastases. Therapeutic research is investigating redifferenciation strategies and targeted therapies to inhibit EGF receptors and neoplastic angiogenesis. Primary prevention of this lethal disease may consist of adequate treatment of differentiated thyroid cancers and goiters in the elderly. ## Prognosis The prognosis is dismal with a mean survival of four to nine months after diagnosis. Long survivors are patients with emerging disease presenting a resectable tumor and receiving adjuvant radiotherapy and/or chemotherapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Anaplastic thyroid carcinoma	c0238461	24,894	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=142	2021-01-23T17:39:09	{"gard": ["664"], "mesh": ["C536910", "D065646"], "umls": ["C0238461"], "icd-10": ["C73"]}
Torn piece of skin next to a fingernail or toenail For other uses, see Hangnail (disambiguation). Hangnail Other namesAgnail The bottom finger has a hangnail. SpecialtyDermatology A hangnail is a tiny, torn piece of skin, more specifically eponychium or paronychium, next to a fingernail or toenail.[1] Hangnails are typically caused by having dry skin, or by trauma to the fingers, such as paper cuts or nail biting.[2] ## Contents * 1 Presentation * 1.1 Complications * 2 Prevention * 3 Treatment * 4 References ## Presentation[edit] ### Complications[edit] Main article: Paronychia Hangnails can become infected and cause paronychia, a type of skin infection that occurs around the nails. Treatments for paronychia vary with severity, but may include soaking in hot salty water, the use of oral antibiotic medication, or clinical lancing. Paronychia itself rarely results in further complications but can lead to abscess, permanent changes to the shape of the nail, or the spread of infection.[3] ## Prevention[edit] Daily use of hand lotion or hand cream may help prevent the formation of hangnails.[4][5] ## Treatment[edit] For home treatment, the American Academy of Dermatology recommends washing the hands, clipping the loose piece of skin with a clean nail clipper or nail scissors, and applying over-the-counter antibiotic ointment if the area appears inflamed. Persistent hangnails should be evaluated by a physician.[6] ## References[edit] 1. ^ Hangnail, The Free Dictionary 2. ^ "Hangnails: Causes, Treatment, Risks, & When to See a Doctor". Healthline. 2018-10-11. Retrieved 2021-01-14. 3. ^ Paronychia, MedLine Plus 4. ^ Treating a Hangnail - Topic Overview, WebMD 5. ^ Thomas P. Habif; M. Shane Chapman; James G. H. Dinulos; Kathryn A. Zug (4 September 2017). Skin Disease E-Book: Diagnosis and Treatment. Elsevier Health Sciences. ISBN 978-0-323-44223-7. 6. ^ Hangnails, American Academy of Dermatology This article about an injury 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	Hangnail	c0423838	24,895	wikipedia	https://en.wikipedia.org/wiki/Hangnail	2021-01-18T18:34:53	{"wikidata": ["Q1211128"]}
Abortion in Israel is permitted when determined by a termination committee, with the vast majority of cases being approved as of 2019[update].[1][2][3] The rate of abortion in Israel has steadily declined since 1988,[1] and compared to the rest of the world, abortion rates in Israel are moderate. According to government data, in Israel, abortion rates in 2016 dropped steadily to 9 per 1,000 women of childbearing age, lower than England (16.2) and the United States (13.2). 99% of abortions are carried out in the first trimester.[4] Despite allegations of permitting abortion under limited circumstances, Haaretz noted in 2019 that this is not the case and abortion is almost always permitted in Israel.[5] Abortion in Israel had been illegal prior to 1977, but became legal, subject to a termination committee's approval, under the penal code of 1978.[6] Prior to 2014 approval for an abortion in Israel by a termination committee was given under limited circumstances, such as if the woman was unmarried, age considerations (if the woman was under the age of 18 - the legal marriage age in Israel - or over the age of 40), the pregnancy was conceived under illegal circumstances (rape, statutory rape, etc.) or an incestuous relationship, birth defects, or risk to the health or life of the mother. Subsequent to 2014, abortion up to the age of 33 can be provided for under the nationally funded health basket.[7] According to the Israel Central Bureau of Statistics report from 2004, in 2003, most abortion requests were granted, with 19,500 legal abortions performed and 200 requests for abortion denied. Reasons for termination went as follows: The woman was unmarried (42%), illegal circumstances (11%), health risks to the woman (about 20%), age of the woman (11%), and fetal birth defects (about 17%).[8] Women who would not qualify for an abortion under the statutory scheme may seek an abortion at a private clinic, although abortion in a private clinic is illegal. It was reported in 2012 that about half of all abortions in Israel were performed in private clinics, i.e., without committee approval. Women who undergo such an abortion do not face criminal penalties, but physicians who perform them face a fine, or up to five years' imprisonment; however, there have been no known prosecutions of physicians for performing non-committee-approved abortions.[9] About 20,000 abortions take place in Israel every year, with the figure remaining steady, despite a substantial increase in the population. ## Contents * 1 Legal position * 1.1 Circumstances under which abortion is approved * 1.2 Structure of the committee * 2 Abortion debate in Israel * 3 See also * 4 References ## Legal position[edit] Clauses 312-321 of the 1977 penal code limit the circumstances when an abortion is legal in Israel. Abortions must be approved by a termination committee. Abortions can only be performed by licensed gynecologists in recognized medical facilities that are specifically and publicly recognized as a provider of abortions.[10] However, the Israeli Cabinet updated the 1977 law in 2014 to allow abortion on demand for nearly every woman in the country seeking an abortion.[11][12] ### Circumstances under which abortion is approved[edit] Under a 1977 abortion law, a termination committee can approve an abortion, under sub-section 316a,[10] in the following circumstances: 1. The woman is younger than the legal marriage age in Israel (which currently is 18, raised from 17 in April 2013),[13] or older than forty. (This was later amended to also include women under the age of twenty.)[11] 2. The pregnancy was conceived under illegal circumstances (rape, statutory rape, etc.), in an incestuous relationship, or outside of marriage. 3. The fetus may have a physical or mental birth defect. 4. Continued pregnancy may put the woman's life in risk, or damage her physically or mentally. Previously, cases where the woman is between the ages of 20–33, and/or was granted an abortion due to the baby having been conceived under illegal circumstances or incest, the fetus had a serious physical or mental defect, the mother was unmarried, or the mother's health was in danger, the state pays for the abortion. However, the law was modified in 2014 to allow a free state-funded "health basket" for any woman seeking an abortion.[11] Women who get pregnant while serving in the IDF are entitled to free, state-funded abortion.[14][15] In practice, most requests for abortion that qualify for the above are granted, and leniency is shown especially under the clause for emotional or psychological damage to the pregnant woman. The committees approve 98% of requests.[16] ### Structure of the committee[edit] There are 41 termination committees operating in public or private hospitals across Israel.[17] These committees consist of three members, two of which are licensed physicians, and one a social worker.[10] Of the two physicians, one must be a specialist in obstetrics and gynaecology, and the other one either OB/GYN, internal medicine, psychiatry, family medicine, or public health. At least one member must be a woman. Six separate committees consider abortion requests when the fetus is beyond 24 weeks old. ## Abortion debate in Israel[edit] There is an abortion debate in Israel, although it is sidelined by more publicized and controversial issues. The debate as to the morality of abortion is antecedent to the debate about separation of religion and state in the context of Israel as a Jewish State and a democracy. Orthodox Jewish organizations, including political parties, strongly oppose abortion because most interpretations of Jewish law view abortion as prohibited in most cases (with some exceptions).[18] Political parties that champion this view include Shas, a Sephardic Haredi party; United Torah Judaism, an Ashkenazi Haredi party; and HaBayit HaYehudi (Jewish Home), a Religious Zionist party. A study published in 2001 found that opposition to abortion among Israelis was correlated to strong religious beliefs - particularly Orthodox Jewish beliefs - below-average income, larger family size, and identification with right-wing politics.[19] The left-wing party Meretz argues in favor of legalized abortion for reasons of personal liberty. In 2006, MK Zehava Gal-On of Meretz proposed a bill that would eliminate the termination committees, effectively decriminalizing unrestricted abortion. Gal-On argued that women with financial means can have abortions in private clinics, bypassing the committee and therefore gaining rights based on their wealth. The bill was rejected by a wide margin. When the relevant section of the penal code was originally written, it contained a "social clause" permitting women to seek abortions for social reasons, such as economic distress.[10] The clause was withdrawn in 1980 under the initiative of the Orthodox Jewish parties (see Shas, United Torah Judaism, and National Religious Party). This clause is still under debate in Israel. In 2004, MK Reshef Chen of Shinui submitted an addendum to reinstate the clause, arguing that under present circumstances, women with financial problems must lie to the termination committee to obtain approval under the emotional or psychological damage clause, and that "no advanced country compels its citizens to lie in order to preserve religious, chauvinistic, patronizing archaic values". Women's organizations such as Naamat supported the proposal.[20] Women's organizations such as Naamat[21] and Shdulat HaNashim (women's lobby)[22] argue in favor for feminist, pro-choice reasons, such as reproductive rights. Efrat[23] is a religious organization that lobbies against abortions, as well as offering financial support to women who are considering abortion for economic reasons. Efrat's campaign includes stickers with the slogan, "Don't abort me" (Hebrew: אל תפילו אותי‎). Be'ad Chaim[24] is a Messianic Christian anti-abortion non-profit association. Another organization which provides financial support and counseling to women considering abortion is Just One Life (J.O.L.) [25] \- which in Hebrew is known as Nefesh Achat B'Yisrael. ## See also[edit] * Judaism and abortion ## References[edit] 1. ^ a b Applications for Pregnancy Termination in 2014 2. ^ Shhh! Don’t Tell Evangelical Supporters of Israel, but Abortion There Is Legal — and Often It’s Free 3. ^ Israel: Reproduction and Abortion: Law and Policy 4. ^ "Israel's abortion rate falls". Haaretz. Retrieved 29 September 2019. 5. ^ https://www.haaretz.com/israel-news/.premium.MAGAZINE-shhh-don-t-tell-evangelical-supporters-of-israel-about-the-country-s-abortion-laws-1.7274968 6. ^ The Penal Regulations (Termination of Pregnancy), 5738-1978 7. ^ סל התרופות 2014: הפלות חינם גם ללא סיבה רפואית 8. ^ (in Hebrew) Central Bureau of Statistics. (August 30, 2005). Patterns of Fertility in Israel in 2004 DOC. Retrieved February 12, 2007. 9. ^ https://www.loc.gov/law/help/israel_2012-007460_IL_FINAL.pdf 10. ^ a b c d Israeli penal code at the Hebrew Wikisource. 11. ^ a b c Update: Israel's abortion law now among world's most liberal -- Free abortions for all women http://www.timesofisrael.com/israels-abortion-law-now-among-worlds-most-liberal/ 12. ^ "הפלה". Friday, 4 December 2020 13. ^ Ynetnews.com, 11.4.13: Knesset raises marriage age to 18. 14. ^ http://www.jta.org/news/article/2012/07/09/3100216/op-ed-dont-set-back-reproductive-rights-for-israeli-women 15. ^ Israel’s abortion law now among world's most liberal 16. ^ Debra Kamin (January 6, 2014). "Israel's abortion law now among world's most liberal". The Times of Israel. 17. ^ "Legal Terms of Abortion in Israel". www.jewishvirtuallibrary.org. Retrieved 2020-01-27. 18. ^ Sales, Ben. "Jewish women express anger after Orthodox rabbis compare abortion to murder". www.timesofisrael.com. Retrieved 2019-02-03. 19. ^ Remennick, Larissa I., & Hetsron, Amir. (2001). Public Attitudes toward Abortion in Israel: A Research Note. Social Science Quarterly, 82 (2), 420–431. Retrieved February 12, 2007. 20. ^ (in Hebrew) Ruti, Sinai. (June 8, 2004). "Proposal: Women in poor financial condition will be able to get an abortion Archived 2012-02-05 at the Wayback Machine." Walla!. Retrieved February 3, 2007. 21. ^ Naamat official site 22. ^ (in Hebrew) IWN official site Archived August 19, 2007, at the Wayback Machine, legal pregnancy termination in Israel 23. ^ "Efrat official site". Archived from the original on 2019-10-19. 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## Summary ### Clinical characteristics. GNE myopathy is a slowly progressive muscle disease that typically presents between age 20 and 40 years with bilateral foot drop caused by anterior tibialis weakness. Lower-extremity muscle involvement progresses from the anterior to the posterior compartment of the lower leg, followed by hamstrings, then hip girdle muscles, with relative sparing of the quadriceps. A wheelchair may be needed about ten to 20 years after the onset of manifestations. The upper extremities, which may be affected within five to ten years of disease onset, do not necessarily follow a distal-to-proximal progression. In advanced stages, neck and core muscles can become affected. ### Diagnosis/testing. The diagnosis of GNE myopathy is suspected in a proband with suggestive clinical findings and muscle histopathology (rimmed vacuoles, no inflammation) and is established by the presence of biallelic pathogenic variants in GNE identified by molecular genetic testing. ### Management. Treatment of manifestations: Evaluation and management are often by a multidisciplinary team that includes neuromuscular specialists, physiatrists, and physical and occupational therapists to address issues secondary to muscle weakness, including the use of assistive ambulatory devices (e.g., ankle-foot orthoses, cane, walker, wheelchair, or powerchair). Adaptive devices to support fine motor function and activities of daily living are needed in advanced stages of the disease. Recommended evaluations also include baseline echocardiogram and pulmonary function tests in nonambulatory individuals, with management by pulmonologists as clinically indicated. Surveillance: Follow up at least annually by neuromuscular specialists, physiatrists, and physical and occupational therapists to evaluate disease progression and address muscle strength, mobility, function, and activities of daily living; by pulmonologists to monitor respiratory muscle function in patients with advanced disease. Agents/circumstances to avoid: Cautious use of medications/drugs with potential myotoxicity (e.g., colchicine and statins); avoidance of weight-lifting and repetitive activities that cause muscle pain. ### Genetic counseling. GNE myopathy is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a GNE pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting both pathogenic variants and being affected, a 50% chance of inheriting one pathogenic variant and being an unaffected carrier, and a 25% chance of inheriting both normal alleles. When the GNE pathogenic variants have been identified in an affected family member, molecular genetic carrier testing of at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings GNE myopathy should be suspected in individuals with the following findings. Clinical findings * Myopathy presenting in young adults with bilateral foot drop caused by anterior tibialis weakness, followed by slowly progressive skeletal muscle weakness. Although there is relative sparing of the quadriceps, they may become affected at late stages of the disease. The clinical picture varies depending on the stage of disease progression at which individuals are evaluated (see Clinical Description). * Serum CK may be normal or up to four times the upper limit of normal. Muscle histopathology * Cryosections of affected muscles show atrophy, variation of fiber size, rimmed vacuoles, and no inflammation. The most prominent finding, the presence of rimmed vacuoles, is best identified in cryosections using modified Gomori trichrome stain and may be missed in paraffin-embedded tissue or hematoxylin and eosin staining. The "rimmed vacuoles" observed on electron microscopy that correspond to autophagic vacuoles are seen in a variety of myopathies with other etiologies that lead to autophagic degeneration (see Differential Diagnosis). * Note: (1) Because histopathologic findings may be difficult to identify in biopsies of muscles that are unaffected or that have been replaced by fibro-fatty tissue, muscle strength or muscle MRI may aid in the identification of suitable muscles to biopsy. (2) Muscle biopsy and histopathologic examination may not be required to suspect or establish the diagnosis of GNE myopathy but remain necessary when variants of unknown significance are identified on molecular genetic testing. ### Establishing the Diagnosis The diagnosis of GNE myopathy is established in a proband with suggestive clinical findings, muscle histopathology (if performed), and biallelic pathogenic variants in GNE identified by molecular genetic testing (see Table 1). Note: Identification of biallelic GNE variants of uncertain significance (or identification of one known GNE pathogenic variant and one GNE variant of uncertain significance) does not establish or rule out a diagnosis of GNE myopathy. Molecular genetic testing approaches can include gene-targeted testing (single-gene testing in probands with suggestive findings or affected sibs; multigene neuromuscular panel in probands with myopathy but unspecific findings) (see Option 1). In some instances, comprehensive genomic testing (exome sequencing or genome sequencing) is performed (see Option 2). #### Option 1 Single-gene testing. Sequence analysis of GNE is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. Note: Targeted analysis for founder pathogenic variants identified in several populations may be appropriate in some circumstances (for more details see Table 6). * p.Met743Thr (c.2228T>C) is a founder variant in individuals of Middle Eastern ancestry [Eisenberg et al 2001, Argov et al 2003]. * p.Asp207Val (c.620A>T) and p.Val603Leu (c.1807G>C), founder variants in individuals of Asian ancestry, account for approximately 70% of disease variants in the Japanese population [Nishino et al 2002, Cho et al 2014]. A multigene panel that includes GNE and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 Comprehensive genomic testing does not require the clinician to determine which gene(s) are 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 GNE Myopathy View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method GNESequence analysis 3>99% 4 Gene-targeted deletion/duplication analysis 5<1% 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Eisenberg et al [2001], Broccolini et al [2004], Celeste et al [2014], Chaouch et al [2014], Cho et al [2014], Cerino et al [2015], Bhattacharya et al [2018], Chen et al [2019] 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\. Del Bo et al [2003], Garland et al [2017], Zhu et al [2017], Chen et al [2019] ## Clinical Characteristics ### Clinical Description GNE myopathy is characterized by adult-onset slowly progressive myopathy typically presenting with bilateral foot drop, followed by distal-to-proximal lower-extremity weakness. The upper extremities, which are affected within five to ten years of disease onset, do not necessarily follow a distal-to-proximal progression, in contrast to the lower extremities. In advanced stages, neck and core muscles can also become affected. Onset. GNE myopathy typically presents in individuals age 20-40 years with foot drop caused by anterior tibialis weakness. Rarely, in case of muscle overuse, other muscles may be affected first [de Dios et al 2014]. Progression. In the lower extremities, the disease progresses to involve muscles from the anterior compartment of the lower leg, followed by calf muscles and hamstrings, followed by hip girdle muscles, with relative sparing of the quadriceps [Argov & Yarom 1984]. The involvement of the quadriceps muscles may become evident in late stages of the disease with the rectus femoris affected first and the vastus lateralis affected last [Huizing et al 2001, Tasca et al 2012, Carrillo et al 2018]. In the upper extremities, shoulder abduction may be affected early in the disease course before grip and hand muscles are affected. Clinical findings depend on the stage of disease progression at the time of evaluation [Quintana et al 2019]: * Disease onset. Young adults describe symptoms such as tripping and changes in gait. On exam, there is bilateral foot drop and inability to stand on the toes or walk on the heels. * Within five years of onset. Complete loss of ankle dorsiflexion strength, decreased knee flexion and shoulder abduction strength. Manifestations include steppage gait, some difficulty climbing stairs, and decreased balance, requiring the use of ankle-foot orthoses (AFOs). * Five to ten years after onset. Complete loss of knee flexion strength; decreased shoulder abduction, forearm, wrist, and hand strength; quadriceps are unaffected. Manifestations include worsening gait, increased risk of falls, and poor balance requiring the use of assistive walking devices; difficulty moving from a sitting position to a standing position; and significant difficulty climbing stairs. Upper extremities: difficulty performing tasks that involve raising arms above head and initial difficulty with hand function. * Ten to 20 years after onset. Decreased strength of hip extensors; quadriceps may be affected; the use of a wheelchair may be needed; significant difficulty with shoulder abduction and fine motor (i.e., hand) tasks. Increasing dependence for assistance with activities of daily living. * In advanced stages. The neck, core, and respiratory muscles can be affected. Ultimately, disease progression may result in complete loss of skeletal muscle function and dependence on caregivers. Life span is not reduced. Other * Respiratory muscle involvement resulting in decreased forced vital capacity has been described in the late stages of the disease; however, clinically significant involvement is rare and typically limited to individuals who are wheelchair dependent [Mori-Yoshimura et al 2013]. * Cardiac muscle is typically not affected. While cardiac involvement has been reported in persons with GNE myopathy [Chai et al 2011, Chamova et al 2015], it remains unclear whether this was due to GNE myopathy or of a different etiology. Laboratory findings * Serum creatine kinase (CK) activity may be normal or elevated; it typically does not exceed four times the normal value. * Creatinine values decrease over time due to decreased muscle mass; hence, cystatin C should be used instead of creatinine to evaluate renal function. * Mild elevation of alanine aminotransferase and aspartate aminotransferase is seen in some individuals, especially those with elevated CK. Electromyogram and nerve conduction velocity are invasive and do not help with the diagnosis. Muscle MRI shows fibro-fatty replacement on T1-weighted images; short tau inversion recovery hyperintensity indicates active disease. ### Genotype-Phenotype Correlations Because reports of GNE myopathy consist mainly of single individuals or relatively small series, correlations between genotype and phenotype are difficult. ### Penetrance Penetrance of biallelic GNE pathogenic variants is likely close to 100%. Only two older individuals with biallelic GNE pathogenic variants have been reported to be asymptomatic: One (age 67 years) was homozygous for the common Middle Eastern variant p.Met743Thr [Argov et al 2003] and one (age 60 years) was homozygous for the common Japanese variant p.Asp207Val [Nishino et al 2002]. ### Nomenclature In order to unify the nomenclature and avoid confusion with unrelated but similarly named disorders, an international consortium proposed the term "GNE myopathy" to replace historically used terms [Huizing et al 2014]. * The phenotype was first described by Nonaka et al [1981] in Japan; at that time, the disorder was referred to as "distal myopathy with rimmed vacuoles (DMRV)" or Nonaka myopathy. * The terms "quadriceps-sparing myopathy" and "hereditary rimmed vacuole myopathy (HIBM)" were used by Argov & Yarom [1984] and Sadeh et al [1993] to describe the GNE myopathy phenotype in affected individuals of Iranian Jewish ancestry. With the identification of the causative gene, GNE [Eisenberg et al 2001], it became apparent that HIBM was the same disease as DMRV [Nishino et al 2002]. ### Prevalence The prevalence of GNE myopathy is estimated at 1-9:1,000,000. To date, more than 1,000 individuals with GNE myopathy and about 255 GNE variants have been reported worldwide. The worldwide carrier rate of a pathogenic GNE variant is estimated at 1:203 individuals. ## Differential Diagnosis The differential diagnosis includes adult-onset distal myopathies and myopathies with rimmed vacuoles (see Table 2). ### Table 2. Genes of Interest in the Differential Diagnosis of GNE Myopathy View in own window GeneDisorderMOIAge at Onset (Years)Initial Muscle Group InvolvedSerum Creatine Kinase ConcentrationMuscle Biopsy ANO5Miyoshi muscular dystrophy 3 (see ANO5 Muscle Disease)AR20-25Posterior lower legs; asymmetry>10x ULNMyopathic changes & (rarely) necrotic fibers DNAJB6LGMD1D 1 (OMIM 603511)AD18-50Lower leg posterior > anterior; ± dysphagiaNormal to 8x ULNMyofibrillar myopathy 2 & rimmed vacuoles DYSFMiyoshi distal myopathy (see Dysferlinopathy)AR15-30Posterior lower leg>10x ULNMyopathic changes LDB3 (ZASP)Zaspopathy 3 (myofibrillar myopathy 4) (OMIM 609452)AD40-70Lower legNormal to 6x ULNMyofibrillar myopathy 2 ± rimmed vacuoles MATR3Amyotrophic lateral sclerosis 21 4 (OMIM 606070)AD35-60Asymmetric lower leg ± hands; dysphagia; dysphoniaNormal to 8x ULNMyopathic changes & rimmed vacuoles MYH7Laing distal myopathy 5AD0-50Anterior lower legNormal to 4x ULNType 1 fiber atrophy MYOTMyotilinopathy 6 (myofibrillar myopathy 3) (OMIM 609200)AD40-70Lower leg post > antNormal to 2x ULNMyofibrillar myopathy 2 ± rimmed vacuoles TIA1Welander distal myopathy 7 (OMIM 604454)AD40-60Finger extensorsNormal or slightly ↑Myopathic changes & rimmed vacuoles TTN (exon 364)Udd distal myopathy – tibial muscular dystrophy 8AD>35Anterior lower legNormal or slightly ↑Myopathic changes ± rimmed vacuoles TTNLimb-girdle muscular dystrophy, autosomal recessive, 10 8 (LGMDR10) (OMIM 608807)AR14-44Anterior lower legNormal to 8x ULNMyopathic changes ± rimmed vacuoles VCPInclusion body myopathy, Paget disease & frontotemporal dementia 9; (IBMPFD)AD>35Hip girdleNormal to 5x ULNMyopathic changes & rimmed vacuoles Modified from Udd & Griggs [2001] AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; ULN = upper limit of normal; XL = X-linked 1\. Sarparanta et al [2012] 2\. Histopathologic characteristics of myofibrillar myopathies include variation in fiber size, amorphous granular or hyaline deposits on trichrome-stained sections, and decrease of oxidative enzyme activities leading to abnormal fibers. 3\. Selcen & Engel [2005] 4\. Senderek et al [2009] 5\. Muelas et al [2010] 6\. Olivé et al [2005] 7\. Hackman et al [2013] 8\. Savarese et al [2016] 9\. Kimonis et al [2008] ## Management Individuals with GNE myopathy are often evaluated and managed by a multidisciplinary team that includes clinical geneticists, neuromuscular specialists, physiatrists, physical and occupational therapists, and if needed, pulmonologists. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with GNE myopathy, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with GNE Myopathy View in own window System/ConcernEvaluationComment MusculoskeletalNeuromuscular, physical medicine & rehabilitation/PT/OT evaluationTo determine extent of disease as determined by: * Muscle strength * Balance * Function * Fine motor skills * Impact on activities of daily living * Need for ongoing PT/OT * Need for AFOs, & assistive ambulatory devices * Need for adaptive devices * Need for handicapped parking RespiratoryRespiratory function tests incl supine & sitting spirometry, MIP, MEPTo evaluate for effects of muscle weakness on respiratory function esp in nonambulatory individuals CardiacBaseline echocardiogramTo evaluate for evidence of cardiac involvement Genetic counselingBy genetics professional 1To review results of genetic testing & to inform patients & families about the nature, MOI, & implications of GNE myopathy to facilitate medical & personal decision making Family support/ ResourcesAssess: * Use of community or online resources, including patient advocacy organizations * Need for social work involvement for caregiver support AFOs = ankle-foot orthoses; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations There is no approved therapy for GNE myopathy. Treatment is symptomatic only (see Table 4). ### Table 4. Treatment of Manifestations in Individuals with GNE Myopathy View in own window Manifestation/ ConcernTreatmentConsiderations/Other MusculoskeletalPT, rehabilitation medicineAmbulatory assistive devices, balanced physical activity, 1 regular exercise as tolerated. Activities of daily livingPT * Transfers (e.g., from bed to wheelchair, wheelchair to car) * Medical alert system for those unable to stand after a fall OT * Techniques & devices to accomplish tasks incl mobility, washing, dressing, eating, cooking, grooming * To assist w/household modifications to meet special needs RespiratoryRespiratory functionA concern mostly in nonambulatory affected individuals OT = occupational therapy; PT = physical therapy 1\. All affected individuals should consult their physician before beginning an exercise program. ### Surveillance Routine follow up with the multidisciplinary team is recommended annually, or more frequently as determined by managing physician (see Table 5). ### Table 5. Recommended Multidisciplinary Team Surveillance for Individuals with GNE Myopathy View in own window System/ConcernEvaluationFrequency NeuromuscularEvaluate disease progression; coordinate care. Rehabilitation medicineEvaluation & monitoring of: * Muscle strength testing using a quantitative scale, e.g., MMT, hand-held dynamometry, or QMA 1 to evaluate progressive muscle involvement * Physical function, e.g., 6-min walk test, AMAT 2 * Activities of daily living At least annually Physical therapyEvaluation & management for balance & need for AFOs, cane, walker, wheelchair, & powerchairAt least annually, or more frequently based on needs Occupational therapyEvaluation & management of fine motor skills & hand function, e.g., Jebsen Hand Function Test 3At least annually RespiratoryPFTs incl supine & sitting spirometry, MIP & MEP on affected individuals at advanced stages of diseaseAs needed, if symptomatic or if abnormal PFTs CardiacFollow up not needed unless symptomatic, or abnormal findings on initial evaluation AFOs = ankle-foot orthoses; AMAT = Adult Myopathy Assessment Tool; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; MMT= manual muscle testing; PFTs = pulmonary function tests; QMA = Quantitative Muscle Assessment 1\. Visser et al [2003] 2\. Harris-Love et al [2015] 3\. Jebsen et al [1969] ### Agents/Circumstances to Avoid It may be prudent to use medications/drugs with potential myotoxicity (e.g., colchicine, statins) with caution. It is strongly recommended that affected individuals have a healthy diet and exercise to avoid developing hypercholesterolemia, in an effort to reduce the risk associated with taking statins. Individuals with GNE myopathy should avoid lifting weights and performing repetitive activities that result in muscle pain. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation N-acetylmanossamine (ManNAc) is the only therapy currently in clinical development for GNE myopathy [Galeano et al 2007, Malicdan et al 2009, Niethamer et al 2012, Xu et al 2017]. Ultragenyx discontinued the clinical development of extended-release sialic acid (Ace-ER) in 2017 following a Phase III trial that failed to detect clinical efficacy [Lochmüller et al 2019]. Preclinical studies are ongoing to advance gene therapy as a potential therapy for GNE myopathy. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	GNE Myopathy	c1853926	24,897	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1262/	2021-01-18T21:24:36	{"mesh": ["C536816"], "synonyms": ["Distal Myopathy with Rimmed Vacuoles (DMRV)", "Hereditary Inclusion Body Myopathy (HIBM)", "Inclusion Body Myopathy Type 2 (IBM2)", "Nonaka Myopathy", "Quadriceps-Sparing Myopathy"]}
A rare renal disease characterized by the association of X-linked Alport syndrome (glomerular nephropathy, sensorineural deafness and ocular anomalies) and benign proliferation of visceral smooth muscle cells along the gastrointestinal, respiratory, and female genital tracts and clinically manifests with dysphagia, dyspnea, cough, stridor, postprandial vomiting, retrosternal or epigastric pain, recurrent pneumonia, and clitoral hypertrophy in females. ## Epidemiology Prevalence of X-linked Alport syndrome-diffuse leiomyomatosis (XLAS-DL) is unknown. It affects both males and females. ## Clinical description Symptoms of glomerular disease (hematuria, progressive proteinuria and renal impairment) typically appear late in childhood, and in males is more severe with faster progression. Patients also have sensorineural deafness and ocular anomalies (anterior lenticonus, congenital cataracts, corneal opacities, maculopathy, fleck retinopathy and temporal retinal thinning). Diffuse leiomyomatosis is severe in males and in females, and typically involves the esophagus, causing dysphagia, postprandial vomiting and retrosternal or epigastric pain. Tracheobronchial lesions lead to dyspnea, cough, stridor and recurrent pneumonia due to aspiration. Affected females show clitoral hypertrophy and variable involvement of labia majora and uterus. Perirectal or perineal leiomyomas are uncommon and associated with constipation. ## Etiology XLAS-DL is due to contiguous gene deletions encompassing the 5' ends of COL4A5 (Xq22.3) and COL4A6 (Xq22.3) genes, which respectively encode the alpha-5 and alpha-6 chain of type IV collagen. COL4A5 is an integral component of the type IV collagen 3,4,5 network, a key component of the glomerular basement membrane (GBM), and COL4A6 is a component of the type IV collagen 5,5,6 network present in Bowman's capsule but not in the healthy GBM. ## Diagnostic methods X-linked Alport syndrome is suspected on clinical presentation and family history of hematuria, deafness and/or renal impairment, and is confirmed by genetic analysis of COL4 genes. Histological evaluation of the kidney is valuable in case of equivocal or unavailable genetic testing. Immunohistochemical assays can also be performed on kidney and skin specimens, and electron microscopy provides ultrastructural analysis of basement membranes. An abnormal expression pattern of type IV collagen chains confirms the diagnosis; however, a normal expression does not eliminate diagnosis. The diagnosis of leiomyomatosis requires a biopsy of the affected tissue. Radiological imaging can identify lesions and the associated deformation of the affected tract. ## Differential diagnosis The differential diagnosis regarding the combination of glomerular disease with deafness includes Fechtner syndrome, Epstein syndrome, MELAS and May-Hegglin thrombocytopenia. The main differential diagnosis for glomerular hematuria is IgA nephropathy, familial benign hematuria and membranoproliferative glomerulonephritis. Leiomyomata can occur as sporadic benign smooth muscle tumors, without AS. ## Antenatal diagnosis Prenatal testing for at risk pregnancies is possible where the COL4A5-COL4A6 deletion has been previously identified in a family member, and if a molecular diagnosis of the inherited deletion can be reliably performed. ## Genetic counseling XLAS-DL is transmitted as X-linked dominant trait and, thus, heterozygous females will also express the disease. Genetic counseling for affected families is recommended. ## Management and treatment Blood pressure regular monitoring and urinalysis are important to identify and treat microalbuminuria/proteinuria or hypertension with angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and to set up adequate clinical management of chronic kidney disease to the point of renal replacement therapy with either preemptive transplantation or dialysis. Surgical intervention is required for symptomatic leiomyomas. Ocular manifestations rarely need intervention but an ophthalmologist is helpful for diagnosis since ocular involvement is often asymptomatic. Audiological evaluation in children should be performed regularly and hearing aids should be prescribed when appropriate. Cardiac evaluation is recommended due to the association described with aortic dilation in males. ## Prognosis The prognosis of AS is poor due to the progression to ESRD (often affecting young adults). Renal transplantation is successful in individuals with AS, since development of anti-glomerular basement membrane antibodies is a rare event. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [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	X-linked Alport syndrome-diffuse leiomyomatosis	c1835488	24,898	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1018	2021-01-23T19:12:16	{"gard": ["2432"], "mesh": ["C537006"], "omim": ["150700", "308940"], "icd-10": ["Q87.8"], "synonyms": ["Xq22.3 microdeletion syndrome"]}
Squamous cell carcinoma of the pancreas is a rare epithelial tumor of the exocrine pancreas, histologically characterized by presence of keratinization and/or intracellular bridges and lymphovascular and perineural invasion, as well as high metastatic potential. Patients present with upper abdominal and back pain, anorexia, weight loss, nausea, vomiting and jaundice. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing 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	Squamous cell carcinoma of pancreas	c2675993	24,899	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424039	2021-01-23T18:04:02	{"icd-10": ["C25.0", "C25.1", "C25.2", "C25.7", "C25.8"], "synonyms": ["Pancreatic squamous cell carcinoma"]}

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