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A syndrome of developmental anomalies characterized by growth deficiency, facial dysmorphism and skull, limb and neural defects secondary to maternal exposure to aminopterin or methotrexate (MTX) during pregnancy. ## Epidemiology At least 51 cases have been reported in the last decades; prevalence and incidence values are not available. ## Clinical description Fetuses and neonates present with short stature, skull anomalies (delayed calvarial ossification, craniosynostosis and cloverleaf skull), facial dysmorphism (hypertelorism, broad nasal bridge, prominent eyes, micrognathia, abnormal external ears), cleft palate, hydrocephalus, limb anomalies (shortness, ossification defects, talipes equinovarus, hypodactyly, syndactyly, hypoplastic toes, hypoplastic nails) and neural tube defects. In some cases, cardiac malformations such as tetralogy of Fallot, pulmonary atresia or ventricular septal defects have been reported. Occasional encephalic anomalies are absent corpus callosum, hypoplastic cerebellum and, more rarely, holoprosencephaly. Psychomotor development is usually normal, but cases with mild to severe intellectual deficit are reported. ## Etiology The syndrome is caused by exposure during the first trimester of pregnancy to aminopterin or MTX, two folate antagonists. Aminopterin is no longer used, but MTX is used as an abortifacient (especially in case of suspected ectopic pregnancy), in inflammatory diseases (Crohn's disease, psoriasis, rheumatoid arthritis) and in malignancies (at higher doses). The teratogenic effect was described very early, given the anti-mitotic activity. The malformation rate after in utero exposure to aminopterin or MTX is not known, but it is dose- and time-related. It has been suggested that the critical period for MTX-induced teratogenicity is from 6 to 8 weeks after conception. Paternal MTX exposure at the time of conception does not seem to raise any major concern for offspring, but therapy discontinuation 3-6 months before conception is usually advised. ## Diagnostic methods Diagnosis is based on clinical examination and a history of maternal/paternal exposure. ## Differential diagnosis Differential diagnosis includes various genetic diseases presenting with one of the following signs: anomalies of the developing calvaria, micrognathia with cleft palate (including Pierre Robin syndrome - see this term), limb reduction defects and hand/feet anomalies. An "aminopterin syndrome sine aminopterin (ASSA) syndrome" (see this term) has been described.. ## Antenatal diagnosis Antenatal diagnosis can be oriented by 2nd-3rd trimester ultrasound if intrauterine growth retardation (IUGR), oligo-polyhydramnios and/or malformations are seen in an at-risk pregnancy. ## Management and treatment MTX and aminopterin should not be administered in pregnant women. A pregnancy could be considered, 3-6 months after MTX treatment has been stopped by women or men. Women with chronic diseases should be counseled to plan their pregnancies. In case of exposure during the 6 months preceding conception, folic acid supplementation (5 mg/day) is recommended in the preconception period (1-3 months) and for the whole first trimester of pregnancy. Folic acid supplementation (5 mg/day) is recommended throughout pregnancy for women exposed to aminopterin or MTX during pregnancy. Pregnancies exposed to aminopterin or MTX should be carefully monitored with second level ultrasounds and fetal heart ultrasound to control potential anomalies. Cardiac malformations can be corrected by surgery. ## Prognosis Prognosis depends on the extent and severity of malformations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Aminopterin/methotrexate embryofetopathy	c0432367	30,300	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1908	2021-01-23T18:32:01	{"gard": ["2294"], "umls": ["C0432367"], "icd-10": ["Q86.8"], "synonyms": ["Aminopterin embryopathy syndrome", "Fetal aminopterin syndrome"]}
Ulnar tunnel syndrome Other namesGuyon's canal syndrome Cartoon depiction of classic ulnar sensory distribution, including mid-4th and 5th fingers. Note that this diagram does not portray hand muscles affected by ulnar neuropathy. SpecialtyOrthopedic surgery Ulnar tunnel syndrome, also known as Guyon's canal syndrome or Handlebar palsy, is caused by entrapment of the ulnar nerve in the Guyon canal as it passes through the wrist.[1] Symptoms usually begin with a feeling of pins and needles in the ring and little fingers before progressing to a loss of sensation and/or impaired motor function of the intrinsic muscles of the hand which are innervated by the ulnar nerve. Ulnar tunnel syndrome is commonly seen in regular cyclists due to prolonged pressure of the Guyon's canal against bicycle handlebars. Another very common cause of sensory loss in the ring and pink finger is due to ulnar nerve entrapment at the cubital tunnel near the elbow, which is known as cubital tunnel syndrome. ## Contents * 1 Causes * 2 Diagnosis * 2.1 Classification * 3 Treatment * 4 See also * 5 References * 6 Further reading ## Causes[edit] While being idiopathic in some cases, causative factors of the ulnar tunnel syndrome include tumors, ganglion cysts, repetitive use, anatomical variations, and diseases of the neighboring blood vessels (thrombosis or aneurysm of the ulnar artery).[2] ## Diagnosis[edit] ### Classification[edit] Three locations (zones) in which the ulnar nerve can be compressed within Guyon canal Ulnar tunnel syndrome may be characterized by the location or zone within the Guyon's canal at which the ulnar nerve is compressed. The nerve divides into a superficial sensory branch and a deeper motor branch in this area. Thus, Guyon's canal can be separated into three zones based on which portion of the ulnar nerve are involved. The resulting syndrome results in either muscle weakness or impaired sensation in the ulnar distribution.[1] Location Symptoms Associations Zone 1 Proximal (prior to ulnar nerve bifurcation) Mixed motor & sensory Ganglia & hook of hammate fractures Zone 2 Surrounding deep motor branch ulnar nerve Motor only Ganglia & hook of hammate fractures Zone 3 Surrounding superficial sensory branch of ulnar nerve Sensory only Ulnar artery pathology Zone 2 type syndromes are most common, while Zone 3 are least common. ## Treatment[edit] Initial line of treatment is with anti-inflammatory drugs or cortisone injections. There have been trials with gloves which help protect the ulnar nerve from compression. The most radical treatment option is surgery to relieve tension in the volar carpal ligament which forms the roof of Guyon's canal, thereby reducing compression on the ulnar nerve.[3][4] ## See also[edit] * Cubital tunnel syndrome * Jean Casimir Félix Guyon * Ulnar claw ## References[edit] 1. ^ a b Hatch, Daniel (August 20, 2014). "Ulnar Tunnel Syndrome". Orthobullets. Retrieved Sep 7, 2014. 2. ^ Depukat, Paweł; Mizia, Ewa; Kuniewicz, Marcin; Bonczar, Tomasz; Mazur, Małgorzata; Pełka, Piotr; Mróz, Izabela; Lipski, Marcin; Tomaszewski, Krzysztof (2015). "Syndrome of canal of Guyon - definition, diagnosis, treatment and complication". Folia Medica Cracoviensia. 55 (1): 17–23. ISSN 0015-5616. PMID 26774628. 3. ^ Okutsu I, Hamanaka I, Yoshida A (April 2009). "Pre- and postoperative Guyon's canal pressure change in endoscopic carpal tunnel release: correlation with transient postoperative Guyon's canal syndrome". J Hand Surg Eur Vol. 34 (2): 208–11. doi:10.1177/1753193408100122. PMID 19282410. 4. ^ Assmus H, Antoniadis G, Bischoff C, Hoffmann R, Martini AK, Preissler P, Scheglmann K, Schwerdtfeger K, Wessels KD, Wüstner-Hofmann M (May 2011). "Cubital tunnel syndrome - a review and management guidelines". Cent Eur Neurosurg. 72 (2): 90–8. doi:10.1055/s-0031-1271800. PMID 21547883. ## Further reading[edit] * Slane, Josh; Timmerman, Mark; Ploeg, Heidi-Lynn; Thelen, Darryl G. (2011). "The influence of glove and hand position on pressure over the ulnar nerve during cycling". Clinical Biomechanics. 26 (6): 642–8. doi:10.1016/j.clinbiomech.2011.03.003. PMID 21458120. * Maimaris, C; Zadeh, H G (1990). "Ulnar nerve compression in the cyclist's hand: Two case reports and review of the literature". British Journal of Sports Medicine. 24 (4): 245–6. doi:10.1136/bjsm.24.4.245. PMC 1478904. PMID 2097022. * Rehak, David C. (Summer 2003). "Cyclist's Hands: Overcoming overuse injuries". Hughston Health Alert. Hughston Clinic. * Bledsoe, Jim. "Cycling injuries - handlebar palsy". Sports Injury Bulletin. * US patent 6845514, Yao, Joseph, "Protective device for the median and ulnar nerves", issued January 25, 2005 * v * t * e Diseases relating to the peripheral nervous system Mononeuropathy Arm median nerve * Carpal tunnel syndrome * Ape hand deformity ulnar nerve * Ulnar nerve entrapment * Froment's sign * Ulnar tunnel syndrome * Ulnar claw radial nerve * Radial neuropathy * Wrist drop * Cheiralgia paresthetica long thoracic nerve * Winged scapula * Backpack palsy Leg lateral cutaneous nerve of thigh * Meralgia paraesthetica tibial nerve * Tarsal tunnel syndrome plantar nerve * Morton's neuroma superior gluteal nerve * Trendelenburg's sign sciatic nerve * Piriformis syndrome Cranial nerves * See Template:Cranial nerve disease Polyneuropathy and Polyradiculoneuropathy HMSN * Charcot–Marie–Tooth disease * Dejerine–Sottas disease * Refsum's disease * Hereditary spastic paraplegia * Hereditary neuropathy with liability to pressure palsy * Familial amyloid neuropathy Autoimmune and demyelinating disease * Guillain–Barré syndrome * Chronic inflammatory demyelinating polyneuropathy Radiculopathy and plexopathy * Brachial plexus injury * Thoracic outlet syndrome * Phantom limb Other * Alcoholic polyneuropathy Other General * Complex regional pain syndrome * Mononeuritis multiplex * Peripheral neuropathy * Neuralgia * Nerve compression 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Ulnar tunnel syndrome	c1142146	30,301	wikipedia	https://en.wikipedia.org/wiki/Ulnar_tunnel_syndrome	2021-01-18T18:31:06	{"wikidata": ["Q786262"]}
Bencze syndrome or hemifacial hyperplasia with strabismus is a malformation syndrome involving the abnormal growth of the facial skeleton as well as its soft tissue structure and organs, and is characterized by mild facial asymmetry with unaffected neurocranium and eyeballs, as well as by esotropia, amblyopia and/or convergent strabismus, and occasionally submucous cleft palate. Transmission is autosomal dominant. There have been no further descriptions in the literature since 1979. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Bencze syndrome	c1841640	30,302	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1241	2021-01-23T19:05:18	{"gard": ["2633"], "mesh": ["C564199"], "omim": ["141350"], "umls": ["C1841640"], "icd-10": ["Q67.4"], "synonyms": ["Hemifacial hyperplasia-strabismus syndrome"]}
A number sign (#) is used with this entry because of evidence that immunodeficiency-47 (IMD47) is caused by hemizygous mutation in the ATP6AP1 gene (300197) on chromosome Xq28. Description Immunodeficiency-47 is an X-linked recessive complex immunodeficiency syndrome characterized by recurrent bacterial infections, hypogammaglobulinemia, liver dysfunction, and defective glycosylation of serum proteins. Some patients may also have neurologic abnormalities (summary by Jansen et al., 2016). Clinical Features Jansen et al. (2016) reported 11 males from 6 unrelated families with a complex immunodeficiency disorder associated with liver disease. Five patients presented in infancy with signs of liver disease, including neonatal jaundice, hepatosplenomegaly, and abnormal liver function tests. Two patients presented in infancy with recurrent infections. The patients were initially ascertained from a cohort of patients with unexplained defective glycosylation of serum proteins, including abnormal N-glycosylation of transferrin, abnormal O-glycosylation of apolipoprotein CIII, and minor accumulations of truncated glycans. These findings were suggestive of defects in Golgi homeostasis and reminiscent of congenital disorders of glycosylation (see, e.g., CDG1A, 212065). All patients eventually developed recurrent bacterial infections associated with hypogammaglobulinemia, and some had poor response to childhood vaccinations. Laboratory studies showed leukopenia, abnormal liver enzymes, low serum copper and ceruloplasmin, and high alkaline phosphatase. Liver biopsies showed variable features that ranged in severity, and included steatosis, fibrosis, micronodular cirrhosis, and abnormal mitochondria. Six patients from 3 families who carried the same mutation (E346K; 300197.0003) had neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities. Two of these 6 patients died of liver failure in early childhood. Three patients from another family had sensorineural hearing loss and hyperopia. Inheritance The transmission pattern of IMD47 in the families reported by Jansen et al. (2016) was consistent with X-linked recessive inheritance. Molecular Genetics In 11 males from 6 unrelated families with IMD47, Jansen et al. (2016) identified 4 different hemizygous missense mutations in the ATP6AP1 gene (300197.0001-300197.0004). The mutations, which were found by exome sequencing in most families, segregated with the disorder. Female carriers were unaffected. Transfection of 2 of the mutations (E346K, 300197.0003 and Y313C, 300197.0004) resulted in significant growth defects in yeast. Jansen et al. (2016) suggested that the variable systems affected in this disorder may result from tissue-specific processing of ATP6AP1, which could cause aberrant acidification and pH regulation, membrane trafficking and fusion, or abnormal glycosylation of proteins. INHERITANCE \- X-linked recessive HEAD & NECK Ears \- Hearing loss, sensorineural (1 family) Eyes \- Hyperopia (1 family) ABDOMEN Liver \- Hepatopathy \- Hepatomegaly \- Steatosis \- Fibrosis \- Cirrhosis \- Abnormal mitochondria Spleen \- Splenomegaly SKIN, NAILS, & HAIR Skin \- Jaundice, neonatal NEUROLOGIC Central Nervous System \- Intellectual disability (in some patients) \- Seizures (in some patients) Behavioral Psychiatric Manifestations \- Behavioral abnormalities (in some patients) IMMUNOLOGY \- Recurrent bacterial infections \- Hypogammaglobulinemia \- Leukopenia \- Poor response to vaccination LABORATORY ABNORMALITIES \- Abnormal liver enzymes \- Defective N- and O-glycosylation of serum proteins \- Low serum copper \- Low serum ceruloplasmin \- High alkaline phosphatase MISCELLANEOUS \- Variable severity MOLECULAR BASIS \- Caused by mutation in the ATPase, H+ transporting, lysosomal, accessory protein 1 gene (ATP6AP1, {300197.0001`}) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	IMMUNODEFICIENCY 47	c4310819	30,303	omim	https://www.omim.org/entry/300972	2019-09-22T16:19:03	{"omim": ["300972"], "synonyms": ["Alternative titles", "IMMUNODEFICIENCY AND HEPATOPATHY WITH OR WITHOUT NEUROLOGIC FEATURES"]}
Astroblastoma Micrograph of an astroblastoma showing the characteristic nuclear pervivascular pseudorosette. H&E stain. SpecialtyOncology Astroblastoma is a rare glial tumor derived from the astroblast, a type of cell that closely resembles spongioblastoma and astrocytes.[1] Astroblastoma cells are most likely found in the supratentorial region of the brain that houses the cerebrum, an area responsible for all voluntary movements in the body.[2] It also occurs significantly in the frontal lobe, parietal lobe, and temporal lobe, areas where movement, language creation, memory perception, and environmental surroundings are expressed. These tumors can be present in major brain areas not associated with the main cerebral hemispheres, including the cerebellum, optic nerve, cauda equina, hypothalamus, and brain stem.[3] The most defining physical symptom of astroblastoma, regardless of location, is elevated intracranial pressure, occurring when cerebrospinal fluid in the subarachnoid space exhibits heavy pressure and decreased blood flow, resulting in throbbing headache or nausea for the patient.[2] Despite widespread localization in the brain, astroblastoma is rarely reported in oncological studies, accounting for only 0.45–2.8% of all brain gliomas since its discovery in 1926.[4][5][6] Without a doubt, astroblastoma remains one of the most challenging and problematic tumors to diagnose and treat among all nervous system cancers. ## Contents * 1 Subtypes * 1.1 General Pathology * 1.2 Abnormal Pathology * 1.3 Associations with Other Tumors * 2 Clinical Symptoms * 2.1 Intracranial pressure * 2.2 Enhanced drowsiness * 2.3 Frequent nausea * 2.4 Impaired vision * 2.5 Motor system imbalance and weakness * 2.6 Decreased sensation * 2.7 Seizures * 2.8 Psychotic episodes * 2.9 Cognitive dysregulation * 3 Diagnosis * 3.1 Classification * 4 Treatment * 4.1 Gross-total resection * 4.2 Radiotherapy * 4.3 Chemotherapy * 4.4 Future advances * 5 Recurrence * 5.1 Low-grade * 5.2 High-grade * 6 Epidemiology * 6.1 Age incidence * 6.2 Gender incidence * 6.3 Environmental incidence * 7 See also * 8 References * 9 External links ## Subtypes[edit] Astroblastoma can be divided into low-grade, well-differentiated tumors and high-grade, anaplastic subtypes.[1] The majority of tumors exhibit a spherical perimeter with either a solid or cystic interior, comprising peripheral vasculature and epithelioid neoplasms. ### General Pathology[edit] Since the early 1890s, astroblastoma has established a stable set of pathological qualities that truly distinguishes itself as a separate and significant entity. Compilations from various case reports reveal the following common characteristics:[2] * Appears "bubbly" in nature * Polarized, unipolar in structure * Peripheral vasculature * Radial arrangement as a pseudorosette * Immunoreactive for GFAP and vimentin (supports astrocytic origin) * Lacks "true rosette" architecture * Lacks structural cohesiveness * Prominent pseudopapillae formation * Localization mostly in cerebral hemispheres * Nodular, non-invasive growth * Strong, associative vasculature in other parts of the body * Tissue fibrosis prominence * High likelihood of vascular hyalinization * Low likelihood to metastasize toward other regions of the brain ### Abnormal Pathology[edit] Beyond normal pathologies, scientists have discovered some abnormal characteristics of astroblastoma in a variety of patients. The presence of a bulky calcification with punctate (pointed) and globular features was noted in a 2009 study of a 12-year-old girl.[7] Computerized tomography confirmed these calcified masses in the posteroinferior region to the fourth ventricle just above the midline. The mass began at the brainstem, extended along the inferior cerebellar peduncle to roof areas against the ventricles through the nodule of vermis, easily detected against normal grey matter surrounding it.[7] Calcification deriving from nervous system tumors is a rare quality in astroblastoma patients, but it is nonetheless easy to identify. Lumbar pain and lower body weakness is also a rarity in astroblastoma patients, even though it is entirely possible for lesions to proliferate toward the spinal cord.[6] ### Associations with Other Tumors[edit] An enormous difficulty lies in classifying an astroblastoma tumor due to its overlapping features with other brain tumors. Certain neuroradiologic features finally distinguish astroblastoma from the common ependymoma, another frequent tumor occurring in the fourth ventricle. In general, when brain lesions are smaller than Grade I, demarcating between these features is near impossible, often mistaking astroblastoma with glial neoplasms, high-grade astrocytes, and embryonal neoplasms. However, the “bubbly” appearance in astroblastoma is entirely exclusive. Researchers have also confirmed astroblastoma distinct from oligodendroglioma, which are invasive nodular cysts that may resemble a "bubbly" interior. Pleomorphic xanthoastrocytoma, dysembryoplastic neuroepithelial tumors, juvenile pilocytic astrocytoma, and hemangioblastoma are well-established, pediatric brain cancer tumors that are often confused with astroblastoma patients. However, further histology has confirmed that special structures and characteristics are unique to astroblastoma. Advances in the 21st century of histology have justified proper diagnosis, eliminating inconsistency that plagued this tumor for several decades. Research going back to early 2000 marks the first complications for satisfying requirements in radiographic and histopathologic studies. Seven astroblastoma cases of comparative genomic hybridization, a molecular technique analyzing chromosomal changes in DNA content of brain cancer cells, suggested that chromosome 19 and chromosome 20q were amplified in astroblastoma cells throughout the brain.[5][6] These genomic features are responsible for widespread proliferation, tumorigenesis, and deregulation of pathways associated with normal housekeeping. Furthermore, the absence of chromosome function in 9q, 10, and X were not observed in other types of neoplasms, such as an ependymoma. Specific neuronal markers further distinguish astroblastoma. Neuron-specific enolase (NSE) positive, NSE negative, synaptophysin negative, neurofilament negative, TUJ1 positive, and nestin positive have been expressed in astroblastoma cell populations, showing significant promise in neuronal stem cell treatment for the tumor.[6] ## Clinical Symptoms[edit] The majority of patients with astroblastoma display a limited set of physical and physiological symptoms. Rare cases in literature reveal atypical conditions, but these are often exclusive to the individual and do not suggest a widespread trend. As research continues, a larger set of symptoms can be properly assessed in the clinic. ### Intracranial pressure[edit] Most patients experience a series of intermittent headaches over a few weeks or sustained, powerful pressure in a matter of days.[2][6] The time-frame for this pressure varies from patient to patient and fluctuate based on the stage of the tumor. Both low-grade and high-grade astroblastoma can exhibit significant discomfort from headaches, although literature supports that higher-grade astroblastoma affect a patient with day-to-day activities, forcing individuals to stay at home away from their jobs and family. Malignant astroblastoma distorts the function of surrounding brain regions, and pressure is the primary result.[1][7][8] ### Enhanced drowsiness[edit] Along with cranial pressure, patients exhibit noticeable lethargy, increasing in severity as the tumor progresses.[8][9][10] In the first few months, morning activities are usually unaffected; over time, these effects become more pronounced, especially late at night.[2][6][7] Lethargy can disrupt vital signs, depleting energy and desire to perform simple cognitive tasks. ### Frequent nausea[edit] The desire to eat normally becomes worse over time, leading to weight loss from vomiting.[2][9][11] Nausea is seen in almost all cases of astroblastoma, especially in low-grade tumors. ### Impaired vision[edit] Vision deficit usually occurs when lesions grow in the occipital lobe of the brain,[1] causing a blurred daze for patients, especially in sensitivity to light. Focusing upon finer objects becomes a challenge, along with edge and border detection.[6][11] Driving behind the wheel is dangerous when astroblastoma grows in residual tissue size, since peripheral vision can be insufficient. Horizontal nystagmus and other involuntary eye disorders can occur.[2][9] ### Motor system imbalance and weakness[edit] Frequent reports show that adolescents and adults with grade III and IV astroblastoma fall frequently before they even reach a doctor's office.[10] Alertness is diminished when walking normally, forcing patients to exhibit awkward gait patterns to avoid imbalance.[6][11] ### Decreased sensation[edit] Since the motor system can be impaired with severe cases, the malignant spread of astroblastoma throughout the body may press against or paralyze the spinal cord, diminishing sensation in upper and lower extremities.[6][8] ### Seizures[edit] Convulsions are observed in older patients with astroblastoma.[8][11] ### Psychotic episodes[edit] Grade III and IV astroblastoma have been shown gradually change the mental stability of a patient.[2] Hallucinations impair cognition to the point where patients experience a loss of identity, although this is not commonly seen in clinic.[6] ### Cognitive dysregulation[edit] Irritability, aggression, memory loss, neurological deficits, and inattentiveness on everyday tasks are the most common forms of deregulation in the mental capabilities of a patient.[10] Verbal communication is affected, but usually not to the point where close friends can detect that the individual is cognitively impaired.[7][9] ## Diagnosis[edit] ### Classification[edit] The World Health Organization, a specialized agency that classifies abnormal tumors affecting the central nervous system and assesses potential risk to life, has difficulty in assigning a proper grade for astroblastoma.[2] The organization’s most recent grade in 2007 assigned astroblastoma as a high-grade III and grade IV neoplasm, signifying that the glial tumor is dangerous for patients, causing fatal problems even after surgery.[5][6] However, recent data compilation from 2011, one that compiled nearly 30 years of clinical information, confirms opposite results from patients: a 95% survival rate exists after astroblastoma is completely removed (gross total resection).[2][4][12] The most important factor for any patient when cancer is concerned – the likelihood of surviving – is still controversial for astroblastoma, but recent advances in the last decade have improved prognosis. ## Treatment[edit] Like most tumors in the brain, astroblastoma can be treated through surgery and various forms of therapy. Many publications within the last decade have suggested a noticeable improvement in success rate of patients. With the advancement of cutting-edge technology and novel approaches in stem cells, patients are hopeful that they be happy and healthy through old age. The following factors influence an oncologist's specific treatment plan: 1. Patient's overall medical history 2. Localization and grade severity of the tumor 3. Age and tolerance to certain medications, procedures, and treatment 4. Predicted progress of recovery 5. Final anticipated outcome of treatment ### Gross-total resection[edit] Complete surgical removal, known as gross-total resection or craniotomy, remains the standard for treating astroblastoma, despite high recurrence rate for high-grade tumors.[13] Since there are so few cases reported around the world each year, the standard for surgery varies from physician to physician and is often difficult to rightfully diagnose. Low-grade astroblastomas exhibit low recurrence rates following resection, but varying reports prove that some patients, despite the severity of the lesion, will unpredictably witness recurrence.[8] In a recent study of a 17-year-old male, a low-grade astroblastoma was resected and recurred within 5 months of the therapy, forcing the oncologist to administer further chemotherapy, radiotherapy, and a second resection to completely put the tumor in remission.[14] ### Radiotherapy[edit] Radiation therapy selectively kills astroblastoma cells while leaving surrounding normal brain tissue unharmed. The use of radiation therapy after an astroblastoma excision has variable results.[2] Conventional external beam radiation has both positive and negative effects on patients, but it is not recommended at this point to treat all types.[2] All in all, the radiosensitivity of astroblastoma to therapy remains unclear, since some research advocate its effectiveness while others diminish the effects. Future studies must be done on patients with both total excision and sub-excision of the tumor to accurately assess whether radiation benefits patients under different circumstances. ### Chemotherapy[edit] Chemotherapy is the preferred secondary treatment after resection. The treatment kills astroblastoma cells left behind after surgery and induces a non-dividing, benign state for remaining tumor cells. Normally, chemotherapy is not recommended until the second required resection, implying that the astroblastoma is a high-grade tumor continuing to recur every few months.[1][13] A standard chemotherapy protocol starts with two rounds of nimustine hydrochoride (ACNU), etoposide, vincristine, and interferon-beta.[6] The patient undergoes a strict drug regimen until another surgery is required. By the third surgery, should recurrence in the astroblastoma occur, a six-round program of ifosfamide, cisplatin, and etoposide will "shock" the patient's system to the point where recurrence halts.[6] Unfortunately, chemotherapy may not always be successful with patients requiring further resection of the tumor, since the tumor cell begins to show superior vasculature and a strong likelihood of compromising a patient's well-being. Oral ingestion of temozolomide for at-home bedside use may be preferred by the patient. ### Future advances[edit] A popular form of surgery involves CyberKnife radiotherapy and Gamma Knife radiosurgery. Their success-rate on cranial lesion is fairly effective, but recurrence is still a problem for severe patients.[6] One of the more exciting and promising routes for treatment involves stem cell use to combat astroblastoma. A study in 2005 profiled cell surface markers of astroblastoma cells removed from an 11-year-old patient. Fluorescence activation suggested that about 1/4 of these cells were CD133 positive CD24, CD34, and CD45 negative. This specific genetic makeup lends to self-renewal, differentiation, and propagation of neural stem cells in the brain.[15] However, the work remains a preliminary insight into the role of neuronal stemlike cells on astroblastoma development.[15] ## Recurrence[edit] More than other brain tumors, astroblastoma is frequently a recurring tumor; its rate remains high, even after resection as treatment. Currently, an unfavorable prognosis exists for patients with high-grade, anaplastic astroblastoma: they tend to recur almost indefinitely, forcing the patient to invest in more invasive surgeries. In contrast, a favorable prognosis exists for patients with well-differentiated, low-grade astroblastoma, since patients usually never require such a treatment.[8][16][14] The strict black-and-white diagnosis of an astroblastoma based on grade does not determine all tumor behaviors, but it can be used as a benchmark for patients with varying degrees of severity. ### Low-grade[edit] The likelihood of low-grade astroblastoma returning after surgery is highly improbable, but some patients have exhibited recurrence.[10][14] Patients with low-grade lesions can remain asymptomatic after surgery and show recurrence 1–2 years in follow-up sessions.[12] However, since residual tissue size is a large determinant for profiling recurrence, it is almost never the case that a low-grade astroblastoma continues to appear in size and strength after the second resection.[16] Usually, patients are not recommended for resection at all and are simply directed towards other therapeutic techniques. Most children can continue to lead productive, healthy lives after a low-grade astroblastoma is treated. ### High-grade[edit] Surviving the symptoms of high-grade astroblastoma is not life-threatening, but a significant portion of patients die due to repeated recurrence of tumors as they continue to grow and spread. Unlike conventional low-grade tumors, high-grade tumors associate a plethora of factors when they metastasize to other areas of the body. Therefore, complications frequently occur after surgery is performed since an oncologist cannot efficiently control the tumor in a suitable time-frame.[13] Cases in literature confirm that high-grade patients face up to five or six resection surgeries and still experience symptoms post-operatively.[8][16] The dual-action of chemotherapy and radiotherapy can slow down recurrence when gross total resection is performed multiple times, but there is no guarantee that the tumor will ever be in remission. onsiderations for specialized astroblastoma therapies, but they are not mentioned in current literature. ## Epidemiology[edit] Astroblastoma predominantly affects children, but young adults are also susceptible to the tumor .[2] Although the tumor is widely considered a pediatric disease, elderly patients are documented throughout literature.[4][11] ### Age incidence[edit] The age distribution of astroblastoma is largely bimodal, suggesting that two distinct diagnosis peaks occur from ages 5–10 and ages 21–30.[2][12] A likely explanation for this discrepancy is that parents of children are more likely to report symptoms of nausea and constant headaches than young adults, who may, at first, disregard these symptoms for a lesser condition. Nevertheless, a combination of age, anatomic location, and image assessment can efficiently evaluate astroblastoma. Furthermore, the age of a patient can aid an oncologist in recommending appropriate treatment plans, along with other factors. ### Gender incidence[edit] In reported cases of the tumor over the last 25 years, the number of affected females with astroblastoma is significantly higher than the number of affected males.[1][13] Sughrue et al. confirmed this trend, stating that 70% of the cases with clearly stated gender were female (100 cases total).[2] While several publications support a genetic predisposition to females, the underlying reasons are still unknown.[4][11] ### Environmental incidence[edit] At this point, no literature has indicated whether environmental factors increase the likelihood of astroblastoma. Although cancer in general is caused by a variety of external factors, including carcinogens, dangerous chemicals, and viral infections, astroblastoma research has not even attempted to classify incidence in this regard. The next few decades will aid in this understanding. ## See also[edit] * Neoplasm * Neuroepithelial cell * Astrocytes * Glial cells * Brain cancer Astroblastoma at Curlie ## References[edit] 1. ^ a b c d e f Unal, Ekrem, and Yavuz Koksal. "Astroblastoma in a Child." Children Nervous System 24.2 (2008): 165–68. 2. ^ a b c d e f g h i j k l m n o Sughrue, Michael E., Jay Choi, Martin Rutkowski, and Derick Aranda. "Clinical Features and Post-surgical Outcome of Patients with Astroblastoma." Journal of Clinical Neuroscience 18.6 (2011): 750–54. 3. ^ Denaro, Luca, Marina Gardiman, and Milena Caliderone. "Intraventricular Astroblastoma. Case Report." Journal of Neurosurgery Pediatrics 1 (2008): 152–55. 4. ^ a b c d Bell, John W., Anne G. Osborn, Karen L. Salzman, Susan I. Blaser, Blaise V. Jones, and Steven S. Chin. "Neuroradiologic Characteristics of Astroblastoma." Diagnostic Neuroradiology 49 (2007): 203–09. 5. ^ a b c Brat, Daniel J., Yuichi Hirose, Kenneth J. Cohen, Burt G. Feuerstein, and Peter C. Burger. "Astroblastoma: Clinicopathologic Features and Chromosomal Abnormalities Defined by Comparative Genomic Hybridization." Brain Pathology 10.3 (2000): 342–52. 6. ^ a b c d e f g h i j k l m n Hirano, Hirofumi, Shunji Yunoue, Masatomo Kaji, Masahiro Tsuchiya, and Kazunori Arita. "Consecutive Histological Changes in an Astroblastoma That Disseminated to the Spinal Cord after Repeated Intracranial Recurrences: a Case Report." Brain Tumor Pathology 25.1 (2008): 25–31. 7. ^ a b c d e Ganapathy, Srinivas, Laurence I. Kleiner, David L. Mirkin, and Emmett Broxson. "Unusual Manifestations of Astroblastoma: a Radiologic–pathologic Analysis." Pediatric Radiology 39.2 (2009): 168–71. 8. ^ a b c d e f g Bonnin JM, Rubinstein LJ. "Astroblastoma: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients." Neurosurgery 25.1 (1989): 6–13. 9. ^ a b c d Kubota, Toshihiko, Kazufumi Sato, Hidetaka Arishima, Hiroaki Takeuchi, Ryuhei Kitai, and Takao Nakagawa. "Astroblastoma: Immunohistochemical and Ultrastructural Study of Distinctive Epithelial and Probable Tanycytic Differentiation." Neuropathology 26.1 (2006): 72–81. 10. ^ a b c d Kemerdere, Rahsan, Reza Dashti, and Mustafa Ulu. "Supratentorial High Grade Astroblastoma: Report of Two Cases and Review of the Literature." Turkish Neurosurgery 19.2 (2009): 149–52. 11. ^ a b c d e f Navarro, Ramon, Aaron Reitman, Guillermo De Leon, and Stewart Goldman. "Astroblastoma in Childhood: Pathological and Clinical Analysis." Children Nervous System (2005): 211–20. 12. ^ a b c Lau, Patrick, Teresa Thomas, Philip Lui, and Aye Khin. "‘Low‐grade’ Astroblastoma with Rapid Recurrence: a Case Report." Pathology 38.1 (2006): 78–80. 13. ^ a b c d Weintraub, David, Stephen Monteith, and Chun Po Yen. "Recurrent Astroblastoma Treated with Gamma Knife Radiosurgery." Journal of Neuro-Oncology 103.3 (2011): 751–54. 14. ^ a b c Masamoto, Kaji, and Takeshima Hideo. "Low-Grade Astroblastoma Recurring With Extensive Invasion-Case Report." (2006). 15. ^ a b Huhn, Stephen L., Yun Yung, Samuel Cheshier, Griffith Harsh, Laurie Ailles, Irving Weissman, Hannes Vogel, and Victor Tse. "Identification of Phenotypic Neural Stem Cells in a Pediatric Astroblastoma." Journal of Neurosurgery: Pediatrics 103.5 (2005): 446–50. 16. ^ a b c W. Mierau, R. Weslie Tyson, Loris M, Gary. "Astroblastoma: Ultrastructural Observations on a Case of High-Grade Type." Ultrastructural Pathology 23.5 (1999): 325–32. ## External links[edit] Classification D * ICD-10: C71.9 * ICD-9-CM: 191.9 * ICD-O: 9430/3 * MeSH: D018302 * DiseasesDB: None * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Astroblastoma	c0334587	30,304	wikipedia	https://en.wikipedia.org/wiki/Astroblastoma	2021-01-18T19:04:52	{"gard": ["10635"], "mesh": ["D018302"], "umls": ["C0334587"], "icd-9": ["191.9"], "icd-10": ["C71.9"], "orphanet": ["251679"], "wikidata": ["Q4811532"]}
Hereditary sensory neuropathy type 1 (HSN1) is a neurological condition characterized by nerve abnormalities in the legs and feet. Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected people do not lose sensation, but instead feel shooting pains in their legs and feet. As HSN1 progresses, sensory problems can affect the hands, arms, shoulders, and abdomen. In rare cases, people with this condition develop sensorineural hearing loss. Symptoms of HSN1 typically begin during a person's teens or twenties and worsen over time. HSN1 is caused by mutations in any of several genes, depending on the form of HSN1 (HSN1A is caused by mutations in the SPTLC1 gene; HSN1B is linked to a gene located in chromosome 3; HSN1C is caused by mutations in the SPTLC2 gene; HSN1D is caused by mutations in the ATL1 gene and HSN1E is caused by mutations in DNMT1 gene. All forms of HSN1 are inherited in an autosomal dominant manner. If symptoms are treated properly, the condition does not appear to affect 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hereditary sensory neuropathy type 1	c0020071	30,305	gard	https://rarediseases.info.nih.gov/diseases/6635/hereditary-sensory-neuropathy-type-1	2021-01-18T18:00:01	{"mesh": ["D009477"], "umls": ["C0020071"], "orphanet": ["36386"], "synonyms": ["HSAN 1", "Neuropathy hereditary sensory radicular, autosomal dominant", "Neuropathy hereditary sensory and autonomic type 1", "HSN1", "Hereditary sensory and autonomic neuropathy type 1"]}
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-1 (LCCS1) is caused by homozygous or compound heterozygous mutation in the mRNA export mediator GLE1 (603371) on chromosome 9q34. Biallelic mutation in the GLE1 gene can also cause congenital arthrogryposis with anterior horn cell disease (CAAHD; 611890), a disorder with overlapping features but with survival beyond the perinatal period. Description Autosomal recessive lethal congenital contracture syndrome (LCCS) is the most severe, neonatally lethal, form of arthrogryposis (see 108120), a disorder characterized by congenital nonprogressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). ### Genetic Heterogeneity of Lethal Congenital Contracture Syndrome See also lethal congenital contracture syndrome-2 (LCCS2; 607598), caused by mutation in the ERBB3 gene (190151); LCCS3 (611369), caused by mutation in the PIP5K1C gene (606102); LCCS4 (614915), caused by mutation in the MYBPC1 gene (160794); LCCS5 (615368), caused by mutation in the DNM2 gene (602378); LCCS6 (616248), caused by mutation in the ZBTB42 gene (613915); LCCS7 (616286), caused by mutation in the CNTNAP1 gene (602346); LCCS8 (616287), caused by mutation in the ADCY6 gene (600294); LCCS9 (616503), caused by mutation in the ADGRG6 gene (612243); LCCS10 (617022), caused by mutation in the NEK9 gene (609798); and LCCS11 (617194), caused by mutation in the GLDN gene (608603). Clinical Features In Finland, Herva et al. (1985) observed 16 cases of a lethal syndrome with multiple congenital contractures resembling in many ways the Pena-Shokeir I syndrome (208150) but differing from it in failure of survival postnatally and by the presence of marked fetal hydrops. Facial abnormalities, especially micrognathia, were found and autopsies demonstrated pulmonary hypoplasia, muscular atrophy, and paucity of anterior horn motor neurons. (Moerman et al. (1983) found degeneration and paucity of anterior horn cells in Pena-Shokeir I syndrome.) Another characteristic that perhaps differentiates the Finnish multiple contracture syndrome from Pena-Shokeir I syndrome is the generalized thinning of tubular bones in many of the Finnish cases; the ribs were exceedingly thin and fishbone-like. The 16 cases belonged to 10 sibships. The grandparents of 8 sibships originated from neighboring rural communities of the northeastern part of Finland. Herva et al. (1988) presented the neuropathologic findings on 5 fetuses in whom the diagnosis had been made by the finding of fetal hydrops on ultrasonography. The fetuses showed a typical pattern of malpositioning of hips and knees with occasional pterygia of the neck and elbows. The muscles were hypoplastic and the spinal cords showed severe thinning, most markedly affecting the ventral half. The loss of axons and anterior horn motor neurons, including changes in the brainstem, suggested a degenerative rather than a dysmorphogenetic process. Vuopala and Herva (1994) reported on 40 fetuses and infants with LCCS identified in Finland through a national morphology-based study of lethal arthrogryposis between 1979 and 1992. The incidence was estimated to be 1 in 19,000 births. There were 20 affected males and 20 affected females in 26 families. In 16 cases, the pregnancy was terminated after the prenatal diagnosis of total akinesia and fetal hydrops on ultrasound. There were 19 stillborn infants and 5 were born showing signs of life, but died within 1 hour. The segregation analyses yielded 0.45 affected by the 'singles' method and 0.34 by the 'sib' method. The birthplaces of grandparents were located in the sparsely populated northeast section of Finland. Vuopala and Herva (1994) illustrated a cross-section of the spinal cord showing marked reduction in the ventral part, a paucity of anterior motor neurons, and hydropic degeneration of descending tracks. Above the decussation of the pyramids, the CNS is normal. Vuopala and Herva (1994) noted that the London Dysmorphology Database listed LCCS as part of the Pena-Shokeir-multiple ankyloses-pulmonary hypoplasia syndrome. The Database noted that this designation covers a number of separate entities. Vuopala and Herva (1994) were of the opinion that LCCS is a distinct autosomal recessive disorder with a recurrence risk of 25%, which is higher than the 10 to 15% risk stated in the London Dysmorphology Database for the Pena-Shokeir syndrome. Makela-Bengs et al. (1997) noted that LCCS leads to prenatal death of the fetus before the thirty-second week of gestation. The highly specific hallmark of LCCS is early-onset degeneration of the anterior horn motor neurons in the spinal cord. Population Genetics In a study of all cases of lethal arthrogryposis diagnosed in Finland between 1987 and 2002, Pakkasjarvi et al. (2006) classified 39 of the total 115 cases as LCCS, characterized by total immobility of the fetus at all ultrasound examinations, multiple joint contractures in upper and lower limbs, hydrops and fetal death before 32 weeks of pregnancy. Pakkasjarvi et al. (2006) concluded that LCCS is a unique Finnish disorder with a prevalence of 1 in 25,250 births and is a major cause of lethal arthrogryposis in Finland. Mapping Using DNA samples of 5 affected fetuses from 2 families, Makela-Bengs et al. (1997) performed a genomewide screen and found that affected sibs shared the same chromosome segments on a 20-cM region of 9q. Further linkage analyses in 10 LCCS families with 19 affected individuals confirmed the linkage to this region; they obtained a maximum pairwise lod score of 4.6 and a multipoint lod score of 6.1. Makela-Bengs et al. (1998) narrowed the assignment of the LCCS locus to a defined region of 9q34, between markers D9S1825 and D9S1830. Linkage disequilibrium analysis restricted the critical chromosomal region to a segment of less than 100 kb in the vicinity of marker D9S61. Two genes, NGAL (600181) and NOTCH1 (190198), were excluded as sites of the mutation causing LCCS. ### Exclusion Studies Since the neuropathologic findings in LCCS closely resemble those of spinal muscular atrophy (SMA; 253300), Vuopala et al. (1995) sought linkage with microsatellite markers assigned to the SMA region on 5q. Linkage was excluded. Molecular Genetics Nousiainen et al. (2008) further restricted the critical chromosome region on 9q34 for the LCCS1 locus in Finnish families. Through systematic sequence analyses of candidate genes in the region, they found potential mutations in the GLE1 gene (603371), which encodes a protein required for export of mRNAs from the nucleus to the cytoplasm in both lower and higher eukaryotic cells. Sequence analyses of genomic DNA from LCCS1 cases identified a homozygous A-to-G substitution located within intron 3 of GLE1, 10 nucleotides upstream of exon 4 (603371.0001). This mutation, referred to by the authors as Fin(Major), was homozygous in 51 of 52 LCCS1 cases in 29 unrelated families. One patient was compound heterozygous for the Fin(Major) mutation and a point mutation predicted to result in an arginine-to-histidine substitution in exon 12 (603371.0002). LCCS is enriched in northeastern Finland, where the carrier frequency of the Fin(Major) mutation was found to be 2%; in the general Finnish population it was 1%. Nousiainen et al. (2008) also studied congenital arthrogryposis with anterior horn cell disease (CAAHD; 611890) to determine whether it is a disorder allelic to LCCS1. They screened 9 unrelated families with LAAHD, for a total of 12 affected individuals with mutation in the GLE1. All 12 cases were compound heterozygotes: 6 were heterozygous for the LCCS1 Fin(Major) and a missense point mutation in exon 13 (603371.0003), and the remaining 6 carried the Fin(Major) mutation and a missense mutation in exon 16 (603371.0004). INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Micrognathia RESPIRATORY Lung \- Pulmonary hypoplasia CHEST Ribs Sternum Clavicles & Scapulae \- Thin fishbone-like ribs SKELETAL Limbs \- Multiple congenital contractures \- Generalized thinning of tubular bones MUSCLE, SOFT TISSUES \- Muscle atrophy \- Muscle hypoplasia NEUROLOGIC Central Nervous System \- Paucity of anterior horn motor neurons PRENATAL MANIFESTATIONS Amniotic Fluid \- Marked fetal hydrops MISCELLANEOUS \- Neonatal death MOLECULAR BASIS \- Caused by mutation in the homolog of the Gle1, (S. cerevisiae) RNA export mediator gene (GLE1, 603371.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	LETHAL CONGENITAL CONTRACTURE SYNDROME 1	c1854664	30,306	omim	https://www.omim.org/entry/253310	2019-09-22T16:24:51	{"doid": ["0060559"], "mesh": ["C537194"], "omim": ["253310"], "orphanet": ["1486"], "synonyms": ["Alternative titles", "LCCS", "MULTIPLE CONTRACTURE SYNDROME, FINNISH TYPE"]}
A number sign (#) is used with this entry because of evidence that axonal Charcot-Marie-Tooth disease type 2X (CMT2X) is caused by homozygous or compound heterozygous mutation in the SPG11 gene (610844) on chromosome 15q21. Biallelic mutations in the SPG11 gene can also cause autosomal recessive spastic paraplegia-11 (SPG11; 604360) and juvenile amyotrophic lateral sclerosis-5 (ALS5; 602099), both of which show overlapping features with CMT2X. Description Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016) For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). Clinical Features Montecchiani et al. (2016) reported 29 affected individuals from 12 unrelated families of various ethnic origins with slowly progressive axonal peripheral neuropathy. Nine of the families were consanguineous. The mean age at disease onset was 11.4 years (range, 4-35) and there was phenotypic variability. All had distal lower limb weakness, often with distal muscle atrophy in the lower limbs, resulting in foot drop and impaired gait. Sixteen patients also had upper limb weakness, often associated with atrophy in the intrinsic hand muscles. Eight patients had fasciculations in the lower limbs, and 4 had proximal muscle weakness of the lower limbs. Additional common features included foot deformities (79%), usually pes cavus, kyphoscoliosis (59%), ankle contractures (48%), and tremor (34%). Hand deformities were present in 7 patients with longer disease duration. About a third of individuals had bladder and/or sexual dysfunction. Three Italian sibs showed thin corpus callosum on brain imaging and mild cognitive impairment, but this was not observed in any other patients or families. Only 1 patient was wheelchair-bound, and no patients had pontobulbar signs or spasticity, although 2 unrelated patients had extensor plantar responses. Electrophysiologic studies were consistent with a motor and sensory axonal neuropathy, more prominent in the lower limbs, with low amplitudes of compound motor and sensory nerve action potentials. Nerve conduction velocities were normal or slightly reduced, consistent with a secondary demyelinating process. EMG showed evidence of chronic denervation/renervation, and sural nerve biopsies showed loss of large-caliber myelinated fibers. Inheritance The transmission pattern of CMT2X in the families reported by Montecchiani et al. (2016) was consistent with autosomal recessive inheritance. Mapping By linkage analysis of 9 consanguineous families with autosomal recessive axonal CMT, Montecchiani et al. (2016) found significant linkage to a region on chromosome 15q (2-point lod score of 11.76 at marker D15S537). Molecular Genetics In affected members of 12 unrelated families with CMT2X, Montecchiani et al. (2016) identified 15 different biallelic mutations in the SPG11 gene (see, e.g., 610844.0001-610844.0003 and 610844.0014-610844.0015). Thirteen mutations had previously been reported as causative of SPG11 or ALS5; 2 mutations were novel. Montecchiani et al. (2016) commented that identical mutations can cause different phenotypes, indicating that genotype/phenotype correlations are often unpredictable. All mutations except 1 were predicted to result in a truncated protein with loss of function; functional studies of the variants were not reported. The mutations, which were found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the families. The families showed different ethnic origins, including Italy, Brazil, Canada, England, Iran, and Japan. INHERITANCE \- Autosomal recessive GENITOURINARY Bladder \- Urinary dysfunction (in some patients) SKELETAL \- Ankle contractures (in some patients) Spine \- Kyphoscoliosis (in some patients) Hands \- Hand deformities (in some patients) Feet \- Foot deformities (in some patients) \- Pes cavus (in some patients) MUSCLE, SOFT TISSUES \- Distal muscle weakness due to peripheral neuropathy, lower limbs more affected than upper limbs \- Distal muscle atrophy due to peripheral neuropathy, lower limbs more affected than upper limbs \- Chronic denervation/reinnervation seen on EMG NEUROLOGIC Central Nervous System \- Tremor (in some patients) \- Cognitive impairment, mild, (1 family) \- Thin corpus callosum (1 family) Peripheral Nervous System \- Axonal neuropathy \- Gait impairment due to neuropathy \- Foot drop \- Hypo- or areflexia \- Distal sensory impairment \- Normal or mildly decreased nerve conduction velocities \- Decreased nerve action potentials \- Sural nerve biopsy shows loss of large caliber myelinated fibers MISCELLANEOUS \- Mean age at onset 11.4 years (range 4 to 35) \- Variable phenotype \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the SPG11 gene (SPG11, 610844.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2X	c4225253	30,307	omim	https://www.omim.org/entry/616668	2019-09-22T15:48:17	{"doid": ["0110176"], "omim": ["616668"], "orphanet": ["466775"], "synonyms": ["CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL RECESSIVE, TYPE 2X", "Autosomal recessive Charcot-Marie-Tooth disease type 2 due to SPG11 mutation", "CMT2X", "ARCMT2X", "Alternative titles", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2X"]}
Variegate porphyria (VP) is an inherited disorder that is caused by mutations in the PPOX gene that lead to the build-up of compounds normally involved in the body’s production of heme. Heme is an important part of hemoglobin, the protein in blood that carries oxygen throughout our bodies. It is used in all the body’s organs. People with variegate porphyria have abnormal production of heme. They are very sensitive to sun exposure (photosensitive) and develop skin blisters and sores when they are exposed to sunlight. People with variegate porphyria can also have neurological symptoms in the form of episodes (acute attacks) of severe stomach pain, nausea and vomiting. Symptoms usually begin in adulthood. Variegate porphyria is caused by mutations in the PPOX gene and is inherited in an autosomal dominant pattern. Some people who have PPOX gene mutations never have symptoms of porphyria. People with variegate porphyria need to avoid sun exposure. Attacks are treated with medication and hospitalization. Attacks can be prevented by avoiding the factors that cause the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Variegate porphyria	c0162532	30,308	gard	https://rarediseases.info.nih.gov/diseases/7848/variegate-porphyria	2021-01-18T17:57:12	{"mesh": ["D046350"], "omim": ["176200"], "orphanet": ["79473"], "synonyms": ["Porphyria variegate", "VP", "Porphyria, South African type", "Protoporphyrinogen oxidase deficiency", "PPOX deficiency"]}
SUNCT syndrome SpecialtyNeurology Frequency50 described cases (as of 2015)[1] Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome), is a rare headache disorder that belongs to the group of headaches called trigeminal autonomic cephalalgia (TACs).[1] Symptoms include excruciating burning, stabbing, or electrical headaches mainly near the eye and typically these sensations are only on one side of the body. The headache attacks are typically accompanied by cranial autonomic signs that are unique to SUNCT. Each attack can last from five seconds to six minutes and may occur up to 200 times daily. TACs are caused by activation of the autonomic nervous system of the trigeminal nerve in the face. As of 2015 about 50 cases have been described in the medical literature.[1] Onset of the symptoms usually come later in life, at an average age of about 50. Although the majority of patients are men over the age of 50, it is not uncommon to find SUNCT present among other age groups, including children and infants. ## Contents * 1 Signs and symptoms * 1.1 Frequency and duration * 1.2 Cranial autonomic symptoms associated with headache attacks * 1.3 Triggers of headache attacks * 2 Diagnosis * 3 Pathophysiology * 4 Treatment * 5 History * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] People affected by SUNCT often describe their headache attacks as excruciating pain. The attacks are severe enough to disrupt daily activities, but hospitalization is not necessary for most affected individuals. ### Frequency and duration[edit] The average number of attacks per day is around 60, ranging from 3 to 200 times.[2] The attacks can be divided into three groups: single stabs, groups of stabs, and attacks with saw-tooth pattern, from the shortest to the longest duration respectively. The attacks usually last from five seconds to 240 seconds. Typically, longer attacks are more painful due to psychological effects, and patients often feel agitated before and during the attack. They occur mostly in the orbital, supraorbital, or temporal region, but can also occur in the retro-orbital (behind the orbit of the eye) region, side, top, and back of head, second and third trigeminal divisions, teeth, neck, and ear. ### Cranial autonomic symptoms associated with headache attacks[edit] SUNCT often accompanies cranial autonomic symptoms, including lacrimation (tear flow), ipsilateral ptosis (drooping of the eyelid which is on the same side as the attacks), eyelid edema (swelling due to fluid accumulation), nasal blockage, and conjunctival injection (redness of eye). Depending on which division of the trigeminal nerve innervates the area affected, autonomic symptoms may be less obvious. Short-lasting unilateral neuralgiform headache attacks with cranial autonomic features (SUNA) is a subset of SUNCT and may be diagnosed when fewer autonomic symptoms are observed during attacks. The majority of SUNCT attacks occur chronically; however, some occur episodically. In chronic SUNCT, attacks can occur regularly or irregularly without a distinct refractory period, whereas in episodic SUNCT, attacks occur only for a certain period of time and then cease for another period. Episodes of attacks last from a few days to a few months, and up to 22 attack episodes in one year have been observed. SUNCT can go into remission even after a chronic period, and relapse either spontaneously or due to some stimulus.[2] ### Triggers of headache attacks[edit] Most of the time SUNCT occurs spontaneously; however, attacks can be triggered by simple daily stimuli such as touching the face or scalp, washing, chewing, eating, talking, coughing, blowing nose, or showering. They also can be triggered by light (including sunlight and fluorescent lights) and injuries. Stimuli capable of triggering a cluster headache, including alcohol, smoke, strong smells and a warm environment, can also trigger SUNCT in a few patients.[2] In some cases, patients with episodic SUNCT only exhibit symptoms biannually, in spring and fall. This periodicity suggests that the hypothalamus, which is responsive to day length and photoperiod for regulating circadian and seasonal rhythms, has a role in its triggering.[3] ## Diagnosis[edit] SUNCT must be properly distinguished from cluster headaches, since cluster headaches also occur several times per day with separate attacks, and share some common symptoms. However, cluster headaches usually last longer (up to three hours), occur less often (three to five attacks per day), and do not accompany cranial autonomic symptoms. IHS standard criteria for the diagnosis of SUNCT specifically includes pain in the trigeminal division of the face, especially in the orbital region, often with cranial autonomic symptoms which last for relatively short periods of time (from five seconds to several minutes) up to 100 times per day. SUNCT is a major subset of SUNA,[4] which does not accompany cranial symptoms; complete separation between the two is inappropriate since SUNCT does not necessarily always accompany cranial autonomic signs. Exact statistical data is not available due to common mis-diagnosis, and setting up diagnostic criteria is important.[2] The International Headache Classification established by the International Headache Society criteria for diagnosing SUNCT for therapeutic purposes is: (i) Type of attack – Attacks of unilateral orbital, supraorbital, or temporal areas from stabbing or pulsating pain accompanied by ipsilateral conjunctival injection and lacrimation (ii) Number of attacks per day – 3 to 200 attacks per day (iii) Attack load in minutes per day – 5–240 seconds Symptoms of SUNCT often lead to misdiagnosis as paroxysmal hemicrania, which is also categorized in the same group. Inefficiency of indomethacin usually indicates SUNCT over paroxysmal hemicrania.[5] Misdiagnosis and indecisive diagnosis in the past has made it difficult to obtain accurate statistics about SUNCT. Proper diagnosis will broaden data availability and facilitate discovery of new treatment options and useful statistics. ## Pathophysiology[edit] The pathophysiology of SUNCT is incompletely understood. Recent studies suggest the existence of a relationship between the hypothalamus and the condition. Functional MRI and deep brain stimulation of a large patient pool showed activation of the posterior hypothalamus during attacks of primary SUNCT, on both sides and contralaterally (on the opposite side).[6] Functional MRI studies suggest brain stem activation during attacks as well.[7] Activation of the trigeminocervical complex and other related structures results from innervation from branches of trigeminal and upper cervical nerves.[8] There exists a direct connection between trigeminal nucleus caudalis, which is located in the brain stem, and the posterior hypothalamus. Therefore, it is possible that stimulation of the peripheral trigeminal nerve activates the hypothalamus and the hypothalamus in turn communicates with the trigeminal nucleus caudalis via neurotransmitters such as orexin. Elevated levels of prolactin, secretion of which is regulated by the hypothalamus, seem to be associated with SUNCT attacks. Some patients with a pituitary tumor only experience attacks at night. These patients only exhibit higher levels of prolactin at night, even where hormone levels, including prolactin, were normal throughout the day.[9] SUNCT is considered a primary headache (or condition), but can also occur as a secondary symptom of other conditions. However, a patient can only be diagnosed with SUNCT as a primary condition. A pituitary tumor causes SUNCT as a secondary headache. Some patients with a pituitary tumor complain of short-lasting heachaches. Upon removal of the tumor, the symptoms of SUNCT may disappear permanently.[10] Although it occurs very rarely, paranasal sinusitis can also cause secondary SUNCT. The symptoms of SUNCT in such cases can be removed permanently with endoscopic sinus surgery.[11] ## Treatment[edit] As diagnostic criteria have been indecisive and its pathophysiology remains unclear, no permanent cure is available. Antiepileptic medications (membrane-stabilizing drugs) such as pregabalin, gabapentin, topiramate, and lamotrigine improve symptoms, but there is no effective permanent or long-term treatment for SUNCT.[12] However, a few short-term treatments are available and can relieve and possibly prevent some symptoms of attacks. Lamotrigine exhibits some long-term prevention and reduction in many patients; however, titration of dose is difficult due to adverse skin reactions. Topiramate also has preventive effects but it is accompanied by a high risk of severe side-effects for patients with a history of kidney stones, glaucoma, depression, or low body weight. Intravenous lidocaine can abolish symptoms during its administration, or reduce frequency and duration of attacks. However, administration of intravenous lidocaine requires careful monitoring of ECG and blood pressure.[13] Methylprednisolone therapy shows some promise in short-term prevention of attacks, even though its mechanism of action is yet to be discovered.[14] The calcium channel blocker verapamil is reported to be useful in alleviating symptoms (lower frequency and duration of attacks), even though some patients experience worsened symptoms.[5] Various medications that are often used in other headache syndromes such as nonsteroidal anti-inflammatory drugs, acetaminophen, tricyclic antidepressants, calcium channel antagonists do not relieve the symptoms of SUNCT. There have been attempts to alter oxygen supply during attacks to alleviate the symptoms since some of the headaches are caused by decreased oxygen supply; however, elevated blood oxygen level did not affect the symptoms. Researchers now[when?] focus on the administration of various combination of medications and therapies to treat symptoms of SUNCT. ## History[edit] In 1977, a 62-year-old male patient was the first to be diagnosed with SUNCT. The patient had experienced unilateral, mild pain in the ocular and periorbital areas since he was 30 years old. The patient started to experience more severe attacks after being struck by a fishing rod in the lower medial supraorbital area when he was 58 years old. The attacks could be provoked by mechanical stimuli and occurred more frequently with symptoms of conjuctival injection, lacrimation, and rhinorrhea. The definitive diagnosis and determination of the role of the trauma (fishing rod strike) could not be made until 10 years later when another similar case occurred. Conditions of the next case ruled out the possibility of SUNCT being a post-traumatic headache.[15] Bad Brains singer H.R. has this disorder, as revealed by his wife.[16] ## See also[edit] Ophthalmodynia periodica ## References[edit] 1. ^ a b c Pomeroy, JL; Nahas, SJ (August 2015). "SUNCT/SUNA: A Review". Current Pain and Headache Reports. 19 (8): 38. doi:10.1007/s11916-015-0511-2. PMID 26092511. 2. ^ a b c d Cohen AS, Matharu MS, Goadsby PJ (October 2006). "Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA)—a prospective clinical study of SUNCT and SUNA". Brain. 129 (Pt 10): 2746–60. doi:10.1093/brain/awl202. PMID 16905753. 3. ^ Irimia P, Gállego-Pérez Larraya J, Martinez-Vila E (January 2008). "Seasonal periodicity in SUNCT syndrome". Cephalalgia. 28 (1): 94–6. doi:10.1111/j.1468-2982.2007.01434.x. PMID 17868283. 4. ^ Tada Y, Ikuta N, Negoro K (2009). "Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)". Intern. Med. 48 (24): 2141–4. doi:10.2169/internalmedicine.48.2602. PMID 20009409. 5. ^ a b Narbone MC, Gangemi S, Abbate M (June 2005). "A case of SUNCT syndrome responsive to verapamil". Cephalalgia. 25 (6): 476–8. doi:10.1111/j.1468-2982.2004.00876.x. PMID 15910576. 6. ^ Cohen, A. S., M. S. Matharu, et al. (2006). "Functional MRI in SUNCT (Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms) shows differential hypothalamic activation with increasing pain." Journal of Neurology, Neurosurgery, and Psychiatry 77(12): 041. 7. ^ Auer T, Janszky J, Schwarcz A, et al. (June 2009). "Attack-related brainstem activation in a patient with SUNCT syndrome: an ictal fMRI study". Headache. 49 (6): 909–12. doi:10.1111/j.1526-4610.2009.01348.x. PMID 19220497. 8. ^ Goadsby PJ, Lipton RB (January 1997). "A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases". Brain. 120 (Pt 1): 193–209. doi:10.1093/brain/120.1.193. PMID 9055807. 9. ^ Bosco D, Labate A, Mungari P, Vero S, Fava A (April 2007). "SUNCT and high nocturnal prolactin levels: some new unusual characteristics". J Headache Pain. 8 (2): 114–8. doi:10.1007/s10194-007-0370-2. PMC 3476135. PMID 17497264. 10. ^ Rocha Filho PA, Galvão AC, Teixeira MJ, et al. (June 2006). "SUNCT syndrome associated with pituitary tumor: case report". Arq Neuropsiquiatr. 64 (2B): 507–10. doi:10.1590/s0004-282x2006000300029. PMID 16917628. 11. ^ Choi JY, Seo WK, Kim JH, Oh K, Yu SW (2008). "Symptomatic SUNCT syndrome associated with ipsilateral paranasal sinusitis". Headache. 48 (10): 1527–30. doi:10.1111/j.1526-4610.2008.01243.x. PMID 19076651. It is observed that TACs share some common phenotypes but have different pathophysiology. 12. ^ Pareja JA, Cuadrado ML, Caminero AB, Barriga FJ, Barón M, Sánchez-del-Río M (April 2005). "Duration of attacks of first division trigeminal neuralgia". Cephalalgia. 25 (4): 305–8. doi:10.1111/j.1468-2982.2004.00864.x. PMID 15773828. 13. ^ Arroyo AM, Durán XR, Beldarrain MG, Pinedo A, García-Moncó JC (January 2010). "Response to intravenous lidocaine in a patient with SUNCT syndrome". Cephalalgia. 30 (1): 110–2. doi:10.1111/j.1468-2982.2009.01871.x. PMID 19438923. 14. ^ Trauninger A, Alkonyi B, Kovács N, Komoly S, Pfund Z (June 2010). "Methylprednisolone therapy for short-term prevention of SUNCT syndrome". Cephalalgia. 30 (6): 735–9. doi:10.1111/j.1468-2982.2009.01971.x. PMID 19673911. 15. ^ Sjaastad O, Russell D, Hørven I, et al. (1978). "Multiple, neuralgiform, unilateral headache attacks associated with conjunctival injection and appearing in clusters. A nosological problem". Proceedings of the Scandinavian Migraine Society. p. 31. 16. ^ Kreps, Daniel (March 16, 2016). "Bad Brains' H.R. Raising Money to Combat Headache Disorder". Rolling Stone. Retrieved 21 October 2016. ## External links[edit] * NINDS SUNCT Information Page * International Classification of Headache Disorders * v * t * e Headache Primary ICHD 1 * Migraine * Familial hemiplegic * Retinal migraine ICHD 2 * Tension * Mixed tension migraine ICHD 3 * Cluster * Chronic paroxysmal hemicrania * SUNCT ICHD 4 * Hemicrania continua * Thunderclap headache * Sexual headache * New daily persistent headache * Hypnic headache Secondary ICHD 5 * Migralepsy ICHD 7 * Ictal headache * Post-dural-puncture headache ICHD 8 * Hangover * Medication overuse headache ICHD 13 * Trigeminal neuralgia * Occipital neuralgia * External compression headache * Cold-stimulus headache * Optic neuritis * Postherpetic neuralgia * Tolosa–Hunt syndrome Other * Vascular [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	SUNCT syndrome	c1262087	30,309	wikipedia	https://en.wikipedia.org/wiki/SUNCT_syndrome	2021-01-18T19:05:57	{"gard": ["9257"], "mesh": ["D050798"], "umls": ["C1262087"], "orphanet": ["57145"], "wikidata": ["Q7501612"]}
A number sign (#) is used with this entry because a heterozygous mutation in the FOXD3 gene (611539) on chromosome 1p31 has been identified in a family with vitiligo mapping to the AIS1 locus. For a discussion of autoimmunity, see 109100. See also vitiligo (606579). Clinical Features Alkhateeb et al. (2002) studied a 3-generation family in which 13 individuals had generalized vitiligo. Seven of these individuals also had Hashimoto thyroiditis (140300), as did 1 other family member who did not manifest vitiligo. Alkhateeb et al. (2005) noted that the vitiligo phenotype in this family was atypical, including early age at onset at age 13 years and slowly progressive diffuse depigmentation. Mapping By genomewide linkage analysis of a large family with vitiligo and Hashimoto thyroiditis, Alkhateeb et al. (2002) identified an oligogenic autoimmune susceptibility locus, termed AIS1, to a 14.4-cM interval at chromosome 1p32.2-p31.3 (multipoint lod score of 2.90). A 2-locus analysis of Hashimoto thyroiditis in family members segregating an AIS1 susceptibility allele showed suggestive linkage to markers in chromosome 6p22.3-q14.1 (affecteds-only multipoint lod score of 1.52), in a region spanning both the major histocompatibility complex and AITD1 (Tomer et al., 1999). The authors concluded that the 1p AIS1 locus is associated with susceptibility to autoimmunity, particularly vitiligo, in this family, and that a chromosome 6 locus, most likely AITD1, may mediate the occurrence of Hashimoto thyroiditis in AIS1-susceptible family members. Following up on the study of Alkhateeb et al. (2002), Fain et al. (2003) performed a genomewide genetic linkage analysis of 70 additional white families with generalized vitiligo from the U.S. and U.K. The results strongly confirmed that AIS1, located on chromosome 1p31, is a major locus for susceptibility to autoimmune disease, specifically vitiligo. Fain et al. (2003) also detected 7 additional suggestive linkage signals that may represent other genes involved in the pathogenesis of vitiligo and perhaps other autoimmune disorders associated with vitiligo. Molecular Genetics In affected members of the large family with autosomal dominant vitiligo previously reported by Alkhateeb et al. (2002), Alkhateeb et al. (2005) identified a heterozygous mutation in the promoter region of the FOXD3 gene (611539.0001). No FOXD3 variants were detected in 96 unrelated Caucasian vitiligo probands. The authors noted that FOXD3 is a regulator of melanoblast differentiation and suggested that increased transcriptional activity conferred by the promoter variant may suppress or alter the differentiation of melanoblasts in these patients. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Vitiligo, generalized \- Depigmentation, slowly progressive and diffuse ENDOCRINE FEATURES \- Hashimoto thyroiditis (some patients) MISCELLANEOUS \- Early age at onset (13 years) MOLECULAR BASIS \- Caused by mutation in the forkhead box D3 gene (FOXD3, 611539.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 1	c1842979	30,310	omim	https://www.omim.org/entry/607836	2019-09-22T16:08:43	{"omim": ["607836"], "synonyms": ["Alternative titles", "VITILIGO-ASSOCIATED MULTIPLE AUTOIMMUNE DISEASE SUSCEPTIBILITY 2", "AUTOIMMUNE DISEASE SUSCEPTIBILITY LOCUS, CHROMOSOME 1p-RELATED"]}
A rare genetic cardiac disease characterized by restrictive ventricular filling due to high ventricular stiffness that results in severe diastolic dysfunction in the absence of dilated or hypertrophied ventricles. ## Epidemiology The prevalence is unknown; however, from a European registry the familial form is reported to account for 30% of restrictive cardiomyopathy. ## Clinical description Clinical presentation of restrictive cardiomyopathy (RCM) is heterogeneous, with onset at any age. Dyspnea is the most common symptom, followed by edema, palpitation, fatigue, orthopnea and chest pain. The typical symptoms upon examination include jugular venous distension, elevated systemic and pulmonary venous pressures, systolic murmur, lower-extremity edema, atrial fibrillation, cardiomegaly, and less frequently atrioventricular block. In advance disease, symptoms include pulmonary congestion, hepatomegaly, ascites and edema. Diastolic volumes are normal or reduced, and whilst initial systolic function is normal or near-normal, it may deteriorate with diseases progression. The ejection fraction is typically above 50%. Mild-to-moderate tricuspid and mitral valve regurgitation is common. Bi-atrial dilatation due chronic elevation of atrial pressure usually develops which along with pulmonary venous congestion and pleural effusions can result in moderate to generalized cardiomegaly. Other changes in cardiac morphology, such as ventricular dilatation, septal and ventricular hypertrophy, typically do not occur in RCM. Myocardial biopsy typically demonstrates interstitial fibrosis, and mild to moderated myocyte hypertrophy, without evidence of amyloid deposition, eosinophil infiltration or other systemic infiltration. Death can occur suddenly or as a result of congestive heart failure, cardiac arrhythmias, or other associated complications. ## Etiology RCM is due to increased ventricle stiffness resulting in restricted ventricular filling either unilaterally or bilaterally. Most cases of RCM remain idiopathic; however, an increasing number of disease causing mutations have been identified and include the sarcomere subunits, such as troponin T (TNNT2, 1q32.1), troponin I (TNNI3, 19q13.42), alpha-actin (ACTC, 15q14), beta-myosin heavy chain (MYH7, 14q11.2), myopalladin (MYPN, 10q21.3), and filamin C (FLNC,7q32.1) as well as kinesin-like protein KIF20A (KIF20A, 5q31.2). ## Diagnostic methods Diagnosis is made with cardiac echocardiography supported by electrocardiogram, cardiac catheterization, and endomyocardial biopsy. Typical findings on echography include enlargement of atria, normal or reduced left ventricular end diastolic dimension and/or volume, restrictive left ventricular filling pattern, normal or near normal systolic function, and normal ventricular wall thickness. Thorough hemodynamic evaluation with cardiac catheterization may be required to exclude the differential diagnosis. ## Differential diagnosis Differential diagnosis includes constrictive pericarditis and infiltrative myocardial disease such as cardiac amyloidosis, and other secondary causes of restrictive myopathy such as storage disease. ## Genetic counseling For patients with known mutation, the pattern of inheritance is autosomal dominant and, therefore, there is a 50% risk of disease transmission from an affected parent to offspring. Autosomal recessive inheritance has been observed in one family. Genetic counseling should be offered to affected families, with clinical screening of asymptomatic family members. ## Management and treatment Cardiac transplant is the sole effective procedure in treating the disease. Pediatric patients should obtain preference on the waiting list due to the high risk of sudden death and to prevent the need for heart-lung transplantation. No single drug improves prognosis of RCM. Whilst diuretics are commonly used to reduce preload, excessive reduction may decrease ventricular filling. Thus, diuretics should be limited to patients presenting with symptomatic pulmonary venous congestion and/or right heart failure. ACE (angiotensin-converting enzyme) inhibitors and vasodilators are considered detrimental for the treatment of RCM. Anti-dysrhythmic therapy or implantable cardioverter defibrillators (AICD) may be an option for patients presenting with atrial fibrillation or ischemia. Pacemaker is considered in the presence of high degree atrioventricular block. Anti-coagulants reduce the risk of thromboembolic events. ## Prognosis Prognosis is usually poor, especially in pediatric patients, with 50 percent of deaths occurring within 2 years of diagnosis. For patients 10 years of age and above, the 5-year survival rate is 64 percent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Familial isolated restrictive cardiomyopathy	c1861861	30,311	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75249	2021-01-23T18:48:48	{"mesh": ["C566168"], "omim": ["115210", "609578", "612422", "615248", "617047"], "icd-10": ["I42.5"], "synonyms": ["Familial or idiopathic restrictive cardiomyopathy"]}
## Clinical Features Shohat et al. (1993) described a preterm (28 weeks) female fetus with a 'new' lethal skeletal dysplasia characterized by distinctive epiphyseal stippling, periosteal cloaking, and unusual microscopic morphology. Radiologically there was marked stippling of the coccygeal and sacral vertebral region as well as of the epiphyses. Long bones showed wide periosteal cloaking and bowing. Sagittal clefting was present in the upper spine. In contrast to the normal morphology of the epiphyses and growth plates, the marrow was filled with loose fibrous tissue containing numerous large multinucleated osteoclasts which were associated with Howship lacunae on the endosteal surface. The morphologic features were consistent with elevated bone resorption. Shohat et al. (1993) suggested the pseudo-eponym 'Pacman dysplasia,' based on the video game in which little round creatures actively 'eat dots.' Wilcox et al. (1998) reported 2 sib fetuses with radiologic and morphologic findings similar to those of Pacman dysplasia. The male and female fetuses were electively terminated at 20 and 16 weeks, respectively, after routine ultrasound studies showed short-limbed dwarfism. The radiographic appearance was characterized by undermineralized bone, stippling, rhizomelic and mesomelic shortness, platyspondyly, and a short, broad pelvis. The metaphyses were dense, but the diaphyseal cortices were thin with undermodeled long bones, and there was a deficient trabecular pattern suggesting marrow replacement. Chondroosseous structure was characterized by deficient trabecular bone formation, a fibrous marrow, and numerous large, multinucleated osteoclasts lining the endosteal surfaces of the metaphyseal bone. Miller et al. (2003) reported a male fetus of a pregnancy electively terminated at 24 weeks due to suspected skeletal dysplasia. Postmortem radiography showed 'nearly identical' features to the original case of Pacman dysplasia (Shohat et al., 1993) with shortening of long bones, mild to moderate femoral bowing, dramatic epiphyseal, tarsal, and spinal puncta, vertebral clefting and platyspondyly, phalangeal shortening, osteopenia, periosteal cloaking about long bones, and metaphyseal lucent bands. Saul et al. (2005) described a female sib of the fetus reported by Miller et al. (2003). She had a clinical course and biochemical, cytologic, and radiographic features consistent with the diagnosis of mucolipidosis type II (ML II; 252500). Saul et al. (2005) suggested that what is called Pacman dysplasia may represent a prenatal manifestation of ML II. Wilcox et al. (2005) stated that Pacman dysplasia is distinct from ML II, noting that enzymatic analysis of cultured fibroblasts from one of the sibs reported by Wilcox et al. (1998) revealed normal activities, thus excluding ML II. Wilcox et al. (2005) commented that radiographic and morphologic criteria cannot be used to distinguish between the disorders; for a definitive diagnosis, pathologic material must be examined for lysosomal storage or enzyme assays must be performed. Inheritance Wilcox et al. (2005) suggested that Pacman dysplasia is an autosomal recessive disorder. Nomenclature Feingold (2006) and Saul et al. (2006) discussed the need for a more appropriate and precise term for this syndrome, perhaps based on the histology or biochemistry of the disorder. Skel \- Lethal skeletal dysplasia \- Bowed long bones Radiology \- Epiphyseal stippling \- Periosteal cloaking \- Stippling of coccygeal and sacral vertebral region \- Sagittal clefting of upper vertebrae Lab \- Marrow filled with loose fibrous tissue containing numerous large multinucleated osteoclasts associated with Howship lacunae on the endosteal surface 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	PACMAN DYSPLASIA	c1833676	30,312	omim	https://www.omim.org/entry/167220	2019-09-22T16:36:47	{"mesh": ["C538095"], "omim": ["167220"], "orphanet": ["1952"], "synonyms": ["Alternative titles", "EPIPHYSEAL STIPPLING WITH OSTEOCLASTIC HYPERPLASIA"]}
## Clinical Features Carter and Sweetnam (1960) noted dominant inheritance in several families that suffered from recurrent dislocation of joints, particularly the shoulder, caused by joint laxity. Other dominant pedigrees were referred to by McKusick (1972). Horton et al. (1980) reported a large family in which many members had joint laxity and of these most also had congenital hip dislocation and some patella dislocation. No chemical studies of collagen were reported. The disorder was indistinguishable from that in the families of Carter and Sweetnam (1960), Beighton and Horan (1970), and others. Nomenclature Horton (1982) agreed that in terms of differential diagnosis this disorder can conveniently be considered a form of the Ehlers-Danlos syndrome; arbitrarily the next number to be assigned is XI. It was the recommendation of a workshop convened in Berlin by Beighton (1986) that the Ehlers-Danlos designation be used for joint hypermobility with skin changes (EDS3; 130020), leaving this as a separate category. In connection with this recommendation, the number EDS XI will be retired (in the manner that MPS V and clotting factor IV were retired as the knowledge concerning them advanced). Joints \- Joint laxity \- Recurrent joint dislocation \- Congenital hip dislocation \- Patella dislocation 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	JOINT LAXITY, FAMILIAL	c0268349	30,313	omim	https://www.omim.org/entry/147900	2019-09-22T16:39:21	{"mesh": ["C535884"], "omim": ["147900"], "orphanet": ["2295"], "synonyms": ["Alternative titles", "FAMILIAL JOINT INSTABILITY SYNDROME", "ARTICULAR HYPERMOBILITY SYNDROME", "EHLERS-DANLOS SYNDROME, TYPE XI, FORMERLY", "EDS XI, FORMERLY", "EDS11, FORMERLY"]}
A number sign (#) is used with this entry because Senior-Loken syndrome 7 (SLSN7), a ciliopathy, is caused by homozygous mutation in the SDCCAG8 gene (613524) on chromosome 1q43. Mutations in SDCCAG8 can also result in Bardet-Biedl syndrome-16 (BBS16; 615993). For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900. Molecular Genetics Otto et al. (2010) used homozygosity mapping followed by exon capture and massively parallel sequencing to identify a homozygous truncating mutation in the SDCCAG8 gene (613524.0001) in 2 sibs with Senior-Loken syndrome-7, who were born of consanguineous parents from Reunion Island. Both patients had biopsy-confirmed nephronophthisis and retinal degeneration, leading to blindness in 1. They found homozygous mutations in SDCCAG8 in 5 other families with a phenotype consistent with Senior-Loken syndrome. Recessive SDCCAG8 mutations accounted for 3.3% (6 of 182) cases from a worldwide SLSN cohort. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	SENIOR-LOKEN SYNDROME 7	c0403553	30,314	omim	https://www.omim.org/entry/613615	2019-09-22T15:58:06	{"doid": ["0050576"], "mesh": ["C537580"], "omim": ["613615"], "orphanet": ["3156"]}
Autosomal recessive spastic paraplegia type 28 is a pure form of hereditary spastic paraplegia characterized by a childhood or adolescent onset of slowly progressive, pure crural muscle spastic paraparesis which manifests with mild lower limb weakness, gait difficulties, extensor plantar responses, and hyperreflexia of lower extremities. Less common manifestations include cerebellar oculomotor disturbance with saccadic eye pursuit, pes cavus and scoliosis. Some patients also present pin and vibration sensory loss in distal legs. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Autosomal recessive spastic paraplegia type 28	c1836295	30,315	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101008	2021-01-23T17:01:57	{"mesh": ["C563732"], "omim": ["609340"], "umls": ["C1836295"], "icd-10": ["G11.4"], "synonyms": ["SPG28"]}
The average age at which intestinal tumors are diagnosed ranges between 10–12 years for cats and 6 to 9 years for dogs. There are many different types of intestinal tumors, including lymphoma, adenocarcinoma, mast cell tumor, and leiomyosarcoma. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Signs and symptoms[edit] The symptoms can vary but include weight loss, diarrhea, vomiting, and anorexia. ## Diagnosis[edit] The veterinarian will typically perform a series of tests such as blood tests and imaging studies. The most definitive way to confirm/rule out intestinal tumors is to perform a medical procedure called endoscopy to visualize the organ and do a tissue biopsy.[1] ## Treatment[edit] Surgical treatment remains the treatment of choice for cats and dogs diagnosed with intestinal tumors who are in otherwise good health. ## References[edit] 1. ^ Withrow SJ, MacEwen EG, eds. (2001). Small Animal Clinical Oncology (3rd ed.). W.B. Saunders Company. ## External links[edit] * Intestinal Cancer in Cats and Dogs from Pet Cancer Center * Gastrointestinal Neoplasia from Merck Veterinary Manual' [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Intestinal cancer in cats and dogs	None	30,316	wikipedia	https://en.wikipedia.org/wiki/Intestinal_cancer_in_cats_and_dogs	2021-01-18T18:34:30	{"wikidata": ["Q6057463"]}
A number sign (#) is used with this entry because Fanconi anemia of complementation group L (FANCL) is caused by homozygous or compound heterozygous mutation in the PHF9 (FANCL; 608111) gene on chromosome 2p16. Description Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650. Clinical Features Meetei et al. (2003) detected little or no PHF9 protein in a cell line (EURA868) from an individual with Fanconi anemia of unassigned complementation group (subsequently designated FANCL). The phenotype of the cells from EURA868 resembled that of other Fanconi anemia cells, including the absence of monoubiquitinated FANCD2 (613984) and hypersensitivity to mitomycin C. These Fanconi anemia defects were corrected by ectopic expression of PHF9. Ali et al. (2009) reported a male patient with FANCL who had developmental delay, a cafe-au-lait spot, mild hypocellularity, and a family history of leukemia. Vetro et al. (2015) reported 2 unrelated infants with a severe form of FANCL presenting as multiple congenital anomalies reminiscent of VACTERL (192350) or VACTERL-H (276950). The first patient (case 1b), born of consanguineous Moroccan parents, was noted to have radial hypoplasia and intrauterine growth retardation on prenatal ultrasound at 14 weeks' gestation. Later investigations showed tetralogy of Fallot, left kidney agenesis, right kidney hydronephrosis, and esophageal atresia. After birth, the patient showed hypertelorism, broad nasal root and puffy cheeks, and bilateral absence of the thumbs. The infant died 2 months later and the abnormalities were confirmed by postmortem examination. Family history included 2 previous fetuses with congenital malformations; data available for 1 in which the pregnancy had been terminated revealed similar features. In the second family, a female Dutch infant (case 2) showed intrauterine growth retardation, hydrocephalus, facial dysmorphism with depressed nasal tip, microtia, microphthalmia, cleft palate, short neck, short forearms, radial club hands with absent thumbs, hypoplastic sacrum, and anal atresia with rectovaginal fistula. She also had cardiac defects and renal hypoplasia. She died at age 2 days. Cells derived from both patients showed increased chromosomal breakage with DEB or MMC, consistent with a diagnosis of Fanconi anemia. Inheritance The transmission pattern of FANCL in the families reported by Vetro et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In a cell line (EUFA868) from an individual with Fanconi anemia of complementation group FANCL, Meetei et al. (2003) found little or no PHF9 protein. PHF9 cDNA from this cell line lacked exon 11, thus removing the conserved PHD finger and part of the third WD40 repeat. The genomic DNA from this individual showed a homo- or hemizygous insertion of 177 bp into a pyrimidine-rich sequence at the splice junction between intron 10 and exon 11 (608111.0001). In a male patient with FANCL, Ali et al. (2009) identified compound heterozygous mutations in the FANCL gene (608111.0002-608111.0003). In 2 unrelated infants with lethal FANCL, Vetro et al. (2015) identified 2 different homozygous truncating mutations in the FANCL gene (608111.0004 and 608111.0005). The mutation in the first patient was found by whole-exome sequencing and segregated with the disorder in the family. The mutation in the second patient was found by targeted sequencing of known Fanconi anemia genes. Cell lines from both patients showed increased chromosomal breakage and increased sensitivity to MMC, which was rescued after transfection with wildtype FANCL. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation (in some patients) HEAD & NECK Face \- Dysmorphic facial features (in some patients) Ears \- Microtia (in some patients) Eyes \- Hypertelorism (in some patients) \- Microphthalmia (in some patients) Nose \- Depressed nasal root (in some patients) \- Broad nasal root (in some patients) Mouth \- Cleft palate (in some patients) Neck \- Short neck (in some patients) CARDIOVASCULAR Heart \- Cardiac malformations (in some patients) RESPIRATORY Airways \- Tracheoesophageal fistula (in some patients) ABDOMEN Gastrointestinal \- Esophageal atresia (in some patients) \- Anal atresia (in some patients) GENITOURINARY External Genitalia (Male) \- Micropenis (in some patients) Kidneys \- Renal hypoplasia (in some patients) SKELETAL Spine \- Vertebral abnormalities (in some patients) Limbs \- Radial ray defects (in some patients) Hands \- Absent thumbs (in some patients) NEUROLOGIC Central Nervous System \- Hydrocephalus (in some patients) \- Developmental delay (in some patients) HEMATOLOGY \- Bone marrow failure (in some patients) LABORATORY ABNORMALITIES \- Increased chromosomal breakage MISCELLANEOUS \- Highly variable phenotype \- Four unrelated patients have been reported (last curated September 2015) \- Two unrelated patients had multiple congenital anomalies and died in early infancy MOLECULAR BASIS \- Caused by mutation in the FANCL gene (FANCL, 608111.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	FANCONI ANEMIA, COMPLEMENTATION GROUP L	c0015625	30,317	omim	https://www.omim.org/entry/614083	2019-09-22T15:56:31	{"doid": ["0111082"], "mesh": ["D005199"], "omim": ["614083"], "orphanet": ["84"], "genereviews": ["NBK1401", "NBK5192"]}
Keratoderma hereditarium mutilans is a rare, diffuse, mutilating, hereditary palmoplantar keratoderma disorder characterized by severe, honeycomb-pattern palmoplantar keratosis and pseudoainhum of the digits leading to autoamputation, associated with mild to moderate congenital sensorineural hearing loss. Additional features include stellate keratosis on the extensor surfaces of the fingers, feet, elbows and knees. Alopecia, onychogryphosis, nail dystrophy or clubbing, spastic paraplegia and myopathy 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Keratoderma hereditarium mutilans	c0265964	30,318	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=494	2021-01-23T18:34:31	{"gard": ["3092"], "mesh": ["C536457"], "omim": ["124500"], "umls": ["C0265964"], "icd-10": ["Q82.8"], "synonyms": ["Mutilating keratoderma of Vohwinkel", "Mutilating keratoderma plus deafness", "Mutilating keratoderma plus hearing loss", "PPK mutilans and deafness", "PPK mutilans and hearing loss", "Vohwinkel syndrome"]}
Idiopathic postprandial syndrome SymptomsShakiness, sense of weakness Idiopathic postprandial syndrome, colloquially but incorrectly known by some as hypoglycemia, describes a collection of clinical signs and symptoms similar to medical hypoglycemia but without the demonstrably low blood glucose levels which characterise said condition. People with this condition suffer from recurrent episodes of altered mood and cognitive efficiency, often accompanied by weakness and adrenergic symptoms such as shakiness. The episodes typically occur a few hours after a meal, rather than after many hours of fasting. The principal treatments recommended are extra small meals or snacks and avoidance of excessive simple sugars. ## Contents * 1 Signs and symptoms * 2 Etymology and history of diagnosis * 2.1 Non-disease * 3 Adrenergic postprandial syndrome * 4 See also * 5 References ## Signs and symptoms[edit] The symptoms include many of the symptoms associated with milder degrees of hypoglycemia, especially the adrenergic symptoms, but do not progress to objective impairment of brain function, seizures, coma, or brain damage.[citation needed] * Shakiness * Sense of weakness * Altered or depressed mood * Confusion * Fatigue * Anxiety * Paleness * Perspiration * Increased pulse or respiratory rate * Hunger ## Etymology and history of diagnosis[edit] The term idiopathic postprandial syndrome, which literally means a syndrome that occurs after eating (postprandial) and is of unknown cause (idiopathic), was coined in an attempt to reserve the term hypoglycemia for those conditions in which low glucose levels could be demonstrated.[1] It was offered as a less confusing alternative to functional hypoglycemia and as a less pejorative alternative to "nonhypoglycemia" or "pseudohypoglycemia". The syndrome resembles reactive hypoglycemia except that low glucose is not found at the time of symptoms. The common usage of the term "hypoglycemia" was noted and countered by doctors writing in the Journal of the American Medical Association in the 1970s: The "syndrome of hypoglycemia" has become popular among patients and physicians alike, primarily because it seems to provide an explanation (?) for obscure symptoms, and it gives the patient something to do, ie, manipulate his or her diet continuously. Here is where the concept of "hypoglycemia" as a disorder meets up with all other modern dietary fads such as "natural" foods, vitamin "lack", and "organic" foods. It is also an area in which the hormones are involved. Hence "glandular causes" and "glandular therapy" play a large role.[2] The author said "a cult has developed, consisting of a believing public aided and abetted by 'nutritionists', medical journalists, and a host of physicians." Hypoglycemia enjoys a popular position in the public's eye as a non-specific medical condition that frequently provides an explanation for the varied symptoms that occur in daily life.[3] These doctors cautioned against the over-diagnosis of reactive hypoglycemia. They said "both physicians and the public deserve major re-education." ### Non-disease[edit] In October 1974, The New England Journal of Medicine carried an article "Non-hypoglycemia as an epidemic condition" which described the condition as a "non-disease".[4] The authors claim Over the past few years people have appeared in droves with the self-diagnosis of "hypoglycemia" – a term that has become the layman's final common pathway for a variety of conditions, only a few of which are related to endocrinologic abnormalities. Most common are somatic complaints such as fatigue, spasms, palpitation, numbness and tingling, pains, severe sweating and mental dullness. Hypoglycemia provides all at once a socially acceptable problem, a quasi-physiologic explanation and the promise of a relatively inexpensive and successful self-help program. The same issue of the Journal carried a "non-editorial on non-hypoglycemia" that acknowledged the "current popular epidemic of non-hypoglycemia" and proposed the term "clinical pseudo-hypoglycemia".[5] After describing the known mechanisms of blood glucose regulation, the authors call for more research: The body's normal response to carbohydrate ingestion includes elaboration of an as yet unidentified hormonal (gut) factor from the upper intestine. They say that a glucose tolerance test is appropriate but caution that: It must be kept in mind that the oral glucose load is far from a normal physiologic meal, and tests only glucose as the provocateur, whereas protein might be as much at fault by stimulating over-production of the gut factor, probably pancreozymin. Thus much more research is indicated to define the norms as well as to characterize the role and nature of the various gut factors and the responses of the beta cells to these factors. ## Adrenergic postprandial syndrome[edit] There is some evidence of the existence of a so-called "adrenergic postprandial syndrome": the glycemia is normal, and the symptoms are caused through autonomic adrenergic counterregulation.[6] Often, this syndrome is associated with emotional distress and anxious behaviour of the patient.[7][8] ## See also[edit] * Chronic Somogyi rebound (The "Somogyi effect") * Idiopathic hypoglycemia * Reactive hypoglycemia ## References[edit] 1. ^ Charles MA, Hofeldt F, Shackelford A, et al. (1981). "Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia: absence of hypoglycemia after meals". Diabetes. 30 (6): 465–70. doi:10.2337/diabetes.30.6.465. PMID 7227659. 2. ^ Rachmiel Levine MD (October 21, 1974) "Hypoglycemia", Journal of the American Medical Association 230(3):462,3 3. ^ F. D. Hofeldt, R.A. Adler, & R.H. Herman (September 22, 1975) "Postprandial Hypoglycemia: Fact or Fiction", Journal of the American Medical Association 233(12): 1309 4. ^ Joel Yager & Roy T. Young (1974) "Non-hypoglycemia as an epidemic condition", The New England Journal of Medicine 291:907,8 5. ^ George F. Cahill, Jr. & J. Stuart Soeldner (1974) "A non-editorial on non-hypoglycemia", The New England Journal of Medicine 291: 905,6 6. ^ "postprandiale Hypoglykämie". Archived from the original on 2007-05-22. Retrieved 2007-07-06. 7. ^ Brun JF, Fedou C, Mercier J (2000). "Postprandial reactive hypoglycemia" (PDF). Diabetes Metab. 26 (5): 337–51. PMID 11119013. Archived from the original (PDF) on 2007-06-30. 8. ^ Berlin I, Grimaldi A, Landault C, Cesselin F, Puech AJ (1994). "Suspected postprandial hypoglycemia is associated with beta-adrenergic hypersensitivity and emotional distress" (PDF). J. Clin. Endocrinol. Metab. 79 (5): 1428–33. doi:10.1210/jcem.79.5.7962339. PMID 7962339. Archived from the original (PDF) on 2007-06-30. Retrieved 2007-06-29. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Idiopathic postprandial syndrome	c0271709	30,319	wikipedia	https://en.wikipedia.org/wiki/Idiopathic_postprandial_syndrome	2021-01-18T18:29:50	{"umls": ["C0271709"], "wikidata": ["Q5988900"]}
Fully female spider (Drassodes saccatus) with left male pedipalp, an example of mosaic gynandromorphism Heteropteryx dilatata gynandromorph Gynandromorph of the small white, Pieris rapae A gynandromorph is an organism that contains both male and female characteristics. The term comes from the Greek γυνή (gynē), female, ἀνήρ (anēr), male, and μορφή (morphē), form, and is used mainly in the field of entomology. Notable gynandromorphic organisms are butterflies, moths and other insects, wherein both types of body part can be distinguished physically due to sexual dimorphism. ## Contents * 1 Occurrence in other genera * 2 Pattern of distribution of male and female tissues in a single organism * 3 Causes * 4 As a research tool * 5 See also * 6 References * 7 External links ## Occurrence in other genera[edit] Gynandromorphism was first discovered by Bridges and Morgan in Drosophila. It has been observed in numerous animal species, including crustaceans, such as lobsters and crabs, spiders and many species of bird.[1][2][3][4][5][6] A clear example in birds involves the zebra finch. These birds have lateralised brain structures in the face of a common steroid signal, providing strong evidence for a non-hormonal primary sex mechanism regulating brain differentiation.[7] ## Pattern of distribution of male and female tissues in a single organism[edit] A gynandromorph can have bilateral asymmetry—one side female and one side male.[8] Alternatively, the distribution of male and female tissue can be more haphazard. Bilateral gynandromorphy arises very early in development, typically when the organism has between 8 and 64 cells.[9] Later stages produce a more random pattern.[citation needed] * Normal female of Papilio androgeus * Mosaic gynandromorph of Papilio androgeus * Normal male of Papilio androgeus ## Causes[edit] The cause of this phenomenon is typically, but not always, an event in mitosis during early development. While the organism contains only a few cells, one of the dividing cells does not split its sex chromosomes typically. This leads to one of the two cells having sex chromosomes that cause male development and the other cell having chromosomes that cause female development. For example, an XY cell undergoing mitosis duplicates its chromosomes, becoming XXYY. Usually this cell would divide into two XY cells, but in rare occasions the cell may divide into an X cell and an XYY cell. If this happens early in development, then a large portion of the cells are X and a large portion are XYY. Since X and XYY dictate different sexes, the organism has tissue that is female and tissue that is male.[10] A developmental network theory of how gynandromorphs develop from a single cell based on internetwork links between parental allelic chromosomes is given in.[11] The major types of gynandromorphs, bilateral, polar and oblique are computationally modeled. Many other possible gynandromorph combinations are computationally modeled, including predicted morphologies yet to be discovered. The article relates gynandromorph developmental control networks to how species may form. The models are based on a computational model of bilateral symmetry.[12] ## As a research tool[edit] Gynandromorphs occasionally afford a powerful tool in genetic, developmental, and behavioral analyses. In Drosophila melanogaster, for instance, they provided evidence that male courtship behavior originates in the brain,[13] that males can distinguish conspecific females from males by the scent or some other characteristic of the posterior, dorsal, integument of females,[14][15] that the germ cells originate in the posterior-most region of the blastoderm,[16] and that somatic components of the gonads originate in the mesodermal region of the fourth and fifth abdominal segment.[17] ## See also[edit] * Androgyny * Chimerism * Gynomorph * Half-sider budgerigar * Hermaphrodite * Intersex ## References[edit] 1. ^ Chen, Xuqi; Agate, Robert J.; Itoh, Yuichiro; Arnold, Arthur P. (2005). "Sexually dimorphic expression of trkB, a Z-linked gene, in early posthatch zebra finch brain". Proceedings of the National Academy of Sciences. 102 (21): 7730–5. Bibcode:2005PNAS..102.7730C. doi:10.1073/pnas.0408350102. PMC 1140405. PMID 15894627. Lay summary – Scientific American (March 25, 2003). 2. ^ Gouldian finch Erythrura gouldiae Gynandromorph Archived 2006-07-16 at the Wayback Machine 3. ^ Powderhill Banding Fall 2004 Archived 2006-12-31 at the Wayback Machine 4. ^ A Gender-bender Colored Cardinal, by Tim Wall, Discovery News, 31 May 2011 [1] 5. ^ "Half-cock chicken mystery solved". BBC News. 11 March 2010. 6. ^ Suzuki, Yuya; Kuramitsu, Kazumu; Yokoi, Tomoyuki (2019-06-14). "Morphology and sex-specific behavior of a gynandromorphic Myrmarachne formicaria (Araneae: Salticidae) spider". The Science of Nature. 106 (7): 34. doi:10.1007/s00114-019-1625-x. ISSN 1432-1904. PMID 31201570. S2CID 189819156. 7. ^ Arnold, Arthur P. (2004). "Sex chromosomes and brain gender". Nature Reviews Neuroscience. 5 (9): 701–8. doi:10.1038/nrn1494. PMID 15322528. S2CID 7419814. 8. ^ Ian Sample, science correspondent (12 July 2011). "Half male, half female butterfly steals the show at Natural History Museum". London: The Guardian. Retrieved August 6, 2011. 9. ^ Malmquist, David (June 15, 2005). "Rare crab may hold genetic secrets". Virginia Institute of Marine Science. 10. ^ Adams, James K. "Gynandromorphs". Department of Natural Sciences, Dalton State College. Archived from the original on 2013-03-07. Retrieved 2005-06-29. 11. ^ Werner, Eric (2012). "A Developmental Network Theory of Gynandromorphs, Sexual Dimorphism and Species Formation". arXiv:1212.5439 [q-bio.MN]. 12. ^ Werner, Eric (2012). "The Origin, Evolution and Development of Bilateral Symmetry in Multicellular Organisms". arXiv:1207.3289 [q-bio.TO]. 13. ^ Hotta, Y, and Benzer, S. (1972). "Mapping of Behaviour in Drosophila mosaics". Nature. 240 (5383): 527–535. Bibcode:1972Natur.240..527H. doi:10.1038/240527a0. PMID 4568399. S2CID 4181921. 14. ^ Nissani, M. (1975). "A new behavioral bioassay for an analysis of sexual attraction and pheromones in insects". Journal of Experimental Zoology. 192 (2): 271–5. doi:10.1002/jez.1401920217. PMID 805823. 15. ^ Hotta, Y., Benzer, S. (1976). "Courtship in Drosophila mosaics: sex-specific foci for sequential action patterns". Proc Natl Acad Sci U S A. 73 (11): 4154–4158. Bibcode:1976PNAS...73.4154H. doi:10.1073/pnas.73.11.4154. PMC 431365. PMID 825859. 16. ^ Nissani, Moti (1977). "Cell lineage analysis of germ cells of Drosophila melanogaster". Nature. 265 (5596): 729–731. Bibcode:1977Natur.265..729N. doi:10.1038/265729a0. PMID 404558. S2CID 4146956. 17. ^ Szabad, Janos, and Nothiger, Rolf (1992). "Gynandromorphs of Drosophila suggest one common primordium for the somatic cells of the female and male gonads in the region of abdominal segments 4 and 5" (PDF). Development. 115 (2): 527–533. PMID 1425338. ## External links[edit] Wikimedia Commons has media related to Gynandromorphs. * "Stunning Dual-Sex Animals" at Live Science * Aayushi Pratap: This rare bird is male on one side and female on the other; on: Sciencenews; October 6, 2020; about a gynandromorph rose-breasted grosbeak. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Gynandromorphism	None	30,320	wikipedia	https://en.wikipedia.org/wiki/Gynandromorphism	2021-01-18T18:43:44	{"wikidata": ["Q430711"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2019) Autoimmune skin disease in dogs are a group of diseases that occur in dogs that are caused by the body's immune system, where the body's white blood cells or body's antibodies attack its own tissues or extracellular protein of the skin.[1] ## Contents * 1 Overview * 2 Clinical symptoms * 3 Disease incidence process * 4 See also * 5 References ## Overview[edit] See also: Autoimmunity The immune system has the ability to differentiate between the body's own cells and foreign cells.[2] However, in the dogs affected by auto-immune disease, the immune system loses the ability to distinguish between body's own cells and foreign cells, causing their immune system to attack the body's own cells.[3] Autoimmune diseases in the base layer of the epidermis are characterized by damage to the connective tissue and vesicle formation located below the epidermis layer and the dermis layer below it.[4][5] ## Clinical symptoms[edit] Pemphigus foliaceus in dogs: hair loss occurs, skin becomes red, and itchy. Dogs suffering from autoimmune diseases of the skin may experience a variety of symptoms, including persistent itching and scratching, lesions, wounds, blisters, and other skin damage, as well as loss of skin pigment.[3] Two cases of autoimmune diseases that are often found include Discoid lupus erythematosus (DLE) and Pemphigus. DLE can develop into Systemic Lupus Erythematosus (SLE).[6] The initial stage of DLE is marked by a loss of skin pigment. The skin becomes red and sores appear on the nose. The palate can undergo erosion, ulceration, and injury to the nasal palate, as well as damage to the nostrils and the tissue around the eyes and ears. In chronic and severe cases, visual scar tissue often occurs.[6] In infections caused by Pemphigus vulgaris, lesions are usually evident in the oral cavity.[6] Sometimes symptoms are characterized by lymphadenopathy, which is characterized by loss of appetite, weakness, fever, and in rare cases, sepsis.[6] Pemphigus foliaceus usually affects areas of the ears and face.[6] Early symptoms are characterized by depigmentation of the nasal palate, dorsal cleft in the mouth, the ear, and the periocular area around the eye. Itching, pain, and weakness of the body have been observed in some cases. ## Disease incidence process[edit] There are two mechanisms of tolerance found in the immune system.[4] The first mechanism is positive selection by the thymus, where only T cells are selected. T cells recognize peptides in the Histocompatibility Complex (MHC).[4] The second mechanism is negative selection, where T cells that recognize self-antigens with too high an affinity are removed through the process of apoptosis and are not allowed to enter the body's circulation. ## See also[edit] * Dog skin disorders ## References[edit] 1. ^ "Autoimmune Skin Disease in Dogs". vca_corporate. Retrieved 2019-11-09. 2. ^ "Immune system", Wikipedia, 2019-10-30, retrieved 2019-11-09 3. ^ a b Auto-immune Diseases 4. ^ a b c Papadogiannakis EI. 2005. Contemporary aspects of the immunopathogenesis of autoimmune diseases of the epidermal basement membrane in the dog. The Journal of the Hellenic Veterinary Medical Society 56(1) p 27-31. 5. ^ "Structure of the Skin in Dogs - Dog Owners". Merck Veterinary Manual. Retrieved 2019-11-09. 6. ^ a b c d e Immune-mediated Skin Diseases. Rimini: 50th Congresso Nazionale Multisala SCIVAC [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Autoimmune skin diseases in dogs	None	30,321	wikipedia	https://en.wikipedia.org/wiki/Autoimmune_skin_diseases_in_dogs	2021-01-18T19:06:26	{"wikidata": ["Q85744316"]}
Hereditary spherocytosis is a condition characterized by hemolytic anemia (when red blood cells are destroyed earlier than normal). Signs and symptoms can range from mild to severe and may include pale skin, fatigue, anemia, jaundice, gallstones, and/or enlargement of the spleen. Other symptoms of hemolytic anemia may include feeling that your heart is pounding or racing (palpitations), feeling dizzy, problems concentrating, and headaches. Some people with a severe form of hereditary spherocytosis may have short stature, delayed puberty, and skeletal abnormalities. The condition is caused by mutations in any of several genes, such as the ANK1, EPB42, SLC4A1, SPTA1, and SPTB genes. It is most commonly inherited in an autosomal dominant manner, but may be inherited in an autosomal recessive manner. There are different types of hereditary spherocytosis, which are distinguished by severity and genetic cause. Depending on severity, treatment may involve splenectomy, red cell transfusions, folic acid supplementation, and/or cholecystectomy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hereditary spherocytosis	c0221409	30,322	gard	https://rarediseases.info.nih.gov/diseases/6639/hereditary-spherocytosis	2021-01-18T18:00:01	{"mesh": ["C536356"], "omim": ["182900"], "orphanet": ["822"], "synonyms": ["Congenital spherocytic hemolytic anemia", "Congenital spherocytosis", "Spherocytic anemia"]}
A number sign (#) is used with this entry because nephrotic syndrome type 7 (NPHS7) and susceptibility to atypical hemolytic uremic syndrome-7 (AHUS7) are caused by homozygous or compound heterozygous mutation in the DGKE gene (601440) on chromosome 17q22. Description Nephrotic syndrome type 7 is an autosomal recessive renal disease characterized by onset of nephrotic syndrome with proteinuria usually in the first decade of life. The disorder is progressive, and some patients develop end-stage renal disease within several years. Renal biopsy typically shows membranoproliferative glomerulonephritis. Some patients may benefit from immunosuppressive therapy (summary by Ozaltin et al., 2013). Atypical hemolytic uremic syndrome-7 is characterized by acute onset in the first year of life of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. After the acute episode, most patients develop chronic renal insufficiency. Unlike other genetic forms of aHUS, AHUS7 is not related to abnormal activation of the complement system (summary by Lemaire et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300). For a general phenotypic description and a discussion of genetic heterogeneity of aHUS, see AHUS1 (235400). Clinical Features Ozaltin et al. (2013) reported 9 patients from 3 unrelated consanguineous families with onset of progressive clinical nephrotic syndrome in early childhood. Renal biopsy in all cases showed glomerular injury with membranoproliferative glomerulonephritis (MPGN). Most had onset in the first 5 years of life, although 2 sibs in 1 family presented at ages 8 and 17 years. At onset, all had proteinuria and most had low serum albumin. In 1 family, the proband presented with nephrotic syndrome and renal insufficiency at age 2 years and died of meningitis a year later. His brother was the most severely affected patient: he developed end-stage renal failure at age 8 years and underwent renal transplant at age 20. Another affected sib developed end-stage renal disease at age 19 years, and the fourth had no end-stage renal disease at age 30. Treatment with immunosuppressive agents failed to induce remission in the patients in this family. Two sibs from a second family showed the mildest phenotype. The sisters developed nephrotic syndrome at ages 8 and 17 years. One developed end-stage renal failure at age 23 despite immunosuppressive treatment, whereas the other responded to immunosuppressive treatment and ACE inhibitors and did not have renal failure at age 19. In the third family, 3 sibs, including a pair of twins, presented with nephrotic syndrome at age 1.5 years, but none developed end-stage renal failure by ages 2 or 12 years. These 3 patients showed partial remission in response to immunosuppressive treatment. Renal biopsies in all patients were consistent with MPGN based on the findings of hypertrophic and hypercellular glomeruli, thickening of the basement membrane with focal capillary obliteration, endothelial cell swelling, splitting of the basement membrane, effacement of podocyte foot processes, and subendothelial deposits. There was some deposition of IgM and IgG, but no C3 (120700) deposition. Renal biopsy in the patient who presented at age 17 years showed some evidence of focal and segmental glomerulosclerosis (FSGS), a nonspecific finding in advanced glomerulopathy. Serum complement components C3 and C4 (see 120810) were normal in all individuals; serum CFH (134370) was not measured. Lemaire et al. (2013) reported 13 patients from 9 unrelated families with onset of atypical hemolytic uremic syndrome within the first year of life. The infants presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal biopsies showed chronic thrombotic microangiopathy with glomerular hypercellularity, split basement membranes, and endothelial cell swelling without electron-dense deposits. Capillary lumens were narrowed, and there was evidence of effaced podocytes. The clinical course was characterized by relapsing episodes of aHUS before age 5 years. None of the patients had abnormalities of the complement system, and 2 patients treated with anticomplement therapy had relapses while on treatment. During follow-up, most patients developed chronic hypertension, microhematuria, and proteinuria, and 3 developed full nephrotic syndrome. Three patients received kidney transplant, none of whom had recurrence of aHUS. Twenty-two percent of sibs of index cases had aHUS, consistent with recessive transmission and high penetrance. Inheritance The transmission pattern of NPHS7 in the families reported by Ozaltin et al. (2013) was consistent with autosomal recessive inheritance. The transmission pattern of AHUS7 in the families reported by Lemaire et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics By homozygosity mapping combined with whole-exome analysis of a consanguineous family with early-onset nephrotic syndrome and MPGN, Ozaltin et al. (2013) identified a homozygous truncating mutation in the DGKE gene (Q43X; 601440.0001). Sequencing of this gene in 142 unrelated patients with a similar disorder identified 2 more consanguineous families with different homozygous truncating mutations (601440.0002 and 601440.0003). DGKE metabolizes and decreases intracellular DAG levels, thus contributing to the regulation of DAG levels. TRPC6 (603652) is a calcium-permeable cation channel expressed in the foot processes of podocytes and is known to be directly activated by DAG. In vitro functional expression studies in HEK293 cells showed that the DGKE mutants did not cause a decrease in TRPC6 current, as was observed with wildtype DGKE, consistent with a loss of DGKE function. The findings indicated that DGKE controls the intracellular concentration of DAG, which is a component of the phosphatidylinositol cycle that participates in multiple cellular functions and in lipid-mediated intracellular signaling. Perturbation of this pathway in podocytes may underlie the disorder. In 13 patients from 9 families with early-onset atypical hemolytic-uremic syndrome, Lemaire et al. (2013) identified homozygous or compound heterozygous mutations in the DGKE gene (see, e.g., 601440.0004-601440.0008). The first mutations in 4 patients from 2 families were found by exome sequencing. Sequencing the DGKE gene in 47 additional unrelated probands with pediatric-onset aHUS and 36 adult-onset aHUS probands, in whom there was no mutation in known aHUS-associated genes or CFH antibodies, identified 6 additional pediatric index cases carrying rare homozygous or compound heterozygous DGKE variants. Another family with 3 affected individuals was identified independently. The mutations included 3 premature termination codons, 2 frameshift mutations, 1 splice site mutation, and 2 missense mutations that altered conserved residues. DGKE was a frequent cause of aHUS in the first year of life (13 (27%) of 49 cases with aHUS) and accounted for 50% of familial disease in this age group (3 of 6 kindreds). This uniformly early age of onset defined a distinct subgroup of aHUS. Renal biopsy of 1 patient showed no DGKE expression, suggesting that loss of DGKE function is the underlying mechanism. Lemaire et al. (2013) noted that DGKE phosphorylates and inactivates arachidonic acid-containing diacylglycerol (AA-DAG) to the corresponding phosphatidic acid. AA-DAG is the major signaling molecule that activates protein kinase C (PKC). PKC, in turn, increases the production of various prothrombotic factors in endothelial cells. Thus, loss of DGKE may result in sustained AA-DAG signaling, causing a prothrombotic state. In addition, DAGs modify slit diaphragm function in podocytes, a disturbance of which is consistent with renal-specific effects. The findings were important because this was the first genetic cause of aHUS not related to defects in genes encoding proteins in the complement cascade pathway. INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Hemolytic uremic syndrome (in some patients) \- Acute renal failure \- Nephrotic syndrome \- Proteinuria \- Membranoproliferative glomerulonephritis seen on biopsy \- Thickening of the glomerular basement membrane \- Splitting of the basement membrane \- Focal capillary obliteration \- Mesangial cell proliferation \- Effacement of podocyte foot processes \- Patchy deposition of IgG and IgM \- Subendothelial deposits \- Swelling of endothelial cells \- Chronic thrombotic microangiopathy \- End-stage renal failure (in some patients) HEMATOLOGY \- Hemolytic anemia (in some patients) \- Thrombocytopenia (in some patients) LABORATORY ABNORMALITIES \- Low serum albumin \- Normal serum complement levels MISCELLANEOUS \- Onset usually in the first decade (range 0.8 to 5 years) \- Atypical hemolytic-uremic syndrome shows onset in first 12 months \- Progressive disorder \- Some patients may show response to immunosuppressive agents \- Some patients do not reach end-stage renal failure MOLECULAR BASIS \- Caused by mutation in the diacylglycerol kinase, epsilon, 64-kD gene (DGKE, 601440.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	NEPHROTIC SYNDROME, TYPE 7	c0268742	30,323	omim	https://www.omim.org/entry/615008	2019-09-22T15:53:28	{"doid": ["0080388"], "mesh": ["D015432"], "omim": ["615008"], "orphanet": ["357008", "329903", "54370", "2134", "544472"], "synonyms": ["D-HUS with DGKE deficiency", "NEPHROTIC SYNDROME, TYPE 7, WITH MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS", "aHUS with DGKE deficiency", "Alternative titles", "Atypical HUS with DGKE deficiency", "Hemolytic-uremic syndrome without diarrhea with DGKE deficiency"], "genereviews": ["NBK1425"]}
Purging disorder is an eating disorder characterized by the DSM-5 as self-induced vomiting, misuse of laxatives, diuretics, or enemas to forcefully evacuate matter from the body.[1] Purging disorder differs from bulimia nervosa (BN) because individuals with purging disorder are not underweight and do not consume a large amount of food before they purge.[2] In current diagnostic systems, purging disorder is a form of other specified feeding or eating disorder. Research indicates that purging disorder, while not rare, is not as commonly found as anorexia nervosa or bulimia nervosa.[3] This syndrome is associated with clinically significant levels of distress, and that it appears to be distinct from bulimia nervosa on measures of hunger and ability to control food intake. Some of the signs of purging disorder are frequent trips to the bathroom directly after a meal, frequent use of laxatives, and obsession over one's appearance and weight. Other signs include swollen cheeks, popped blood vessels in the eyes, and clear teeth which are all signs of excessive vomiting.[4][5] Purging disorder is studied far less often than anorexia nervosa and bulimia nervosa as it is not considered an independent diagnosis in the DSM-5, published in 2013.[3] However, it has been argued that purging disorder should be considered a distinct eating disorder, separate from bulimia nervosa.[6][7][8][9] Because of this, little information is known about the risk factors for purging disorder, including how gender, race, and class could contribute to the risk for purging disorder. As with most eating disorders, it is suggested that purging disorder is gender specific because of cultural forces and social pressures. These social pressures are associated with a severe preoccupation with shape and weight, this puts women and transgender individuals at the most risk for eating disorders, including purging disorder.[3] In one study of the risk factors for purging disorder 77% of the participants who presented with symptoms of purging disorder were female.[10] Purging disorder progressing into bulimia nervosa has been observed, while it is extremely rare for the reverse situation, bulimia nervosa progressing into purging disorder. This was observed once in a transgender patient with a severe history of bulimia nervosa but presented with symptoms of purging disorder to an eating disorder treatment facility in New Zealand.[3] Estimates of lifetime prevalence of purging disorder have been estimated from 1.1% to 5.3%.[11] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Risk Factors * 2.2 Genetic * 3 Diagnosis * 3.1 Complications * 4 Treatment * 5 Prognosis * 6 References * 7 External links ## Signs and symptoms[edit] * Recurrent purging to influence body weight or shape[6] * Absence of binging episiode(s)[6] * Purge behaviors occur at least once per week for at least 3 months[6] * Undue influence of body shape and weight[6] * Russell's sign[12] ## Causes[edit] ### Risk Factors[edit] * Dieting[13] * Thin-ideal internalization[13] * Body dissatisfaction[13] ### Genetic[edit] The heritability of some eating disorders has been well established,[14] but to date there are no documented family studies of purging disorder to understand the familial nature of purging disorder.[15] ## Diagnosis[edit] The DSM-5 is used as a reference to diagnose Purging Disorder. A patient with Purging disorder will be diagnosed with other specified feeding or eating disorder.[11] ### Complications[edit] Purging behaviors, specifically self-induced vomiting and laxative use are associated with the following medical complications: * Subconjunctival hemorrhages (small bleeds in the eyes)[12] * Cuts or scars on the top of the hands (Russell's sign)[12] * Dental abnormalities such as enamel erosion[12] * Swelling of the parotid gland[12] * Mild esophagitis, heartburn, or acid reflux[12] * Renal (kidneys) inflammation[12] ## Treatment[edit] Treatment for purging disorder can be multidisciplinary. One approach to treatment is cognitive behavioral therapy.[16] ## Prognosis[edit] Children and teenagers with purging disorder have been found to have poorer health-related quality of life than their healthy peers.[17] A small review of 11 cases of purging disorder where death occurred found that only 5 of the 11 deaths could be contributed to the purging disorder.[16] The remaining 6 deaths were a result of suicide.[16] ## References[edit] 1. ^ Diagnostic and statistical manual of mental disorders : DSM-5. Internet Archive. Arlington, VA : American Psychiatric Association. 2013. ISBN 978-0-89042-554-1.CS1 maint: others (link) 2. ^ Keel, Pamela K. (2019). "Purging disorder: recent advances and future challenges". Current Opinion in Psychiatry. 32 (6): 518–524. doi:10.1097/YCO.0000000000000541. ISSN 0951-7367. PMC 6768735. PMID 31306252. 3. ^ a b c d Surgenor, Lois J.; Fear, Jennifer L. (December 1998). "Eating disorder in a transgendered patient: A case report". International Journal of Eating Disorders. 24 (4): 449–452. doi:10.1002/(sici)1098-108x(199812)24:4<449::aid-eat14>3.0.co;2-w. PMID 9813772. ProQuest 211126302. 4. ^ Carcieri, Elisha (2019). "Purging Disorder". Mirror-Mirror. 5. ^ "Little-known purging disorder is often missed". NBC News. Associated Press. 19 September 2007. 6. ^ a b c d e Castillo, Marigold; Weiselberg, Eric (2017-04-01). "Bulimia Nervosa/Purging Disorder". Current Problems in Pediatric and Adolescent Health Care. 47 (4): 85–94. doi:10.1016/j.cppeds.2017.02.004. ISSN 1538-5442. 7. ^ Keel, Pamela K.; Striegel-Moore, Ruth H. (2009). Walsh, B. Timothy (ed.). "The validity and clinical utility of purging disorder". International Journal of Eating Disorders. 42 (8): 706–719. doi:10.1002/eat.20718. 8. ^ Keel, Pamela K. (2007). "Purging disorder: subthreshold variant or full-threshold eating disorder?". The International Journal of Eating Disorders. 40 Suppl: S89–94. doi:10.1002/eat.20453. ISSN 0276-3478. PMID 17868124. 9. ^ Koch, Sonja; Quadflieg, Norbert; Rief, Winfried; Fichter, Manfred (2013). "[Purging disorder--a distinct diagnosis? Review about the current state of research]". Psychotherapie, Psychosomatik, Medizinische Psychologie (in German). 63 (8): 305–317. doi:10.1055/s-0032-1331212. ISSN 1439-1058. PMID 23382033. 10. ^ Allen, Karina L.; Byrne, Susan M.; Crosby, Ross D. (19 September 2014). "Distinguishing Between Risk Factors for Bulimia Nervosa, Binge Eating Disorder, and Purging Disorder". Journal of Youth and Adolescence. 44 (8): 1580–1591. doi:10.1007/s10964-014-0186-8. PMID 25233874. S2CID 28204545. 11. ^ a b Smith, Kathryn E.; Crowther, Janis H.; Lavender, Jason M. (2018). "A review of purging disorder through meta-analysis". Journal of Abnormal Psychology. 126 (5): 565–592. doi:10.1037/abn0000243. ISSN 1939-1846. PMC 5741973. PMID 28691846. 12. ^ a b c d e f g Forney, K. Jean; Buchman-Schmitt, Jennifer M.; Keel, Pamela K.; Frank, Guido K. W. (2016). "The medical complications associated with purging". The International Journal of Eating Disorders. 49 (3): 249–259. doi:10.1002/eat.22504. ISSN 1098-108X. PMC 4803618. PMID 26876429. 13. ^ a b c Stice, Eric (2016). "Interactive and Mediational Etiologic Models of Eating Disorder Onset: Evidence from Prospective Studies". Annual Review of Clinical Psychology. 12: 359–381. doi:10.1146/annurev-clinpsy-021815-093317. ISSN 1548-5951. PMID 26651521. 14. ^ Rikani, Azadeh A.; Choudhry, Zia; Choudhry, Adnan M.; Ikram, Huma; Asghar, Muhammad W.; Kajal, Dilkash; Waheed, Abdul; Mobassarah, Nusrat J. (2013). "A critique of the literature on etiology of eating disorders". Annals of Neurosciences. 20 (4): 157–161. doi:10.5214/ans.0972.7531.200409. ISSN 0972-7531. PMC 4117136. PMID 25206042. 15. ^ Thornton, Laura M.; Mazzeo, Suzanne E.; Bulik, Cynthia M. (2011). "The Heritability of Eating Disorders: Methods and Current Findings". Current topics in behavioral neurosciences. 6: 141–156. doi:10.1007/7854_2010_91. ISSN 1866-3370. PMC 3599773. PMID 21243474. 16. ^ a b c Koch, Sonja; Quadflieg, Norbert; Fichter, Manfred (2014-03-01). "Purging disorder: a pathway to death? A review of 11 cases". Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 19 (1): 21–29. doi:10.1007/s40519-013-0082-3. ISSN 1590-1262. 17. ^ Wu, Xiu Yun; Yin, Wen Qiang; Sun, Hong Wei; Yang, Shu Xiang; Li, Xin Yang; Liu, Hong Qing (2019). "The association between disordered eating and health-related quality of life among children and adolescents: A systematic review of population-based studies". PLOS One. 14 (10): e0222777. doi:10.1371/journal.pone.0222777. ISSN 1932-6203. PMC 6777752. PMID 31584956. ## External links[edit] * Defining Purging Disorder in Practice * "Professor Identifies New Eating Disorder - Purging Disorder". MedicalNewsToday. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Purging disorder	None	30,324	wikipedia	https://en.wikipedia.org/wiki/Purging_disorder	2021-01-18T19:04:55	{"wikidata": ["Q7261223"]}
A number sign (#) is used with this entry because Niemann-Pick disease type C2 (NPC2) is caused by homozygous mutation in the NPC2 gene (601015) on chromosome 14q24. Description Niemann-Pick type C (NPC) disease is an autosomal recessive lipid storage disorder characterized by progressive neurodegeneration. Approximately 95% of cases are caused by mutations in the NPC1 gene (607623), referred to as type C1 (257220); 5% are caused by mutations in the NPC2 gene (601015), referred to as type C2. The clinical manifestations of types C1 (257220) and C2 are similar because the respective genes are both involved in egress of lipids, particularly cholesterol, from late endosomes or lysosomes (summary by Vance, 2006). Clinical Features Vanier et al. (1996) reported 5 patients with NPC2. Three patients presented with a 'new' rare phenotype associated with severe pulmonary involvement leading to death within the first year of life. A fourth case in that group had typical neurovisceral disease with infantile neurologic onset and rapid course; the fifth case and her affected sister had a typical juvenile form of the disease. There was no common ethnic origin for the group 2 cases. Two were North African, whereas the other 3 were Italian, French, and German. Tissue lipid storage pattern, intralysosomal cholesterol storage, and abnormalities in cholesterol homeostasis were similar to NPC1. Millat et al. (2001) reported the first comprehensive study of 8 unrelated families with NPC2, originating from France, Algeria, Italy, Germany, the Czech Republic, and Turkey. These cases represented essentially all patients with NPC2 who had been reported, as well as those known to the authors. Seven families demonstrated severe and rapid disease course, with age at death being 6 months to 4 years. A remarkable feature was the pronounced lung involvement, leading, in 6 patients, to early death caused by respiratory failure. Two patients also developed a severe neurologic disease with onset during infancy. Klunemann et al. (2002) reported 2 sisters with a novel phenotypic variant of NPC2, confirmed by molecular analysis. Both sisters presented in their early forties with vertical supranuclear gaze paresis, dysarthria, and cognitive decline characterized by expressive aphasia, perseverative behavior, and impaired conceptualization and planning. The proband developed ataxia and athetoid movements, and her sister developed facial dyskinesias and bradykinesia. Cholesterol esterification of cultured fibroblasts from 1 patient was abnormally low at 26% of normal. Detailed histories revealed that both patients exhibited early cognitive symptoms in adolescence. Postmortem examination of the proband revealed frontal lobe atrophy and neuronal lysosomes with oligolamellar inclusions typical for NPC, but no visceromegaly. Diagnosis ### Prenatal diagnosis Millat et al. (2001) performed prenatal diagnosis by mutation analysis of an uncultured chorionic villus sample. Heterogeneity ### Genetic Heterogeneity From complementation studies, Steinberg et al. (1994) found evidence of genetic heterogeneity in Niemann-Pick disease type C. In a study of 12 patients representing a wide clinical spectrum, one was found to differ from the others and to represent a minor complementation group which they referred to as group beta. Vanier et al. (1996) used somatic cell hybridization to demonstrate 2 categories of patients. The major complementation group (NPC1) comprised 27 unrelated patients and the second minor group (termed NPC2) comprised 5 patients. Linkage analysis in 1 multiplex family belonging to the minor complementation group showed that the mutated gene did not map to the NPC1 locus at 18q11-q12. One of the 5 families in group 2 studied by Vanier et al. (1996) was the family studied by Steinberg et al. (1994) and was found to fall into a separate group. Molecular Genetics In 2 patients with NPC2, Naureckiene et al. (2000) identified homozygous mutations in the HE1 (NPC2) gene (601015.0001-601015.0002). In 6 unrelated patients with NPC2, Verot et al. (2007) identified 5 different mutations in the NPC2 gene (see, e.g., 601015.0008-601015.0010). The authors stated that a total of 15 disease-causing mutations had been identified in 22 unrelated families to date. E20X (601015.0001) was the most common mutation, accounting for 34% of mutant alleles. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Vertical supranuclear gaze palsy RESPIRATORY Lung \- Pulmonary involvement, severe \- Respiratory failure ABDOMEN Liver \- Hepatomegaly \- Neonatal jaundice Spleen \- Splenomegaly Gastrointestinal \- Dysphagia NEUROLOGIC Central Nervous System \- Hypotonia \- Developmental delay \- Dysarthria \- Loss of speech \- Mental deterioration \- Dementia \- Spasticity \- Dystonia \- Seizures \- Cerebellar ataxia \- Cataplexy \- Neurofibrillary tangles Behavioral Psychiatric Manifestations \- Poor school performance \- Behavioral problems \- Perseverative behavior \- Psychosis HEMATOLOGY \- Foam cells on bone marrow biopsy \- 'Sea-blue' histiocytes PRENATAL MANIFESTATIONS \- Fetal ascites LABORATORY ABNORMALITIES \- Normal or mildly reduced sphingomyelinase activity \- Low cholesterol esterification rates \- Abnormal cholesterol homeostasis \- Foam cells in visceral organs and CNS \- Foam cells contain polymorphic cytoplasmic inclusions consisting of lamellar osmiophilic membranes on electron microscopy MISCELLANEOUS \- Highly variable phenotype and age of onset \- Neurologic involvement may occur in the absence of visceral involvement \- Early death from respiratory failure may occur \- Genetic heterogeneity (see NPC1, 257220 ) MOLECULAR BASIS \- Caused by mutation in the epididymal secretory protein HE1 gene (NPC1, 601015.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	NIEMANN-PICK DISEASE, TYPE C2	c0220756	30,325	omim	https://www.omim.org/entry/607625	2019-09-22T16:08:58	{"doid": ["0070114"], "mesh": ["D052556"], "omim": ["607625"], "orphanet": ["646"], "genereviews": ["NBK1296"]}
A number sign (#) is used with this entry because ataxia-telangiectasia (AT) is caused by homozygous or compound heterozygous mutation in the ATM gene (607585) on chromosome 11q22. Description Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to killing by ionizing radiation (IR), and abnormally resistant to inhibition of DNA synthesis by ionizing radiation. The latter trait has been used to identify complementation groups for the classic form of the disease (Jaspers et al., 1988). At least 4 of these (A, C, D, and E) map to chromosome 11q23 (Sanal et al., 1990) and are associated with mutations in the ATM gene. Clinical Features ### Homozygotes Patients present in early childhood with progressive cerebellar ataxia and later develop conjunctival telangiectases, other progressive neurologic degeneration, sinopulmonary infection, and malignancies. Telangiectases typically develop between 3 and 5 years of age. The earlier ataxia can be misdiagnosed as ataxic cerebral palsy before the appearance of oculocutaneous telangiectases. Gatti et al. (1991) contended that oculocutaneous telangiectases eventually occur in all patients, while Maserati et al. (1988) wrote that patients without telangiectases are not uncommon. A characteristic oculomotor apraxia, i.e., difficulty in the initiation of voluntary eye movements, frequently precedes the development of telangiectases. Gonadal dysfunction in ataxia-telangiectasia was discussed by Miller and Chatten (1967), Zadik et al. (1978), and others. Thibaut et al. (1994) reviewed cases of necrobiosis lipoidica in association with ataxia-telangiectasia. According to Boder (1985), the oldest known AT patients were a man who died in November 1978 at age 52 years and his sister who died in July 1979 at the age of almost 49 years. The sister was the subject of the report by Saxon et al. (1979) on T-cell leukemia in AT. The possibility of heteroalleles at the ataxia-telangiectasia loci might be suggested. ### Neurologic Manifestations AT may be the most common syndromic progressive cerebellar ataxia of early childhood. Truncal ataxia precedes appendicular ataxia. Oculomotor apraxia is progressive and opticokinetic nystagmus is absent. Choreoathetosis and/or dystonia occur in 90% of patients and can be severe. Deep tendon reflexes become diminished or absent by age 8 and patients later develop diminished large-fiber sensation. Gatti et al. (1991) pointed out that 'a significant proportion of older patients in their twenties and early thirties develop progressive spinal muscular atrophy, affecting mostly hands and feet, and dystonia.' Interosseous muscular atrophy in the hands in combination with the early-onset dystonic posturing leads to striking combined flexion-extension contractures of the fingers, which they illustrated. Mental retardation is not a feature of AT, although some older patients have a severe loss of short-term memory. Neurologic dysfunction is a clinically invariable feature in homozygotes. Woods and Taylor (1992) studied 70 affected persons in the British Isles, 29 females and 41 males with an age range of 2 to 42 years. Most presented by 3 years of age with truncal ataxia. All had ataxia, ocular motor apraxia, an impassive face, and dysarthria, although clinical immune deficiency was present only in 43 of 70 patients. Ocular telangiectases was seen in all but one. All 60 tested showed increased sensitivity to ionizing radiation, 43 of 48 had an elevated alpha-fetoprotein level, and 14 of 21 had an immunoglobulin deficiency. ### Malignancy Patients with AT have a strong predisposition to malignancy. Hecht et al. (1966) observed lymphocytic leukemia in patients with AT. A nonleukemic sib and 2 unrelated patients with AT had multiple chromosomal breaks and impaired responsiveness to phytohemagglutinin. This was the first report of chromosomal breakage in AT. Leukemia and chromosomal abnormalities occur in at least 2 other mendelian disorders--Fanconi pancytopenia (FA; 227650) and Bloom syndrome (BS; 210900). Saxon et al. (1979) demonstrated thymic origin of the neoplastic cells in a 48-year-old woman with AT and chronic lymphatic leukemia. The neoplastic cells had the specific 14q+ translocation and showed both helper and suppressor function, suggesting that the malignant transformation had occurred in an uncommitted T-lymphocyte precursor that was capable of differentiation. This is a situation comparable to chronic myeloid leukemia in which the Philadelphia chromosome occurs in a stem cell progenitor of both polymorphs and megakaryocytes. In general, lymphomas in AT patients tend to be of B-cell origin (B-CLL), whereas the leukemias tend to be of the T-CLL type. Rosen and Harris (1987) discussed the case of a 30-year-old man with AT who developed a malignant lymphoma of B-cell type involving the tonsil and lungs. Haerer et al. (1969) described a black sibship of 12, of whom 5 had ataxia-telangiectasia; 2 of those affected died of mucinous adenocarcinoma of the stomach at ages 21 and 19 years. Bigbee et al. (1989) demonstrated an increased frequency of somatic cell mutation in vivo in individuals with AT. Obligate heterozygotes for the disease did not appear to have a significantly increased frequency of such mutations. The authors speculated that the predisposition to somatic cell mutation may be related to the increased susceptibility to cancer in AT homozygotes. Other solid tumors, including medulloblastomas and gliomas, occur with increased frequency in AT (Gatti et al., 1991). ### Immune Disorders Defects of the immune mechanism and hypoplasia of the thymus have been demonstrated. Serum IgG2 or IgA levels are diminished or absent in 80% and 60% of patients, respectively (Gatti et al., 1991). IgE levels can be diminished, IgM levels diminished or normal. Peripheral lymphopenia as well as decreased cellular immunity to intradermally injected test antigens can be seen early in the disorder. Sinopulmonary infections are frequent, but their severity cannot be simply correlated with the degree of immunodeficiency. Carbonari et al. (1990) found that patients with AT have more circulating T cells bearing gamma/delta receptors characteristic of immature cells than alpha/beta receptors typical of mature cells. Normal ratios were found in the patients with other immune deficits, except for 1 child with a primary T-cell defect. Peterson and Funkhouser (1990) proposed that these findings are consistent with a defect in genetic recombination leading to the switch from gamma/delta to alpha/beta. There may also be a defect in DNA ligation or some other aspect of DNA repair. Elucidation of the molecular abnormalities of lymphocytes may demonstrate fundamental molecular mechanisms for cellular differentiation not only of lymphocytes but of other cell systems such as the nervous system. ### Variant Ataxia-Telangiectasia (Atypical) Ying and Decoteau (1981) described a family in which a brother and sister may have had an allelic (and milder) form of AT. The proband, a 58-year-old male of Saskatchewan Mennonite origin, had spinocerebellar degeneration associated with choreiform movements beginning at about age 10 years. Despite considerable physical handicap, he was able to work as a delivery man in the family store. No telangiectases were found at age 44 (they were carefully sought because of typical AT in a niece) or on later examinations. He showed total absence of IgA in serum and concentrated saliva and low IgE in serum. He was anergic on skin testing. Glucose tolerance was markedly decreased. Serum alpha-fetoprotein was 840 ng per ml (normal, less than 10 ng per ml). Lymphocyte response to phytohemagglutinin was blunted. He died of lymphoma at age 58. He showed cytogenetic abnormalities typical of AT; 4 abnormal clones were identified, all involving chromosome 14 in some way. The proband had 4 brothers and 2 sisters. A brother died of leukemia at age 16. A sister was likewise diagnosed as having spinocerebellar degeneration with choreiform movements at age 46; she died at age 55 of breast cancer. The proband's niece with typical AT had telangiectases of the bulbar conjunctivae and earlobes noted at age 3, when she began to have recurrent and severe sinopulmonary infections. She died at age 20 of staphylococcal pneumonia superimposed on bronchiectasis. The brother and sister who died in their 50s may have been genetic compounds. Their parents denied consanguinity. Taylor et al. (1987) described 3 patients who were atypical in terms of clinical features and cellular features as observed in vitro. One of the patients was a 45-year-old woman with onset of neurologic manifestations in her early twenties. Maserati et al. (1988) described 2 sisters, aged 9 and 11 years, with a progressive neurologic disorder similar to AT, chromosome instability with rearrangements involving chromosomes 7 and 14, but no telangiectases or immunologic anomalies typical of AT. Byrne et al. (1984) reported similar cases of ataxia without telangiectases with selective IgE deficiency but normal IgA and alpha-fetoprotein. Ziv et al. (1989) described 2 Turkish sibs with an atypically prolonged course and atypical behavior of cultured fibroblasts. See 208910 and 208920 for AT-like syndromes. Rare cases of AT patients with milder manifestations of the clinical or cellular characteristics of the disease have been reported and have been designated 'AT variants.' Gilad et al. (1998) quantified ATM protein levels in 6 patients with an AT variant and searched their ATM genes for mutations. Cell lines from these patients exhibited considerable variability in radiosensitivity while showing the typical radioresistant DNA synthesis of AT cells. Unlike classic AT patients, however, these patients exhibited 1 to 17% of the normal level of ATM. The underlying genotypes were either homozygous for mutations expected to produce mild phenotypes or compound heterozygous for a mild and a severe mutation. In an attempt to determine whether the AT(Fresno) variation correlated with ATM mutations and levels of ATM protein expression, Gilad et al. (1998) searched for ATM mutations in a cell line derived from one of the sisters studied by Curry et al. (1989). This cell line was found to be devoid of the ATM protein and homozygous for a severe ATM mutation. Gilad et al. (1998) concluded that certain AT variant phenotypes, including some of those without telangiectasia, represent ATM mutations. Saviozzi et al. (2002) noted that milder cases of AT, termed 'AT variants,' comprise a heterogeneous group characterized by later onset of clinical symptoms, slower progression, extended life span compared to most AT patients, and decreased levels of chromosomal instability and cellular radiosensitivity. In these patients, telangiectasia and/or immunodeficiency may be absent, while the neurologic features are present. The genotype of AT variants is most often compound heterozygous for a severe mutation together with a mild or leaky mutation, which expresses some ATM protein with residual function. In 2 sisters with variant AT with onset of ataxia at 27 years, polyneuropathy, choreoathetosis, and absence of telangiectasia, immunodeficiency, and cancer, Saviozzi et al. (2002) identified compound heterozygosity in the ATM gene for a missense (607585.0028) and a frameshift (607585.0029) mutation. Western blot analysis showed a low level of ATM protein with residual phosphorylation activity, which the authors suggested contributed to the milder phenotype. Hiel et al. (2006) reported 3 brothers and an unrelated woman with late-onset AT. All 4 were ambulatory and ranged in age from 37 to 43 years; unsteady gait developed approximately 10 years earlier. Cerebellar signs were mild, but all had striking distal muscular atrophy and weakness, decreased or absent ankle reflexes, and normal or borderline delayed motor conduction velocities with markedly decreased compound muscle action potentials. Muscle biopsies showed neurogenic changes. The patients had normal sensation and normal sensory studies. Other features included severe resting tremor, slight intention tremor, and mild dysarthria. ATM phosphorylation activity was only slightly decreased, suggesting that other factors were involved in damage to anterior horn neurons. Verhagen et al. (2009) provided a retrospective analysis of 13 adult patients with variant AT from 9 families and 6 unrelated patients with classic AT. All patients were from the Netherlands; 2 of the patients with variant AT had been reported by Hiel et al. (2006). All patients with classic AT were diagnosed in childhood, presented with ataxic gait, and were wheelchair-bound by age 11 years. Five of the 6 died between ages 21 and 27. Those with variant AT were only correctly diagnosed in adulthood, although 7 presented with slowly progressive chorea-athetosis from early childhood. Five with variant AT presented with resting tremor between age 12 to 34, and the remaining patient with variant AT presented with distal muscle weakness of the lower extremities at age 6. Five patients with variant AT became wheelchair-bound between ages 15 and 43, and 2 had died of malignancy at ages 51 and 23 years, respectively. All variant AT patients had dysarthria by adulthood, 9 had choreoathetosis, 8 had resting tremor, 7 had oculomotor apraxia, and 5 had nystagmus. Eight patients had normal cerebellum on MRI, whereas 4 had cerebellar atrophy. Only 7 of 13 had ocular telangiectasia, but all had increased serum alpha-fetoprotein. Six with variant AT had polyneuropathy. Four developed a malignancy, including ALL, pituitary tumor, and breast cancer. Only 1 had slightly decreased IgG levels. Chromosomal instability was found in 8 variant AT patients tested. Those with the mildest form of the disorder had residual ATM protein expression with kinase activity. Saunders-Pullman et al. (2012) reported 13 patients from 3 Canadian Mennonite families with variant AT due to a homozygous missense mutation in the ATM gene (A2067D; 607585.0033). The patients had onset of dystonia in the first 2 decades (range, 1-20 years). Dystonia mostly affected the neck, face, tongue, and limbs, and became generalized in 60% of patients. Dysarthria was very common. Additional features in some patients included myoclonus, facial choreiform movements, and irregular tremor. Some patients had clumsy gait, and although none had overt ataxia, 2 patients had ataxia in childhood that spontaneously resolved. None had prominent telangiectases. Postmortem examination showed mild loss of cerebellar Purkinje cells in 1 patient, but cerebellar atrophy was not a prominent finding in any of the patients. Cells from 2 mutation carriers showed increased radiosensitivity and only trace amounts of ATM protein. Heterozygous mutation carriers did not have dystonia. Family history revealed that 2 homozygous mutation carriers in 1 family had died of malignancy in adulthood. ### Cancer Risk in Heterozygotes Welshimer and Swift (1982) studied families of homozygotes for AT, Fanconi anemia (FA), and xeroderma pigmentosum (XP; see 278700) to test the hypothesis that heterozygotes may be predisposed to some of the same congenital malformations and developmental disabilities that are common among homozygotes. Among XP relatives, 11 of 1,100 had unexplained mental retardation, whereas only 3 of 1,439 relatives of FA and AT homozygotes showed mental retardation. Four XP relatives but no FA or AT relatives had microcephaly. Idiopathic scoliosis and vertebral anomalies occurred in excess in AT relatives, while genitourinary and distal limb malformations were found in FA families. Swift (1980) defended, from the viewpoint of not causing anxiety, the usefulness and safety of cancer risk counseling of heterozygotes for AT. Swift et al. (1987) examined the cancer risk of heterozygotes for AT in 128 families, including 4 of Amish ancestry, 110 white non-Amish families, and 14 black families. They measured documented cancer incidence rather than cancer mortality based solely on death certificates and compared the cancer incidence in adult blood relatives of probands directly with that in spouse controls. The incidence rates in AT relatives were significantly elevated over those in spouse controls. In persons heterozygous for AT, the relative risk of cancer was estimated to be 2.3 for men and 3.1 for women. Breast cancer in women was the cancer most clearly associated with heterozygosity for AT. Swift et al. (1987) estimated that 8 to 18% of patients with breast cancer in the U.S. white population would be heterozygous for AT. Pippard et al. (1988) reported an excess of breast cancer deaths in British mothers of AT patients (significant at the 5% level), but no excess mortality from malignant neoplasms in the grandparents. Morrell et al. (1990) reported cancer incidence measured retrospectively in 574 close blood relatives of AT patients and 213 spouse controls in 44 previously unreported families. For heterozygous carriers of the AT gene, the relative risk of cancer was estimated to be 6.1 as compared with non-heterozygotes. The most frequent cancer site in the blood relatives was the female breast, with 9 cancers observed. Gatti et al. (1991) provided a review in which they noted the possibly high frequency of breast cancer in AT heterozygotes. Swift et al. (1991) reported the results of a prospective study of 1,599 adult blood relatives of patients with AT and 821 of their spouses distributed in 161 families. Cancer rates were significantly higher among the blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the AT gene. The estimated risk of cancer of all types among heterozygotes as compared with noncarriers was 3.8 in men and 3.5 in women, and that for breast cancer in carrier women was 5.1. Among the blood relatives, women with breast cancer were more likely to have been exposed to selected sources of ionizing radiation than controls without cancer. Male and female blood relatives also had 3-fold and 2.6-fold excess mortality from all causes, respectively, from the ages of 20 through 59 years. Swift et al. (1991) suggested that diagnostic or occupational exposure to ionizing radiation increases the risk of breast cancer in women heterozygous for AT. The work of Swift et al. (1991) on the frequency of breast cancer in AT was critiqued by numerous authors, including Bridges and Arlett (1992). Since the genes responsible for most cases of AT are located on 11q, Wooster et al. (1993) typed 5 DNA markers in the AT region in 16 breast cancer families. They found no evidence for linkage between breast cancer and these markers and concluded that the contribution of AT to familial breast cancer is likely to be minimal. Athma et al. (1996) determined the AT gene carrier status of 776 blood relatives in 99 AT families by tracing the ATM gene in each family through tightly linked flanking DNA markers. There were 33 women with breast cancer who could be genotyped; 25 of these were AT heterozygotes, compared to an expected 14.9. For 21 breast cancers with onset before age 60, the odds ratio was 2.9 and for 12 cases with onset at age 60 or older, the odds ratio was 6.4. Thus, the breast cancer risk for AT heterozygous women is not limited to young women but appeared to be even higher at older ages. Athma et al. (1996) estimated that, of all breast cancers in the U.S., 6.6% may occur in women who are AT heterozygotes. This proportion is several times greater than the estimated proportion of carriers of BRCA1 mutations (113705) in breast cancer cases with onset at any age. The reported increased risk for breast cancer for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40 and 59 years (Easton, 1994). To test this hypothesis, FitzGerald et al. (1997) undertook a germline mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. They detected a heterozygous ATM mutation in 2 of 202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2 of 401 (0.5%) women with early onset of breast cancer (P = 0.6). FitzGerald et al. (1997) concluded that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer. The results of FitzGerald et al. (1997) are discrepant with those of Athma et al. (1996), who conducted a study 'from the other direction' by following identified AT mutations through the families of those with clinically recognized AT. Analysis of DNA markers flanking the AT gene allowed them to identify precisely which female relatives with breast cancer carried the AT mutation. On the basis of the genetic relationship between each case and the AT proband, the a priori probability that these 2 share the AT mutation was calculated. This led to an estimated relative risk of 3.8 as compared to noncarriers. This result was similar to that found by Easton (1994), who reanalyzed the previous studies of breast cancer risk in mothers (and other close relatives) of AT cases. Bishop and Hopper (1997) analyzed these 2 studies and suggested that they may not be discrepant. Indeed, they estimated that the study of FitzGerald et al. (1997) yielded an upper limit of the 95% confidence interval for the proportion of early onset breast cancer occurring in AT heterozygotes as 2.4% (assuming that their assay identified 75% of all mutations). In a family with multiple cancers, Bay et al. (1999) described heterozygosity for a mutant allele of ATM that caused skipping of exon 61 in the mRNA (607585.0020) and was associated with a previously undescribed polymorphism in intron 61. The mutation was inherited by 2 sisters, one of whom developed breast cancer at age 39 years and the second at age 44 years, from their mother, who developed kidney cancer at age 67 years. Studies of irradiated lymphocytes from both sisters revealed elevated numbers of chromatid breaks, typical of AT heterozygotes. In the breast tumor of the older sister, loss of heterozygosity (LOH) was found in the ATM region of 11q23.1, indicating that the normal ATM allele was lost in the breast tumor. LOH was not seen at the BRCA1 (113705) or BRCA2 (600185) loci. BRCA2 was considered an unlikely cancer-predisposing gene in this family because each sister inherited different chromosomes 13 from each parent. The findings suggested that haploinsufficiency at ATM may promote tumorigenesis, even though LOH at the ATM locus supported a more classic 2-hit tumor suppressor gene model. The finding that ATM heterozygotes have an increased relative risk for breast cancer had been supported by some studies but not confirmed by others. Broeks et al. (2000) analyzed germline mutations of the ATM gene in a group of Dutch patients with breast cancer using normal blood lymphocytes and the protein truncation test followed by genomic sequence analysis. A high percentage of ATM germline mutations was demonstrated among patients with sporadic breast cancer. The 82 patients included in this study had developed breast cancer before the age of 45 years and had survived 5 years or more (mean, 15 years), and in 33 (40%) of the patients a contralateral breast tumor had been diagnosed. Among these patients, 7 (8.5%) had germline mutations of the ATM gene, of which 5 were distinct. One splice site mutation, IVS10-6T-G (607585.0021), was detected 3 times in this series. Four heterozygous carriers had bilateral breast cancer. Broeks et al. (2000) concluded that ATM heterozygotes have an approximately 9-fold increased risk of developing a type of breast cancer characterized by frequent bilateral occurrence, early age at onset, and long-term survival. They suggested that the characteristics of this population of patients may explain why such a high frequency was found here and not in other series. Olsen et al. (2005) reported on an extended and enlarged follow-up study of cancer incidence in blood relatives of 75 patients with verified AT from 66 Nordic families. When 7 mothers of probands were excluded, no clear relationship was observed between the allocated mutation carrier probability of each family member and the extent of breast cancer risk. They concluded that the increased risk for female breast cancer seen in 66 Nordic AT families appeared to be restricted to women under the age of 55 years and was due mainly to a very high risk in the group of mothers. Olsen et al. (2005) concluded that the findings of breast cancer risk in mothers, but not in other likely mutation carriers, in this and other studies raised questions about the hypothesis of a simple causal relationship with ATM heterozygosity. Although the defining characteristic of recessive diseases is the absence of a phenotype in heterozygous carriers, Watts et al. (2002) suggested that expression profiling by microarray techniques might reveal subtle manifestations. Individual carriers of AT cannot be identified; as a group, however, carriers of a mutant AT allele have a phenotype that distinguishes them from normal control individuals: increased radiosensitivity and risk of cancer. Watts et al. (2002) showed that the phenotype was also detectable, in lymphoblastoid cells from AT carriers, as changes in expression level of many genes. The differences were manifested both in baseline expression levels and in response to ionizing radiation. The findings showed that carriers of the recessive disease may have an 'expression phenotype,' which suggested a new approach to the identification of carriers and enhanced understanding of their increased cancer risk. Renwick et al. (2006) screened individuals from 443 familial breast cancer pedigrees and 521 controls for ATM sequence variants and identified 12 mutations in affected individuals and 2 in controls (p = 0.0047). Their results demonstrated that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% CI = 1.57-3.78, p = 0.0003). Other Features Waldmann and McIntire (1972) showed raised alpha-fetoprotein in the blood of patients with AT. This, they felt, suggests immaturity of the liver and is consistent with the view that the primary defect is in tissue differentiation, specifically, a defect in the interaction necessary for differentiation of gut-associated organs such as the thymus and liver. Ishiguro et al. (1986) concluded that the elevated alpha-fetoprotein in patients with AT probably originates in the liver. On the circulating monocytes of AT patients, Bar et al. (1978) demonstrated an 80 to 85% decrease in insulin receptor affinity. This decrease was not observed in the cultured fibroblasts of AT patients or in the monocytes and fibroblasts of relatives of these patients. In addition, they found that whole plasma and immunoglobulin-enriched fractions of plasma from AT patients inhibited the normal binding of insulin to its receptors on cultured human lymphocytes and on human placental membranes. This suggested the presence of antireceptor immunoglobulins. AT and type B acanthosis nigricans have several features in common that suggest the possibility of similar causes for the insulin resistance each demonstrates. Shaham and Becker (1981) showed that the AT clastogenic (chromosome breaking) factor present in plasma of AT patients and in the culture medium of AT skin fibroblasts is a peptide with a molecular weight in the range of 500 to 1000. No clastogenic activity could be demonstrated in extracts of cultured AT fibroblasts. Mohamed et al. (1987) found marked reduction of topoisomerase II (126430) in some but not all AT cell lines. DNA topoisomerases I and II are enzymes that introduce transient single- and double-strand breaks into DNA and thus are capable of interconverting various DNA conformations. The isolation of mutants of the 2 enzymes in yeast and the increased levels of DNA topoisomerase II in cells undergoing DNA synthesis provide evidence for the role of these enzymes in DNA replication and in chromosome segregation and organization. Inheritance In a study of 47 families ascertained throughout the United Kingdom, Woods et al. (1990) found a low parental consanguinity rate; no parents were first cousins or more closely related, whereas 10% had been expected. Furthermore, the incidence of the disorder in 79 sibs of index cases was 1 in 7, rather than the expected 1 in 4. Diagnosis The presence of early-onset ataxia with oculocutaneous telangiectases permits diagnosis of AT. The clinical diagnosis of AT can be problematic before the appearance of telangiectases. Oculomotor apraxia is a useful aid to early clinical diagnosis. Early-onset cerebellar ataxia and oculomotor apraxia are also typical of X-linked Pelizaeus-Merzbacher disease (312080) and can be seen in Joubert syndrome (213300). These disorders can be distinguished by leukoencephalopathy in the former, and by profound cerebellar hypoplasia in the latter. See also 257550. Elevated levels of alpha-fetoprotein (126430) and carcinoembryonic antigen are the most useful readily available markers for confirmation of the diagnosis of AT (Gatti et al., 1991). Dysgammaglobulinemia, decreased cellular immune responses, and peripheral lymphopenia are supportive findings but are not invariable. Henderson et al. (1985) devised a rapid diagnostic method based on the hypersensitivity of AT lymphocytes to killing by gamma irradiation. Similar studies in fibroblasts require skin biopsy and a prolonged culture time. Llerena et al. (1989) concluded that in chorionic villus sampling, gamma radiation is a reliable way of discriminating between unaffected fetuses and those with AT. The reliability of this approach is in question, however. Painter and Young (1980) suggested that the radiosensitivity of AT cells may be caused by their failure to respond to DNA damage with a delay in DNA synthesis that could give time for repair to take place. Shiloh et al. (1989) presented evidence that the extent of chromatid damage induced in the G2 phase of the cell cycle by moderate dosage of x-rays is markedly higher in AT heterozygous cells than in normal controls. They used this as a test of heterozygosity. Rosin and Ochs (1986) applied the exfoliated cell micronucleus test to the question of in vivo chromosomal instability in AT. This test is performed on exfoliated cells from the oral cavity collected by swabbing the mucosa with a moistened tongue depressor and also on urinary bladder cells obtained by centrifugation of freshly voided urine specimens. Micronuclei in these cells result from fragmentation of chromosomes in the dividing cells from the epithelium, resulting in acentric fragments which are excluded from the main nucleus when the cell divides. These fragments form their own membrane and can be identified as extranuclear Feulgen-positive bodies in daughter cells which migrate up through the epithelium to be exfoliated. Rosin and Ochs (1986) found that AT homozygotes had a 5- to 14-fold increase in the frequency of exfoliated cell micronuclei. Heterozygotes could be reliably identified by this method (Rosin et al., 1989). Using X-radiation with 1 Gy on G2-phase lymphocytes from 7 AT patients, 13 obligate AT heterozygotes, and 14 normal controls, Tchirkov et al. (1997) found that both AT homozygotes and heterozygotes showed significantly increased levels of radiation-induced chromatid damage relative to that of normal controls. Clinical Management Patients with AT and their cultured cells are unusually sensitive to x-ray just as patients and cells with xeroderma pigmentosum are sensitive to ultraviolet. Treatment of malignancy with conventional dosages of radiation can be fatal to AT patients. Cytogenetics Oxford et al. (1975) found that chromosome 14 was often involved in rearrangements in AT and that band 14q12 was a highly specific exchange point. In addition to the changes in chromosome 14, a pericentric inversion of chromosome 7 is characteristic. McCaw et al. (1975) described t(14;14)(q11;q32) translocation in T-cell malignancies of patients with AT. T cells show a t(14;14)q12q32 rearrangement in about 10% of AT patients. Croce et al. (1985) assigned the alpha subunit of the T-cell antigen receptor (TCRA; see 186880) to the region of one of the common breakpoints in AT (14q11.2) and suggested that the oncogene TCL1 (186960) is located in the region of the other breakpoint (14q32.3). It is thought that the TCL1 gene may be activated by chromosome inversion or translocation, either of which results in juxtaposition of the TCL1 gene and the TCRA gene. In AT, circulating lymphocytes show characteristic rearrangements involving the site of the T-cell receptor gamma gene (7p15) (TCRG; see 186970), T-cell receptor beta genes (7q35) (TCRB; see 186930), T-cell receptor alpha genes (14q11), and immunoglobulin heavy chain genes (14q32) (IGHG1; 147100) (McFarlin et al., 1972; Ying and Decoteau, 1981). Aurias et al. (1986) described a possible 'new' type of chromosome rearrangement, namely, telomere-centromere translocation (tct) followed by double duplication. This type of rearrangement was found between chromosomes 7 and 14 in cases of AT. Gatti et al. (1985) and Aurias and Dutrillaux (1986) found that the sites of breaks in rearrangements (7p14, 7q35, 14q12, 14qter, 2p11, 2p12, and 22q11-q12) are those where members of the immunoglobulin superfamily are located: IGK, IGH, IGL, TCRA, TCRB, TCRG. The somatic gene rearrangement must precede expression of these genes. Kennaugh et al. (1986) studied a patient with an inversion of 14q which had been present for many years in T cells. It was found that the breakpoint in 14q32 lay outside the IgH locus and proximal to it. The constant region gene of the T-cell receptor alpha chain (TCRA) locus was translocated to the 14q32 position. Johnson et al. (1986) found that the 14q32 breakpoint in the 14/14 translocation found in T-CLL cells and in an AT patient occurred within the immunoglobulin gene cluster. The AT patient had the characteristic chromosome 14 tandem translocation in 100% of karyotyped T cells 10 years before her death from T-cell leukemia. (This was the same patient described earlier by Saxon et al. (1979).) Stern et al. (1988) used in situ chromosomal hybridization to map the TCRA gene in 3 different nonmalignant T-cell clones derived from patients with AT. The constant region was translocated in each clone; the variable region remained in its original position in 2 clones and was deleted in 1 which lost the derivative chromosome 14. Stern et al. (1988) mapped the 14q32.1 recurrent breakpoint of AT clones by in situ hybridization. They found that the breakpoint lay between D14S1 (107750) and PI (107400). In a t(14;14) clone they found an interstitial duplication including D14S1 and a part of the IGH locus. Studying the chromosomes by R-banding, Zhang et al. (1988) concluded that the distal breakpoint in the chromosome 14 inversion in an AT clone was different from that in the chromosome 14 inversion in a malignant T-cell line; specifically, in AT, the breakpoint was centromeric to both the immunoglobulin heavy chain locus and the D14S1 anonymous locus (107750). They suggested that this finding favors the existence of an unknown oncogene in band 14q32.1. Russo et al. (1989) presented evidence for a cluster of breakpoints in the 14q32.1 region, the site of the putative oncogene TCL1, in cases of ataxia-telangiectasia with chronic lymphocytic leukemia. The 14q32.1 breakpoint is at least 10,000 kb centromeric to the immunoglobulin heavy chain locus. In a cell line with a translocation t(14;14)(q11;q32) from an AT patient with T-cell chronic lymphocytic leukemia, Russo et al. (1989) showed that a J(alpha) sequence from the TCRA locus was involved. This was again the patient first reported by Saxon et al. (1979). Humphreys et al. (1989) found some rearrangements involving chromosomes 7 and 14 at the usual 4 sites associated with AT--7p14, 7q35, 14q12, and 14q32--all sites of T-cell receptor genes. Kojis et al. (1989) suggested that the very high frequency of lymphocyte-associated rearrangements (LARs) in peripheral blood chromosome preparations is a diagnostic criterion of the disease. They pointed out a striking difference in the types of rearrangements observed in lymphocytes and fibroblasts. LARs are not commonly observed in fibroblasts, despite the increased but random instability of chromosomes from these cells relative to lymphocytes. The region of location of the AT gene, 11q22-q23, is not involved in site-specific rearrangements in either lymphocytes or fibroblasts. Lipkowitz et al. (1990) showed that an abnormal V(D)J recombination, joining V segments of the T-cell receptor gamma gene (186970) with J segments of the T-cell receptor beta gene (186930), occurs in peripheral blood lymphocytes of AT patients at a frequency 50- to 100-fold higher than normal. This frequency is roughly the same as the increase in the risk for lymphoid malignancy in these individuals. There is also an increase in the frequency of the lymphocyte-specific cytogenetic abnormalities thought to be due to interlocus recombination in non-AT patients with non-Hodgkin lymphoma, further suggesting a relationship between these translocations and lymphoid malignancies. Agriculture workers occupationally exposed to pesticides used in the production and storage of grain have a high frequency of cytogenetic abnormalities in peripheral blood lymphocytes in a pattern reminiscent of those in AT patients. Furthermore, these agriculture workers have an increased risk of developing T- and D-lymphoid malignancies. Lipkowitz et al. (1992) used a PCR-based assay developed for the study of AT patients to demonstrate a 10- to 20-fold increased frequency of hybrid antigen-receptor genes in peripheral blood lymphocytes of agriculture workers with chemical exposure. Mapping By linkage to RFLP markers, Gatti et al. (1988) localized the AT gene to 11q22-q23. They had previously excluded 171 markers, comprising approximately 35% of the genome. The most promising marker in a large Amish pedigree was found to be THY1 (188230), which is located at 11q22.3; it showed linkage with maximum lod = 1.8 at theta = 0.00. When data from the other 4 informative group A AT families were added, the maximum lod score rose to 3.63 with no observed recombinants. The maximum lod score for all 31 families studied for linkage of AT to THY1 was 4.34 at theta = 0.10. The large Amish pedigree diagrammed in their Figure 1 is the kindred reported by McKusick and Cross (1966), Ginter and Tallapragada (1975), and Rary et al. (1975). By further mapping with a panel of 10 markers, Sanal et al. (1990) concluded that the AT locus is in band 11q23. The site of the AT1 gene (11q22-q23) is the same as or adjacent to the region occupied by the CD3 (186790), THY1, and NCAM (116930) genes, all of which are members of the immunoglobulin-gene superfamily and therefore may be subject to the same defect that afflicts the T-cell receptor and immunoglobulin molecules in AT. Concannon et al. (1990) excluded the AT1 gene from a region extending 15 cM to either side of ETS1 (164720), which maps to 11q24. According to Gatti (1990), the gene in families from complementation groups A, C, and D, representing approximately 97% of all families, has been mapped to 11q23. Thus, a single gene may exist with various intragenic defects permitting complementation. In studies of 35 consecutively obtained families in the British Isles, McConville et al. (1990) found support for linkage with THY1 at zero recombination. They found evidence suggesting a second AT locus on 11q, centromeric to the site previously postulated. With 3 exceptions, the families had not been assigned to complementation groups. The series of families included the only group E family described to date. They quoted Jaspers et al. (1988) as giving the proportion of group A, group C, and group D cases as approximately 56%, 28%, and 14%, respectively. By linkage studies in a Jewish-Moroccan family with AT of the group C type, Ziv et al. (1991) found that the disorder was linked to the same region (11q22-q23) as found in group A families. McConville et al. (1990) located the AT1 gene to a 5-cM region in 11q22-q23, flanked by NCAM and DRD2 (126450) on one side and STMY1 (185250) on the other. On the basis of an 18-point map of the 11q23 region of 11q, derived from linkage analysis of 40 CEPH families, Foroud et al. (1991) analyzed 111 AT families from Turkey, Israel, England, Italy, and the United States, localizing the gene to an 8-cM sex-averaged interval between the markers STMY1 and D11S132/NCAM. Ziv et al. (1992) obtained results from linkage study indicating that the ATA gene in 3 large Arab families was located in 11q23. However, in a Druze family unassigned to a specific complementation group, several recombinants between AT and the same markers were observed. Sobel et al. (1992) pointed to linkage evidence suggesting that there are 2 AT loci on 11q and that group D AT may be located distal to the site of groups A and C in the 11q23 region. In linkage studies of 14 Turkish families, 12 of which were consanguineous, Sanal et al. (1992) obtained results indicating that the most likely location for a single AT locus is within a 6-cM sex-averaged interval defined by STMY and the marker CJ77. However, it appeared that there are at least 2 distinct AT loci (ATA and ATD) at 11q22-q23, with perhaps a third locus, ATC, located very near the ATA gene. Hernandez et al. (1993) described a large inbred family in which 2 adult cousins had AT with a somewhat milder clinical course than usual. Since genetic linkage analysis did 'not provide any evidence that the gene for AT in this family is located at 11q22-23,' further locus heterogeneity was suggested. In 2 families clinically diagnosed with AT and previously reported by Hernandez et al. (1993) and Klein et al. (1996), respectively, Stewart et al. (1999) identified mutations in the MRE11A gene (600814). Consistent with the clinical outcome of these mutations, cells established from the affected individuals within the 2 families exhibited many of the features characteristic of both AT and Nijmegen breakage syndrome (251260), including chromosomal instability, increased sensitivity to ionizing radiation, defective induction of stress-activated signal transduction pathways, and radioresistant DNA synthesis. The authors designated the disorder ATLD, for AT-like disorder (604391). Because the MRE11A gene maps to 11q21 and the ATM gene maps to 11q23, Stewart et al. (1999) concluded that only a very detailed linkage analysis would separate ATLD from AT purely on the basis of genetic data. Assuming that the mutation rate is proportional to the length of the coding sequences of the 2 genes, they suggested that approximately 6% of AT cases might be expected to have MRE11A mutations. Gatti et al. (1993) reported prenatal genotyping in this disorder. They pointed out that although at least 5 complementation groups have been defined, linkage studies of more than 160 families from various parts of the world have failed to show linkage heterogeneity. All but 2 families were linked to a 6-cM (sex-averaged) region at 11q22.3 defined by the markers STMY1 and D11S385. A further analysis of 50 British families narrowed the localization to a 4-cM (sex-averaged) region defined by D11S611 and D11S535. The demonstrated complementation groups may represent different intragenic mutations or separate ataxia-telangiectasia genes clustered within the 11q22.3 region, neither of which would challenge the validity of linkage or haplotyping studies. A possible reinterpretation of the complementation data is that the radiosensitivity of AT fibroblasts can be complemented by many genes besides the AT gene or genes. Gatti et al. (1993) used the flanking markers to show that the haplotypes in a fetus were identical to those in a previously born affected child. The parents chose to continue the pregnancy. Heterogeneity ### Complementation Groups On the basis of complementation studies of DNA repair in cultured fibroblasts, Paterson et al. (1977) suggested the existence of 2 distinct types of ataxia-telangiectasia. By genetic complementation analysis, Jaspers and Bootsma (1982) concluded that extensive genetic heterogeneity exists in AT. Their method involved cell fusion and was based on the observation that the rate of DNA synthesis is inhibited by x-rays to a lesser extent in AT cells than in normal cells. At least 5 complementation groups have been identified (Murnane and Painter, 1982; Jaspers and Bootsma, 1982). Heterogeneity in AT has also been indicated by the clinical work of Fiorilli et al. (1983). Jaspers et al. (1988) reported the results of complementation studies on fibroblast strains from 50 patients with AT or Nijmegen breakage syndrome (NBS; 251260), using the radioresistant DNA replication characteristic as a marker. Six different genetic complementation groups were identified. Four of these, called AB, C, D, and E (of which AB is the largest), represented patients with clinical signs of AT. (According to Gatti (1990), the frequencies of these 4 groups are approximately 55%, 28%, 14%, and 3%, respectively.) Patients having NBS fell into 2 groups, designated V1 and V2. A patient with clinical symptoms of both AT and NBS was found in group V1, indicating that the 2 disorders are closely related (Curry et al., 1989). No group-specific patterns of clinical characteristics or ethnic origin were apparent among the AT cases. In addition to the radiosensitive ATs, a separate category of patients was found, characterized by a relatively mild clinical course and weak radiosensitivity. Jaspers et al. (1988) concluded that a defect in 1 of at least 6 different genes may underlie inherited radiosensitivity in humans. Curry et al. (1989) used the designation AT(Fresno) (607585.0014) for the V1 disorder in twin girls who had clinical features combining those of ataxia-telangiectasia and the Nijmegen breakage syndrome. Complementation studies with Sendai virus-mediated fusion of fibroblast cell lines showed complementation with AT groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome. Hernandez et al. (1993) cited evidence for the existence of 4 complementation groups: AB, C, D, and E. Loci for AB, C, and D have been identified on 11q. However, Komatsu et al. (1996) could demonstrate that the gene for the V2 form of Nijmegen breakage syndrome is not located on chromosome 11. They found that cells from a patient with this form were highly sensitive to radiation and that the sensitivity was unchanged after the transfer of an extra copy of normal chromosome 11. Gatti et al. (1988) noted the existence of at least 4 clinically indistinguishable complementation groups (A, C, D, and E) among 80 affected individuals (Jaspers et al., 1985; Jaspers et al., 1988). The Amish pedigree represents group A. This locus was designated ATA (HGM9). Since the Thy-1 glycoproteins are major cell surface constituents of rodent thymocytes and neurons (Tse et al., 1985), the question might be raised as to whether mutation in the THY1 gene is the basis of AT. The fact that recombination was found between THY1 and AT in the overall study may indicate that AT is not due to a defect in THY1 or it may mean that complementation group A is caused by mutation in THY1 but a mutation at another site is responsible for other forms of the disorder. When genetic linkage data from group C families are pooled, it appears that group C also may be linked to 11q22-q23 (Gatti, 1989). The group D defect is correctable by transfer of chromosome 11 into an SV40-transformed fibroblast cell line (Komatsu et al., 1990). Ejima et al. (1990) corrected the radiosensitivity of a group D fibroblast line by introducing an 11q fragment into these cells. Lambert et al. (1991) showed by microcell-mediated chromosome transfer that immortalized AT cells from complementation group D were corrected by genetic material from region 11q22-q23. A deoxyribophosphodiesterase deficiency has been identified in cells from group E patients. Together, groups A and C encompass about 85% of AT patients. Genetic linkage studies should also clarify whether AT variant families are linked to chromosome 11q22-q23 or to group D or E defects. Molecular Genetics Savitsky et al. (1995) identified mutations in the ATM gene in ataxia-telangiectasia cases of complementation groups A, C, D, and E and in 4 other patients in whom the complementation group was not determined (see, e.g., 607585.0001). Thus it appears that the complementation that is observed is intragenic and that all AT patients have mutations in a single gene. Concannon and Gatti (1997) discussed the genetic heterogeneity in AT and provided an update of mutations in the ATM gene. They noted that most AT patients from nonconsanguineous families were compound heterozygotes. Mutation detection at the ATM locus is difficult because of the large size of the gene (66 exons), the fact that mutations are located throughout the gene with no hotspots, and the difficulty of distinguishing mutations from polymorphisms. Buzin et al. (2003) used a method called DOVAM-S (Detection of Virtually All Mutations by SSCP), a robotically-enhanced, multiplexed scanning method that is a highly sensitive modification of SSCP. They studied 43 unrelated patients and 4 obligate carriers. The results of this complete scan showed that 86% of causative ATM mutations were truncating and 14% were missense. See MOLECULAR GENETICS section in 607585. Pathogenesis Using 2 recombination vectors to study recombination in AT and control human fibroblast lines, Meyn (1993) found that the spontaneous intrachromosomal recombination rates were 30 to 200 times higher in AT fibroblast lines than in normal cells, whereas extrachromosomal recombination frequencies were near normal. Increased recombination is thus a component of genetic instability in AT and may contribute to the cancer risk. Other evidence of in vitro and in vivo genomic instability includes increased frequencies of translocations and other chromosomal aberrations in lymphocytes and fibroblasts, micronucleus formation in epithelial cells, and loss of heterozygosity in erythrocytes. Hyperrecombination is a specific feature of the AT phenotype rather than a genetic consequence of defective DNA repair because a xeroderma pigmentosum cell line exhibited normal spontaneous recombination rates. At least 2 stages in the cell cycle are regulated in response to DNA damage, the G1-S and the G2-M transitions (Hartwell, 1992). These transitions serve as checkpoints at which cells delay progress through the cell cycle to allow repair of damage before entering either S-phase, when damage would be perpetuated, or M-phase, when breaks would result in the loss of genomic material. Checkpoints are thought to consist of surveillance mechanisms that can detect DNA damage, signal transduction pathways that transmit and amplify the signal to the replication or segregation machinery, and possibly repair activities. Both the G1-S and G2-M checkpoints are known to be under genetic control, since there are mutants that abolish the arrest or delay occurring in normal cells in response to DNA damage. Painter et al. (1982) showed that the G1-S checkpoint is abolished in cells from AT patients. Kastan et al. (1992) provided strong evidence that the tumor-suppressor protein p53 (191170) is necessary for the G1-S checkpoint. They found that the AT gene(s) is upstream of the p53 gene in a pathway that activates the G1-S checkpoint. p53 levels increase 3- to 5-fold by a posttranscriptional mechanism after gamma-irradiation, coincident with a delay of the G1-S transition (Kastan et al., 1991); the induction of p53 does not occur in AT cells (Kastan et al., 1992). Induction by ionizing radiation of the GADD45 gene (126335), an induction that is also defective in AT cells, is dependent on wildtype p53 function (Kastan et al., 1992). Thus, Kastan et al. (1992) identified 3 participants--AT gene(s), p53, and GADD45--in a signal transduction pathway that controls cell cycle arrest following DNA damage. Abnormalities in this pathway probably contribute to tumor development. Kastan et al. (1992) pointed out that lymphoid malignancies are the most common tumor seen both in AT patients and in p53-deficient mice. Lymphoid cells normally experience DNA strand breaks during gene rearrangements. The G1 checkpoint may be important in the avoidance of errors in that process. Breast cancer and other nonlymphoid cancers are increased in individuals heterozygous for germline mutations of either p53 (e.g., the Li-Fraumeni syndrome; 191170.0001) or the AT gene(s) (Swift et al. (1987, 1991)). P53 is a sequence-specific DNA-binding transcription factor that induces cell cycle arrest or apoptosis in response to genotoxic stress. Activation of p53 by DNA-damaging agents is critical for eliminating cells with damaged genomic DNA and underlies the apoptotic response of human cancers treated with ionizing radiation and radiomimetic drugs. Both the levels of p53 protein and its affinity for specific DNA sequences increase in response to genotoxic stress. In vitro, the affinity of p53 for DNA is regulated by its carboxyl terminus. Waterman et al. (1998) therefore examined whether this region of p53 is targeted by DNA-damage signaling pathways in vivo. In nonirradiated cells, serines 376 and 378 of p53 were phosphorylated. IR led to dephosphorylation of ser376, creating a consensus binding site for 14-3-3 proteins (113508) and leading to association of p53 with 14-3-3. In turn, this increased the affinity of p53 for sequence-specific DNA. Consistent with the lack of p53 activation by ionizing radiation in AT, neither ser376 dephosphorylation nor the interaction of p53 with 14-3-3 proteins occurred in AT cells. Brown et al. (1999) reviewed studies identifying direct downstream targets of ATM and providing clues about the biologic function of these interactions. They placed the findings in the context of the pleiotropic phenotype displayed by patients with ataxia-telangiectasia and by Atm-deficient mice. The identified targets include ABL (189980), replication protein A (179835), p53, and beta-adaptin (see 600157). Since these targets are located in the nucleus and in the cytoplasm, the ATM protein is most likely involved in several distinct signaling pathways. In the thymus, p53 is phosphorylated directly by ATM after ionizing radiation, probably in the nucleus, leading to transcriptional activation of p21 and consequential cell cycle arrest. In the absence of ATM, this pathway is disrupted, and this defect perhaps results in the immunodeficiency and abnormal cellular responses to IR seen in patients with AT. Furthermore, the infertility noted in both AT patients and Atm-deficient mice is due to abnormal meiotic progression and subsequent germ-cell degeneration, a phenotype that is partially corrected by concomitant loss of p53 and p21 function. ATM interactions with beta-adaptin in the cytoplasm might mediate axonal transport and vesicle trafficking in the central nervous system and so account for the neuronal dysfunction and eventual neurodegeneration seen in ataxia-telangiectasia. Thus, the phenotypic pleiotropy of ataxia-telangiectasia results from the fact that different tissues express different ATM targets and perhaps also express a different complement of ATM family members whose functions may overlap with those of ATM and partially replace ATM. Jung et al. (1995) isolated cDNA that corrected the radiation sensitivity and DNA synthesis defects in fibroblasts from an AT1 group D patient by expression cloning, and showed that the cDNA encoded NFKBI, a truncated form of I-kappa-B (164008), which is an inhibitor of NFKB1, the nuclear factor kappa-B transcriptional activator (164011). The parental AT1 fibroblast expressed large amounts of the NFKBI transcript and showed constitutive activation of NFKB1. The AT1 fibroblast transfected with the truncated NFKBI expressed normal amounts of the NFKBI transcript and showed regulated activation of NFKB1. Since the NFKBI gene is located on chromosome 14 and not chromosome 11, it is probably not the site of the primary defect; Jung et al. (1995) hypothesized that its contribution to the ataxia-telangiectasia phenotype may work downstream of the gene representing the primary defect. Shackelford et al. (2001) investigated the possibility that the AT phenotype is a consequence, at least in part, of an inability to respond appropriately to oxidative damage. In comparison to normal human fibroblasts, AT dermal fibroblasts exhibited increased sensitivity to t-butyl hydroperoxide toxicity. These cells failed to show G1 to G2 phase checkpoint functions or to induce p53 in response to oxidative challenge. In an analysis of expression phenotypes among AT carriers, AT patients, and noncarrier controls, Smirnov and Cheung (2008) uncovered a regulatory pathway in which ATM regulates expression of TNFSF4 (603594) through MIRN125B (see 610104). In AT carriers and AT patients, this pathway is disrupted. As a result, the level of MIRN125B is lower and the level of its target gene, TNFSF4, is higher than in noncarriers. A decreased level of MIRN125B is associated with breast cancer, and an elevated level of TNFSF4 is associated with atherosclerosis. Thus, Smirnov and Cheung (2008) concluded that their findings provided a mechanistic suggestion for the increased risk of breast cancer and heart disease in AT carriers. Iourov et al. (2009) observed a 2- to 3-fold increase of stochastic aneuploidy affecting different chromosomes in the cerebellum and the cerebrum of the AT brain. Degenerating cerebellum in AT demonstrated a 5- to 20-fold increase of nonrandom DNA double-strand breaks and aneuploidy affecting chromosomes 14 and, to a lesser extent, chromosomes 7 and X. Novel recurrent chromosome hotspots associated with cerebellar degeneration were mapped to chromosome 14q12 containing the 2 candidate genes FOXG1B (164874) and NOVA1 (602157). Iourov et al. (2009) hypothesized that the existence of nonrandom breaks disrupting specific chromosomal loci in neural cells with DNA repair deficiency is evidence for programmed somatic rearrangements of the neuronal genome. Population Genetics On the basis of a 'vigorous case finding' in the United States in 2 time periods, Swift et al. (1986) estimated the incidence and gene frequency of AT. The highest observed incidence was in the state of Michigan for the period 1965 to 1969 when white AT patients were born at the rate of 11.3 per million births. Based on the incidence data, the minimum frequency of a single hypothetical AT gene in the U.S. white population was estimated to be 0.0017. Pedigree analysis, which estimates the gene frequency from the proportion of affected close blood relatives of homozygous probands, estimated the most likely gene frequency to be 0.007 on the assumption that AT is a single homogeneous genetic syndrome. Given that complementation analysis has demonstrated genetic heterogeneity in AT, the AT heterozygote frequency might fall between 0.68% and 7.7%, with 2.8% being a likely estimate. In the West Midlands of England, the birth frequency of AT was estimated to be about 1 in 300,000. Stankovic et al. (1998) reported the spectrum of 59 ATM mutations observed in AT patients in the British Isles. Of the 51 ATM mutations identified in families native to the British Isles, 11 were founder mutations, and 2 of these 11 conferred a milder clinical phenotype with respect to both cerebellar degeneration and cellular features. In 2 AT families, a 7271T-G mutation of the ATM gene appeared to be associated with an increased risk of breast cancer in both homozygotes and heterozygotes, although there was a less severe AT phenotype in terms of the degree of cerebellar degeneration. This mutation was associated with expression of full-length ATM protein at a level comparable to that in unaffected individuals. In addition, Stankovic et al. (1998) studied 18 AT patients, in 15 families, who developed leukemia, lymphoma, preleukemic T-cell proliferation, or Hodgkin lymphoma, mostly in childhood. A wide variety of ATM mutation types, including missense mutations and in-frame deletions, were seen in this group of patients. The authors showed that 25% of all AT patients carried in-frame deletions or missense mutations, many of which were also associated with expression of mutant ATM protein. Ejima and Sasaki (1998) studied 8 unrelated Japanese families with ataxia-telangiectasia for mutations in the ATM gene. Six different mutations were found on 12 of the 16 alleles examined. Two mutations, 4612del165 (607585.0014) and 7883del5, were found more frequently than the others; 7 of 16 (44%) of the mutant alleles had 1 of these 2 mutations. Microsatellite genotyping demonstrated that a common haplotype was shared by the mutant alleles for both common mutations. The authors suggested that the 2 founder mutations may be predominant among Japanese ATM mutant alleles. Telatar et al. (1998) found that 4 mutations accounted for 86 to 93% of 41 Costa Rican AT patients studied. They suggested that the Costa Rican population might be useful for analyzing the role of ATM heterozygosity in cancer. Sasaki et al. (1998) presented the results of a mutation screen in 14 unrelated AT patients, most of them Japanese. They used a hierarchical strategy in which they extensively analyzed the entire coding region of the cDNA. In the first stage, point mutations were sought by PCR-SSCP in short patches. In the second and third stages, the products of medium- and long-patch PCR, each covering the entire region, were examined by agarose gel electrophoresis to search for length changes. They found a total of 15 mutations (including 12 new) and 4 polymorphisms. Abnormal splicing of ATM was frequent among Japanese, and no hotspot was obvious, suggesting no strong founder effects in that ethnic group. Eleven patients carried either 1 homozygous or 2 compound heterozygous mutations, 1 patient carried only 1 detectable heterozygous mutation, and no mutation was found in 2 patients. Overall, mutations were found in at least 75% of the different ATM alleles examined. Sandoval et al. (1999) investigated the mutation spectrum of the ATM gene in a cohort of AT patients living in Germany. They amplified and sequenced all 66 exons and the flanking untranslated regions from genomic DNA of 66 unrelated AT patients. They identified 46 different ATM mutations and 26 sequence polymorphisms and variants scattered throughout the gene; 34 mutations had not previously been described in other populations. Seven mutations occurred in more than 1 family, but none of these accounted for more than 5 alleles in the patient group. Most of the mutations were truncating, which confirmed that the absence of full-length ATM protein is the most common molecular basis of AT. Transcript analyses demonstrated single exon skipping as the consequence of most splice site substitutions, but a more complex pattern was observed for 2 mutations. In 4 cases, immunoblot studies of cell lines carrying ATM missense substitutions or in-frame deletions detected residual ATM protein. One of these mutations, a valine deletion proximal to the kinase domain (607585.0017), resulted in ATM protein levels more than 20% of normal in an AT lymphoblastoid cell line. Castellvi-Bel et al. (1999) used SSCP analysis to screen the ATM gene in 92 AT patients from different populations. Of 177 expected mutations, approximately 70% were identified using this technique. Thirty-five new mutations and 34 new intragenic polymorphisms or rare variants were described. Laake et al. (2000) screened 41 AT families from Denmark, Finland, Norway, and Sweden for ATM mutations. They were able to characterize 67 of the 82 disease-causing alleles. Of the 37 separate mutations detected, 25 had not previously been reported. In 28 of the probands, mutations were found in both alleles; in 11 of the probands only 1 mutated allele was detected; and in 2 Finnish probands, no mutations were detected. One-third of the probands (13) were homozygous, whereas the majority of the probands (26) were compound heterozygous with at least 1 identified allele. Ten alleles were found more than once; 1 Norwegian founder mutation, 3245delATCinsTGAT (607585.0016), an insertion/deletion mutation, constituted 57% of the Norwegian alleles. Due to the large size of the ATM gene and the existence of over 400 mutations, identifying mutations in patients with ataxia-telangiectasia is labor intensive. Campbell et al. (2003) compared the single-nucleotide polymorphism (SNP) and short tandem repeat (STR) haplotypes of AT patients from varying ethnicities who were carrying common ATM mutations. They used SSCP to determine SNP haplotypes. To their surprise, all of the most common ATM mutations in their large multiethnic cohort were associated with specific SNP haplotypes, whereas the STR haplotypes varied, suggesting that ATM mutations predate STR haplotypes but not SNP haplotypes. They concluded that these frequently observed ATM mutations are not hotspots, but have occurred only once and spread with time to different ethnic populations. More generally, a combination of SNP and STR haplotyping could be used as a screening strategy for identifying mutations in other large genes by first determining the ancestral SNP and STR haplotypes in order to identify specific founder mutations. Campbell et al. (2003) estimated that this approach will identify approximately 30% of mutations in AT patients across all ethnic groups. In a mutation screen of 24 Polish AT families, Mitui et al. (2005) found that 3 founder mutations accounted for 58% of the alleles. They identified 44 (92%) of the expected 48 mutations: 69% were nonsense mutations, 23% caused aberrant splicing, and 5% were missense mutations. Four mutations had not been previously described. Two of the Polish mutations had been observed previously in Amish and Mennonite AT patients; this was considered compatible with historical records. Shared mutations had the same SNP and STR haplotypes, indicating common ancestries. See monographs edited by Bridges and Harnden (1982) and Gatti and Swift (1985) for a perspective on the development of this disorder. Anheim et al. (2010) found that AT was the third most common form of autosomal recessive cerebellar ataxia in a cohort of 102 patients evaluated in Alsace, France. Of 57 patients in whom a molecular diagnosis could be determined, 4 were affected with AT. The authors estimated the prevalence of AT to be 1 in 450,000 in this region. FRDA was the most common diagnosis, found in 36 of 57 patients, and AOA2 (606002) was the second most common diagnosis, found in 7 patients. Animal Model Barlow et al. (1996) created a murine model of ataxia-telangiectasia by disrupting the Atm locus via gene targeting. Mice homozygous for the disrupted Atm allele displayed growth retardation, neurologic dysfunction, male and female infertility secondary to the absence of mature gametes, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. Most of the animals developed malignant thymic lymphomas between 2 and 4 months of age. Several chromosomal anomalies were detected in one of these tumors. Fibroblasts from these mice grew slowly and exhibited abnormal radiation-induced G1 checkpoint function. Atm-disrupted mice recapitulated the ataxia-telangiectasia phenotype in humans. The authors noted that humans also show incomplete sexual maturation in ATM (Boder, 1975). Elson et al. (1996) generated a mouse model for ataxia-telangiectasia using gene targeting to generate mice that did not express the Atm protein. Atm-deficient mice were retarded in growth, did not produce mature sperm, and exhibited severe defects in T-cell maturation while going on to develop thymomas. Atm-deficient fibroblasts grew poorly in culture and displayed a high level of double-stranded chromosome breaks. Atm-deficient thymocytes underwent spontaneous apoptosis in vitro significantly more often than controls. Atm-deficient mice then exhibited many of the same symptoms found in ataxia-telangiectasia patients and in cells derived from them. Furthermore, Elson et al. (1996) demonstrated that the Atm protein exists as 2 discrete molecular species, and that loss of 1 or both of these can lead to the development of the disease. Xu and Baltimore (1996) disrupted the mouse ATM gene by homologous recombination. Xu et al. (1996) reported that Atm -/- mice are viable, growth-retarded, and infertile. The infertility results from meiotic failure, as meiosis is arrested at the zygotene/pachytene stage of prophase I as a result of abnormal chromosomal synapsis and subsequent chromosome fragmentation. The cerebella of Atm -/- mice appear normal by histologic examination, and the mice have no gross behavioral abnormalities. Atm -/- mice exhibit multiple immune defects similar to those of AT patients, and most develop thymic lymphomas at 3 to 4 months of age and die of the tumors by 4 months. Xu and Baltimore (1996) showed that mouse Atm -/- cells are hypersensitive to gamma irradiation and defective in cell cycle arrest following radiation, and Atm -/- thymocytes are more resistant to apoptosis induced by gamma radiation than normal thymocytes. They also provide direct evidence that ATM acts as an upregulator of p53. Ataxia-telangiectasia is characterized by markedly increased sensitivity to ionizing radiation. Ionizing radiation oxidizes macromolecules and causes tissue damage through the generation of reactive oxygen species (ROS). Barlow et al. (1999) therefore hypothesized that AT is due to oxidative damage resulting from loss of function of the ATM gene product. To assess this hypothesis, they employed an animal model of AT, i.e., the mouse with a disrupted Atm gene. They showed that organs that develop pathologic changes in the Atm-deficient mice are targets of oxidative damage, and that cerebellar Purkinje cells are particularly affected. They suggested that these observations provide a mechanistic basis for the AT phenotype and lay a rational foundation for therapeutic intervention. Barlow et al. (1999) exposed Atm +/+ and Atm +/- littermates to a sublethal dose, 4 Gy (400 Rad) of ionizing radiation. The Atm +/- mice had premature graying and decreased life expectancy (median survival 99 weeks vs 71 weeks in wildtype and heterozygous mice, respectively, P = 0.0042). Tumors and infections of similar type were found in all autopsied animals, regardless of genotype. Worgul et al. (2002) noted that in vitro studies have shown that cells from individuals homozygous for AT are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene may be slightly more radiosensitive in vitro, it remained to be determined whether their greater susceptibility translated into an increased sensitivity for late effects in vivo, although there was a suggestion that radiotherapy patients heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. Worgul et al. (2002) chose cataract formation in the lens as a means of assaying the effects of ATM deficiency in a late-responding tissue. One eye each of wildtype, Atm heterozygous, and Atm homozygous knockout mice was exposed to various levels of x-rays. Cataract development in the mice of all 3 groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Cataracts appeared earlier in heterozygous versus wildtype mice. The data suggested that ATM heterozygotes in the human population may also be radiosensitive. Worgul et al. (2002) proposed that this information may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage. Wong et al. (2003) examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and Terc. These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency. A generalized proliferation defect was evident in all cell types and tissues examined, and this defect extended to tissue stem/progenitor cell compartments, thereby providing a basis for progressive multiorgan system compromise, accelerated aging, and premature death. Wong et al. (2003) showed that Atm deficiency and telomere dysfunction act together to impair cellular and whole-organism viability, thus supporting the view that aspects of ataxia-telangiectasia pathophysiology are linked to the functional state of telomeres and its adverse effects on stem/progenitor cell reserves. Ziv et al. (2005) augmented specific features of AT by generating mouse strains that combined Atm deficiency with dysfunction of other proteins. Increasing oxidative stress by combining deficiencies in Atm and superoxide dismutase-1 (SOD1; 147450) exacerbated growth retardation and markedly reduced the mean survival time following ionizing radiation. In contrast, increasing genomic instability by combining deficiencies of Atm and the mismatch repair protein Mlh1 (120436) caused a moderate increase in radiation sensitivity and dramatic increase in aggressive lymphomas, compared with the Atm-knockout mice. Atm, Mlh1, or Mlh1/Atm single or double heterozygosity did not significantly affect the life span of the various genotypes. The genomic region on mouse chromosome 15 containing c-Myc (190080) was commonly amplified in tumors, and elevated levels of the c-Myc protein were subsequently observed in the tumors. Ziv et al. (2005) suggested that impaired genomic instability may be an important contributing factor to cancer predisposition in AT, whereas oxidative stress may be more important in the radiation sensitivity and growth retardation facets of this disease. (See also ANIMAL MODEL in 607585). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Sinusitis RESPIRATORY Airways \- Bronchitis \- Bronchiectasis GENITOURINARY Internal Genitalia (Male) \- Hypogonadism \- Impaired spermatogenesis Internal Genitalia (Female) \- Hypogonadism SKIN, NAILS, & HAIR Skin \- Cutaneous telangiectasia \- Cafe-au-lait spots \- Progeric skin changes \- Sclerodermatous skin changes Hair \- Progeric hair changes NEUROLOGIC Central Nervous System \- Cerebellar cortical degeneration \- Cerebellar ataxia \- Reduced/absent deep tendon reflexes \- Dysarthric speech \- Choreoathetosis \- Dystonia \- Myoclonus \- Tremor \- Seizures \- Oculomotor abnormalities ENDOCRINE FEATURES \- Delayed puberty \- Diabetes mellitus \- Glucose intolerance IMMUNOLOGY \- Thymus hypoplasia \- Normal numbers of B cells \- Defective B cell differentiation \- Lymphocytopenia \- Reduced numbers of T cells \- Reduced CD4+ T cells \- Increased levels of T cells bearing gamma/delta antigen receptor \- Reduced levels of cells with IgM receptors NEOPLASIA \- Non-Hodgkin lymphoma \- Leukemia \- Hodgkin lymphoma \- Increased risk in heterozygotes LABORATORY ABNORMALITIES \- Increased levels of alpha fetoprotein \- Increased levels of carcinoembryonic antigen \- Reduced IgA levels \- Reduced IgE levels \- Reduced IgG levels, particularly the IgG2 subclass \- Monomeric IgM \- Immunoglobulin antibodies present \- CD4+/CD8+ ratio is reversed MISCELLANEOUS \- Ataxia becomes evident at the end of the first year of life \- Telangiectasia become evident between the second and eighth year of life \- Hypersensitivity to ionizing radiation \- Variant AT may present with dystonia only MOLECULAR BASIS \- Caused by mutation in the ataxia-telangiectasia mutated gene (ATM, 607585.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	ATAXIA-TELANGIECTASIA	c0004135	30,326	omim	https://www.omim.org/entry/208900	2019-09-22T16:30:39	{"doid": ["12704"], "mesh": ["D001260"], "omim": ["208900"], "orphanet": ["100"], "synonyms": ["Alternative titles", "AT1", "LOUIS-BAR SYNDROME"], "genereviews": ["NBK26468"]}
A subtype of inflammatory pseudotumor of the liver characterized by a benign, well-circumscribed tumor with diffuse lymphoplasmacytic infiltration with histological features of IgG4-related disease (numerous IgG4-positive plasma cells, prominent eosinophils, stromal fibrosis, fibroblastic proliferations and, frequently, obliterative phlebitis), and that is likely located around the hepatic hilum. Most often it is discovered as an incidental finding. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Lymphoplasmacytic inflammatory pseudotumor of the liver	None	30,327	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=555437	2021-01-23T18:09:51	{"icd-10": ["K76.8"], "synonyms": ["IgG4-related inflammatory pseudotumor of the liver"]}
A rare chronic, local immune-mediated disease of the esophagus characterized clinically by symptoms of esophageal dysfunction (including, dysphagia, feeding disorders, food impaction, vomiting and abdominal pain) and histologically by eosinophil-predominant inflammation in esophageal biopsies. ## Epidemiology Prevalence in adults is estimated at 1/2,370 and in children 1/2,900 in Europe and North America; however, a steady rise in incidence and prevalence is observed. Males are predominantly affected (male/female ratio being 2.5). ## Clinical description Most cases of eosinophilic esophagitis (EoE) present in children and young adults, but it may occur at any age. Infants and toddlers manifest with food refusal, vomiting, choking with meals and in rare cases, failure to thrive. School-aged children most commonly present with dysphagia, choking/gagging with meals, food impactions and, less commonly, regurgitation, vomiting, and chest/abdominal pain. Adults manifest mainly with dysphagia as well as food avoidance, food impactions and intractable heartburn. Symptoms may be chronic or intermittent, with some patients appearing asymptomatic during long periods, although this is mostly due to adaptive behaviors. Overall, symptoms may persist up to 4 to 5 years before a diagnosis is reached. In 75% of cases, there is a personal or family history of other atopic diseases (i.e. dermatitis, rhinitis, asthma). Common food triggers include cow's milk, wheat, egg and, in Mediterranean countries, legumes. ## Etiology EoE is due to development of a deficient esophageal mucosal barrier and an abnormal immune reaction to environmental allergens mediated by Th2 interleukins causing esophageal lesions, dysmotility, secondary remodeling and fibrosis. The disease is multifactorial with genetic inheritance suggested to contribute a 7% risk of developing the disease; the environment appears to be the main determinant, in particular early-life exposures (including antibiotic use, acid suppression, maternal fever, cesarean delivery, and newborn intensive care unit admission) are associated with increased risk of EoE. ## Diagnostic methods Diagnosis is based on clinical and endoscopic examination of the esophagus revealing linear furrowing, white speckled exudates, concentric rings, Schatzki ring and linear mucosal tears after introduction of endoscope (but in up to 30% of cases the esophagus may appear normal). An esophageal mucosal biopsy is essential in the diagnosis and is based on the presence of at least 15 eosinophils/high power field (HPF), irrespective of the results of pH-monitoring. ## Differential diagnosis Differential diagnoses include gastroesophageal reflux disease, esophageal candidiasis and other local and systemic causes of esophageal eosinophilia (including eosinophilic gastroenteritis and hypereosinophilic syndrome, Crohn's disease involving the esophagus, parasite infectations, drug hypersensitivity, achalasia, vasculitis, phenphigoid, connective tissue disorders and graft-versus-host disease). ## Management and treatment PPIs, dietary modifications, or swallowed topical steroids might be offered as first line anti-inflammatory therapy. An effective anti-inflammatory therapy should be used as maintenance treatment in the long term. Endoscopic follow up of any therapy should be 6 to 12-week's after the initial course. Elemental diets are the most effective dietary therapy, but are expensive, badly tolerated and impractical in the long term. Currently, available food allergy tests are suboptimal to predict food triggers, and are typically not recommended. Empiric elimination of most common food triggers is the standard dietary approach. Sequential food reintroduction followed by endoscopies and biopsies identifies specific food triggers. Simpler four-food elimination diet, and specially two-food elimination diet allows faster identification of triggers, with fewer endoscopies. Endoscopic dilation should be considered for fibrostenotic abnormalities, preferably after a trial of anti-inflammatory therapy. Leukotriene receptor antagonist, histamine-1 blockers and mast cell stabilizers are not recommended. ## Prognosis Left untreated, persistence inflammation may lead to fibrosis with stricture formation and functional damage. The disease causes significant emotional distress and restriction of social activities. Both drugs (PPS and steroids) and dietary modification are able to achieve histologic remission, symptomatic improvement and, to some degree, restore quality 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Eosinophilic esophagitis	c0341106	30,328	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=73247	2021-01-23T18:47:20	{"mesh": ["D057765"], "omim": ["610247", "613412"], "umls": ["C0341106"], "icd-10": ["K20"], "synonyms": ["EoE"]}
A subcutaneous tissue disease characterized by a spectrum of clinical signs ranging from the classical triad of painful and progressively deformed joints, subcutaneous nodules, and progressive hoarseness (due to laryngeal involvement) that presents in infancy, to varying phenotypes with respiratory and neurologic involvement. ## Epidemiology Approximately 200 cases of Farber disease have been reported worldwide in the literature to date. ## Clinical description A high clinical variability is seen between patients. The classic phenotype presents at around 3-6 months of age with painful, swollen and stiff joints of the hands and feet, prominent subcutaneous nodules over pressure points, and progressive hoarseness leading to aphonia due to vocal cord infiltration. Patients can also develop cardiac, pulmonary and neurological defects. Progressive neurological deterioration can be marked in some forms with seizures, paraparesis and developmental delay. The most severe neonatal form presents at birth with hydrops fetalis, lethargy, and failure to thrive, as well as hepatosplenomegaly, rapid neurological deterioration, and granulomatous infiltrations to various other organs (i.e. liver, spleen, lungs). Milder forms have also been described with no neurological defects and a longer life-expectancy. In some patients, the disease manifests in childhood as a spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA-PME) in the absence of subcutaneous nodules. ## Etiology Farber disease is caused by mutations in the N-acylsphingosine amidohydrolase (ASAH1) gene (8p22) which encodes acid ceramidase, a lysosomal enzyme that hydrolyzes ceramide into sphingosine and free fatty acid. A deficient activity of this enzyme leads to an accumulation of ceramide in most tissues. ## Diagnostic methods Diagnosis is based on clinical and laboratory findings by assaying the activity of acid ceramidase in peripheral blood leukocytes, cultured lymphoid cells or cultured skin fibroblasts. Alternatively, diagnosis can be performed by determining ceramide concentration in cultured cells or tissues or by studying lysosomal ceramide catabolism in cultured living cells. Identification of mutations in the ASAH1 gene by molecular genetic testing usually allows for diagnostic confirmation. ## Differential diagnosis Differential diagnoses include juvenile idiopathic arthritis, stiff skin syndrome and lethal restrictive dermopathy. Encephalopathy due to prosaposin deficiency should also be excluded. ## Antenatal diagnosis Prenatal diagnosis by DNA testing is possible in families with a known disease-causing mutation. Alternatively, prenatal diagnosis can be performed by measuring acid ceramidase activity in cultured amniotic fluid cells or chorionic villi. ## Genetic counseling The pattern of inheritance is autosomal recessive. Genetic counseling should be proposed to affected families informing them of a 25% risk of transmitting the disease where both parents are unaffected carriers. ## Management and treatment There is currently no effective specific therapy for Farber disease, and symptomatic treatment is based on analgesics, corticotherapy, and plastic surgery. However, allogeneic hematopoietic stem cell transplantation provides a promising approach for patients with limited neurological involvement. ## Prognosis The prognosis varies, with some patients dying within the first few days of life (severe neonatal form) and others living until adolescence or early adulthood (milder forms). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Farber disease	c0268255	30,329	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=333	2021-01-23T18:53:04	{"gard": ["6426"], "mesh": ["D055577", "C537075"], "omim": ["228000"], "umls": ["C0268255", "C2936785"], "icd-10": ["E75.2"], "synonyms": ["Acid ceramidase deficiency", "Farber lipogranulomatosis"]}
Brain ischemia Other namesCerebral ischemia, Cerebrovascular ischemia CT scan slice of the brain showing a right-hemispheric cerebral infarct (left side of image). SpecialtyVascular surgeon Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand.[1] This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction / ischemic stroke.[2] It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage.[3] Ischemia leads to alterations in brain metabolism, reduction in metabolic rates, and energy crisis.[4] There are two types of ischemia: focal ischemia, which is confined to a specific region of the brain; and global ischemia, which encompasses wide areas of brain tissue. The main symptoms of Brain ischemia involve impairments in vision, body movement, and speaking. The causes of brain ischemia vary from sickle cell anemia to congenital heart defects. Symptoms of brain ischemia can include unconsciousness, blindness, problems with coordination, and weakness in the body. Other effects that may result from brain ischemia are stroke, cardiorespiratory arrest, and irreversible brain damage. An interruption of blood flow to the brain for more than 10 seconds causes unconsciousness, and an interruption in flow for more than a few minutes generally results in irreversible brain damage.[5] In 1974, Hossmann and Zimmermann demonstrated that ischemia induced in mammalian brains for up to an hour can be at least partially recovered.[6] Accordingly, this discovery raised the possibility of intervening after brain ischemia before the damage becomes irreversible.[7] ## Contents * 1 Symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 4.1 Classification * 4.1.1 Focal brain ischemia * 4.1.2 Global brain ischemia * 5 Treatment * 6 Management * 7 Research * 8 See also * 9 References * 10 Bibliography * 11 Further reading * 12 External links ## Symptoms[edit] The symptoms of brain ischemia reflect the anatomical region undergoing blood and oxygen deprivation. Ischemia within the arteries branching from the internal carotid artery may result in symptoms such as blindness in one eye, weakness in one arm or leg, or weakness in one entire side of the body. Ischemia within the arteries branching from the vertebral arteries in the back of the brain may result in symptoms such as dizziness, vertigo, double vision, or weakness on both sides of the body[citation needed]. Other symptoms include difficulty speaking, slurred speech, and the loss of coordination.[8] The symptoms of brain ischemia range from mild to severe. Further, symptoms can last from a few seconds to a few minutes or extended periods of time. If the brain becomes damaged irreversibly and infarction occurs, the symptoms may be permanent.[9] Similar to cerebral hypoxia, severe or prolonged brain ischemia will result in unconsciousness, brain damage or death, mediated by the ischemic cascade.[10] Multiple cerebral ischemic events may lead to subcortical ischemic depression, also known as vascular depression. This condition is most commonly seen in elderly depressed patients.[citation needed] Late onset depression is increasingly seen as a distinct sub-type of depression, and can be detected with an MRI.[11] ## Causes[edit] Brain ischemia has been linked to a variety of diseases or abnormalities. Individuals with sickle cell anemia, compressed blood vessels, ventricular tachycardia, plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of heart attack, and congenital heart defects have a higher predisposition to brain ischemia in comparison their healthy counterparts. Sickle cell anemia may cause brain ischemia associated with the irregularly shaped blood cells. Sickle shaped blood cells clot more easily than normal blood cells, impeding blood flow to the brain. Compression of blood vessels may also lead to brain ischemia, by blocking the arteries that carry oxygen to the brain. Tumors are one cause of blood vessel compression. Ventricular tachycardia represents a series of irregular heartbeats that may cause the heart to completely shut down resulting in cessation of oxygen flow. Further, irregular heartbeats may result in formation of blood clots, thus leading to oxygen deprivation to all organs. Blockage of arteries due to plaque buildup may also result in ischemia. Even a small amount of plaque build up can result in the narrowing of passageways, causing that area to become more prone to blood clots.[citation needed] Large blood clots can also cause ischemia by blocking blood flow. A heart attack can also cause brain ischemia due to the correlation that exists between heart attack and low blood pressure. Extremely low blood pressure usually represents the inadequate oxygenation of tissues. Untreated heart attacks may slow blood flow enough that blood may start to clot and prevent the flow of blood to the brain or other major organs. Extremely low blood pressure can also result from drug overdose and reactions to drugs. Therefore, brain ischemia can result from events other than heart attacks. Congenital heart defects may also cause brain ischemia due to the lack of appropriate artery formation and connection. People with congenital heart defects may also be prone to blood clots. Other pathological events that may result in brain ischemia include cardiorespiratory arrest, stroke, and severe irreversible brain damage. Recently, Moyamoya disease has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood circulation to the brain, consequently leading to oxygen deprivation.[12] ## Pathophysiology[edit] During brain ischemia, the brain cannot perform aerobic metabolism due to the loss of oxygen and substrate. The brain is not able to switch to anaerobic metabolism and, because it does not have any long term energy stored, the levels of adenosine triphosphate (ATP) drop rapidly, approaching zero within 4 minutes. In the absence of biochemical energy, cells begin to lose the ability to maintain electrochemical gradients. Consequently, there is a massive influx of calcium into the cytosol, a massive release of glutamate from synaptic vesicles, lipolysis, calpain activation, and the arrest of protein synthesis.[13] Additionally, removal of metabolic wastes is slowed.[14] The interruption of blood flow to the brain for ten seconds results in the immediate loss of consciousness. The interruption of blood flow for twenty seconds results in the stopping of electrical activity.[5] An area called a penumbra may result, wherein neurons do not receive enough blood to communicate, however do receive sufficient oxygenation to avoid cell death for a short period of time.[15] ## Diagnosis[edit] ### Classification[edit] The broad term, "stroke" can be divided into three categories: brain ischemia, subarachnoid hemorrhage and intracerebral hemorrhage. Brain ischemia can be further subdivided, by cause, into thrombotic, embolic, and hypoperfusion.[3] Thrombotic and embolic are generally focal or multifocal in nature while hypoperfusion affects the brain globally. #### Focal brain ischemia[edit] Focal brain ischemia occurs when a blood clot has occluded a cerebral vessel.[16] Focal brain ischemia reduces blood flow to a specific brain region, increasing the risk of cell death to that particular area.[17] It can be either caused by thrombosis or embolism. #### Global brain ischemia[edit] Global brain ischemia occurs when blood flow to the brain is halted or drastically reduced. This is commonly caused by cardiac arrest. If sufficient circulation is restored within a short period of time, symptoms may be transient. However, if a significant amount of time passes before restoration, brain damage may be permanent. While reperfusion may be essential to protecting as much brain tissue as possible, it may also lead to reperfusion injury. Reperfusion injury is classified as the damage that ensues after restoration of blood supply to ischemic tissue.[16] Due to different susceptibility to ischemia of various brain regions, a global brain ischemia may cause focal brain infarction. The cerebral cortex and striatum are more susceptible than the thalamus, and the thalamus in turn is more sensitive than the brainstem.[18] Partial cerebral cortex infarction from global brain ischemia typically manifests as watershed stroke.[19] ## Treatment[edit] Alteplase (t-PA) is an effective medication for acute ischemic stroke. When given within 3 hours, treatment with tpa significantly improves the probability of a favourable outcome versus treatment with placebo. The outcome of brain ischemia is influenced by the quality of subsequent supportive care. Systemic blood pressure (or slightly above) should be maintained so that cerebral blood flow is restored. Also, hypoxaemia and hypercapnia should be avoided. Seizures can induce more damage; accordingly, anticonvulsants should be prescribed and should a seizure occur, aggressive treatment should be undertaken. Hyperglycaemia should also be avoided during brain ischemia.[20] ## Management[edit] When someone presents with an ischemic event, treatment of the underlying cause is critical for prevention of further episodes. Anticoagulation with warfarin or heparin may be used if the patient has atrial fibrillation. Operative procedures such as carotid endarterectomy and carotid stenting may be performed if the patient has a significant amount of plaque in the carotid arteries associated with the local ischemic events. ## Research[edit] Therapeutic hypothermia has been attempted to improve results post brain ischemia[citation needed]. This procedure was suggested to be beneficial based on its effects post cardiac arrest. Evidence supporting the use of therapeutic hypothermia after brain ischemia, however, is limited. A closely related disease to brain ischemia is brain hypoxia. Brain hypoxia is the condition in which there is a decrease in the oxygen supply to the brain even in the presence of adequate blood flow. If hypoxia lasts for long periods of time, coma, seizures, and even brain death may occur. Symptoms of brain hypoxia are similar to ischemia and include inattentiveness, poor judgment, memory loss, and a decrease in motor coordination.[21] Potential causes of brain hypoxia are suffocation, carbon monoxide poisoning, severe anemia, and use of drugs such as cocaine and other amphetamines.[8] Other causes associated with brain hypoxia include drowning, strangling, choking, cardiac arrest, head trauma, and complications during general anesthesia. Treatment strategies for brain hypoxia vary depending on the original cause of injury, primary and/or secondary.[21] ## See also[edit] * Mechanism of anoxic depolarization in the brain * Watershed stroke ## References[edit] 1. ^ Sullivan, Jonathon. "What is Brain Ischemia?". WSU Emergency Medicine Cerebral Resuscitation Laboratory. Archived from the original on 2009-01-06. Retrieved 2008-11-11. 2. ^ "Brain Ischemia (Cerebral Ischemia)". Cure Hunter Incorporated. 2003. pp. Relationship Network. Retrieved 2008-11-11. 3. ^ a b "UpToDate Inc". 4. ^ Vespa, Paul; Bergsneider, Marvin; Hattori, Nayoa; Wu, Hsiao-Ming; Huang, Sung-Cheng; Martin, Neil A; Glenn, Thomas C; McArthur, David L; Hovda, David A (2005). "Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study". Journal of Cerebral Blood Flow & Metabolism. 25 (6): 763–74. doi:10.1038/sj.jcbfm.9600073. PMC 4347944. PMID 15716852. 5. ^ a b Raichle, Marcus (1983). "The Pathophysiology of Brain Ischemia" (PDF). Neurological Progress. Archived from the original (PDF) on 2009-02-19. Retrieved 2008-11-11. 6. ^ Hossmann, Konstantin-Alexander; Zimmermann, Volker (1974). "Resuscitation of the monkey brain after 1 H complete ischemia. I. Physiological and morphological observations". Brain Research. 81 (1): 59–74. doi:10.1016/0006-8993(74)90478-8. PMID 4434196. 7. ^ Raichle, Marcus; Ann Neurol (1983). "The pathophysiology of brain ischemia" (PDF). Neurological Process. Archived from the original (PDF) on 2009-02-19. Retrieved 2009-04-22. 8. ^ a b Beers, Mark; Andrew Fletcher; Thomas Jones; Robert Porter (2003). The Merck Manual of Medical Information. New York, New York: Merck & Co. Inc. pp. 458–461. ISBN 84-494-3359-2. 9. ^ Caplan, Louis; Scott Kasner; John Dashe. "Differential diagnosis of brain ischemia". Up to Date For Patients. UpToDate. Retrieved 2008-11-11. 10. ^ Lipton, Peter (1999). "Ischemic cell death in brain neurons". Physiological Reviews. 79 (4): 1431–568. doi:10.1152/physrev.1999.79.4.1431. PMID 10508238. 11. ^ Baldwin, Robert C. (2005). "Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence". International Journal of Geriatric Psychiatry. 20 (1): 1–11. doi:10.1002/gps.1255. PMID 15578670. 12. ^ Sparks, Gareth (2002). "What is Moyamoya disease?". eSSORTMENT. Archived from the original on 2009-03-27. Retrieved 2009-04-13. 13. ^ Sullivan, Jonathon. "Bad Things Happen in Ischemia". WSU Emergency Medicine Cerebral Resuscitation Laboratory. Emergency Medicine Cerebral Resuscitation Lab. Retrieved 2008-11-11. 14. ^ "Ischemic and Hemorrhagic". Archived from the original on 2009-02-16. Retrieved 2008-11-11. 15. ^ Hakim AM (1998). "Ischemic penumbra: the therapeutic window". Neurology. 51 (3 Suppl 3): S44–6. doi:10.1212/wnl.51.3_suppl_3.s44. PMID 9744833. 16. ^ a b Sullivan, Jonathon. "Two Flavors of Ischemia". Brain Ischemia 101. Emergency Medicine Cerebral Resuscitation Lab. Retrieved 2008-10-13. 17. ^ Miettinen, S.; Fusco, F. R.; Yrjanheikki, J.; Keinanen, R.; Hirvonen, T.; Roivainen, R.; Narhi, M.; Hokfelt, T.; Koistinaho, J. (1997). "Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2". Proceedings of the National Academy of Sciences. 94 (12): 6500–5. Bibcode:1997PNAS...94.6500M. doi:10.1073/pnas.94.12.6500. JSTOR 42387. PMC 21079. PMID 9177247. 18. ^ Dimitri P. Agamanolis, M.D. "Neuropathology - Chapter 2: Cerebral ischemia and stroke". Updated: October, 2017 19. ^ Porth, C.M. (2009). Pathophysiology: Concepts of Altered Health States (Eighth Edition). Philadelphia: Wolters Kluwer Health \| Lippincott Williams & Wilkins. p. 1301. ISBN 978-16054-7390-1. 20. ^ Hinds CJ (1985). "Prevention and treatment of brain ischaemia". British Medical Journal. 291 (6498): 758–60. doi:10.1136/bmj.291.6498.758. PMC 1417168. PMID 3929929. 21. ^ a b "Cerebral Hypoxia Information Page". National Institute of Neurological Disorders and Stroke. National Institutes of Health. 2008-05-07. Archived from the original on 2009-05-05. Retrieved 2009-04-28. ## Bibliography[edit] * Gusev, Eugene I.; Skvortsova, Veronica I. (2003). Brain ischemia. New York: Kluwer Academic/Plenum Publishers. ISBN 0-306-47694-0. ## Further reading[edit] * Chang, Steven; Doty, James; Skirboll, Stephen; Steinberg, Gary. Cerebral ischemia . cgi.stanford.edu. URL last accessed February 26, 2006.[dead link] ## External links[edit] Classification D * ICD-10: G45.9, I67.8 * ICD-9-CM: 435X,437X * MeSH: D002545 * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Ischaemia and infarction Ischemia * Location * Brain ischemia * Heart * Large intestine * Small intestine Infarction * Types * Anemic * Hemorrhagic * Location * Heart * Brain * Spleen * Limb * Gangrene [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Brain ischemia	c0917798	30,330	wikipedia	https://en.wikipedia.org/wiki/Brain_ischemia	2021-01-18T18:28:29	{"mesh": ["D002545"], "umls": ["C0917798"], "icd-9": ["435X", "437X"], "icd-10": ["G45.9"], "wikidata": ["Q4862390"]}
Ménétrier disease (MD) is a rare premalignant hyperproliferative gastropathy characterized by massive overgrowth of foveolar cells in the gastric lining, resulting in large gastric folds, and manifesting with epigastric pain, nausea, vomiting, peripheral edema and, less commonly, anorexia and weight loss. ## Epidemiology Exact prevalence and incidence data are not available. MD appears to affect males slightly more than females. ## Clinical description The usual age of onset is between 30 and 60 years (average 55 years), although cases in childhood have been reported. The childhood variant often involves sudden onset and spontaneous regression. In adults, onset is often insidious with a wide spectrum of clinical manifestations. Affected patients typically present with abdominal pain, vomiting and nausea. Edema of peripheral tissues is often found. Other symptoms include asthenia, anorexia, and weight loss. Some individuals with MD are only mildly affected or are asymptomatic. Loss of protein from the gastrointestinal tract leads to hypoalbuminemia and peripheral edema. Mucosal ulceration is also described and can result in gastrointestinal bleeding. Disease course tends to be progressive, leading to gastric adenocarcinoma in 2-15% of cases. Complications include severe or recurrent infections and vascular thromboembolism. ## Etiology The etiology is currently unknown but is thought to be acquired and to involve enhanced epidermal growth factor receptor (EGFR) signaling in the gastric mucosa with local overproduction of transforming growth factor-alpha (TGF-alpha). In children, some MD cases have been linked to cytomegalovirus (CMV) and in adults some have been linked to Helicobacter pylori; however, the possible role of these infections remains to be elucidated. Rare familial cases point to a possible genetic component. The mechanism(s) underlying carcinogenesis in MD remain unknown. ## Diagnostic methods MD is suspected on the basis of the constellation of clinical signs and symptoms but there are no formal diagnostic criteria. Diagnosis requires gastroscopic examination (showing enlarged gastric folds primarily involving the gastric corpus) with biopsy, preferably of full thickness gastric mucosa, which reveals characteristic histological features (extensive foveolar hyperplasia with corkscrew morphology in the absence of distortion of overall linear architecture, decreased or absent parietal cells, variable amounts of chronic inflammation with scattered clusters of eosinophils, and scattered strands of smooth muscle between mucous glands). Gastric acid secretion is generally markedly decreased or absent, while gastric mucous secretion is elevated. Serum gastrin levels remain relatively normal. ## Differential diagnosis Differential diagnoses include Zollinger-Ellison syndrome (see this term), hypertrophic hypersecretory gastropathy, hypertrophic lymphocytic gastritis, infiltrating neoplasm, polyps, and polyposis syndromes (e.g. juvenile polyposis syndrome, Peutz-Jeghers syndrome, and gastric adenocarcinoma and proximal polyposis of the stomach; see these terms). ## Genetic counseling MD is an acquired gastropathy but a genetic predisposition with autosomal dominant inheritance has been suggested in a few families. ## Management and treatment There is no recommended standard treatment. In some patients, treatment may be limited to supportive care with a high-protein diet. Inconsistent results have been achieved with anticholinergic drugs, acid suppression therapy, treatment against CMV infection in children, and H. pylori eradication in adults. Treatment with cetuximab, an EGFR neutralizing monoclonal antibody, has been successfully carried out. If there is concern about malignant transformation or in severe cases, partial or total gastrectomy may be required. Although there is no official recommendation, endoscopic surveillance may be offered every 1-3 years. ## Prognosis MD tends to be a progressive disorder. Most of the patients ultimately require gastrectomy, either due to worsening symptoms or the risk of developing gastric cancer. The risk of malignant transformation is not well characterized. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Ménétrier disease	c0017155	30,331	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2494	2021-01-23T18:39:07	{"gard": ["2436"], "mesh": ["D005758"], "omim": ["137280"], "umls": ["C0017155", "C2936660"], "icd-10": ["K29.6"], "synonyms": ["Giant hypertrophic gastritis", "Hypoproteinemic hypertrophic gastropathy"]}
## Clinical Features Jones et al. (1977) described a family with gingival fibromatosis (see 135300) associated with progressive sensorineural hearing loss in 5 generations. Whereas 9 persons had GF without demonstrated or reported deafness, all 16 persons with a hearing loss had GF. The proband with the full syndrome was 10 years old. Hartsfield et al. (1985) reported 5 cases of GFD in 3 generations with male-to-male transmission. Inheritance The transmission pattern of gingival fibromatosis with progressive deafness in the families reported by Jones et al. (1977) and Hartsfield et al. (1985) was consistent with autosomal dominant inheritance. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, progressive sensorineural Mouth \- Gingival fibromatosis ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	FIBROMATOSIS, GINGIVAL, WITH PROGRESSIVE DEAFNESS	c1851112	30,332	omim	https://www.omim.org/entry/135550	2019-09-22T16:41:13	{"mesh": ["C535886"], "omim": ["135550"], "orphanet": ["2027"], "synonyms": ["Alternative titles", "GINGIVAL FIBROMATOSIS WITH SENSORINEURAL HEARING LOSS", "JONES SYNDROME"]}
Disease of silkworms Flacherie (literally: "flaccidness") is a disease of silkworms, caused by silkworms eating infected or contaminated mulberry leaves. Flacherie infected silkworms look weak and can die from this disease. Silkworm larvae that are about to die from Flacherie are a dark brown. There are two kinds of flacherie: essentially, infectious (viral) flacherie and noninfectious (bouffee) flacherie. Both are technically a lethal diarrhea. Bouffée flacherie is caused by heat waves (bouffée means "sudden heat spell" in French). Viral flacherie is ultimately caused by infection with Bombyx mori infectious flacherie virus (BmIFV, Iflaviridae), Bombyx mori densovirus (BmDNV, Parvoviridae) or Bombyx mori cypovirus 1 (BmCPV-1, Reoviridae). This either alone or in combination with bacterial infection destroys the gut tissue. Bacterial pathogens contributing to infectious flaccherie are Serratia marcescens, and species of Streptococcus and Staphylococcus in the form known as thatte roga. Louis Pasteur, who began his studies on silkworm diseases in 1865, was the first one able to recognize that mortality due to viral flacherie was caused by infection. (Priority, however, was claimed by Antoine Béchamp.[1]) Richard Gordon described the discovery: "The French silk industry was meanwhile plummeting from a 130 million to an 8 million francs annual income, because the silkworms had all caught pébrine, black pepper disease…He [Pasteur] went south from Paris to Alais, and rewarded them by discovering the silkworm epidemic to be inflicted by some sort of living microbe…Pasteur threw in another disease, flâcherie, silkworm diarrhoea. The cures for both were culling the insects which showed the peppery spots — the peasants bottled the silkworm moths in brandy, for display to the experts — and rigorous hygiene of the mulberry leaf."[2] ## References[edit] 1. ^ A. Béchamp, "La maladie microzymateuse des vers à soie et les granulations moléculaires", Comptes rendus de l'Académie des sciences, 67 (1868), p. 443, available on Gallica. 2. ^ Richard Gordon. The Alarming History of Medicine: Amusing Anecdotes from Hippocrates to Heart Transplants. New York: St. Martin’s Press, 1993. p. 19. This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Flacherie	None	30,333	wikipedia	https://en.wikipedia.org/wiki/Flacherie	2021-01-18T19:02:37	{"wikidata": ["Q678421"]}
A number sign (#) is used with this entry because of evidence that susceptibility to late-onset Alzheimer disease-9 (AD9) is conferred by heterozygous variation in the ABCA7 gene (605414) on chromosome 19p13. For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300. Clinical Features Van den Bossche et al. (2016) characterized the phenotype of 22 Belgian patients with AD9 who carried putative pathogenic variants in the ABCA7 gene. The mean age at onset was 73 years, with a wide age range between 54 and 90 years. The phenotype was classic for AD, mainly including progressive memory loss. About half of patients developed frontal signs, including disinhibition or behavioral changes. Other manifestations included language difficulties, depression, and delusions. One patient presented with parkinsonism, and a few showed mild extrapyramidal symptoms. Brain imaging tended to show atrophy of various brain regions, and many patients had chronic microvascular lesions. Cerebrospinal fluid examination of 2 patients showed decreased beta-amyloid(1-42) and increased total tau, consistent with AD. Neuropathologic examination of 4 patients showed cortical atrophy and neuronal loss in the hippocampus. Senile plaques and neurofibrillary tangles were also apparent. The patients had previously been reported by Cuyvers et al. (2015) and included a family with autosomal dominant inheritance (DR170). Inheritance The transmission pattern of AD9 the family reported by Van den Bossche et al. (2016) was consistent with autosomal dominant inheritance. Mapping Late-onset familial Alzheimer disease is a genetically heterogeneous and complex disease. The Bayesian Markov chain-Monte Carlo (MCMC) linkage analysis methods provide a computationally tractable approach for complex trait analysis. These methods are particularly suitable for multilocus trait models. Wijsman et al. (2004) applied this approach to an analysis of late-onset AD on 5 chromosomes with previous reports of linkage. They identified strong evidence of a late-onset AD locus on 19p13.2. They also obtained weak evidence of linkage to chromosome 10 at the same location as a previous report of linkage (AD6; 605526) but found no evidence for linkage of late-onset AD age-at-onset loci on chromosomes 9, 12 (see 103950), or 21 (AD1; 104760). By linkage analysis of 5 Amish families from the midwestern U.S. in which 49 individuals had late-onset dementia or mild cognitive impairment, Hahs et al. (2006) obtained 2-point lod scores greater than 1.5 at marker D19S586 on 19p13 (lod scores of 2.06 and 1.82). The results were obtained under a model assuming autosomal dominant inheritance. Molecular Genetics Hollingworth et al. (2011) undertook a combined analysis of 4 genomewide association datasets of patients with late-onset Alzheimer disease (stage 1) and identified 10 newly associated variants with p = 1 x 10(-5) or less. They tested these variants for association in an independent sample (stage 2). Three SNPs at 2 loci replicated and showed evidence for association in a further sample (stage 3). One of these SNPs was in the ABCA7 gene, and metaanalyses of all data provided compelling evidence for ABCA7 (rs3764650, meta p = 4.5 x 10(-17); including the Alzheimer's Disease Genetic Consortium (ADGC) data, meta p = 5.0 x 10(-21)). Among 3,419 Icelanders with Alzheimer disease and 151,805 controls, Steinberg et al. (2015) found a significant association between loss-of-function variants in the ABCA7 gene (see, e.g., 605414.0001) (odds ratio (OR) 2.12, p = 2.2 x 10(-13)). A significant association was also found for a splice site variant (c.5570+5G-C; rs200538373) that was shown to cause premature termination (OR 1.91, p = 3.8 x 10(-6)). The association with loss-of-function variants was replicated in study groups from Europe and the United States (OR 2.03, p = 6.8 x 10(-15)). Cuyvers et al. (2015) found an association between variation in the ABCA7 gene and susceptibility to late-onset Alzheimer disease (AD9). Targeted resequencing of the ABCA7 gene found an increased frequency of predicted loss-of-function variants (7 variants) among 772 unrelated Belgian patients compared to 757 controls (relative risk 4.03, p = 0.0002). One of these was a frameshift mutation (Glu709fs; 605414.0001) that segregated with the disorder in a family and showed a founder effect in the population. Expression of ABCA7 was reduced in brain tissue from 2 carriers of loss-of-function mutations, including Glu709fs and W1214X (605414.0002). The strongest association with AD was for an intronic variant (rs78117248), which showed minor allele frequencies of 3.8% in 58 patients and 1.8% in 28 controls (OR 2.07, p = 0.0016). The variant occurred in a transcription factor binding region; however, no difference in expression of ABCA7 was noted in cells derived from carriers of the variant compared to controls. The SNP rs78117248 was in linkage disequilibrium with GWAS SNPs rs3764650, rs4147929, and rs3752246; regression analysis removed the association between the GWAS SNPs and disease. In the Belgian study, the c.5570+5G-C variant identified by Steinberg et al. (2015) occurred at a frequency of more than 1% in both patients and controls, and was not associated with AD. By targeted resequencing of the ABCA7 gene in 2 Caucasian cohorts totaling 330 patients with late-onset AD and in the ExAC database, Vardarajan et al. (2015) found a significant association between an E1769X variant and AD (p = 5.3 x 10(-4)). Among 484 French patients with onset of AD before 65 years and 590 controls, Le Guennec et al. (2016) found a significant association between loss-of-function and missense ABCA7 variants and AD (OR 3.40, p = 0.0002). Variants were found in 6.6% of patients and in 2.0% of controls. A metaanalysis using previously reported data (Steinberg et al., 2015; Cuyvers et al., 2015) in a combined sample of 1,256 patients and 1,347 controls yielded an OR of 2.81 (p = 3.60 x 10(-7)). No functional studies of the variants were performed. ### Exclusion Studies Klein et al. (2013) found no mutations in exons 20 and 21 of the DNMT1 gene (126375) on chromosome 19p13 in 364 patients with autopsy-confirmed late-onset Alzheimer disease, thus likely excluding a role for this gene in AD9. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Alzheimer disease \- Memory loss, progressive \- Language difficulties \- Extrapyramidal signs (in some patients) \- Dyspraxia (in some patients) \- Cortical atrophy \- Hippocampal atrophy \- Neuropathology shows neurofibrillary tangles \- Senile plaques Behavioral Psychiatric Manifestations \- Frontal signs \- Disinhibition \- Depression MISCELLANEOUS \- Mean age at onset 73 years (range 54 to 90) MOLECULAR BASIS \- Susceptibility conferred by mutation in the ATP-binding cassette, subfamily A, member 7 gene (ABCA7, {605414.0001)} ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	ALZHEIMER DISEASE 9, SUSCEPTIBILITY TO	c4282179	30,334	omim	https://www.omim.org/entry/608907	2019-09-22T16:06:57	{"omim": ["608907"], "synonyms": ["Alternative titles", "ALZHEIMER DISEASE 9, LATE-ONSET"]}
Focal task-specific dystonia (FTSD) is a movement disorder that is localized to a specific part of the body. The dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions, tremors, and other uncontrolled movements. FTSD interferes with the performance of particular tasks, such as writing, playing a musical instrument, or participating in a sport. Additionally, FTSD has been reported in tailors, shoemakers, hair stylists, and people who frequently type or use a computer mouse. While the abnormal movements associated with focal dystonia are usually painless, they can cause high levels of anxiety. The causes of focal dystonia are unknown, although the disorder likely results from a combination of genetic and environmental factors. It is possible that the different forms of FTSD have different underlying causes. Researchers have found that at least some cases are related to malfunction of the basal ganglia, which are structures deep within the brain that help start and control movement. Most cases of focal dystonia are sporadic, which means they occur in people with no history of the condition in their family. However, at least 10 percent of affected individuals have a family history which seems to follow an autosomal dominant pattern of inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Focal task-specific dystonia	c1969807	30,335	gard	https://rarediseases.info.nih.gov/diseases/6458/focal-task-specific-dystonia	2021-01-18T18:00:26	{"mesh": ["C566973"], "omim": ["611284"], "orphanet": ["1866"], "synonyms": ["FTSD", "Focal task specific dystonia", "Task-specific focal dystonia", "Focal dystonia", "Focal, segmental or multifocal dystonia", "Task-specific dystonia"]}
Longitudinal erythronychia presents with longitudinal red bands in the nail plate that commence in the matrix and extend to the point of separation of the nail plate and nailbed, and may occur on multiple nails with inflammatory conditions such as lichen planus or Darier's disease.[1]:790 ## See also[edit] * Nail anatomy * List of cutaneous conditions ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. This condition of the skin appendages article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Longitudinal erythronychia	None	30,336	wikipedia	https://en.wikipedia.org/wiki/Longitudinal_erythronychia	2021-01-18T18:48:33	{"wikidata": ["Q6674008"]}
Postoperative residual curarization Electromyographic monitoring at the adductor policies muscle. SpecialtyAnesthesia Postoperative residual curarization (PORC) or residual neuromuscular blockade (RNMB) is a residual paresis after emergence from general anesthesia that may occur with the use of neuromuscular-blocking drugs.[1][2] Today residual neuromuscular blockade is defined as a train of four ratio[3] of less than 0.9 when measuring the response to ulnar nerve stimulation at the adductor pollicis muscle using mechanomyography or electromyography.[4] A meta-analysis reported that the incidence of residual neuromuscular paralysis was 41% in patients receiving intermediate neuromuscular blocking agents during anaesthesia.[1] It is possible that > 100,000 patients annually in the USA alone, are at risk of adverse events associated with undetected residual neuromuscular blockade.[5] Neuromuscular function monitoring and the use of the appropriate dosage of sugammadex to reverse blockade produced by rocuronium can reduce the incidence of postoperative residual curarization.[6] In this study, with usual care group receiving reversal with neostigmine resulted in a residual blockade rate of 43%. ## Contents * 1 Incidence * 2 Types of neuromuscular blocking agents * 2.1 Non-depolarizing neuromuscular blocking agents * 2.2 Depolarizing neuromuscular blocking agents * 3 Adverse events from inadequate neuromuscular blockade reversal * 4 Monitoring neuromuscular blockade * 4.1 Peripheral nerve stimulation patterns and definitions * 4.1.1 Train-of-four (TOF): * 4.1.2 Train-of-four ratio (TOFR): * 4.1.3 Train-of-four count (TOFC) * 4.1.4 Train-of-four ratio <0.9 * 4.2 Subjective monitoring * 4.3 Objective/quantitative monitoring * 5 Reversal of NMBDs and methods to avoid residual neuromuscular blockade * 6 References ## Incidence[edit] Multiple studies have demonstrated that incomplete reversal of NMBDs is an important risk factor for postoperative morbidity and mortality. Multiple studies have shown that postoperative residual curarization in the post-anesthesia care unit (PACU) is a common complication, with 40% of patients exhibiting signs of residual paralysis. The incidence of this complication continues to be high and does not seem to be decreasing over time.[7] ## Types of neuromuscular blocking agents[edit] Classified into two main groups: •Depolarizing NMBDs: produces skeletal muscle relaxation by binding directly with nAChRs to cause prolonged depolarization. •Non-depolarizing NMBDs: competitive antagonists (competing with acetylcholine [ACh] for the binding sites at the nAChRs), preventing the initiation of action potential.[8] ### Non-depolarizing neuromuscular blocking agents[edit] Non-depolarizing NMBAs are classified based on their duration of action (short, intermediate, or long-acting agents. The two most commonly used non-depolarizing NMBDs in the operating room are rocuronium and vecuronium. Both are intermediate-acting, steroidal NMBAs. Vecuronium and rocuronium can be reversed by anticholinesterases (neostigmine) or sugammadex. If sufficient spontaneous recovery has not been achieved, neostigmine (or sugammadex) should be administered.[9] ### Depolarizing neuromuscular blocking agents[edit] Succinylcholine is the only depolarizing NMBA available for clinical use. It produces a neuromuscular blockade that is the fastest in onset and has the shortest duration of all NMBDs. Due to these properties, succinylcholine is often used for rapid sequence induction and intubation. When a continuous infusion, repeated doses, or a large dose of succinylcholine (>4 mg/kg) is used, the risk of a Phase II block and prolonged paralysis is increased. This type of block occurs when the desensitizing phase sets in and the muscle is no longer responsive to acetylcholine and full neuromuscular blockade is achieved. TOF fade is indicative of phase II block that is likely to occur in patients who received succinylcholine and may resemble features of a nondepolarizing block. During phase II, reversal with neostigmine should not be attempted. Anticholinesterase agents can worsen paralysis in this setting.[10] Prolonged paralysis after succinylcholine administration may be due to butyrylcholinesterase (pseudocholinesterase) deficiency and may require prolonged mechanical ventilation. Unlike non-depolarizing NMBDs, reversal with neostigmine should not be attempted and sugammadex will have no effect on recovery.[11] ## Adverse events from inadequate neuromuscular blockade reversal[edit] Inadequate reversal of NMBAs is an important risk factor for anesthesia related complications. Even small degrees of residual paralysis are associated with weakness of upper airway muscles which may lead to airway obstruction and increased risk of aspiration. The hypoxic ventilatory response (HRV) can also be severely depressed as well leading to hypoxemia and need for reintubation.[7] Studies have shown that incomplete neuromuscular recovery is associated with an increased increased risk of pulmonary complications. A prospective observational study including patients who underwent general anesthesia for noncardiac surgery reported that the "use of NMBAs was independently associated with an increase in postoperative pulmonary complications within 28 days of surgery."[12] ## Monitoring neuromuscular blockade[edit] ### Peripheral nerve stimulation patterns and definitions[edit] #### Train-of-four (TOF):[edit] TOF stimulation consists of four successive supramaximal stimuli delivered at 2 Hz. After administration of a nondepolarizing NMBD, responses at this frequency progressively decrease in amplitude (referred to as "fade" or a decrease in the TOF ratio from a normal ratio of 1). #### Train-of-four ratio (TOFR):[edit] A TOF ratio (TOFR) is calculated by dividing the amplitude of the fourth response by the amplitude of the first response (requires an quantitative measure of the response to stimulation).[13] #### Train-of-four count (TOFC)[edit] The TOF count (TOFC) is defined as the "number of detectable evoked responses, and it correlates with the degree of neuromuscular block, as follows: * TOFC = 1 : >95 percent of nicotinic acetylcholine receptors (nAChRs) blocked * TOFC = 2 : 85 to 90 percent of nAChRs blocked * TOFC = 3 : 80 to 85 percent of nAChRs blocked * TOFC = 4 : 70 to 75 percent of nAChRs blocked[13] #### Train-of-four ratio <0.9[edit] Data suggests that a TOF ratio measured qualitatively with EMG, MMG, or AMG must reach the threshold value of >0.9 to assure recovery of neuromuscular function. TOF ratios <0.9 are associated with residual blockade and paralysis and have demonstrated an increased risk of aspiration.[14] ### Subjective monitoring[edit] Subjective monitoring refers to the clinical evaluation of assessing the TOFC or degree of fade by using methods such as physically touching the patient and feeling movement or visibly observing a twitch in response to neurostimulation provided by a peripheral nerve stimulator. If subjective monitoring is used, its limitations should be recognized: "clinicians tend to overestimate the TOFC when using subjective evaluation, especially at moderate levels of block. Likewise, the level of fade is difficult to detect subjectively, with most clinicians unable to detect fade when TOF ratios >0.4."[15] ### Objective/quantitative monitoring[edit] Due to the difficulty detecting fade subjectively (TOF ratios between 0.4 and 0.9) when using peripheral nerve stimulators, clinicians are unable to reliably exclude residual neuromuscular blockade. TOF ratios >0.4 can be measured accurately and displayed numerically using quantitative neuromuscular monitoring. However, TOF ratios >4 can be measured accurately by using quantitative monitoring methods such as electromyography (EMG), kinemyography (KMG), phonomyography (PMG), and acceleromyography (AMG).[14] ## Reversal of NMBDs and methods to avoid residual neuromuscular blockade[edit] •Using short-acting or intermediate-acting NBMDs whenever possible can decrease the risk of residual neuromuscular blockade when compared with long-acting NMBDs. •Use objective neuromuscular monitoring (acceleromyography, electromyography, kinemyography) if possible. Peripheral nerve stimulators may be more readily available and can be used as well. However, peripheral nerve stimulators can only subjectively determine the depth of block (train-of-four count) and cannot provide accurate information needed for the timing and dosing of reversal agents as well as ensure full recovery (TOF fade).[16] •If spontaneous recovery has not reached a TOFC = 4, use sugammadex rather than neostigmine for reversal of steroidal NMBDs.[17] •If sugammadex is unavailable, wait for spontaneous recovery to achieve a TOFC = 4 before administering neostigmine. •Extubate the trachea only after a TOFR ≥0.9 is achieved (if quantitative monitors are available) •If objective monitoring is not available, administer reversal agents (neostigmine) only when TOFC = 4. Wait at least 10 minutes after neostigmine is given to ensure enough time for the neuromuscular blockade to be fully reversed before tracheal extubation.[18] ## References[edit] 1. ^ a b Naguib M, Kopman AF, Ensor JE (2007). "Neuromuscular monitoring and postoperative residual curarisation: a meta-analysis". Br J Anaesth. 98 (3): 302–316. doi:10.1093/bja/ael386. PMID 17307778. 2. ^ Baillard C (2005). "Postoperative residual neuromuscular block: a survey of management". Br J Anaesth. 95 (5): 622–626. doi:10.1093/bja/aei240. PMID 16183681. 3. ^ Ortega R, Brull SJ, Prielipp R, Gutierrez A, De La Cruz R, Conley CM (2018-01-25). "Monitoring Neuromuscular Function". New England Journal of Medicine. 378 (4): e6. doi:10.1056/nejmvcm1603741. ISSN 0028-4793. PMID 29365307. 4. ^ Naguib M, Brull SJ, Johnson KB (2017). "Conceptual and technical insights into the basis of neuromuscular monitoring". Anaesthesia. 72 (S1): 16–37. doi:10.1111/anae.13738. ISSN 1365-2044. PMID 28044330. 5. ^ Brull SJ, Naguib M, Miller RD (2008). "Residual Neuromuscular Block: Rediscovering the Obvious". Anesthesia & Analgesia. 107 (1): 11–14. doi:10.1213/ane.0b013e3181753266. ISSN 0003-2999. PMID 18635461. 6. ^ Brueckmann B, Sasaki N, Grobara P, Li MK, Woo T, de Bie J, Maktabi M, Lee J, Kwo J (November 2015). "Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study". British Journal of Anaesthesia. 115 (5): 743–751. doi:10.1093/bja/aev104. ISSN 0007-0912. PMID 25935840. 7. ^ a b Murphy GS, Brull SJ (July 2010). "Residual Neuromuscular Block: Lessons Unlearned. Part I". Anesthesia & Analgesia. 111 (1): 120–128. doi:10.1213/ANE.0b013e3181da832d. PMID 20442260. S2CID 207132635. 8. ^ Naguib M, Flood P, McArdle JJ, Brenner HR (January 2002). "Advances in Neurobiology of the Neuromuscular Junction: Implications for the Anesthesiologist". Anesthesiology. 96 (1): 202–231. doi:10.1097/00000542-200201000-00035. PMID 11753022. S2CID 28588587. 9. ^ Tran DT, Newton EK, Mount VA, Lee JS, Wells GA, Perry JJ (29 October 2015). "Rocuronium versus succinylcholine for rapid sequence induction intubation". Cochrane Database of Systematic Reviews (10): CD002788. doi:10.1002/14651858.CD002788.pub3. PMC 7104695. PMID 26512948. 10. ^ Naguib M, Lien CA, Aker J, Eliazo R (June 2004). "Posttetanic Potentiation and Fade in the Response to Tetanic and Train-of-Four Stimulation During Succinylcholine-Induced Block". Anesthesia & Analgesia. 98 (6): 1686–1691. doi:10.1213/01.ane.0000113544.21754.a5. PMID 15155329. S2CID 20439614. 11. ^ Davis L, Britten JJ, Morgan M (March 1997). "Cholinesterase Its significance in anaesthetic practice". Anaesthesia. 52 (3): 244–260. doi:10.1111/j.1365-2044.1997.084-az0080.x. PMID 9124666. S2CID 25107062. 12. ^ Kirmeier E, Eriksson LI, Lewald H, Jonsson Fagerlund M, Hoeft A, Hollmann M, Meistelman C, Hunter JM, Ulm K, Blobner M (February 2019). "Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study". Lancet. Respir Med. 7 (2): 129–140. doi:10.1016/S2213-2600(18)30294-7. PMID 30224322. (Erratum: doi:10.1016/S2213-2600(18)30467-3, PMID 30224322) 13. ^ a b Lee C (September 1975). "Train-of-4 Quantitation of Competitive Neuromuscular Block". Anesthesia & Analgesia. 54 (5): 649–653. doi:10.1213/00000539-197509000-00021. PMID 1237253. S2CID 24218901. 14. ^ a b Brull, Sorin J.; Murphy, Glenn S. (July 2010). "Residual Neuromuscular Block: Lessons Unlearned. Part II". Anesthesia & Analgesia. 111 (1): 129–140. doi:10.1213/ANE.0b013e3181da8312. PMID 20442261. S2CID 23738174. 15. ^ Cammu G, De Witte J, De Veylder J, Byttebier G, Vandeput D, Foubert L, Vandenbroucke G, Deloof T (February 2006). "Postoperative Residual Paralysis in Outpatients Versus Inpatients". Anesthesia & Analgesia. 102 (2): 426–429. doi:10.1213/01.ane.0000195543.61123.1f. PMID 16428537. S2CID 9670756. 16. ^ Bhananker SM, Treggiari MM, Sellers BA, Cain KC, Ramaiah R, Thilen SR (October 2015). "Comparison of train-of-four count by anesthesia providers versus TOF-Watch® SX: a prospective cohort study". Canadian Journal of Anesthesia. 62 (10): 1089–1096. doi:10.1007/s12630-015-0433-9. PMID 26224034. S2CID 39769290. 17. ^ Kirkegaard H, Heier T, Caldwell JE (January 2002). "Efficacy of Tactile-guided Reversal from Cisatracurium-induced Neuromuscular Block". Anesthesiology. 96 (1): 45–50. doi:10.1097/00000542-200201000-00013. PMID 11753000. 18. ^ Kopman AF, Zank LM, Ng J, Neuman GG (January 2004). "Antagonism of Cisatracurium and Rocuronium Block at a Tactile Train-of-Four Count of 2: Should Quantitative Assessment of Neuromuscular Function Be Mandatory?". Anesthesia & Analgesia. 98 (1): 102–106. doi:10.1213/01.ane.0000094985.19305.e9. PMID 14693596. S2CID 24936824. * v * t * e Anesthesia and anesthesiology Types * General * Sedation * Twilight anesthesia * Local * Topical * Intercostal nerve block * Neuraxial blockade * Spinal * Epidural * Dental * Inferior alveolar nerve Techniques * Airway management * Anesthesia provision in the US * Arterial catheter * Bronchoscopy * Capnography * Dogliotti's principle * Drug-induced amnesia * Intraoperative neurophysiological monitoring * Nerve block * Penthrox inhaler * Tracheal intubation Scientific principles * Blood–gas partition coefficient * Concentration effect * Fink effect * Minimum alveolar concentration * Second gas effect Measurements * ASA physical status classification system * Baricity * Bispectral index * Entropy monitoring * Fick principle * Goldman index * Guedel's classification * Mallampati score * Neuromuscular monitoring * Thyromental distance Instruments * Anaesthetic machine * Anesthesia cart * Boyle's machine * Gas cylinder * Laryngeal mask airway * Laryngeal tube * Medical monitor * Odom's indicator * Relative analgesia machine * Vaporiser * Double-lumen endotracheal tube * Endobronchial blocker Complications * Emergence delirium * Allergic reactions * Anesthesia awareness * Local anesthetic toxicity * Malignant hyperthermia * Perioperative mortality * Postanesthetic shivering * Postoperative nausea and vomiting * Postoperative residual curarization Subspecialties * Cardiothoracic * Critical emergency medicine * Geriatric * Intensive care medicine * Obstetric * Oral sedation dentistry * Pain medicine Professions * Anesthesiologist * Anesthesiologist assistant * Nurse anesthetist * Operating department practitioners * Certified Anesthesia Technician * Certified Anesthesia Technologist * Anaesthetic technician * Physicians' assistant (anaesthesia) History * ACE mixture * Helsinki Declaration for Patient Safety in Anaesthesiology * History of general anesthesia * History of neuraxial anesthesia * History of tracheal intubation Organizations * American Association of Nurse Anesthetists * American Society of Anesthesia Technologists & Technicians * American Society of Anesthesiologists * Anaesthesia Trauma and Critical Care * Association of Anaesthetists of Great Britain and Ireland * Royal College of Anaesthetists * Association of Veterinary Anaesthetists * Australian and New Zealand College of Anaesthetists * Australian Society of Anaesthetists * International Anesthesia Research Society * Category * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Postoperative residual curarization	c4042763	30,337	wikipedia	https://en.wikipedia.org/wiki/Postoperative_residual_curarization	2021-01-18T18:44:40	{"mesh": ["D055191"], "wikidata": ["Q1981337"]}
Seborrheic-like psoriasis Other namesSebopsoriasis,[1] and Seborrhiasis SpecialtyDermatology Seborrheic-like psoriasis is a skin condition characterized by psoriasis with an overlapping seborrheic dermatitis.[2]:193 ## See also[edit] * Psoriasis * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Seborrheic-like psoriasis	None	30,338	wikipedia	https://en.wikipedia.org/wiki/Seborrheic-like_psoriasis	2021-01-18T18:55:51	{"wikidata": ["Q7442801"]}
Abortion in Burkina Faso is only legal if the abortion will save the woman's life, the pregnancy gravely endangers the woman's physical or mental health, the child will potentially be born with an incurable disease, or in cases where the pregnancy is a result of rape or incest, so long as it is proven by a state prosecutor.[1] Even these abortions are limited to the first ten weeks of pregnancy.[1] In Burkina Faso, any abortion performed under other conditions subjects the person who performs the procedure subject to one to five years’ imprisonment and imposition of a fine of 300,000 to 1,500,000 CFA francs.[2] ## Impact of restricted abortion laws[edit] In the early 1990s, at least 5% of women admitted into healthcare facilities for maternal health concerns had life-threatening complications from unsafe abortions, and 70% of these women were between 16 and 24 years of age.[1] During the same time period, 35% of women who sought medical treatment for infertility had previously been recipients of an illegal abortion.[1] ## References[edit] 1. ^ a b c d Abortion Policies: Afghanistan to France. United Nations Publications. 2001. ISBN 9789211513653. Retrieved 4 December 2014. 2. ^ "Burkina Faso". United Nations Abortion Policies. Retrieved 22 April 2016. * v * t * e Abortion in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion (France) * Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category This abortion-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Abortion in Burkina Faso	None	30,339	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Burkina_Faso	2021-01-18T18:55:54	{"wikidata": ["Q19568853"]}
Deafness onychodystrophy osteodystrophy and mental retardation (DOOR) syndrome is a rare genetic disorder that is usually recognized shortly after birth. The term DOOR is an acronym with each letter representing a common feature in affected individuals: (D)eafness due to a defect of the inner ear or auditory nerve; (O)nychodystrophy or malformation of the nails; (O)steodystrophy, meaning malformation of certain bones; and mild to profound intellectual disability (represented by the "R"). In some cases, individuals may also experience seizures. This condition is inherited in an autosomal recessive fashion; the exact genetic cause 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	DOOR syndrome	c0795927	30,340	gard	https://rarediseases.info.nih.gov/diseases/1685/door-syndrome	2021-01-18T18:00:50	{"mesh": ["C538204"], "omim": ["220500"], "umls": ["C1857345"], "orphanet": ["79500"], "synonyms": ["Digitorenocerebral syndrome", "Autosomal recessive deafness-onychodystrophy syndrome", "Deafness-onychodystrophy-osteodystrophy-intellectual disability syndrome", "Deafness-onychoosteodystrophy-intellectual disability syndrome", "DOORS syndrome"]}
Congenital dyserythropoietic anemia type 2 (CDA II) is an inherited blood disorder characterized by mild to severe anemia. It is usually diagnosed in adolescence or early adulthood. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly) and gallstones. This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type II have mediastinal tumors. CDA type II usually results from mutations in the SEC23B gene. It is inherited in an autosomal recessive pattern. Treatment depends on the severity of the symptoms and may involve blood transfusions, iron chelation therapy and removal of the spleen and gallbladder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Congenital dyserythropoietic anemia type 2	c1306589	30,341	gard	https://rarediseases.info.nih.gov/diseases/2001/congenital-dyserythropoietic-anemia-type-2	2021-01-18T18:01:10	{"mesh": ["D000742"], "omim": ["224100"], "umls": ["C1306589"], "orphanet": ["98873"], "synonyms": ["CDAN2", "Anemia, dyserythropoietic, congenital type 2", "CDA II", "Dyserythropoietic anemia, HEMPAS type", "HEMPAS anemia", "Hereditary Erythroblastic Multinuclearity with Positive Acidified-Serum test", "CDA type II", "Congenital dyserythropoietic anemia type II", "Hereditary erythroblastic multinuclearity with a positive acidified-serum test (hempas)", "SEC23B-CDG"]}
A number sign (#) is used with this entry because a skeletal malformation with features overlapping those of brachydactyly types D and E (BDE; 113300) can be caused by mutation in the HOXD13 gene (142989). Clinical Features This type of brachydactyly is characterized by short and broad terminal phalanges of the thumbs and big toes. Thomsen (1928) described this anomaly. In a unilateral case he pointed out that the epiphyseal line at the base of the anomalous phalanx was obliterated but was still demonstrable in the corresponding position on the normal thumb. Goodman et al. (1965) also studied this 'normal' morphologic trait in detail. The trait has picturesque designations such as 'potter's thumb' and 'murderer's thumb.' It occurs as part of the Rubinstein syndrome (180849). Gray and Hurt (1984) concluded that penetrance is complete in females and incomplete in males. About three-fourths of affected persons, both males and females, express the trait bilaterally. Robin et al. (1999) studied 6 affected individuals from a 4-generation family with brachydactyly type D. All affected individuals had either bilateral and symmetric or unilateral first distal phalangeal hypoplasia. Metacarpal-phalangeal profiles showed that some affected individuals also had a more generalized involvement of the apical skeleton. However, other than first distal phalangeal hypoplasia, there was no consistent pattern of associated skeletal involvement. Linkage analysis with 6 loci known to contain genes involved in apical skeletal patterning showed no significant linkage. Molecular Genetics The HOXD13 gene, the most 5-prime gene of the HOXD cluster, encodes a homeodomain transcription factor with important functions in limb patterning and growth. Heterozygous mutations of HOXD13, encoding polyalanine expansions or frameshifts, appear to act by dominant-negative or haploinsufficiency mechanisms and are predominantly associated with synpolydactyly phenotypes. Johnson et al. (2003) described 2 mutations in the homeodomain of HOXD13, ile314 to leu (I314L; 142989.0004) and ser308 to cys (S308C; 142989.0005), which were associated with distinctive limb phenotypes in which brachydactyly of specific metacarpals, metatarsals, and phalangeal bones was the most constant feature, exhibiting overlap with brachydactyly types D and E (113300). Radiology \- Obliterated epiphyseal line at base of distal thumb phalanx Limbs \- Brachydactyly \- Short and broad distal phalanges of thumbs and great toes Growth \- Normal 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	BRACHYDACTYLY, TYPE D	c0220664	30,342	omim	https://www.omim.org/entry/113200	2019-09-22T16:44:08	{"mesh": ["C562420"], "omim": ["113200"], "synonyms": ["Alternative titles", "STUB THUMB"]}
Skin manifestations of sarcoidosis SpecialtyHematology Sarcoidosis, an inflammatory disease, involves the skin in about 25% of patients. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in two to four weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems.[1] ## Contents * 1 Classification * 1.1 Morphology * 1.2 Pattern * 1.3 Location * 2 References * 3 External links ## Classification[edit] ### Morphology[edit] Ulcerative sarcoidosis is a cutaneous condition affecting roughly 5% of people with sarcoidosis.[2]:710 Annular sarcoidosis is a cutaneous condition characterized by papular skin lesions arranged in annular patterns, usually with a red-brown hue.[2]:709 ### Pattern[edit] Morpheaform sarcoidosis is a very rare cutaneous condition characterized by specific cutaneous skin lesions of sarcoidosis accompanied by substantial fibrosis, simulating morphea.[2]:711 Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.[2]:710 Hypopigmented sarcoidosis is a cutaneous condition characterized by areas of hypopigmented skin. It is usually diagnosed in darkly pigmented races and may be the earliest sign of sarcoidosis.[2]:709 Papular sarcoid is a cutaneous condition characterized by papules, which are the most common morphology of cutaneous sarcoidosis.[2]:708 Ichthyosiform sarcoidosis is a cutaneous condition resembling ichthyosis vulgaris or acquired ichthyosis, with fine scaling usually on the distal extremities, by caused by sarcoidosis.[2]:710 ### Location[edit] Subcutaneous sarcoidosis (also known as "Darier–Roussy disease"[3] and "Darier-Roussy sarcoid") is a cutaneous condition characterized by numerous 0.5- to 0.3-cm deep-seated nodules on the trunk and extremities.[2]:710 Scar sarcoid (also known as "Sarcoidosis in scars") is a cutaneous condition characterized by infiltration and elevation of tattoos and old flat scars due to sarcoidosis.[2]:710 Mucosal sarcoidosis is a cutaneous condition characterized by pinhead-sized papules that may be grouped and fused together to form a flat plaque.[2]:711 Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.[2]:710 ## References[edit] 1. ^ Harrison's Practice, Sarcoidosis. 2. ^ a b c d e f g h i j k James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1421. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: D86.3 (ILDS D86.330) * v * t * e Sarcoidosis * Skin * Lupus pernio * Neurosarcoidosis * Löfgren syndrome * Heerfordt's 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Skin manifestations of sarcoidosis	c0036203	30,343	wikipedia	https://en.wikipedia.org/wiki/Skin_manifestations_of_sarcoidosis	2021-01-18T18:54:30	{"umls": ["C0036203"], "wikidata": ["Q4769722"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Fracture blister" – news · newspapers · books · scholar · JSTOR (April 2013) (Learn how and when to remove this template message) Fracture blister Example of fracture blister SpecialtyDermatology Fracture blisters occur on skin overlying a fractured bone, and fractures complicated by the development of overlying blisters remain a clinical dilemma in orthopedics.[1][2]:43 Fracture blisters are tense vesicles or bullae that arise on markedly swollen skin directly overlying a fracture. Fracture blisters pop up in trauma patients occasionally. A fracture blister typically occurs near fractures where the skin has little subcutaneous tissue between it and bone. These include elbows, knees, ankles, and wrists. They tend to complicate fracture management because they interfere with splinting, casting, and incision planning for open reduction procedures.[3] They can appear anytime within a few hours of injury to 2–3 weeks later. These blisters are thought to be caused by shearing forces applied at the time of injury.[3] There are two types described, based on their color: clear fluid and hemorrhagic. The difference lies in the level of the shear. Clear fluid blisters have separated within the epidermis, and hemorrhagic blisters separate at the dermal-epidermal junction. The clinical difference is healing time; clear blisters take about 12 days and hemorrhagic blisters heal in about 16 days. The decision to pop the blisters in order to treat the fracture, or wait for them to heal first usually hinges on the preferences of the orthopaedic surgeon as there is a lack of data on what treatment is ideal.[3] Waiting delays care an average of 7 days, and longer for tibial plateau and calcaneal fractures. Operating immediately anecdotally increases wound infection rates. ## Additional images[edit] Hemorrhagic fracture blisters on medial aspect of left foot and ankle. X-ray shows a Weber type B fracture of the ankle ## References[edit] 1. ^ Strauss EJ, Petrucelli G, Bong M, Koval KJ, Egol KA (October 2006). "Blisters associated with lower-extremity fracture: results of a prospective treatment protocol". J Orthop Trauma. 20 (9): 618–22. doi:10.1097/01.bot.0000249420.30736.91. PMID 17088664. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 3. ^ a b c Uebbing CM, Walsh M, Miller JB, Abraham M, Arnold C (February 2011). "Fracture blisters". The Western Journal of Emergency Medicine. 12 (1): 131–3. PMC 3088393. PMID 21691490. * v * t * e General wounds and injuries Abrasions * Abrasion * Avulsion Blisters * Blood blister * Coma blister * Delayed blister * Edema blister * Fracture blister * Friction blister * Sucking blister Bruises * Hematoma/Ecchymosis * Battle's sign * Raccoon eyes * Black eye * Subungual hematoma * Cullen's sign * Grey Turner's sign * Retroperitoneal hemorrhage Animal bites * Insect bite * Spider bite * Snakebite Other: * Ballistic trauma * Stab wound * Blunt trauma/superficial/closed * Penetrating trauma/open * Aerosol burn * Burn/Corrosion/Chemical burn * Frostbite * Occupational injuries * Traumatic amputation By region * Hand injury * Head injury * Chest trauma * Abdominal trauma This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Fracture blister	c0559878	30,344	wikipedia	https://en.wikipedia.org/wiki/Fracture_blister	2021-01-18T18:45:22	{"umls": ["C0559878"], "wikidata": ["Q5477585"]}
Lichen myxedematosus SpecialtyDermatology Lichen myxedematosus is a group of cutaneous disorders considered mucinoses.[1][2]:183 Conditions included in this group are:[2]:183 * Generalized lichen myxedematosus * Localized lichen myxedematosus * Discrete papular lichen myxedematosus * Acral persistent papular mucinosis * Self-healing papular mucinosis * Self-healing juvenile cutaneous mucinosis * Papular mucinosis of infancy * Atypical lichen myxedematosus * Atypical tuberous myxedema ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 2. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. ## External links[edit] Classification D * ICD-10: L98.5 (ILDS L98.530) * DiseasesDB: 31368 * v * t * e Mucinosis/Lichen myxedematosus Localized lichen myxedematosus * Discrete papular lichen myxedematosus * Acral persistent papular mucinosis * Self-healing papular mucinosis/Self-healing juvenile cutaneous mucinosis * Papular mucinosis of infancy * Atypical lichen myxedematosus * Atypical tuberous myxedema * Nodular lichen myxedematosus Other primary mucinoses * Cutaneous focal mucinosis * Cutaneous lupus mucinosis * Eccrine mucinosis * Alopecia mucinosa * Perifollicular mucinosis * Stiff skin syndrome * Generalized lichen myxedematosus Secondary mucinoses * Basal-cell carcinoma * Granuloma annulare [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Lichen myxedematosus	c0263390	30,345	wikipedia	https://en.wikipedia.org/wiki/Lichen_myxedematosus	2021-01-18T18:43:06	{"mesh": ["D053718"], "umls": ["C0263390"], "icd-10": ["L98.5"], "orphanet": ["402007"], "wikidata": ["Q6543199"]}
19p13.12 microdeletion syndrome is a newly described syndrome characterized by moderate to severe developmental delay, language delay, bilateral sensorineural and/or conductive hearing loss and facial dysmorphism. ## Epidemiology It has been reported in 6 patients to date. ## Clinical description Facial dysmorphism includes brachycephaly, anteverted nares, and ear malformations. Cardiac defects and abnormal behavior characterized by auto- and hetero-aggressivity and hyperactivity can be observed. ## Etiology This interstitial microdeletion was identified by comparative genomic hybridization (CGH) microarray and its size is variable. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	19p13.12 microdeletion syndrome	c4304579	30,346	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254346	2021-01-23T19:10:07	{"gard": ["10991"], "icd-10": ["Q93.5"], "synonyms": ["Del(19)(p13.12)", "Monosomy 19p13.12"]}
Nathan et al. (1994) identified a membrane form of L-glutamate decarboxylase and purified it to apparent homogeneity from hog brain. The purified GAD was established as an integral membrane protein by phase-partitioning assay, charge-shift electrophoresis, and chromatography on a hydrophobic interaction column. This membrane GAD has a native molecular mass of 96 +/- 5 kD and is a homodimer of 48 +/- 3 kD subunits. Immunoprecipitation and immunoblotting demonstrated antibodies against this membrane GAD in sera from patients with insulin-dependent diabetes mellitus. Nathan et al. (1994) suggested that this form of GAD is more likely to be involved in the pathogenesis of insulin-dependent diabetes and related autoimmune disorders such as stiff man syndrome (184850) than is soluble GAD. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	GLUTAMIC ACID DECARBOXYLASE, BRAIN, MEMBRANE FORM	c1841911	30,347	omim	https://www.omim.org/entry/138277	2019-09-22T16:40:39	{"omim": ["138277"]}
Microspherophakia Schematic diagram of the human eye(normal) SpecialtyOphthalmology Microspherophakia is a rare congenital autosomal recessive condition where the lens of the eye is smaller than normal and spherically shaped. This condition may be associated with a number of disorders including Peter's anomaly, Marfan syndrome, and Weill–Marchesani syndrome.[1] The spherical shape is caused by an underdeveloped zonule of Zinn, which doesn't exert enough force on the lens to make it form the usual oval shape.[2] It is a result of a homozygous mutation to the LTBP2 gene.[3] ## Contents * 1 See also * 2 References * 3 Further reading * 4 External links ## See also[edit] * Ectopia lentis ## References[edit] 1. ^ "Spherophakia". University of Arizona. Retrieved 2012-08-20. 2. ^ Nirankari, M.S.; Maudgal, M.C. (1959). "Microphakia". British Journal of Ophthalmology. 43 (5): 314–316. doi:10.1136/bjo.43.5.314. PMC 509814. PMID 13651569. 3. ^ Kumar et al. (October 2010). "A homozygous mutation in LTBP2 causes isolated microspherophakia". Human Genetics. 128 (4): 365–371. doi:10.1007/s00439-010-0858-8. PMID 20617341. S2CID 24209247.CS1 maint: uses authors parameter (link) ## Further reading[edit] Microspherophakia at Online Mendelian Inheritance in Man ## External links[edit] Classification D * ICD-10: Q12.4 * ICD-9-CM: 743.36 * OMIM: 251750 * MeSH: C563255 * SNOMED CT: 416671000 This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Microspherophakia	c3538951	30,348	wikipedia	https://en.wikipedia.org/wiki/Microspherophakia	2021-01-18T18:58:44	{"umls": ["C3538951"], "icd-9": ["743.36"], "icd-10": ["Q12.8", "Q12.4"], "orphanet": ["238763"], "wikidata": ["Q3857010"]}
Lucey-Driscoll syndrome, also known as transient familial hyperbilirubinemia, is a rare condition that leads to very high levels of bilirubin in a newborn's blood. Bilirubin comes from the breakdown of red blood cells and is handled by the liver. Babies with this condition may be born with jaundice, causing yellow skin, yellow eyes and excess sleepiness (lethargy). The cause of Lucey-Driscoll syndrome is thought to be due to compounds in the mother's and baby's blood that block the breakdown of bilirubin. In some babies, this condition may be the result of a genetic change in the UGT1A1 gene, a risk factor for high levels of bilirubin. The diagnosis is made based on the symptoms. Treatment for Lucey-Driscoll syndrome includes phototherapy, placing the baby under a blue light to treat the high level of bilirubin in the blood. Sometimes, replacing the baby's blood with different blood (exchange transfusion) is necessary. If untreated, high levels of bilirubin can cause seizures, neurologic problems (kernicterus) and even death. Most babies with Lucey-Driscoll will have no additional complications after treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Lucey-Driscoll syndrome	c0270210	30,349	gard	https://rarediseases.info.nih.gov/diseases/3304/lucey-driscoll-syndrome	2021-01-18T17:59:18	{"mesh": ["C562692"], "omim": ["237900"], "umls": ["C0270210"], "orphanet": ["2312"], "synonyms": ["Transient familial neonatal hyperbilirubinemia", "Transient familial hyperbilirubinemia"]}
Complex regional pain syndrome type 2 (CRPS2), or causalgia is a form of complex regional pain syndrome that develops after damage to a peripheral nerve and is characterized by spontaneous pain, allodynia and hyperalgesia , not necessarily limited to the territory of the injured nerve, as well as at some point, edema, changes in skin blood flow or sudomotor dysfunction in the pain area. ## Clinical description . [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Complex regional pain syndrome type 2	c0007462	30,350	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99994	2021-01-23T18:43:40	{"mesh": ["D002422"], "umls": ["C0007462"], "icd-10": ["G56.4"], "synonyms": ["Causalgia"]}
Viral infection of the skin Molluscum contagiosum Other namesWater warts Typical flesh-colored, dome-shaped and pearly lesions SpecialtyDermatology SymptomsSmall, raised, pink lesions with a dimple in the center[1] Usual onsetChildren 1 to 10 years of age[2] DurationUsually 6-12 months, may last up to four years[1] TypesMCV-1, MCV-2, MCV-3, MCV-4[3] CausesMolluscum contagiosum virus spread by direct contact or contaminated objects[4] Risk factorsWeak immune system, atopic dermatitis, crowded living conditions[2] Diagnostic methodBased on appearance[3] Differential diagnosisWarts, herpes simplex, chickenpox, folliculitis[5] PreventionHand washing, not sharing personal items[6] TreatmentNone, freezing, opening up the lesion and scraping the inside, laser therapy[7] MedicationCimetidine, podophyllotoxin[7] Frequency122 million / 1.8% (2010)[8] Molluscum contagiosum (MC), sometimes called water warts, is a viral infection of the skin that results in small raised pink lesions with a dimple in the center.[1] They may become itchy or sore, and occur singularly or in groups.[1] Any area of the skin may be affected, with abdomen, legs, arms, neck, genital area, and face being the most common.[1] Onset of the lesions is around seven weeks after infection.[3] They usually go away within a year without scarring.[1] The infection is caused by a poxvirus called the molluscum contagiosum virus (MCV).[1] The virus is spread either by direct contact, including sexual activity, or via contaminated objects such as towels.[4] The condition can also be spread to other areas of the body by the person themselves.[4] Risk factors include a weak immune system, atopic dermatitis, and crowded living conditions.[2] Following one infection, it is possible to get re-infected.[9] Diagnosis is typically based on the appearance of the lesions.[3] Prevention includes hand washing and not sharing personal items.[6] While treatment is not necessary, some may wish to have the lesions removed for cosmetic reasons or to prevent spread.[7] Removal may occur with freezing, laser therapy, or opening up the lesion and scraping the inside.[7] Scraping the lesion can, however, result in scarring.[9] The oral medication cimetidine, or podophyllotoxin cream applied to the skin, may also be used for treatment.[7] Approximately 122 million people globally were affected by molluscum contagiosum as of 2010 (1.8% of the population).[8] It is more common in children between the ages of one and ten years old.[2] The condition has become more common in the United States since 1966.[2] But having an infection is not a reason to keep a child out of school or daycare.[10] ## Contents * 1 Signs and symptoms * 2 Transmission * 3 Diagnosis * 4 Management * 4.1 Medications * 4.1.1 Imiquimod * 4.2 Surgery * 4.3 Laser * 5 Prognosis * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Molluscum lesions on an arm Molluscum contagiosum lesions are flesh-coloured, dome-shaped, and pearly in appearance. They are often 1–5 mm in diameter, with a dimpled center.[11] Molluscum lesions are most commonly found on the face, arms, legs, torso, and armpits in children. Adults typically have molluscum lesions in the genital region and this is considered to be a sexually transmitted infection; because of this, if genital lesions are found on a child, sexual abuse should be suspected.[3] These lesions are generally not painful, but they may itch or become irritated. Picking or scratching the bumps may lead to a spread of the viral infection responsible for molluscum contagiosum, an additional bacterial infection, and scarring.[3][12] In about 10% of the cases, eczema develops around the lesions.[citation needed] Individual molluscum lesions may go away on their own within two months and generally clear completely without treatment or scarring in six to twelve months.[3] Mean durations for an outbreak are variously reported from eight[13] to about 18 months,[14][15] but durations are reported as widely as six months to five years, lasting longer in immunosuppressed individuals.[15] ## Transmission[edit] As the name implies, molluscum contagiosum is extremely contagious.[3] Transmission of the molluscum contagiosum virus can occur many different ways including direct skin contact (e.g., contact sports or sexual activity), contact with an infected surface (fomite), or autoinoculation (self-infection) by scratching or picking molluscum lesions and then touching other parts of the skin not previously affected by the virus.[3] Children are particularly susceptible to autoinoculation and may have widespread clusters of lesions.[citation needed] The viral infection is limited to a localised area on the topmost layer of the superficial layer of the skin.[16] Once the virus-containing head of the lesion has been destroyed, the infection is gone. The central waxy core contains the virus.[citation needed] ## Diagnosis[edit] Diagnosis is made on the appearance; the virus cannot routinely be cultured. The diagnosis can be confirmed by excisional biopsy. Histologically, molluscum contagiosum is characterized by molluscum bodies (also known as Henderson-Patersen bodies) in the epidermis, above the stratum basale, which consist of cells with abundant large granular eosinophilic cytoplasmic inclusion bodies (accumulated virions) and a small nucleus that has been pushed to the periphery.[17][18] * Low magnification micrograph of a molluscum contagiosum lesion * Low-magnification micrograph of molluscum contagiosum, H&E stain * High-magnification micrograph of molluscum contagiosum, showing the characteristic molluscum bodies, H&E stain ## Management[edit] Because molluscum contagiosum usually resolves without treatment and treatment options can cause discomfort to children, initial recommendations are often to simply wait for the lesions to resolve on their own.[19] Of the treatments available, a meta-analysis of randomized controlled trials suggested that there is no difference between treatments in short term improvement, and no single treatment is significantly better than natural resolution of the condition.[20] Bumps located in the genital area may be treated in an effort to prevent them from spreading.[15] When treatment has resulted in elimination of all bumps, the infection has been effectively cured and will not reappear unless the person is reinfected.[21] ### Medications[edit] For mild cases, over-the-counter wart medicines, such as salicylic acid may[22] shorten infection duration. Daily topical application of tretinoin cream may also trigger resolution.[23] Studies have found cantharidin to be an effective and safe treatment for removing molluscum contagiosum.[24] This medication is usually well tolerated though mild side effects such as pain or blistering are common.[24] There is no high-quality evidence for cimetidine.[25] However, oral cimetidine has been used as an alternative treatment for the pediatric population as it is generally well tolerated and less invasive.[26] #### Imiquimod[edit] Imiquimod is a form of immunotherapy initially proposed as a treatment for molluscum based on promising results in small case series and clinical trials.[27] However, two large randomized controlled trials, specifically requested by the U.S. Food and Drug Administration under the Best Pharmaceuticals for Children Act both demonstrated that imiquimod cream applied three times per week was no more effective than placebo cream for treating molluscum after 18 weeks of treatment in a total of 702 children aged 2–12 years.[28] In 2007, results from those trials—which remain unpublished—were incorporated into FDA-approved prescribing information for imiquimod, which states: "Limitations of Use: Efficacy was not demonstrated for molluscum contagiosum in children aged 2–12."[28][29] In 2007, the FDA also updated imiquimod's label concerning safety issues raised in the two large trials and an FDA-requested pharmacokinetic study (the latter of which was published).[28] The updated safety label reads as follows: * Potential adverse effects of imiquimod use: "Similar to the studies conducted in adults, the most frequently reported adverse reaction from 2 studies in children with molluscum contagiosum was application site reaction. Adverse events which occurred more frequently in Aldara-treated subjects compared with vehicle-treated subjects generally resembled those seen in studies in indications approved for adults and also included otitis media (5% Aldara vs. 3% vehicle) and conjunctivitis (3% Aldara vs. 2% vehicle). Erythema was the most frequently reported local skin reaction. Severe local skin reactions reported by Aldara-treated subjects in the pediatric studies included erythema (28%), edema (8%), scabbing/crusting (5%), flaking/scaling (5%), erosion (2%) and weeping/exudate (2%)."[citation needed] * Potential systemic absorption of imiquimod, with negative effects on white blood cell counts overall, and specifically neutrophil counts: "Among the 20 subjects with evaluable laboratory assessments, the median WBC count decreased by 1.4109/L and the median absolute neutrophil count decreased by 1.42×109 L−1."[30] ### Surgery[edit] Surgical treatments include cryosurgery, in which liquid nitrogen is used to freeze and destroy lesions, as well as scraping them off with a curette. Application of liquid nitrogen may cause burning or stinging at the treated site, which may persist for a few minutes after the treatment. With liquid nitrogen, a blister may form at the treatment site, but it will slough off in two to four weeks. Cryosurgery and curette scraping can be painful procedures and can result in residual scarring.[31] ### Laser[edit] A 2014 systematic review of case reports and case series concluded that the limited available data suggest pulsed dye laser therapy is a safe and effective treatment for molluscum contagiosum and is generally well tolerated by children.[31] Side effects seen with pulsed dye laser therapy included mild temporary pain at the site of therapy, bruising (lasting up to 2–3 weeks), and temporary discoloration of the treated skin (as long as 1–6 months).[31] No cases of permanent scarring have been reported.[31] As of 2009, however, there is no evidence for genital lesions.[32] ## Prognosis[edit] Most cases of molluscum contagiosum will clear up naturally within two years (usually within nine months). So long as the skin growths are present, there is a possibility of transmitting the infection to another person. When the growths are gone, the possibility of spreading the infection is ended.[21] Unlike herpesviruses, which can remain inactive in the body for months or years before reappearing, molluscum contagiosum does not remain in the body when the growths are gone from the skin and will not reappear on their own.[21] ## Epidemiology[edit] As of 2010, approximately 122 million people were affected worldwide by molluscum contagiosum (1.8% of the population).[8] ## See also[edit] Acrochordons (also called skin tags—similar in appearance and grow in similar areas) * Basal-cell carcinoma * Wart (caused by the Human papillomavirus; also similar in appearance to molluscum) ## References[edit] 1. ^ a b c d e f g "Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 16 June 2017. Retrieved 10 June 2017. 2. ^ a b c d e "Risk Factors \| Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 10 June 2017. Retrieved 10 June 2017. 3. ^ a b c d e f g h i Ramdass, P; Mullick, S; Farber, HF (December 2015). "Viral Skin Diseases". Primary Care (Review). 42 (4): 517–67. doi:10.1016/j.pop.2015.08.006. PMID 26612372. 4. ^ a b c "Transmission \| Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 10 June 2017. Retrieved 10 June 2017. 5. ^ Ferri, Fred F. (2010). Ferri's differential diagnosis : a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders (2nd ed.). Philadelphia, PA: Elsevier/Mosby. p. Chapter M. ISBN 978-0323076999. 6. ^ a b "Prevention \| Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 17 June 2017. Retrieved 10 June 2017. 7. ^ a b c d e "Treatment Options \| Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 17 June 2017. Retrieved 10 June 2017. 8. ^ a b c Vos, Theo; Flaxman, D; Naghavi, A; et al. (December 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607. 9. ^ a b "Long Term Effects \| Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 17 June 2017. Retrieved 10 June 2017. 10. ^ "Day Care Centers and Schools \| Molluscum Contagiosum". www.cdc.gov. 11 May 2015. Archived from the original on 17 June 2017. Retrieved 10 June 2017. 11. ^ Likness, LP (June 2011). "Common dermatologic infections in athletes and return-to-play guidelines". The Journal of the American Osteopathic Association. 111 (6): 373–379. doi:10.7556/jaoa.2011.111.6.373. PMID 21771922. 12. ^ Basta-Juzbašić, A; Čeović, R (March 2014). "Chancroid, lymphogranuloma venereum, granuloma inguinale, genital herpes simplex infection, and molluscum contagiosum". Clinics in Dermatology (Review). 32 (2): 290–8. doi:10.1016/j.clindermatol.2013.08.013. PMID 24559566. 13. ^ Weller R, O'Callaghan CJ, MacSween RM, White MI (1999). "Scarring in molluscum contagiosum: comparison of physical expression and phenol ablation". BMJ. 319 (7224): 1540. doi:10.1136/bmj.319.7224.1540. PMC 28297. PMID 10591712. 14. ^ MedlinePlus Encyclopedia: Molluscum Contagiosum 15. ^ a b c Tyring SK (2003). "Molluscum contagiosum: the importance of early diagnosis and treatment". Am. J. Obstet. Gynecol. 189 (3 Suppl): S12–6. doi:10.1067/S0002-9378(03)00793-2. PMID 14532898. 16. ^ "Pamphlets: Molluscum Contagiosum". American Academy of Dermatology. 2006. Archived from the original on 2008-12-01. Retrieved 2008-11-30. 17. ^ Chen, X; Anstey, AV; Bugert, JJ (October 2013). "Molluscum contagiosum virus infection". Lancet Infectious Diseases. 13 (10): 877–88. doi:10.1016/S1473-3099(13)70109-9. PMID 23972567. 18. ^ Rao, K; Priya, N; Umadevi, H; Smitha, T (January 2013). "Molluscum contagiosum". Journal of Oral and Maxillofacial Pathology. 17 (1): 146–7. doi:10.4103/0973-029X.110726. PMC 3687174. PMID 23798852. 19. ^ Prodigy knowledgebase (July 2003). "Molluscum Contagiosum". National Health Service. Archived from the original on 2010-10-13. Retrieved 2010-04-20. 20. ^ van der Wouden, Johannes C; van der Sande, Renske; Kruithof, Emma J; Sollie, Annet; van Suijlekom-Smit, Lisette WA; Koning, Sander (2017-05-17). "Interventions for cutaneous molluscum contagiosum". Cochrane Database of Systematic Reviews. 5: CD004767. doi:10.1002/14651858.CD004767.pub4. ISSN 1465-1858. PMC 6481355. PMID 28513067. 21. ^ a b c "Frequently Asked Questions: For Everyone. CDC Molluscum Contagiosum". United States Centers for Disease Control and Prevention. Archived from the original on 2008-12-19. Retrieved 2008-12-08. 22. ^ Schmitt, Jochen; Diepgen, Thomas L. (2008). "Molluscum contagiosum" (PDF). In Berthold Rzany; Williams, Hywel; Bigby, Michael E.; Diepgen, Thomas L.; Herxheimer, Andrew; Luigi Naldi (eds.). Evidence-Based Dermatology. Evidence-based Medicine. London: BMJ Books. ISBN 978-1-4051-4518-3. Archived from the original (PDF) on 2009-02-19. 23. ^ Credo, BV; Dyment, PG (1996). "Molluscum Contagiosum". Adolesc Med. 7 (1): 57–62. PMID 10359957. 24. ^ a b Torbeck R, Pan M, DeMoll E, Levitt J (June 2014). "Cantharidin: a comprehensive review of the clinical literature". Dermatology Online Journal (Review). 20 (6). PMID 24945640. Archived from the original on 2016-03-04. 25. ^ Scheinfeld N (March 2003). "Cimetidine: a review of the recent developments and reports in cutaneous medicine". Dermatol. Online J. 9 (2): 4. PMID 12639457. Archived from the original on 2008-09-28. 26. ^ "Treatment Options - Molluscum Contagiosum - Pox viruses - CDC". www.cdc.gov. 2 October 2017. 27. ^ Hanna D, Hatami A, Powell J, et al. (2006). "A prospective randomized trial comparing the efficacy and adverse effects of four recognized treatments of molluscum contagiosum in children". Pediatric Dermatology. 23 (6): 574–9. doi:10.1111/j.1525-1470.2006.00313.x. PMID 17156002. S2CID 43224667. 28. ^ a b c Katz, KA (February 2015). "Dermatologists, imiquimod, and treatment of molluscum contagiosum in children: righting wrongs". JAMA Dermatology. 151 (2): 125–6. doi:10.1001/jamadermatol.2014.3335. PMID 25587702. 29. ^ Katz, KA; Swetman, GL (July 2013). "Imiquimod, molluscum, and the need for a better "best pharmaceuticals for children" act". Pediatrics. 132 (1): 1–3. doi:10.1542/peds.2013-0116. PMID 23796740. S2CID 29556501. 30. ^ DailyMed. Aldara (imiquimod) Cream for Topical use (Prescribing information): "DailyMed". Archived from the original on 2013-07-16. Retrieved 2013-07-17. 31. ^ a b c d Griffith, RD; Yazdani Abyaneh, MA; Falto-Aizpurua, L; Nouri, K (November 2014). "Pulsed dye laser therapy for molluscum contagiosum: a systematic review". Journal of Drugs in Dermatology (Review). 13 (11): 1349–52. PMID 25607701. 32. ^ Brown, M; Paulson, C; Henry, SL (Oct 15, 2009). "Treatment for anogenital molluscum contagiosum". American Family Physician. 80 (8): 864. PMID 19835348. ## External links[edit] Wikimedia Commons has media related to Molluscum contagiosum. * Molluscum—Center for Disease Control * Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae Classification D * ICD-10: B08.1 * ICD-9-CM: 078.0 * MeSH: D008976 * DiseasesDB: 8337 External resources * MedlinePlus: 000826 * eMedicine: derm/270 * 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 Sexually transmitted infections (STI) Bacterial * Chancroid (Haemophilus ducreyi) * Chlamydia, lymphogranuloma venereum (Chlamydia trachomatis) * Donovanosis (Klebsiella granulomatis) * Gonorrhea (Neisseria gonorrhoeae) * Mycoplasma hominis infection (Mycoplasma hominis) * Syphilis (Treponema pallidum) * Ureaplasma infection (Ureaplasma urealyticum) Protozoal * Trichomoniasis (Trichomonas vaginalis) Parasitic * Crab louse * Scabies Viral * AIDS (HIV-1/HIV-2) * Cancer * cervical * vulvar * penile * anal * Human papillomavirus (HPV) * Genital warts (condyloma) * Hepatitis B (Hepatitis B virus) * Herpes simplex * HSV-1 & HSV-2 * Molluscum contagiosum (MCV) General inflammation female Cervicitis Pelvic inflammatory disease (PID) male Epididymitis Prostatitis either Proctitis Urethritis/Non-gonococcal urethritis (NGU) * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Molluscum contagiosum	c0026393	30,351	wikipedia	https://en.wikipedia.org/wiki/Molluscum_contagiosum	2021-01-18T19:07:09	{"mesh": ["D008976"], "umls": ["C0026393"], "wikidata": ["Q659584"]}
A rare congenital limb malformation characterized by complete or partial absence of the fibula bone combined with dysplasia and hypoplasia of the tibia and dysplasia, hypoplasia or aplasia of parts of the foot. ## Epidemiology Fibular hemimelia incidence is reported to be between 1/50,000 and 1/135,000 births. A slight male preponderance has been reported in some studies, whereas other reports describe an equal sex distribution. ## Clinical description Unilateral involvement is found in most cases. Bilateral fibular hemimelia is rare. Fibular hemimelia may vary from partial absence of the fibula with mild shortening and a relatively normal-appearing limb, to absence of the fibula with severe shortening and pro-curvatum of the tibia, knee joint instability and foot and ankle deformity. The foot frequently shows deficiency of the lateral rays with or without tarsal coalitions, and an equinovalgus position. Clubfoot-type fibular hemimelia presents with a clubfoot-like foot deformity. Shortening of the leg results from a constant growth inhibition that allows for prediction of leg length discrepancy at maturity. In many cases, fibular hemimelia is associated with congenital femoral deficiency of the femur (CFD), which can be very mild with only mild shortening and distal femur valgus. Most cases do not show any additional anomalies or other birth defects. In rare cases other skeletal anomalies (craniosynostosis, syndactyly, brachydactyly, oligodactyly and ectrodactyly) may be present. Fibular hemimelia can also be found in generalized skeletal dysplasias and dysostoses. Very rarely, fibular hemimelia is associated with non-skeletal malformations (eye abnormalities such as anterior chamber anomalies or anophthalmia, cardiac anomalies, renal dysplasia, thrombocytopenia, thoracoabdominal schisis, spina bifida). ## Etiology The etiology is unclear. The deformity is probably due to disruptions during the critical period of embryonic limb development, between 4th and 7th week of gestation. A somatic gene mutation has been suggested. ## Diagnostic methods Diagnosis is based on clinical examination and X-rays. ## Differential diagnosis Differential diagnoses include skeletal dysplasias and dysostoses with asymmetrical involvement of the lower limbs such as femoral-facial syndrome. ## Antenatal diagnosis Prenatal diagnosis of fibular hemimelia has been reported. The rate of true positive prenatal diagnosis is depending on the severity of shortening and the presence of foot anomalies like absent rays or clubfoot. ## Genetic counseling Most cases are sporadic. A family history has been reported in a small percentage of cases with an autosomal dominant pattern of inheritance and incomplete penetrance. ## Management and treatment Management requires a multidisciplinary approach (genetic counselors, pediatric orthopedic surgeons,). Orthopedic treatment aims at correcting the leg length discrepancy, and, in bilateral cases, correcting the asymmetrical dwarfism. However, the functional outcome in more severe cases is primarily depending on correction and management of the deformities and anomalies at the knee and foot and ankle. In less severe cases with minimal hypoplasia of the fibula and a stable knee and foot and ankle, simple bone lengthening is used to equalize limb length. In moderate to severe fibular hemimelia, limb lengthening needs to be combined with a correction of the complex deformities at the foot and ankle. If instability at the knee joint is clinically significant it also needs to be addressed with reconstructive procedures. Very rarely, for cases with most severe shortening and a non-functional foot, amputation with prosthetic fitting in early childhood may be considered. However, even then tibial procurvatum and knee flexion contracture need to be addressed. ## Prognosis Fibular hemimelia is usually a benign condition, although severe cases might need multiple surgeries throughout childhood. The functional result mostly depends on the status or quality of reconstruction of the knee and foot and ankle. In case of syndromic presentation, prognosis depends on the nature of the associated anomalies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Fibular hemimelia	None	30,352	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93323	2021-01-23T18:20:48	{"icd-10": ["Q72.6"], "synonyms": ["Congenital longitudinal deficiency of the fibula", "Fibular longitudinal meromelia"]}
A rare, genetic, intestinal disease characterized by early-onset, chronic diarrhea and intestinal inflammation due to overactivity of guanylate cyclase 2C. Additional manifestations include meteorism, dehydration, metabolic acidosis and electrolyte disturbances. Intestinal dysmotility, small-bowel obstruction and esophagitis (with or without esophageal hernia), as well as irritable bowel syndrome (without severe abdominal pain) and Crohn's disease, are frequently 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Chronic infantile diarrhea due to guanylate cyclase 2C overactivity	c3553270	30,353	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314373	2021-01-23T17:51:27	{"omim": ["614616"], "icd-10": ["P78.3"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2013) This article needs attention from an expert in Medicine. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Medicine may be able to help recruit an expert. (January 2019) Peripheral vasculopathy is a general classification for disorders of the blood vessels relative to a person's arms, legs or extremities including peripheral vascular disease.[1] ## References[edit] 1. ^ "American Heritage Dictionary". Houghton Mifflin Company. Retrieved 26 November 2013.The American Heritage® Medical Dictionary * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Peripheral vasculopathy	None	30,354	wikipedia	https://en.wikipedia.org/wiki/Peripheral_vasculopathy	2021-01-18T18:49:37	{"wikidata": ["Q16919543"]}
A number sign (#) is used with this entry because Verheij syndrome (VRJS) can be caused by heterozygous mutation in the PUF60 gene (604819) on chromosome 8q24.3. The same VRJS phenotype results from a contiguous gene deletion involving the PUF60 and SCRIB (607733) genes on 8q24.3. Description Verheij syndrome is characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects (summary by Verheij et al., 2009 and Dauber et al., 2013). Clinical Features ### Chromosome 8q24.3 Deletion Syndrome Verheij et al. (2009) reported 2 unrelated Dutch children born with multiple and somewhat overlapping congenital anomalies associated with large heterozygous de novo deletions of chromosome 8q24. A 20-month-old boy had delayed psychomotor development, poor growth, seizures, ventricular septal defect, postaxial polydactyly, and hip dislocation. Dysmorphic features included plagiocephaly, anteverted nares, short columella, high palate, micrognathia, low-set and posteriorly rotated ears, short neck, and coloboma. He also had laryngotracheomalacia. Brain MRI showed hypoplastic corpus callosum, delayed myelination, and cerebral atrophy. The second child was a girl with poor growth, unilateral coloboma, atrial septal defects, clenched thumbs, syndactyly of the hands and feet, metatarsal fusion, unilateral hip luxation, severe failure to thrive, and seizures. Dysmorphic features included triangular ears with flattened helices, prominent nasal tip, and hypoplastic nasal alae. Some features were reminiscent of Langer-Giedion syndrome (150230), but she died at age 11 months from a subdural hematoma before classic features of that syndrome could develop. Dauber et al. (2013) reported 5 unrelated children with 5 different heterozygous de novo interstitial deletions of chromosome 8q24.3; the children were identified from a cohort of patients who underwent array comparative genomic hybridization (aCGH). The 5 children ranged in age from 3 to 17 years, and all had facial dysmorphism and global growth retardation, including 3 with microcephaly; all but 1 had developmental delay. Common dysmorphic facial features included long philtrum, anteverted nares, short nose, thin upper lip, and broad nasal root. More variable features included microretrognathia, coloboma, short neck, preauricular pits, and bitemporal narrowing. All but 1 patient had renal abnormalities, including unilateral renal agenesis, renal hypoplasia, polycystic kidneys, and ectopic renal fusion. Three patients had vertebral abnormalities, such as sacral dysplasia, coccyx agenesis, vertebral fusion, or hemivertebrae, and 4 had joint laxity or hip dislocation. Two patients had cardiac ventricular defects. ### Verheij Syndrome with PUF60 Mutations Dauber et al. (2013) reported a patient with features similar to those reported by Verheij et al. (2009), including severe growth retardation, delayed psychomotor development, microcephaly (-4.1 SD), dysmorphic facial features, seizures, ventricular septal defect, hip dislocation, hemivertebrae, and scoliosis. Coloboma and renal abnormalities were not present. Exome sequencing of this patient identified a heterozygous de novo missense mutation in the PUF60 gene (see MOLECULAR GENETICS). El Chehadeh et al. (2017) reported 5 patients with features of Verheij syndrome who had de novo heterozygous mutations in the PUF60 gene. All of the patients had facial features similar to those seen in patients with 8q24.3 microdeletions and developmental delay. Other findings included feeding difficulties (3/5), cardiac defects (4/5), short stature (4/5), joint laxity and/or dislocation (4/5), vertebral anomalies (2/5), bilateral microphthalmia and iridoretinal coloboma (1/5), bilateral optic nerve hypoplasia (2/5), renal anomalies (2/5), and branchial arch defects (2/5). Low et al. (2017) reported 12 patients with features of Verheij syndrome and de novo heterozygous mutations in PUF60. Based on the phenotype in their patients and those previously reported, Low et al. (2017) suggested that short stature, relative microcephaly, and developmental delay are consistent findings, although one of their patients had macrocephaly, hydrocephalus, and normal stature. Similar findings with the reported cases included abnormal segmentation of the vertebrae, minor developmental abnormalities of the distal limbs (e.g., clinodactyly, brachydactyly of the fifth fingers, and preaxial polydactyly), ocular colobomas, renal malformations, and congenital heart defects. Other findings included seizures, feeding difficulties, and recurrent respiratory infections. Characteristic facial findings included thin upper lip, long philtrum, flaring of eyebrows, and narrow almond-shaped palpebral fissures. Low et al. (2017) noted striking phenotypic variability among the patients, making the phenotype difficult to recognize. Santos-Simarro et al. (2017) reported 3 patients with Verheij syndrome with heterozygous mutations in PUF60. The patients had intellectual disability, growth restriction, microcephaly, a consistent facial phenotype, and other malformations, including cardiac defects in 2 patients, eye colobomas in 2 patients, and talipes, white matter abnormalities on brain imaging, and unilateral hypoplasia of the depressor anguli oris muscle, each in 1 patient. Graziano et al. (2017) reported a 4-year-old boy with features of Verheij syndrome and a heterozygous mutation in PUF60. The child had a developmental eye defect, characterized by bilateral iris, optic nerve, and chorioretinal coloboma associated with a fibrous stalk of vasculature (persistent fetal vasculature syndrome) from the optic nerve head. Inferior lens subluxation and mild microphthalmia were also present. Based on this patient and their review of previously reported patients, Graziano et al. (2017) suggested that ocular developmental defects, especially coloboma, are frequent in patients with a mutation in the PUF60 gene. Cytogenetics Verheij et al. (2009) reported 2 unrelated Dutch children with multiple similar congenital anomalies associated with de novo heterozygous deletions of chromosome 8q24. Cytogenetic and FISH analysis showed deletions of 15.1 Mb and 23.5 Mb. The deletion in the second patient included both the TRPS1 (604386) and EXT1 (608177) genes, consistent with a diagnosis of Langer-Giedion syndrome. The commonly deleted region shared by the patients was 8.35 Mb and included the KCNQ3 gene (602232). Dauber et al. (2013) identified 5 unrelated patients with 5 different heterozygous de novo interstitial deletions of chromosome 8q24.3. The deletions ranged from 78 kb to 1 Mb, and none of the breakpoints were the same. The minimal common deletion encompassed 3 genes: SCRIB, NRBP2 (615563), and PUF60. Morpholino knockout of these genes in zebrafish suggested that haploinsufficiency for SCRIB and PUF60 was responsible for the phenotype, whereas loss of NRBP2 was considered unlikely to contribute to the clinical features. Dauber et al. (2013) found that morpholino-mediated knockdown of either Puf60 or Scrib in zebrafish recapitulated some of the human phenotypes. Knockdown of either gene caused short stature, microcephaly, and reduced jaw size. Knockdown of Scrib alone resulted in coloboma and renal abnormalities, whereas knockdown of Puf60 alone resulted in cardiac structural defects. Knockdown of both genes exacerbated the short stature phenotype. Dauber et al. (2013) concluded that haploinsufficiency of both genes drives the majority of the syndromic phenotypes found in patients with the copy number variation. The authors noted that the zebrafish approach is limited to the assessment of anatomic phenotypes, and that contributions to cognitive and behavioral defects is not possible. Molecular Genetics By exome sequencing in a 21-year-old woman with features of Verheij syndrome (VRJS; 615583), Dauber et al. (2013) identified a heterozygous de novo missense mutation in the PUF60 gene (H169Y; 604819.0001). By whole-exome sequencing (WES) in 5 patients with features of VRJS, El Chehadeh et al. (2017) identified heterozygous de novo mutations in the PUF60 gene (see 604819.0002-604819.0006), including splice site, frameshift, nonsense, and missense variants. Low et al. (2017) identified 12 patients with VRJS who had de novo heterozygous mutations in PUF60. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, included 4 frameshift mutations resulting in premature stop codons, 3 missense mutations that clustered within the RNA recognition motif, and 5 essential splice site mutations. Analysis of cDNA from a fibroblast cell line from one of the patients with a splice site mutation confirmed aberrant splicing. Using next-generation sequencing of a custom panel of genes involved in intellectual disability, autism spectrum disorders, and other disorders, Santos-Simarro et al. (2017) identified 3 patients with VRJS who had de novo heterozygous mutations in PUF60 (see, e.g., E18K, 604819.0007). All of the mutations were confirmed by Sanger sequencing. In a 4-year-old boy with VRJS, Graziano et al. (2017) identified de novo heterozygosity for the same E18K mutation in the PUF60 gene that had been identified by Santos-Simarro et al. (2017). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of approximately 700 WES sequencing tested persons, mainly of Italian origin. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Other \- Growth retardation HEAD & NECK Head \- Microcephaly Face \- Bitemporal narrowing \- Long philtrum Eyes \- Coloboma Nose \- Short nose \- Broad nasal root Mouth \- Thin upper lip Neck \- Short neck CARDIOVASCULAR Heart \- Septal defects ABDOMEN Gastrointestinal \- Poor feeding GENITOURINARY Kidneys \- Renal hypoplasia \- Renal agenesis \- Renal cysts \- Renal fusion SKELETAL Spine \- Vertebral abnormalities \- Hemivertebrae \- Fused vertebrae \- Scoliosis Pelvis \- Hip dislocation Limbs \- Elbow subluxation Hands \- Short fifth fingers \- Clinodactyly \- Malpositioned thumbs NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Cerebral atrophy LABORATORY ABNORMALITIES \- Deletion (78kb to 1Mb) of chromosome 8q24.3 including the SCRIB ( 607733 ) and PUF60 ( 604819 ) genes MISCELLANEOUS \- Onset at birth \- Highly variable phenotype MOLECULAR BASIS \- Caused by mutation in the poly-U-binding splicing factor, 60kD gene (PUF60, 604819.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	VERHEIJ SYNDROME	c3810023	30,355	omim	https://www.omim.org/entry/615583	2019-09-22T15:51:35	{"omim": ["615583"], "orphanet": ["508488", "508498"], "synonyms": ["Alternative titles", "Monosomy 8q24.3", "CHROMOSOME 8q24.3 DELETION SYNDROME", "Deletion 8q24.3", "Verheij syndrome", "Del(8)(q24.3)"]}
A number sign (#) is used with this entry because of evidence that Fanconi anemia complementation group W (FANCW) is caused by compound heterozygous mutation in the RFWD3 gene (614151) on chromosome 16q23. One such patient has been reported. For a discussion of genetic heterogeneity of Fanconi anemia, see FANCA (227650). Clinical Features Knies et al. (2017) reported a 12-year-old German girl (patient 1143), born of unrelated parents, with typical Fanconi anemia. She was born with intrauterine growth retardation at 35 weeks' gestation and showed duodenal atresia, radial ray malformations, bilateral absent thumbs, and small midface. Ultrasound showed enlarged brain ventricles, hypoplastic left kidney, and polysplenia. Brain MRI showed rarefied periventricular white matter, narrow corpus callosum, abnormal pituitary, and Chiari malformation type I, but cognitive development was normal and she had no neurologic signs. She had poor overall growth and microcephaly, and she was treated for hypothalamic partial growth hormone deficiency. From age 10 years, she developed bone marrow abnormalities, including cytopenia, reduced hematopoiesis, and mild dysplastic features, such as dysmyelopoiesis, dysmegakaryopoiesis, and megaloblastoid erythropoiesis. Myelodysplastic syndrome was excluded on several occasions. The cytopenia was restricted to the bone marrow; peripheral blood counts remained stable. Cultured lymphocytes and fibroblasts showed hypersensitivity to DNA cross-linking agents, confirming the diagnosis of Fanconi anemia. Inheritance The transmission pattern of FANCW in the family reported by Knies et al. (2017) was consistent with autosomal recessive inheritance. Molecular Genetics In a 12-year-old German girl (patient 1143) with FANCW, Knies et al. (2017) identified compound heterozygous mutations in the RFWD3 gene (c.205_206dupCC, 614151.0001 and I639K, 614151.0002). Patient cells showed increased chromosomal breakage, reduced survival, and cell cycle arrest in G2 following exposure to mitomycin C (MMC) and additional DNA cross-linking agents, and these defects could be restored by expression of wildtype RFWD3. The specific results suggested a defect in BRCA2 (600185)-dependent homologous recombination (HR). In vitro studies of the I639K variant indicated that it had less relocalization to the nucleus and to chromatin compared to wildtype, had disrupted physical interaction with RPA proteins (see, e.g., RPA2, 179836), and caused impaired HR in transduced cells. Three different cellular models with generation of RFWD3 mutants recapitulated the defects observed in patient cells, indicating that RFWD3 normally promotes HR induced by DNA interstrand cross-links. Knies et al. (2017) concluded that RFWD3 is positioned late in the FA/BRCA pathway, downstream of BRCA2/FANCD1. Animal Model Knies et al. (2017) found that Rfwd3-null mice were viable and did not show overt phenotypic abnormalities, although there was some evidence for increased embryonic lethality, earlier death, and subfertility, associated with testicular and ovarian atrophy in mutant mice. Mutant mouse embryonic fibroblasts were hypersensitive to DNA cross-linking agents and showed increased chromosomal breakage compared to controls. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Poor postnatal growth HEAD & NECK Head \- Microcephaly Face \- Midface hypoplasia ABDOMEN Spleen \- Polysplenia Gastrointestinal \- Duodenal atresia GENITOURINARY Kidneys \- Hypoplastic kidney SKELETAL Limbs \- Radial ray abnormalities Hands \- Absent thumbs NEUROLOGIC Central Nervous System \- Enlarged ventricles \- Variable brain abnormalities \- Normal development \- Normal cognition \- Periventricular white matter abnormalities \- Narrow corpus callosum \- Pituitary structural abnormalities \- Chiari malformation HEMATOLOGY \- Bone marrow abnormalities \- Cytopenia in the bone marrow \- Normal peripheral values \- Dysplastic bone marrow \- Dysmyelopoiesis \- Dysmegakaryopoiesis \- Megaloblastoid erythropoiesis LABORATORY ABNORMALITIES \- Patient cells show hypersensitivity to DNA cross-linking agents MISCELLANEOUS \- Onset at birth \- One German girl has been reported (last curated November 2017) MOLECULAR BASIS \- Caused by mutation in the ring finger and WD repeat domains-containing protein 3 gene (RFWD3, 614151.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	FANCONI ANEMIA, COMPLEMENTATION GROUP W	c4521564	30,356	omim	https://www.omim.org/entry/617784	2019-09-22T15:44:45	{"omim": ["617784"], "genereviews": ["NBK1401"]}
A number sign (#) is used with this entry because of evidence that Griscelli syndrome with primary neurologic impairment and without immunologic impairment, referred to as type 1, is caused by homozygous mutation in the gene encoding myosin VA (MYO5A; 160777) on chromosome 15q21. Description Griscelli syndrome type 1 (GS1) represents hypomelanosis with a primary neurologic deficit and without immunologic impairment or manifestations of hemophagocytic syndrome (Menasche et al., 2002). Griscelli syndrome with immune impairment, or Griscelli syndrome type 2 (607624), is caused by mutation in the RAB27A gene (603868). Griscelli syndrome type 3 (609227), characterized by hypomelanosis with no immunologic or neurologic manifestations, can be caused by mutation in the melanophilin (MLPH; 606526) or MYO5A genes. Griscelli syndrome is a rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. While most patients also develop hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation (Menasche et al., 2000), some show severe neurologic impairment early in life without apparent immune abnormalities. Bahadoran et al. (2003) characterized GS1 as comprising hypomelanosis and severe central nervous system dysfunction, corresponding to the 'dilute' phenotype in the mouse, and GS2 as comprising hypomelanosis and lymphohistiocytotic hemophagocytosis, corresponding to the 'ashen' phenotype in mouse. Anikster et al. (2002), Menasche et al. (2002), Huizing et al. (2002), and Bahadoran et al. (2003, 2003) suggested that Elejalde syndrome (256710) in some patients and GS1 represent the same entity. Clinical Features As the original patients described by Griscelli et al. (1978) manifested signs of an immune dysfunction, these patients are discussed in the entry for GS2 (607624). Pastural et al. (1997, 2000) described patients with Griscelli syndrome who were found to have mutations in the MYO5A gene. Both patients were referred because of hypotonia, marked motor development delay, and mental retardation, without a history of infections or 'accelerated phase' characterized by uncontrolled T lymphocyte and macrophage activation. Duran-McKinster et al. (1999) described 7 patients thought to have Elejalde syndrome. The patients had silvery hair and profound neurologic dysfunction. Immune impairment was not found. The age of onset of neurologic signs ranged from 1 month to 11 years. The signs included severe muscular hypotonia, ocular alterations, and seizures. Mental retardation since the first months of life was noted in 4 cases. Psychomotor development was normal in 3 cases, but suddenly the patients presented with a regressive neurologic process. Four patients died between 6 months and 3 years after the onset of neurologic dysfunction. In addition to the silver-leaden hair, bronze skin developed after sun exposure. Large granules of melanin unevenly distributed in the hair shaft were observed. Duran-McKinster et al. (1999) recommended that the differential diagnosis include Chediak-Higashi syndrome (214500) and Griscelli syndrome. Ivanovich et al. (2001) reported a 12-year-old male with Elejalde syndrome, also known as neuroectodermal melanolysosomal disease, and compared this condition with Chediak-Higashi and Griscelli syndromes. Their patient had severe developmental delay, seizure activity, exotropia, nystagmus, ataxia, and silvery gray hair and eyebrows. His skin was not hypopigmented but bronzed with diffuse freckling in sun-exposed areas. He had no history of recurrent infections and had normal immunologic studies. The authors suggested that their case may be the oldest living child with this condition reported in the literature. Bahadoran et al. (2003) noted that 2 groups of patients with Elejalde syndrome, possibly representing separate entities, were described. In the original description patients showed the characteristic hair shaft melanin granule clumping of Griscelli syndrome, but melanosome transfer to keratinocytes appeared normal, melanocyte maturation appeared abnormal, and inclusion bodies occurred in other cell types. By contrast, the second series of Elejalde syndrome patients (Duran-McKinster et al., 1999; Ivanovich et al., 2001) had clinical and histologic features suggestive of GS1. Thomas et al. (2009) reported 2 sisters, born of consanguineous Iraqi parents, with Griscelli syndrome type 1 confirmed by genetic analysis. Both had pigmentary abnormalities of the hair and skin. Neurologic signs included roving eye movements, seizures, hypotonia, and delayed psychomotor development with mental retardation. Both developed scoliosis and became wheelchair-bound, likely due to neurologic impairment. A maternal uncle was reportedly affected. Molecular Genetics Pastural et al. (1997) used linkage analysis in 3 consanguineous families and 1 nonconsanguineous family to map Griscelli syndrome to 15q21. Because of the similarities to the phenotype in the 'dilute' mouse, which is due to mutation in an unconventional myosin gene, they looked at regions of chromosomes 19, 10, and 18 known to contain genes of this type and excluded linkage to those areas. On the other hand, a peak lod score of 4.40 was obtained for a cluster of markers on chromosome 15, in a region containing the MYO5A gene. Pastural et al. (1997) demonstrated a nonsense mutation in MYO5A (160777.0002) in a Turkish patient. Menasche et al. (2002) discussed the relationship between Griscelli syndrome type 1 and Elejalde syndrome (256710). Anikster et al. (2002) suggested that neurologic involvement in some patients with Griscelli syndrome occurred secondarily to the hemophagocytic syndrome and that patients with primary central nervous system (CNS) complications and MYO5A mutations have Elejalde syndrome. Several reports established that neurologic manifestations in patients with Griscelli syndrome caused by RAB27A (603868) (GS2) were related to lymphocyte infiltration of the CNS (Menasche et al., 2000; Pastural et al., 2000; de Saint Basile and Fischer, 2001), whereas patients with Griscelli syndrome caused by MYO5A mutations (GS1) exhibited a primary neurologic disease, potentially described as Elejalde syndrome, unrelated to the hematopoietic lineage, as observed in Myo5a mutant 'dilute' mice (de Saint Basile and Fischer, 2001; Ivanovich et al., 2001). MYO5A and RAB27A interact in the same molecular pathway, resulting in melanosome transport on actin filaments to dock at the plasma membrane. Menasche et al. (2002) suggested that patients with partial albinism and manifestations of hemophagocytic syndrome, with or without neurologic involvement, should be screened for mutation in RAB27A, and patients with partial albinism and primary neurologic disease without hemophagocytic syndrome should be screened for MYO5A mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Roving eye movements \- Poor visual fixation SKIN, NAILS, & HAIR Skin \- Skin hypopigmentation \- Accumulation of melanosomes in melanocytes Hair \- Silver-gray hair \- Melanin pigment aggregation in hair shafts NEUROLOGIC Central Nervous System \- Developmental delay \- Hypotonia \- Mental retardation \- Seizures IMMUNOLOGY \- No immunologic abnormalities MISCELLANEOUS \- Onset in infancy or early childhood \- May be same entity as Elejalde syndrome ( 256710 ) \- See also Griscelli syndrome type 2 ( 607624 ) for a similar disorder with characteristic immunologic abnormalities and \- Griscelli syndrome type 3 ( 609227 ) for a similar disorder without neurologic or immunologic abnormalities MOLECULAR BASIS \- Caused by mutation in the myosin VA gene (MYO5A, 160777.0002 ) ▲ 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	GRISCELLI SYNDROME, TYPE 1	c1859194	30,357	omim	https://www.omim.org/entry/214450	2019-09-22T16:29:47	{"doid": ["0060832"], "mesh": ["C537301"], "omim": ["214450"], "orphanet": ["79476", "381"], "synonyms": ["Alternative titles", "GRISCELLI SYNDROME WITH NEUROLOGIC IMPAIRMENT", "PARTIAL ALBINISM AND PRIMARY NEUROLOGIC DISEASE WITHOUT HEMOPHAGOCYTIC SYNDROME", "GRISCELLI SYNDROME, CUTANEOUS AND NEUROLOGIC TYPE"]}
A number sign (#) is used with this entry because of evidence that atrioventricular septal defect-5 (AVSD5) is caused by heterozygous mutation in the GATA6 gene (601656) on chromosome 18q11. Description The term 'atrioventricular septal defect' (AVSD) covers a spectrum of congenital heart malformations characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. In ostium primum atrial septal defect (ASD) there are separate atrioventricular valvar orifices despite a common junction, whereas in complete AVSD the valve itself is also shared (summary by Craig, 2006). AVSD, also designated endocardial cushion defect or atrioventricular canal defect (AVCD), is known to occur in either a nonsyndromic (isolated) form or, more commonly, as part of a malformation syndrome. The 2 syndromes most frequently associated with AVSD are Down syndrome (190685), in which AVSD is the most frequent congenital heart defect, and Ivemark syndrome (208530) (summary by Carmi et al., 1992). For a discussion of genetic heterogeneity of atrioventricular septal defects, see AVSD1 (606215). Molecular Genetics In a Hispanic patient with atrioventricular septal defect, Maitra et al. (2010) identified heterozygosity for a gain-of-function missense mutation in the GATA6 gene (A178V; 601656.0004). No DNA was available from family members, but the mutation was not found in 288 control individuals, including 96 of Hispanic ethnicity. The patient had unbalanced AVSD, hypoplastic left ventricle, and 2 muscular ventricular septal defects with no additional evidence of heterotaxy syndrome (see 306955). INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrioventricular septal defect, unbalanced \- Hypoplastic left ventricle \- Ventricular septal defect, muscular MOLECULAR BASIS \- Caused by mutation in the GATA-binding protein-6 gene (GATA6, 601656.0004 ) ▲ 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	ATRIOVENTRICULAR SEPTAL DEFECT 5	c1389018	30,358	omim	https://www.omim.org/entry/614474	2019-09-22T15:55:08	{"doid": ["0050651"], "mesh": ["C562831"], "omim": ["614474"], "orphanet": ["98722"]}
Spinocerebellar ataxia type 2 (SCA2) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA2 include additional movement problems, speech and swallowing difficulties, and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to involuntary back-and-forth eye movements (nystagmus) and a decreased ability to make rapid eye movements (saccadic slowing). Over time, individuals with SCA2 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle wasting (atrophy), uncontrolled muscle tensing (dystonia), and involuntary jerking movements (chorea). Some people with SCA2 develop a group of movement abnormalities known as parkinsonism, which includes unusually slow movement (bradykinesia), involuntary trembling (tremor), and muscle stiffness (rigidity). Individuals with SCA2 may have problems with short term memory, planning, and problem solving, or experience an overall decline in intellectual function (dementia). Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA2 usually survive 10 to 20 years after symptoms first appear. ## Frequency The prevalence of SCA2 is unknown. This condition is estimated to be one of the most common types of spinocerebellar ataxia; however, all types of spinocerebellar ataxia are relatively rare. SCA2 is more common in Cuba, particularly in the Holguín province, where approximately 40 per 100,000 individuals are affected. ## Causes Mutations in the ATXN2 gene cause SCA2. The ATXN2 gene provides instructions for making a protein called ataxin-2. This protein is found throughout the body, but its function is unknown. Ataxin-2 is found in the fluid inside cells (cytoplasm), where it appears to interact with a cell structure called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Researchers believe that ataxin-2 may be involved in processing RNA, a chemical cousin of DNA. Ataxin-2 is also thought to play a role in the production of proteins from RNA (translation of DNA's genetic information). The ATXN2 gene mutations that cause SCA2 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated approximately 22 times within the gene, but it can be repeated up to 31 times without causing any health problems. Individuals with 33 or more CAG repeats in the ATXN2 gene develop signs and symptoms of SCA2. People with 33 to 34 repeats tend to first experience signs and symptoms of SCA2 in late adulthood, while people with more than 45 repeats usually have signs and symptoms by their teens. Most people with SCA2 have between 37 and 39 CAG repeats in the ATXN2 gene. It is unclear how the abnormally long CAG segment affects the function of the ataxin-2 protein. The abnormal protein apparently leads to cell death, as people with SCA2 show loss of brain cells in different parts of the brain. Over time, the loss of brain cells causes the movement problems characteristic of SCA2. ### Learn more about the gene associated with Spinocerebellar ataxia type 2 * ATXN2 ## 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. An affected person usually inherits the altered gene from one affected parent. However, some people with SCA2 do not have a parent with the disorder. Individuals who have an increase in the number of CAG repeats in the ATXN2 gene, but do not develop SCA2, are at risk of having children who will develop the disorder. As the altered ATXN2 gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATXN2 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Spinocerebellar ataxia type 2	c0752121	30,359	medlineplus	https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-2/	2021-01-27T08:24:38	{"gard": ["4072"], "mesh": ["D020754"], "omim": ["183090"], "synonyms": []}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article may require cleanup to meet Wikipedia's quality standards. The specific problem is: article is messy and out-of-date. Relational disorder is not included in DSM, ICD, PDM, etc Please help improve this article if you can. (May 2013) (Learn how and when to remove this template message) This article's factual accuracy may be compromised due to out-of-date information. Please update this article to reflect recent events or newly available information. (May 2013) This article needs attention from an expert in Psychology. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Psychology may be able to help recruit an expert. (March 2020) (Learn how and when to remove this template message) According to Michael First of the DSM-5 working committee[1] the focus of a relational disorder, in contrast to other DSM-IV disorders, "is on the relationship rather than on any one individual in the relationship".[2] Relational disorders involve two or more individuals and a disordered "juncture", whereas typical Axis I psychopathology describes a disorder at the individual level. An additional criterion for a relational disorder is that the disorder cannot be due solely to a problem in one member of the relationship, but requires pathological interaction from each of the individuals involved in the relationship.[2] For example, if a parent is withdrawn from one child but not another, the dysfunction could be attributed to a relational disorder. In contrast, if a parent is withdrawn from both children, the dysfunction may be more appropriately attributable to a disorder at the individual level.[3] First states that "relational disorders share many elements in common with other disorders: there are distinctive features for classification; they can cause clinically significant impairment; there are recognizable clinical courses and patterns of comorbidity; they respond to specific treatments; and they can be prevented with early interventions. Specific tasks in a proposed research agenda: develop assessment modules; determine the clinical utility of relational disorders; determine the role of relational disorders in the etiology and maintenance of individual disorders; and consider aspects of relational disorders that might be modulated by individual disorders."[2] The proposed new diagnosis defines a relational disorder as "persistent and painful patterns of feelings, behaviors, and perceptions" among two or more people in an important personal relationship, such a husband and wife, or a parent and children.[4] According to psychiatrist Darrel Regier, MD, some psychiatrists and other therapists involved in couples and marital counseling have recommended that the new diagnosis be considered for possible incorporation into the Diagnostic and Statistical Manual of Mental Disorders (DSM IV).[4] ## Contents * 1 History * 2 Kinds * 2.1 Marital * 2.2 Parent–child abuse * 3 See also * 4 Notes * 5 External links ## History[edit] The idea of a psychology of relational disorders is far from new. According to Adam Blatner, MD,[5] some of the early psychoanalysts alluded to it more or less directly, and the history of marital couple therapy began with a few pioneers in 1930s. J.L. Moreno, the inventor of psychodrama and a major pioneer of group psychotherapy and social psychology, noted the idea that relationships could be "sick" even if the people involved were otherwise "healthy," and even vice versa: Otherwise "sick" people could find themselves in a mutually supportive and "healthy" relationship.[5] Moreno's ideas may have influenced some of the pioneers of family therapy, but also there were developments in general science, namely, cybernetic theory, developed in the mid-1940s, and noting the nature of circularity and feedback in complex systems. By the 1950s, the idea that relationships themselves could be problematic became quite apparent. So, diagnostically, in the sense not of naming a disease or disorder, but just helping people think through what was really going on, the idea of relational disorder was nothing new.[5] ## Kinds[edit] The majority of research on relational disorders concerns three relationship systems: adult children and their parents, minor children and their parents, and the marital relationship. There is also an increasing body of research on problems in dyadic gay relationships and on problematic sibling relationships.[6] ### Marital[edit] Marital disorders are divided into "Marital Conflict Disorder Without Violence" and "Marital Abuse Disorder (Marital Conflict Disorder With Violence)."[7] Couples with marital disorders sometimes come to clinical attention because the couple recognize long-standing dissatisfaction with their marriage and come to the clinician on their own initiative or are referred by a health care professional. Secondly, there is serious violence in the marriage which is "usually the husband battering the wife".[8] In these cases the emergency room or a legal authority often is the first to notify the clinician. Most importantly, marital violence "is a major risk factor for serious injury and even death and women in violent marriages are at much greater risk of being seriously injured or killed" (National Advisory Council on Violence Against Women 2000).[9] The authors of this study add that "There is current considerable controversy over whether male-to-female marital violence is best regarded as a reflection of male psychopathology and control or whether there is an empirical base and clinical utility for conceptualizing these patterns as relational."[9] Recommendations for clinicians making a diagnosis of "Marital Relational Disorder" should include the assessment of actual or "potential" male violence as regularly as they assess the potential for suicide in depressed patients. Further, "clinicians should not relax their vigilance after a battered wife leaves her husband, because some data suggest that the period immediately following a marital separation is the period of greatest risk for the women. Many men will stalk and batter their wives in an effort to get them to return or punish them for leaving. Initial assessments of the potential for violence in a marriage can be supplemented by standardized interviews and questionnaires, which have been reliable and valid aids in exploring marital violence more systematically."[9] The authors conclude with what they call "very recent information"[10] on the course of violent marriages which suggests that "over time a husband's battering may abate somewhat, but perhaps because he has successfully intimidated his wife." The risk of violence remains strong in a marriage in which it has been a feature in the past. Thus, treatment is essential here; the clinician cannot just wait and watch.[10] The most urgent clinical priority is the protection of the wife because she is the one most frequently at risk, and clinicians must be aware that supporting assertiveness by a battered wife may lead to more beatings or even death.[10] In some cases, men are abuse victims of their wives; there is not exclusively male-on-female physical violence, although this is more common than female-on-male violence. ### Parent–child abuse[edit] Research on parent–child abuse bears similarities to that on marital violence, with the defining characteristic of the disorder being physical aggression by a parent toward a child. The disorder is frequently concealed by parent and child, but may come to the attention of the clinician in several ways, from emergency room medical staff to reports from child protection services.[10] Some features of abusive parent–child relationships that serve as a starting point for classification include: (a) the parent is physically aggressive with a child, often producing physical injury, (b) parent–child interaction is coercive, and parents are quick to react to provocations with aggressive responses, and children often reciprocate aggression, (c) parents do not respond effectively to positive or prosocial behavior in the child, (d) parents do not engage in discussion about emotions, (e) parent engages in deficient play behavior, ignores the child, rarely initiates play, and does little teaching, (f) children are insecurely attached and, where mothers have a history of physical abuse, show distinctive patterns of disorganized attachment, and (g) parents relationship shows coercive marital interaction patterns.[11] Defining the relational aspects of these disorders can have important consequences. For example, in the case of early appearing feeding disorders, attention to relational problems may help delineate different types of clinical problems within an otherwise broad category. In the case of conduct disorder, the relational problems may be so central to the maintenance, if not the etiology, of the disorder that effective treatment may be impossible without recognizing and delineating it.[11] ## See also[edit] * Classification of mental disorders * DSM-IV Codes * Relational psychoanalysis * Relationship counseling * Social psychiatry * Social psychology (psychology) * Social psychology (sociology) ## Notes[edit] 1. ^ http://www.dsm5.org/Pages/Default.aspx/ 2. ^ a b c Michael B. First, MD. A Research Agenda for DSM-V: Summary of the DSM-V Preplanning White Papers. Published in May 2002. 3. ^ Jerrold F. Rosenbaum, MD, Rachel Pollock, PhD. DSM V – Plans and Perspectives, Medscape 2002 4. ^ a b Smith, Michael. Is Your Relationship a Disorder? Review of "Spouse Joust", by Richard Trubo 5. ^ a b c Blatner, A. (2002). Thinking About The Diagnosis Of Relational Disorders 6. ^ First, M.B., Bell, C.C., Cuthbert, B., Krystal, J.H., Malison, R., Offord, D.R., Riess, D., Shea, T., Widiger, T., Wisner, K.L. (2002). Personality Disorders and Relational Disorders, p. 161. Chapter 4 of Kupfer, D.J., First, M.B., & Regier, D.A.: A Research Agenda For DSM-V. Published by American Psychiatric Association 7. ^ First, M.B., Bell, C.C., Cuthbert, B., Krystal, J.H., Malison, R., Offord, D.R., Riess, D., Shea, T., Widiger, T., Wisner, K.L. (2002). Personality Disorders and Relational Disorders, pp. 164, 166. Chapter 4 of Kupfer, D.J., First, M.B., & Regier, D.A.: A Research Agenda For DSM-V. Published by American Psychiatric Association 8. ^ First, M.B., Bell, C.C., Cuthbert, B., Krystal, J.H., Malison, R., Offord, D.R., Riess, D., Shea, T., Widiger, T., Wisner, K.L. (2002). Personality Disorders and Relational Disorders, p. 163. Chapter 4 of Kupfer, D.J., First, M.B., & Regier, D.A.: A Research Agenda For DSM-V. Published by American Psychiatric Association 9. ^ a b c First, M.B., Bell, C.C., Cuthbert, B., Krystal, J.H., Malison, R., Offord, D.R., Riess, D., Shea, T., Widiger, T., Wisner, K.L. (2002). Personality Disorders and Relational Disorders. p. 166. Chapter 4 of Kupfer, D.J., First, M.B., & Regier, D.A.: A Research Agenda For DSM-V. Published by American Psychiatric Association 10. ^ a b c d First, M.B., Bell, C.C., Cuthbert, B., Krystal, J.H., Malison, R., Offord, D.R., Riess, D., Shea, T., Widiger, T., Wisner, K.L. (2002) Personality Disorders and Relational Disorders. p. 167, 168. Chapter 4 of Kupfer, D.J., First, M.B., & Regier, D.A.: A Research Agenda For DSM-V. Published by American Psychiatric Association 11. ^ a b First, M.B., Bell, C.C., Cuthbert, B., Krystal, J.H., Malison, R., Offord, D.R., Riess, D., Shea, T., Widiger, T., Wisner, K.L. (2002). Personality Disorders and Relational Disorders, p. 169. Chapter 4 of Kupfer, D.J., First, M.B., & Regier, D.A.: A Research Agenda For DSM-V. Published by American Psychiatric Association ## External links[edit] * Blatner, Adam, MD. Thinking about the diagnosis of Relational Disorders [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Relational disorder	c0425168	30,360	wikipedia	https://en.wikipedia.org/wiki/Relational_disorder	2021-01-18T18:42:41	{"umls": ["C0425168"], "wikidata": ["Q7310715"]}
X-linked ichthyosis Other namesSteroid sulfatase deficiency, X-linked recessive ichthyosis[1] X-linked recessive inheritance: Affected boys may inherit a deletion or mutation of the STS gene from their mothers SpecialtyMedical genetics X-linked ichthyosis (abbreviated XLI) is a skin condition caused by the hereditary deficiency of the steroid sulfatase (STS) enzyme that affects 1 in 2000 to 1 in 6000 males.[2] XLI manifests with dry, scaly skin[3] and is due to deletions[4][5] or mutations[6] in the STS gene. XLI can also occur in the context of larger deletions causing contiguous gene syndromes.[4] Treatment is largely aimed at alleviating the skin symptoms.[7] The term is from the Ancient Greek 'ichthys' meaning 'fish'. ## Contents * 1 Signs and symptoms * 1.1 Associated medical conditions * 2 Genetics * 2.1 Genetic counseling issues * 2.2 Physiology/biochemistry * 3 Diagnosis * 4 Treatment * 5 History * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] X linked ichthyosis The major symptoms of XLI include scaling of the skin, particularly on the neck, trunk, and lower extremities. The extensor surfaces are typically the most severely affected areas. The >4 mm diameter scales adhere to the underlying skin and can be dark brown or gray in color. Symptoms may subside during the summer.[2] ### Associated medical conditions[edit] Aside from the skin scaling, XLI is not typically associated with other major medical problems.[8] Atrial fibrillation or atrial flutter may affect up to 1 in 10 males with XLI [9] Corneal opacities may be present but do not affect vision. Cryptorchidism is reported in some individuals.[2] Individuals with XLI appear at increased risk of developmental disorders such as autism and Attention Deficit Hyperactivity Disorder and some affected individuals exhibit mood problems [10] Individuals with XLI can exhibit intellectual disability, although this is thought to be due to deletions encompassing neighboring genes in addition to STS.[11] Female carriers generally do not experience any of these problems but can have difficulty during childbirth, as the STS expressed in the placenta plays a role in normal labor.[12] Female carriers may also be at slightly increased risk of developing mental health problems following childbirth [13] For these reasons carriers should ensure their obstetrician is aware of the condition.[citation needed] ## Genetics[edit] X linked ichthyosis - this boy has an infant brother and maternal uncle with the same affliction The STS gene is located on the X chromosome at band Xp22.3. Thus, the syndrome is an X-linked condition, and it affects males and females differently. The 23rd pair of chromosomes is typically termed the "sex chromosomes". Females have two X chromosomes and males have one X and one Y chromosome. Therefore, in normal individuals, males carry a single copy of the STS gene and females carry two copies. This gene partially escapes X-inactivation and females normally express higher amounts of the STS enzyme than males.[14] XLI can occur through new deletions or mutations of the STS gene but is more commonly inherited from a carrier mother.[15] A hemizygous deletion or mutation of the STS gene in a male results in complete absence of enzyme activity, while a female carrier of a mutation or deletion is heterozygous and still has a normal copy of the STS gene. Female carriers of an STS deletion or mutation still express the STS enzyme, although with decreased enzyme activity.[16] For this reason, XLI most commonly affects males, although individuals with numeric abnormalities of the sex chromosomes (45,X and 47,XXY) who also carry STS deletions or mutations would be exceptions to this rule.[citation needed] In addition, a female could be affected if she were the offspring of an affected male and a carrier female and inherited a deletion or mutation of the STS gene on both X chromosomes. ### Genetic counseling issues[edit] Since the majority of cases appear to occur through transmission of an STS deletion from a carrier mother,[15] enzyme testing or DNA testing should be performed in the mother of any newly diagnosed simplex case (i.e. the first case in a family). In the case of an extended family with many affected individuals, carrier status can often be assigned based on pedigree analysis. * Males with XLI will transmit the X chromosome harboring the STS deletion or mutation to each of his female offspring, who will therefore be an obligate carrier. However, all male offspring will be unaffected, since they receive their father's Y chromosome. * Female carriers of an STS deletion or mutation have a 50% chance with each pregnancy of transmitting it to an offspring. Thus, each male offspring has a 50% chance of being affected by XLI, while each female offspring has a 50% chance of being a carrier for this condition. Any individual that inherits the mother's normal copy of the STS gene will be unaffected and will have an extremely low chance of having a child affected with this condition. Due to random segregation of the chromosomes during gametogenesis, each pregnancy will be subject to the same probabilities, regardless of the number of previously affected or unaffected offspring. The above recurrence risks are based on the assumption that an affected male or carrier female will have children with an unaffected or non-carrier individual. The risks of having affected offspring would clearly increase in the case of a union between a male with XLI and a carrier female. ### Physiology/biochemistry[edit] DHEA sulfate The STS enzyme (EC 3.1.6.2), also referred to as Arylsulfatase C, is expressed throughout the body, with highest expression in the skin, liver, lymph nodes, and placenta, and lower expression in breast tissue and brain[17] STS catalyzes the hydrolysis of sulfated steroids, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS), to non-sulfated steroids estradiol and androstenediol, respectively.[18] Prenatally, the enzyme is involved in placental estrogen production.[19] The enzyme is also involved in adrenal steroid production as well as conversion of sulfated steroids in other tissues.[citation needed] There seems to be a particularly important role for the enzyme in skin. Deficiency of the enzyme leads to the characteristic dry and scaly skin seen in ichthyosis. Recent research indicates that the skin abnormalities seen in XLI may be due to accumulation of cholesterol sulfate in the outer epidermis, leading to abnormal barrier function and corneocyte retention.[20] ## Diagnosis[edit] XLI can be suspected based on clinical findings, although symptoms can take varying amounts of time to become evident, from a few hours after birth, up to a year in milder cases. The diagnosis is usually made by a dermatologist, who also typically formulates the treatment plan (see below). STS enzyme deficiency is confirmed using a clinically available biochemical assay. Carrier detection can be performed in mothers of affected sons using this test (see Genetics, below).[16] Molecular testing for DNA deletions or mutations is also offered, and can be particularly useful in the evaluation of individuals with associated medical conditions (see below). Prenatal diagnosis is possible using either biochemical or molecular tests. However, the use of prenatal diagnosis for genetic conditions that are considered to be generally benign raises serious ethical considerations and requires detailed genetic counseling.[citation needed] ## Treatment[edit] Because XLI is caused by a gene mutation or deletion, there is no "cure." One of the aims of treatment is to reduce scaling by removing the excess, flaky scales, and keep the skin hydrated. This can be achieved using a variety of topical creams.[2][7] * Keratolytic agents such as Ammonium lactate (Lac-Hydrin) are used to facilitate the release of retained corneocytes. * Topical isotretinoin * The topical receptor-selective retinoid tazarotene [21] Research is ongoing with regard to the use of gene therapy to treat XLI.[22] ## History[edit] In the 1960s, recessive x-linked ichthyosis was distinguished clinically from other ichthyoses.[23]:486[24]:561 ## See also[edit] * Ichthyosis * Carvajal syndrome ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b c d Carlo Gelmetti; Caputo, Ruggero (2002). Pediatric Dermatology and Dermatopathology: A Concise Atlas. T&F STM. p. 160. ISBN 978-1-84184-120-5. 3. ^ Online Mendelian Inheritance in Man (OMIM): ICHTHYOSIS, X-LINKED - 308100 4. ^ a b Ballabio A, Parenti G, Carrozzo R, et al. (1987). "Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis". Proc. Natl. Acad. Sci. U.S.A. 84 (13): 4519–23. Bibcode:1987PNAS...84.4519B. doi:10.1073/pnas.84.13.4519. PMC 305121. PMID 3474618. 5. ^ Bonifas JM, Morley BJ, Oakey RE, Kan YW, Epstein EH (December 1987). "Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis". Proc. Natl. Acad. Sci. U.S.A. 84 (24): 9248–51. Bibcode:1987PNAS...84.9248B. doi:10.1073/pnas.84.24.9248. PMC 299730. PMID 3480541. 6. ^ Basler E, Grompe M, Parenti G, Yates J, Ballabio A (March 1992). "Identification of point mutations in the steroid sulfatase gene of three patients with X-linked ichthyosis". Am. J. Hum. Genet. 50 (3): 483–91. PMC 1684279. PMID 1539590. 7. ^ a b Ichthyosis, X-Linked at eMedicine: Treatment Section 8. ^ DiGiovanna JJ, Robinson-Bostom L (2003). "Ichthyosis: etiology, diagnosis, and management". Am J Clin Dermatol. 4 (2): 81–95. doi:10.2165/00128071-200304020-00002. PMID 12553849. 9. ^ Brcic L, Underwood JFW, Kendall KM et al. (2020) Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank. J. Med. Genet. 0:1-7 PMID:32139392 doi:10.1136/jmedgenet-2019-106676 URL:https://jmg.bmj.com/content/early/2020/03/05/jmedgenet-2019-106676 10. ^ Chatterjee S, Humby T, Davies W (2016) Behavioural and psychiatric phenotypes in men and boys with X-linked ichthyosis: evidence from a worldwide online survey. PLoS One 11(10):e0164417 PMID:27711218 doi:10.1371/journal.pone.0164417 URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164417 11. ^ Van Esch H, Hollanders K, Badisco L, et al. (2005). "Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis". Hum. Mol. Genet. 14 (13): 1795–803. doi:10.1093/hmg/ddi186. PMID 15888481. 12. ^ Bradshaw KD, Carr BR (1986). "Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis". Obstet Gynecol Surv. 41 (7): 401–13. PMID 3531932. 13. ^ Cavenagh A, Chatterjee S, Davies W (2019) Behavioural and psychiatric phenotypes in female carriers of genetic mutations associated with X-linked ichthyosis. PLoS One 14(2):e0212330 PMID:30768640 doi:10.1371/journal.pone.0212330 URL:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212330 14. ^ Lykkesfeldt G, Lykkesfeldt AE, Skakkebaek NE (1984). "Steroid sulphatase in man: a non inactivated X-locus with partial gene dosage compensation". Hum. Genet. 65 (4): 355–7. doi:10.1007/BF00291559. PMID 6582028. S2CID 2625156. 15. ^ a b Valdes-Flores M, Kofman-Alfaro SH, Jimenez-Vaca AL, Cuevas-Covarrubias SA (August 2001). "Carrier identification by FISH analysis in isolated cases of X-linked ichthyosis". Am. J. Med. Genet. 102 (2): 146–8. doi:10.1002/ajmg.1450. PMID 11477606. 16. ^ a b Cuevas-Covarrubias SA, Kofman-Alfaro S, Orozco Orozco E, Diaz-Zagoya JC (1995). "The biochemical identification of carrier state in mothers of sporadic cases of X-linked recessive ichthyosis". Genet. Couns. 6 (2): 103–7. PMID 7546451. 17. ^ Selcer KW, Difrancesca HM, Chandra AB, Li PK (2007). "Immunohistochemical analysis of steroid sulfatase in human tissues". J. Steroid Biochem. Mol. Biol. 105 (1–5): 115–23. doi:10.1016/j.jsbmb.2006.12.105. PMID 17604157. S2CID 22124602. 18. ^ Reed MJ, Purohit A, Woo LW, Newman SP, Potter BV (April 2005). "Steroid sulfatase: molecular biology, regulation, and inhibition". Endocr. Rev. 26 (2): 171–202. doi:10.1210/er.2004-0003. PMID 15561802. 19. ^ Jöbsis AC, De Groot WP, Tigges AJ, et al. (1980). "X-linked ichthyosis and X-linked placental sulfatase deficiency: a disease entity. Histochemical observations". Am. J. Pathol. 99 (2): 279–89. PMC 1903491. PMID 6929654. 20. ^ Elias PM, Crumrine D, Rassner U, et al. (2004). "Basis for abnormal desquamation and permeability barrier dysfunction in RXLI". J. Invest. Dermatol. 122 (2): 314–9. doi:10.1046/j.1523-1747.2003.22258.x. PMID 15009711. 21. ^ Cotellessa C, Cuevas-Covarrubias SA, Valeri P, Fargnoli MC, Peris K (2005). "Topical tazarotene 0.05% versus glycolic acid 70% treatment in X-linked ichthyosis due to extensive deletion of the STS gene". Acta Derm. Venereol. 85 (4): 346–8. doi:10.1080/00015550510026613. PMID 16191859. 22. ^ Freiberg RA, Choate KA, Deng H, Alperin ES, Shapiro LJ, Khavari PA (1997). "A model of corrective gene transfer in X-linked ichthyosis". Hum. Mol. Genet. 6 (6): 927–33. doi:10.1093/hmg/6.6.927. PMID 9175741. 23. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 24. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. ## External links[edit] Classification D * ICD-10: Q80.1 * ICD-9-CM: 757.1 * OMIM: 308100 * MeSH: D016114 * DiseasesDB: 29136 External resources * eMedicine: derm/191 * Orphanet: 461 * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia * v * t * e Inborn errors of steroid metabolism Mevalonate pathway * HMG-CoA lyase deficiency * Hyper-IgD syndrome * Mevalonate kinase deficiency To cholesterol * 7-Dehydrocholesterol path: Hydrops-ectopic calcification-moth-eaten skeletal dysplasia * CHILD syndrome * Conradi-Hünermann syndrome * Lathosterolosis * Smith–Lemli–Opitz syndrome * desmosterol path: Desmosterolosis Steroids Corticosteroid (including CAH) * aldosterone: Glucocorticoid remediable aldosteronism * cortisol/cortisone: CAH 17α-hydroxylase * CAH 11β-hydroxylase * both: CAH 3β-dehydrogenase * CAH 21-hydroxylase * Apparent mineralocorticoid excess syndrome/11β-dehydrogenase Sex steroid To androgens * 17α-Hydroxylase deficiency * 17,20-Lyase deficiency * Cytochrome b5 deficiency * 3β-Hydroxysteroid dehydrogenase deficiency * 17β-Hydroxysteroid dehydrogenase deficiency * 5α-Reductase deficiency * Pseudovaginal perineoscrotal hypospadias To estrogens * Aromatase deficiency * Aromatase excess syndrome Other * X-linked ichthyosis * Antley–Bixler 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	X-linked ichthyosis	c0079588	30,361	wikipedia	https://en.wikipedia.org/wiki/X-linked_ichthyosis	2021-01-18T18:49:01	{"gard": ["7904"], "mesh": ["D016114"], "umls": ["C0079588"], "icd-9": ["757.1"], "orphanet": ["461"], "wikidata": ["Q3804555"]}
Gastrinoma Micrograph of a neuroendocrine tumour of the stomach. H&E stain. SpecialtyGeneral surgery Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger-Ellison syndrome (ZES).[1] A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region (gastrinoma triangle).[2] Most gastrinomas are sporadic (75%–80%), whereas approximately 20% to 25% are associated with multiple endocrine neoplasia type 1(MEN-1).[3] Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and liver. One fourth of gastrinomas are related to Multiple endocrine neoplasia type 1, Zollinger- Ellison Syndrome, Peptic Ulcer disease.[4] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 Research * 8 See Also * 8.1 References * 8.2 External links ## Signs and symptoms[edit] Gastrinoma in the early stages will have signs and symptoms of indigestion or similar to Irritable Bowl disease (IBD) such as: * Hypergastrinemia * Ulcers of the duodenum, stomach, and small intestine. * Severe diarrhea. * Generalized cancer symptoms. * Pain and Bleeding in stool. * Obstruction of intestine.[5] * Weight loss/ poor appetite * Anemia (Due to Vitamin B12 malabsorption, and bleeding) * Hematemesis * Acid Reflux * Esophageal complications (Barrett esophagus, esophagitis, stricture formation)[6] * Vomiting * Steatorrhea[4] * Depression ## Pathophysiology[edit] Gastrin is secreted by the G cells. G cells are primarily found in the pyloric antrum but can also be found in the duodenum and the pancreas.[7] Primary function of gastrin is to induce the release of hydrochloric acid (HCl) from the parietal cells located in the fundus of the stomach. Parietal cells are responsible for hydrochloric (HCl) secretion along with intrinsic factor that binds to vitamin B12 and helps with its’ uptake in the terminal ileum. Other functions of Gastrin include stimulation the growth of gastric mucosa and gastric motility, promoting gastric emptying. These mechanisms of the gastrointestinal tract (GIT) are up-regulated by the vagus nerve of the parasympathetic nervous system (PNS), that carries out majority of its’ functions by the release of neurotransmitter Acetylcholine (Ach), and to a lesser extent Gastrin releasing peptide (GRP) protein. On the contrary, the functions of GIT are down-regulated by the activation sympathetic nervous system (SNS), which carries out its’ functions mostly via neurotransmitter epinephrine. Meal consumption causes distention of the stomach, leading to stimulation of the parasympathetic vagus nerve in the gastric mucosa,[8] which causes the release of GRP protein. In gastrinoma, GRP protein causes larger than normal amounts of gastrin secretion, which leads to hyperplasia of the parietal cells. Hyperplasia of parietal cells causes an abnormal release of HCl into the duodenum, which causes the ulcers of the duodenum. Excessive HCl production also causes hyperperistalsis,[9] a condition marked by excessive rapidity of the passage of food through the stomach and intestine and inhibits the activity of lipase, causing severe fatty diarrhea known as steatorrhea. Evenly the long standing hyper-secretion of gastrin stimulate proliferation of the enterochromaffin like cells (ECL). These cells are found along the side the gastric lumen of the digestive tract.[10] They play a main role in regulation of gastric secretion and motility when stimulated by nervous system. These cells in return will undergo progressive dysplastic changes starting with hyperplasia to neoplasia throughout the gastrointestinal tract. ## Diagnosis[edit] In many cases, gastrinoma is diagnosed based on the patient's history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens.[11] To confirm the diagnosis of gastrinoma a series of blood tests must be made. One of those tests is the serum gastrin level, which is the most reliable test for patients suffering from gastrinoma. The normal levels of gastrin are 150 pg/mL ( > 72.15 pmol/L); therefore elevated levels of > 1000 pg/mL (> 480 pmol/L) would establish the diagnosis of gastrinoma.[12] Another test that can be conducted is the secretin stimulated test,[4] which is useful in patents who have the sign and symptoms of gastrinoma but the gastrin levels are below < 1000 pg/mL. Usually, an Intravenous bolus consisting of secretin 2mcg/kg and is measured in 10 minute intervals up tp 30 minutes total. Secretin, which is a hormone released from the duodenal S cells that induce the release of pancreatic bicarbonate (HCO3) that would neutralize the acidic environment due to high gastrin levels. Therefore, if the patient's level of gastrin remains consistently high indicating gastrin release due to tumor such as gastrinoma.[12] Other commonly used tests to further confirm the diagnosis are * CT scan of the abdominal area * Somatostatin receptor scintigraphy which is used to identify the location of the tumor * PET scan * Endoscopic ultrasound if there are no signs of tumor metastases.[12] * ## Treatment[edit] Surgery is first line treatment in gastrinomas, however often fails to be curative.:[13] * Proton Pump Inhibitors such as Omeprazole. This group of medication would suppress the acid secretion. * H2- receptor antagonist would similarly decrease acid secretion. * Octreotide injections would directly release somatostatin hormone that would inhibit gastrin release. * Chemotherapy. ## Prognosis[edit] Patients with gastrinomas that are also known to be part of neuroendocrine neoplasms must have to deal with two factors released to this tumor. First, controlling the high amounts by using medications that inhibit gastrin levels. The second part is stabilizing the tumor progression. Gastrinomas have a rate of 60%-90% that will become malignant.[10] Patients who do not seek medical treatment such anti-ulcer medication have high rate of recurrence and death secondary to ulcer disease.The prognosis of gastrinoma depends on the level of metastases of the tumor. If patients present with hepatic metastases they might have remaining life span of 1 year with a 5 year survival rate of 20-30%. In patients with localized tumor or localized lymph spread the survival rate of 5 years id 90%. Lastly, surgical resection of local tumor could lead to complete cure without recurrence in 20-25% of patients.[14] ## Epidemiology[edit] Gastrinoma is the second most common functional pancreatic neuroendocrine tumor (pNET), with a yearly incidence of approximately 0.5 to 21.5 cases per a million of people worldwide.[3] Gastrinomas are located predominantly in the duodenum (70%) and pancreas (25%).[15] Pancreatic gastrinomas are larger than their duodenal counterparts, may occur in any portion of the pancreas, and comprise 25% of these tumors. Gastrinomas are also the most common functional and malignant pancreatic endocrine tumors.[16] They are characterized by gastric hypersecretion that results in peptic ulcers and diarrhea; this condition is known as Zollinger–Ellison syndrome (ZES).[15] ## Research[edit] Recently, research studies have been conducted to seek new medical advances in relation to gastrinoma and Zollinger-Ellison syndrome. The recent studies have shown improved understanding of pathogenesis of pancreatic neuroendocrine tumors, classifications of those tumors, and new treatments/ preventions to control the gastrin levels in the gastrointestinal tract. In addition, what is the best and safest approach for patients and effectiveness of surgery. The study concluded that the wide use of proton pump inhibitors itself might further induce hypergastrinemia (increased gastrin levels in circulatory system) by feedback inhibition. The body will try to induce further release when gastrin level is depleted. Some of the new treatments might include medication that are directed towards the liver such as embolization, chemoembolization, and radioembolization in addition to the current offered treatments such as chemotherapy, somatostatin analogs. Other treatments that are still in phase three of clinical trials include liver transplantation and peptide-radioreceptor therapy.[17] # See Also[edit] * Multiple Endocrine Neoplasia-1 * Zollinger-Ellison Syndrome * Peptic Ulcer disease * Pancreatic Endocrine Tumors * ## References[edit] 1. ^ Jensen, Robert T.; Niederle, Bruno; Mitry, Emmanuel; Ramage, John K.; Steinmüller, Thomas; Lewington, V.; Scarpa, Aldo; Sundin, Anders; Perren, Aurel; Gross, David; O’Connor, Juan M. (2006). "Gastrinoma (Duodenal and Pancreatic)". Neuroendocrinology. 84 (3): 173–182. doi:10.1159/000098009. ISSN 0028-3835. PMID 17312377. S2CID 5096249. 2. ^ Yantiss, RHONDA K.; Antonioli, DONALD A. (2009-01-01), Odze, ROBERT D.; Goldblum, JOHN R. (eds.), "CHAPTER 18 - Polyps of the Small Intestine", Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas (Second Edition), Philadelphia: W.B. Saunders, p. 473, ISBN 978-1-4160-4059-0, retrieved 2020-12-18 3. ^ a b Falconi, M.; Eriksson, B.; Kaltsas, G.; Bartsch, D. K.; Capdevila, J.; Caplin, M.; Kos-Kudla, B.; Kwekkeboom, D.; Rindi, G.; Klöppel, G.; Reed, N. (2016). "ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors". Neuroendocrinology. 103 (2): 153–171. doi:10.1159/000443171. ISSN 0028-3835. PMC 4849884. PMID 26742109. 4. ^ a b c "Gastrinoma". The National Pancreas Foundation. Retrieved 2020-11-12. 5. ^ "Gastrinoma - Digestive Disorders". Merck Manuals Consumer Version. Retrieved 2020-11-09. 6. ^ "Gastrinoma Clinical Presentation: History, Physical Examination". emedicine.medscape.com. Retrieved 2020-11-12. 7. ^ Prosapio, Jordon G.; Sankar, Parvathy; Jialal, Ishwarlal (2020), "Physiology, Gastrin", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30521243, retrieved 2020-12-18 8. ^ Hall, John E.; Guyton, Arthur C. (2011), "Sports physiology", Guyton and Hall Physiology Review, Elsevier, pp. 249–254, doi:10.1016/b978-1-4160-5452-8.00024-x, ISBN 978-1-4160-5452-8, retrieved 2020-12-18 9. ^ "Gastrinoma: Background, Pathophysiology, Epidemiology". 2020-10-12. Cite journal requires `\|journal=` (help) 10. ^ a b Jensen, Robert T.; Ito, Tetsuhide (2000), Feingold, Kenneth R.; Anawalt, Bradley; Boyce, Alison; Chrousos, George (eds.), "Gastrinoma", Endotext, South Dartmouth (MA): MDText.com, Inc., PMID 25905301, retrieved 2020-12-18 11. ^ Banasch, Matthias; Schmitz, Frank (2007). "Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors". Wiener Klinische Wochenschrift. 119 (19–20): 573–578. doi:10.1007/s00508-007-0884-2. ISSN 0043-5325. PMID 17985090. S2CID 128989. 12. ^ a b c "Gastrinoma - Gastrointestinal Disorders". Merck Manuals Professional Edition. Retrieved 2020-12-18. 13. ^ Auernhammer, Christoph J.; Göke, Burkhard (November 2007). "Medical treatment of gastrinomas". Wiener klinische Wochenschrift. 119 (19–20): 609–615. doi:10.1007/s00508-007-0877-1. ISSN 0043-5325. PMID 17985097. S2CID 21838326. 14. ^ "Gastrinoma: Background, Pathophysiology, Epidemiology". 2020-10-12. Cite journal requires `\|journal=` (help) 15. ^ a b Gong, Shu; Li, Zhi; Liu, Xu-Bao; Wang, Xin; Shen, Wen-Wu (December 2019). "Gastrinoma in multiple endocrine neoplasia type 1 after total pancreatectomy". Medicine. 98 (50): e18275. doi:10.1097/MD.0000000000018275. ISSN 0025-7974. PMC 6922403. PMID 31852099. 16. ^ Cingam, Shashank R.; Botejue, Mahesh; Hoilat, Gilles J.; Karanchi, Harsha (2020), "Gastrinoma", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 28722872, retrieved 2020-12-18 17. ^ Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T (November 2013). "Zollinger-Ellison syndrome: Recent advances and controversies". Current Opinion in Gastroenterology. 29 (6): 650–661. doi:10.1097/MOG.0b013e328365efb1. ISSN 0267-1379. PMC 5555311. PMID 24100728. ## External links[edit] * Emedicine Classification D * ICD-O: M8153/1 * MeSH: D015408 External resources * eMedicine: med/2678 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma * v * t * e Tumours of endocrine glands Pancreas * Pancreatic cancer * Pancreatic neuroendocrine tumor * α: Glucagonoma * β: Insulinoma * δ: Somatostatinoma * G: Gastrinoma * VIPoma Pituitary * Pituitary adenoma: Prolactinoma * ACTH-secreting pituitary adenoma * GH-secreting pituitary adenoma * Craniopharyngioma * Pituicytoma Thyroid * Thyroid cancer (malignant): epithelial-cell carcinoma * Papillary * Follicular/Hurthle cell * Parafollicular cell * Medullary * Anaplastic * Lymphoma * Squamous-cell carcinoma * Benign * Thyroid adenoma * Struma ovarii Adrenal tumor * Cortex * Adrenocortical adenoma * Adrenocortical carcinoma * Medulla * Pheochromocytoma * Neuroblastoma * Paraganglioma Parathyroid * Parathyroid neoplasm * Adenoma * Carcinoma Pineal gland * Pinealoma * Pinealoblastoma * Pineocytoma MEN * 1 * 2A * 2B [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Gastrinoma	c0017150	30,362	wikipedia	https://en.wikipedia.org/wiki/Gastrinoma	2021-01-18T18:46:43	{"mesh": ["D015408"], "umls": ["C0017150"], "icd-10": ["E16.4"], "wikidata": ["Q786852"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive limb-girdle muscular dystrophy-3 (LGMDR3) is caused by homozygous or compound heterozygous mutation in the alpha-sarcoglycan gene (SGCA; 600119) on chromosome 17q21. Description Autosomal recessive limb-girdle muscular dystrophy-3 affects mainly the proximal muscles and results in difficulty walking. Most individuals have onset in childhood; the disorder is progressive. Other features may include scapular winging, calf pseudohypertrophy, and contractures. Cardiomyopathy has rarely been reported (summary by Babameto-Laku et al., 2011). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600). Nomenclature At the 229th ENMC international workshop, Straub et al. (2018) reviewed, reclassified, and/or renamed forms of LGMD. The proposed naming formula was 'LGMD, inheritance (R or D), order of discovery (number), affected protein.' Under this formula, LGMD2D was renamed LGMDR3. Clinical Features Romero et al. (1994) reported a French family with a progressive form of muscular dystrophy that was clinically milder than severe autosomal recessive muscular dystrophy (SCARMD; 253700). Four sibs had mild to overt symptoms, including proximal muscle weakness beginning at about age 10 years, calf hypertrophy, and elevated serum creatine kinase. Muscle biopsies showed variable degrees of necrosis and regeneration with little fibrosis. In all 4 cases, the 50-kD dystrophin-associated glycoprotein adhalin was completely absent in muscle sections, whereas dystrophin and other members of the dystrophin-associated protein complex were normal, except for the 35-kD dystrophin-associated glycoprotein gamma-sarcoglycan (SGCG; 608896), which was slightly reduced. Linkage analysis excluded the SCARMD locus on chromosome 13q, indicating a genetically distinct disorder. Romero et al. (1994) stated that there are 2 kinds of myopathies with adhalin deficiency: one with a primary defect of adhalin and one in which absence of adhalin is secondary to a separate gene defect on chromosome 13. Fadic et al. (1996) demonstrated adhalin deficiency in a 13-year-old boy who had previously been given a diagnosis of Becker muscular dystrophy (300376) and was referred for dilated cardiomyopathy and congestive heart failure. He had been asymptomatic until 9 years of age when proximal muscle weakness developed. Examination at that time showed flexion contracture at the ankles, hypertrophy of the calf muscle, and Gowers sign. The serum creatine kinase level was very high. There was no family history of consanguinity or neuromuscular disease. Both his sister and his mother had normal serum creatine kinase levels. His congestive heart failure was refractory to diuretic therapy and to inotropic therapy. He required a left ventricular assist device for circulatory support for 6 weeks and then underwent successful heart transplantation. Cardiac abnormalities had been described in patients with adhalin deficiency or muscular dystrophy but expression of dystrophin-associated proteins, including adhalin, in cardiac muscle had not been determined. Fadic et al. (1996) found normal immunostaining in both skeletal and cardiac muscle with antibodies directed against the 3 portions of the dystrophin molecule. On the other hand, immunostaining of adhalin was drastically reduced in skeletal muscle and undetectable by immunofluorescence in cardiac muscle. The disorder was thought to be recessive in this patient. McNally et al. (1996) commented that mutations in several genes can cause adhalin deficiency and that the patient reported by Fadic et al. (1996) did not necessarily have a mutation in the SGCA gene. McNally et al. (1996) noted that mutation in any of 3 proteins in the 'sarcoglycan complex,' alpha-, beta-, or gamma-sarcoglycan, can cause muscular dystrophy as well as a decrease in immunostaining for all 3 sarcoglycan components. Angelini et al. (1998) described 2 sibs with a homozygous mutation in the alpha-sarcoglycan gene (600119.0005) who presented strikingly different clinical phenotypes. The brother was asymptomatic and the sister had mild limb-girdle muscular dystrophy that was steroid responsive. Immunohistochemistry for alpha-sarcoglycan showed reduced intensity in the sister and findings similar to normal in the brother. Unknown epigenetic or environmental factors appeared to be important in determining protein and clinical phenotype expression. The sister, 40 years old at the time of report, had presented at the age of 10 to 12 years with mild thoracic scoliosis. At the age of 20 years she presented with waddling gait. Proximal weakness in the lower limbs was noted at 28 years, together with difficulty getting up from the floor or rising from a low chair. Weakness in the upper limbs was noted at the age of 30 years, with difficulty lifting objects over her head. The 35-year-old brother had increased creatine kinase levels but a negative neuromuscular examination, except for mild scoliosis. Passos-Bueno et al. (1999) studied 140 patients from 40 Brazilian families with one of 7 autosomal recessive limb-girdle muscular dystrophies (LGMD2A-LGMD2G). Among the sarcoglycanopathies, serum creatine kinase levels were highest in the LGMD2D patients. Babameto-Laku et al. (2011) reported 2 Albanian sibs, born of consanguineous parents, with LGMD2D. The 7-year-old sister showed difficulty climbing stairs and getting up at age 3 years. This proximal muscle weakness progressed, with frequent falls, waddling gait, toe-walking, and difficulty raising the arms above the head. She also had calf pseudohypertrophy, Achilles tendon contractures, mild scapular winging, and hyperlordosis. Her younger brother started to manifest similar clinical symptoms of proximal muscle weakness between 2 and 3 years of age. Both patients had increased serum creatine kinase, and muscular biopsy showed dystrophic changes with decreased staining for alpha- and gamma-sarcoglycan (SGCG; 608896). The phenotype in both patients was clinically severe enough to suggest Duchenne muscular dystrophy. Mapping Passos-Bueno et al. (1993) found 4 Brazilian families with Duchenne-like muscular dystrophy who were not linked to 13q, indicating genetic heterogeneity for the disorder. In a large French family with autosomal recessive limb-girdle muscular dystrophy in which Romero et al. (1994) excluded linkage to markers on 13q, Roberds et al. (1994) found perfect cosegregation between the disease and 1 allelic variant of a polymorphic microsatellite located within intron 6 of the adhalin gene on chromosome 17q. Passos Bueno et al. (1995) performed linkage analysis with chromosome 17q markers in 3 autosomal recessive limb-girdle muscular dystrophy families and in 4 Duchenne-like muscular dystrophy families, all with adhalin deficiency and unlinked to any of the 3 chromosome sites where forms of autosomal recessive limb-girdle muscular dystrophy had been mapped: 15q (LGMDR1; 253600); 2p (LGMDR2; 253601), and 13q (LGMDR5; 253700). Linkage to 17q was observed only among 3 families with a mild phenotype. Passos Bueno et al. (1995) referred to the 17q-linked muscular dystrophy as LGMD2D. Molecular Genetics In a French family with mild autosomal recessive limb-girdle muscular dystrophy reported by Romero et al. (1994), Roberds et al. (1994) identified missense mutations in the adhalin gene (see, e.g., 600119.0001-600119.0002). The family was nonconsanguineous and the affected members were compound heterozygotes, with one mutation coming from each parent. Piccolo et al. (1995) described several additional mutations (null and missense) in the adhalin gene (see, e.g., 600119.0003) in 10 affected families from Europe and North Africa. Disease severity varied in age of onset and rate of progression, and patients with null mutations were the most severely affected. In 3 affected Brazilian families with a mild phenotype showing linkage to 17q, Passos Bueno et al. (1995) identified the same missense mutation in the adhalin gene (600119.0003). Trabelsi et al. (2008) identified biallelic mutations in sarcoglycan genes in 46 (67%) of 69 patients with a clinical diagnosis of autosomal recessive LGMD. Twenty-six (56.5%) patients had SGCA mutations, 8 (17.3%) had SGCB (600900) mutations, and 12 (26%) had SGCG mutations. A total of 23 different mutations, including 10 novel mutations, were identified in SGCA, with a relatively high frequency of mutations in exon 3 (13 of 26, 50%) and exon 5 (6 of 26, 23%). In 2 Albanian sibs, born of consanguineous parents, with LGMD2D, Babameto-Laku et al. (2011) identified a homozygous mutation in the SGCA gene (R192X; 600119.0007). Each unaffected parent was heterozygous for the mutation. Genotype/Phenotype Correlations Duggan et al. (1997) undertook to determine the frequency of sarcoglycan gene mutations and the relationship between the clinical features and genotype in 556 patients with myopathy but normal dystrophin genes. Antibody against alpha-sarcoglycan was used to stain muscle-biopsy specimens from these patients. Those whose biopsy specimens showed deficiency of alpha-sarcoglycan on immunostaining were studied for mutations of the alpha-, beta-, and gamma-sarcoglycan genes with reverse transcription of muscle RNA, analysis involving single-strand conformation polymorphisms, and sequencing. Levels of alpha-sarcoglycan were found to be decreased on immunostaining of muscle biopsy specimens from 54 of the 556 patients (10%); in 25 of these patients no alpha-sarcoglycan was detected. Screening for sarcoglycan gene mutations in 50 of the 54 patients revealed mutations in 29 patients (58%): 17 had mutations in the SGCA gene, 8 in the SGCB gene, and 4 in the SGCG gene. The prevalence of sarcoglycan gene mutations was highest among patients with severe (Duchenne-like) muscular dystrophy that began in childhood (18 of 83 patients, or 22%); the prevalence among patients with proximal (limb-girdle) muscular dystrophy with a later onset was 6% (11 of 180 patients). Gene Therapy In a double-blind randomized control trial of 3 nonambulatory patients with genetically confirmed LGMD2D, Mendell et al. (2009) found that replacement of the SGCA gene using an adeno-associated virus type 1 (AAV1) vector resulted in 4- to 5-fold increased SGCA expression and restoration of the full sarcoglycan complex in a small foot muscle of the treated side compared to the untreated side in each patient. Examination after 3 months in 1 patient showed increased muscle fiber size in the transduced muscle. There were no adverse side effects. The study used the muscle-specific creatine kinase promoter to improve the safety profile of gene transfer targeting muscle. Mendell et al. (2010) reported 3 additional patients treated with SGCA gene replacement therapy similar to their previous report (Mendell et al., 2009). At 6 months after gene therapy, 2 of the 3 patients showed sustained increased SGCA expression reaching wildtype levels, but only 1 had clear evidence of increased muscle fiber diameter. The third patient showed no increased SGCA gene expression after 6 months and also had early humoral and T-cell responses to the AAV1 capsid, suggestive of an amnestic inflammatory response. Combined with the earlier study, the findings provided an overall favorable response to SGCA gene therapy in patients with LGMD2D. Population Genetics Hayashi et al. (1995) performed an immunocytochemical survey of muscle biopsies from 243 Japanese muscular dystrophy patients over 2.5 years. They identified 5 unrelated Japanese patients (3 females and 2 males with no family history) as having adhalin deficiency. There was extremely faint but positive staining of the sarcolemma similar to that described in the 13q-linked congenital muscular dystrophy prevalent in North Africa. From these data they predicted the gene frequency for this deficiency in Japan to be between 0.1 and 0.2%, with a prevalence of the deficiency in the Japanese population to be about 1 x 10(-6). In their series, Hayashi et al. (1995) found this deficiency to account for only 4% of patients with DMD/BMD. Ljunggren et al. (1995) screened the entire adhalin coding sequence in muscle biopsy specimens from 30 muscular dystrophy patients, finding a compound heterozygosity only in a single African American girl with childhood onset muscular dystrophy. The authors concluded that primary adhalin deficiency in patients with muscular dystrophy but normal dystrophin is relatively infrequent in North America. Animal Model Sampaolesi et al. (2003) reported success in treating Sgca-null mice, a model for LGMD2D, with wildtype mesoangioblasts, a class of vessel-associated stem cells that differentiate into mesodermal cell types. After intraarterial delivery, the mesoangioblasts diffused from the arterial tree into skeletal muscle, where they were incorporated into muscle fibers and restored expression of the adhalin protein. Treated mice exhibited correction of the dystrophic phenotype, both morphologically and functionally. Sampaolesi et al. (2003) also showed that mesoangioblasts isolated from juvenile Sgca-null mice and transduced with a lentiviral vector expressing SGCA reconstituted skeletal muscle similar to that seen in wildtype mice. Imamura et al. (2005) established several transgenic mouse lines that overexpressed Sgce (604149) in skeletal muscle. Overexpression in normal mice resulted in substitution of Sgce for Sgca in the sarcoglycan complex of skeletal muscle without any obvious abnormalities. Mice overexpressing Sgce were crossed with Sgca-deficient mice, and Sgca-deficient mice overexpressing Sgce exhibited no skeletal muscle cell membrane damage or abnormal contraction. Imamura et al. (2005) suggested that overexpression of SGCE may represent a therapeutic strategy for treatment of LGMD2D. Gargioli et al. (2008) found that intramuscular injection of 12-month-old Sgca-null mice with tendon fibroblasts containing an angiogenic factor (PGF; 601121) and a metalloproteinase (MMP9; 120361) resulted in generation of a vascular network and decreased collagen deposition. Intramuscular injection ameliorated subsequent intraarterial cell delivery of Sgca-expressing mesoangioblasts. Mice treated with both Pgf and Mmp9 showed restoration of regenerating muscle fibers reaching 60 to 70% of the numbers observed in wildtype mice. By adeno-associated virus type 1 (AAV1)-mediated delivery of human SGCA to skeletal muscle fibers of Sgca-null mice, Rodino-Klapac et al. (2008) observed sustained SGCA expression for up to 12 weeks without evidence of cytotoxicity and restored expression of the dystrophin-glycoprotein complex. Quantified analysis by fiber counts yielded 60 to 70% successful myofiber transduction for 2 muscle creatine kinase (CKM; 123310) promoters and 34% fiber transduction with a desmin (DES; 125660) promoter. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Cardiomyopathy (rare) SKELETAL \- Contractures Spine \- Scoliosis may occur MUSCLE, SOFT TISSUES \- Limb-girdle muscle weakness \- Limb-girdle muscle atrophy \- Unsteady gait \- Calf muscle hypertrophy \- Necrosis and degeneration seen on muscle biopsy \- Adhalin deficiency seen on muscle biopsy \- Decreased immunostaining for alpha-sarcoglycan \- Myopathic changes seen on EMG NEUROLOGIC Central Nervous System \- Loss of reflexes due to myopathy LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset in childhood (3 to 10 years) \- Loss of independent walking by teenage years (in some) \- Progressive disorder \- Variable severity MOLECULAR BASIS \- Caused by mutation in the alpha-sarcoglycan gene (SGCA, 600119.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 3	c2936332	30,363	omim	https://www.omim.org/entry/608099	2019-09-22T16:08:15	{"doid": ["0110278"], "mesh": ["D058088"], "omim": ["608099"], "orphanet": ["62"], "synonyms": ["Alternative titles", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2D", "DUCHENNE-LIKE AUTOSOMAL RECESSIVE MUSCULAR DYSTROPHY, TYPE 2", "ADHALINOPATHY, PRIMARY"]}
Bart-Pumphrey syndrome is characterized by nail and skin abnormalities and hearing loss. People with Bart-Pumphrey syndrome typically have a white discoloration of the nails (leukonychia); the nails may also be thick and crumbly. Affected individuals often have wart-like (verrucous) skin growths called knuckle pads on the knuckles of the fingers and toes. They may also have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). The skin abnormalities generally become noticeable during childhood. The hearing loss associated with Bart-Pumphrey syndrome ranges from moderate to profound and is typically present from birth (congenital). The signs and symptoms of this disorder may vary even within the same family; while almost all affected individuals have hearing loss, they may have different combinations of the other associated features. ## Frequency Bart-Pumphrey syndrome is a rare disorder; its exact prevalence is unknown. Only a few affected families and individual cases have been identified. ## Causes Bart-Pumphrey syndrome is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules. Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis). The GJB2 gene mutations that cause Bart-Pumphrey syndrome change single protein building blocks (amino acids) in the connexin 26 protein. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses. ### Learn more about the gene associated with Bart-Pumphrey syndrome * GJB2 ## 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. In most cases, an affected person has one parent with the condition. Other cases result from new mutations in the gene and 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Bart-Pumphrey syndrome	c0266004	30,364	medlineplus	https://medlineplus.gov/genetics/condition/bart-pumphrey-syndrome/	2021-01-27T08:25:49	{"gard": ["3125"], "mesh": ["C537210"], "omim": ["149200"], "synonyms": []}
## Clinical Features Halal et al. (1982) described a French Canadian kindred with these features in multiple persons in an autosomal dominant pedigree pattern. The proband, a 14-year-old girl, presented with bleeding antral ulcer; she had had pigmented spots over the back since age 2 years and wore spectacles for myopia from an early age. Male-to-male transmission was noted. Other syndromes with peptic ulcer are multiple endocrine neoplasia (131100) and the tremor-nystagmus-ulcer syndrome (190310). Eyes \- Myopia Inheritance \- Autosomal dominant Facies \- Hypertelorism GI \- Peptic ulcer \- Hiatal hernia Skin \- Multiple lentigines \- Cafe-au-lait spots ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	GASTROCUTANEOUS SYNDROME	c1850899	30,365	omim	https://www.omim.org/entry/137270	2019-09-22T16:40:47	{"mesh": ["C535651"], "omim": ["137270"], "orphanet": ["2069"], "synonyms": ["Alternative titles", "PEPTIC ULCER/HIATAL HERNIA, MULTIPLE LENTIGINES/CAFE-AU-LAIT SPOTS, HYPERTELORISM, MYOPIA"]}
A number sign (#) is used with this entry because Neu-Laxova syndrome-1 (NLS1) is caused by homozygous mutation in the PHGDH gene (606879) on chromosome 1p12. See also PHGDH deficiency (601815), an allelic disorder with a less severe phenotype. Description Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies (lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum), limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears (summary by Manning et al., 2004). ### Genetic Heterogeneity of Neu-Laxova Syndrome NLS2 (616038) is caused by mutation in the PSAT1 gene (610936) on chromosome 9q21. Clinical Features Neu et al. (1971) described 3 sibs with intrauterine growth retardation and multiple congenital anomalies, including microcephaly and abnormal limbs, skin, external genitalia, and placenta. Two girls were stillborn and a boy died at 7 weeks. Laxova et al. (1972) likewise reported 3 sibs. The parents were first cousins. Povysilova et al. (1976) reported 3 affected sibs. Lazjuk et al. (1979) reported a sporadic case. Autopsy showed a brain that weighed only 19.8 gm, the smallest recorded weight for brain in a 39-week fetus. Winter et al. (1981) described 2 patients with Neu-Laxova syndrome and 1 patient with cerebrooculofacioskeletal (COFS) syndrome (214150) and discussed possible genetic relationships of the 2 disorders. Scott et al. (1981) reported additional cases of Neu-Laxova syndrome, bringing the total to 13. They summarized as follows: 'The Neu-Laxova syndrome is a lethal dysplasia-malformation syndrome with abnormalities of placentation, severe intrauterine growth retardation, edema, ectodermal dysplasia, and the CAD complex with severe CNS developmental defect.' CAD is the acronym for cerebroarthrodigital syndrome (Spranger et al., 1980). Scott et al. (1981) concluded that the patients of Spranger et al. (1980) did not have the Neu-Laxova syndrome, but a possibly teratogenic malformation syndrome with better prognosis than in the Neu-Laxova syndrome. Fitch et al. (1982) reported parental consanguinity and discussed further the differentiation from the COFS syndrome. The classic COFS syndrome does not include short neck, ichthyosis, subcutaneous swelling or syndactyly; retardation of development of the brain is much less severe than in the Neu-Laxova syndrome and neonatal lethality is not a feature. See also review by Curry (1982). Prominence of the eyes (exophthalmos) is a conspicuous feature of the Neu-Laxova syndrome; absence of the eyelids exaggerates the exophthalmos. Curry (1982) suggested that there may be two types of this syndrome, each caused by mutation in a separate gene. Group 1 cases, represented by patients such as that of Fitch et al. (1982), have no edema and no increased fat layer, whereas those of group 2, represented by the patient reported by Muller et al. (1987), among others, show an increased layer of subcutaneous adipose tissues with hypertrophy of fat cells. Karimi-Nejad et al. (1987) emphasized ichthyotic skin lesions as a prominent characteristic change and called attention to the increased fatty tissue beneath the epidermis and the atrophic muscles embedded therein. Naveed et al. (1990) described the ichthyotic skin lesions in an affected infant born of consanguineous South Indian parents. Ostrovskaya and Lazjuk (1988) reviewed cerebral abnormalities on the basis of 3 cases. Meguid and Temtamy (1991) reported an affected female from 2 different families in each of which 4 other members were affected. Severe microcephaly with slanting forehead and protuberant eyes, generalized edema, contractures of the limbs, and generalized ichthyotic skin lesions were features. Kuseyri et al. (1993) described an affected newborn female, the offspring of consanguineous Turkish parents. Rouzbahani (1995) described an affected male infant of a nonconsanguineous Iranian couple; in addition to typical manifestations, the infant had cleft lip and palate, short limbs with hypoplastic forearms, recognizable thumbs and 3 fingers, 3 recognizable toes, and atrial and ventricular septal defects. In a review of the literature, Manning et al. (2004) found reports of 61 purported cases of NLS. Although most were sporadic, a number of cases had been reported in consanguineous families. At least 10 families with multiple affected children had been described. The families were from diverse ethnic backgrounds. Manning et al. (2004) concluded that the data from these patients suggested that NLS represents a heterogeneous phenotype. Manar and Asma (2010) reported a Jordanian girl, born of consanguineous parents, with Neu-Laxova syndrome. The patient presented at 31 weeks' gestation with severe intrauterine growth retardation. Ultrasound showed severe microcephaly, large mouth, decreased fetal movement, fixed flexion of upper and lower limbs with clubfeet, and kyphosis. At birth, the infant had poor respiration requiring mechanical ventilation. There were significant dysmorphic features, including proptotic eyes with extremely hyperemic conjunctivae and hazy cornea, closed fontanels, hypertelorism, depressed nose, and high-arched palate. The skin was thick, shiny, and very tight with fissuring at the flexion areas, abdomen, and chest, consistent with ichthyosis. The hips were in fixed flexion, the digits were short, and the hands and feet were edematous. She had no spontaneous movement, no spontaneous eye movement, and the pupils were small and nonreactive. Brain CT revealed a very small brain with lissencephaly and intraventricular and intracerebral hemorrhages. She died on day 4 of life. Acuna-Hidalgo et al. (2014) reported 4 fetuses from 3 unrelated families with NLS1. Clinical features included intrauterine growth retardation, decreased fetal movements, microcephaly, facial dysmorphism, limb and digital deformities, rocker-bottom feet, swollen hands or feet, and ichthyosis. Inheritance Consanguinity and multiple affected sibs support autosomal recessive inheritance of Neu-Laxova syndrome (Manning et al., 2004). Diagnosis Muller et al. (1987) demonstrated the usefulness of ultrasonography in the monitoring of 'at risk' pregnancies. Shapiro et al. (1992) made the diagnosis of presumed NLS by ultrasonography in a 32-week fetus. The findings included intrauterine growth retardation, Dandy-Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of the limbs. Massive swelling of hands and feet seen in classic cases was missing; edema was noted only in the scalp. Kainer et al. (1996) also pointed out the usefulness of ultrasonographic demonstration of abnormal fetal movement patterns in the prenatal diagnosis of this disorder. At 34, 35, and 36 weeks' gestation, no breathing movements, no sucking, and no swallowing were observed. Also there were no hiccups or normal isolated arm or leg movements. Already at that time the diagnosis was evident from extensive edema of hands and ocular hypertelorism with protruding eyes. The lips were thick with a round, gaping mouth. Manning et al. (2004) presented 2 patients with Neu-Laxova syndrome with striking prenatal diagnostic findings and described the detailed postmortem examinations. They suggested that prenatal ultrasound findings of marked ocular proptosis in a growth-restricted, edematous fetus should prompt consideration of the diagnosis. Molecular Genetics In 3 patients from unrelated consanguineous Saudi families with NLS, Shaheen et al. (2014) identified 2 different homozygous missense mutations in the PHGDH gene (G140R, 606879.0007 and R163Q, 606879.0008). The mutations were found by a combination of autozygosity mapping and exome sequencing. Both substitutions occurred at highly conserved residues within the NAD(P)-binding domain and at the PHGDH dimer interface, suggesting that they would interfere with enzyme function. In vitro studies of the variants were not performed. In addition to manifesting classic features of the disorder, 1 of the patients had a dried blood spot that showed low concentrations of serine and glycine, consistent with a biochemical diagnosis of PHGDH deficiency. Shaheen et al. (2014) suggested that the severe phenotype observed in these patients reflects the extreme end of the inborn error of serine metabolism. Acuna-Hidalgo et al. (2014) identified biallelic mutations in the PHGDH gene (see, e.g., 606879.0009 and 606879.0010) in affected individuals from 3 unrelated families with NLS1. Functional studies of the variants were not performed. ### Associations Pending Confirmation See 172480.0003 for discussion of a possible association between variation in the PSPH gene and Neu-Laxova syndrome. INHERITANCE \- Autosomal recessive GROWTH Other \- Prenatal onset growth retardation HEAD & NECK Head \- Microcephaly Face \- Sloping forehead \- Micrognathia Ears \- Large ears Eyes \- Hypertelorism \- Protruding eyes \- Absent eyelids \- Cataract \- Microphthalmia \- Absent eyelashes Nose \- Flattened nose Mouth \- Round, gaping mouth \- Thick lips \- Cleft lip \- Cleft palate Neck \- Short neck CARDIOVASCULAR Heart \- Patent foramen ovale \- Atrial septal defect \- Ventricular septal defect Vascular \- Transposition of great vessels \- Patent ductus arteriosus RESPIRATORY Lung \- Pulmonary hypoplasia GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Bifid uterus Kidneys \- Renal agenesis SKELETAL \- Poorly mineralized bones Limbs \- Short limbs \- Flexion contractures of joints \- Pterygia Hands \- Finger syndactyly \- Puffiness of hands \- Camptodactyly \- Clinodactyly Feet \- Toe syndactyly \- Puffiness of feet \- Calcaneovalgus \- Vertical talus SKIN, NAILS, & HAIR Skin \- Yellow subcutaneous tissue covered by thin, scaly skin \- Generalized tissue edema Hair \- Absent scalp hair \- Absent eyelashes NEUROLOGIC Central Nervous System \- Lissencephaly \- Absence of corpus callosum \- Cerebellar hypoplasia \- Absence of olfactory bulbs \- Hydranencephaly \- Spina bifida \- Dandy-Walker malformation \- Choroid plexus cyst MISCELLANEOUS \- Decreased fetal activity \- Stillborn \- Polyhydramnios \- Short umbilical cord \- Small placenta \- Most patients are stillborn or die in immediate neonatal period MOLECULAR BASIS \- Caused by mutation in the phosphoglycerate dehydrogenase gene (PHGDH, 606879.0007 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	NEU-LAXOVA SYNDROME 1	c0265218	30,366	omim	https://www.omim.org/entry/256520	2019-09-22T16:24:23	{"doid": ["0080076"], "mesh": ["C536405"], "omim": ["256520"], "orphanet": ["2671"], "synonyms": ["Alternative titles", "NEU-LAXOVA SYNDROME"]}
## Clinical Features Carey et al. (1978) gave the name OEIS complex to a combination of defects comprising omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. This rare complex is thought to represent the most severe end of a spectrum of birth defects, the exstrophy-epispadias sequence, which, in order of increasing severity, includes phallic separation with epispadias, pubic diastasis, exstrophy of the bladder (600057), cloacal exstrophy, and OEIS complex. Very few instances of recurrence of anomalies in this cluster have been reported. Kallen et al. (2000) studied the cluster of associated malformations called the OEIS complex among 5,260 infants with multiple malformations identified in 4 large registers of congenital malformations, corresponding to 5.84 million births. The existence of the OEIS complex was clearly demonstrated. In addition to the 4 classic malformations (omphalocele, bladder exstrophy, imperforate anus, and spine malformation), a strong association with spina bifida and intersex was stressed. Spine malformations occurred not only in the lumbosacral level but also more cranially, and an association also with upper spina bifida could be demonstrated. No specific association with any other malformation, including cardiac defects, was apparent. They concluded that the OEIS complex is an unusually clearly defined entity among the various nonrandom associations that had been described. Bohring (2002) reviewed the papers and editorial comments of Martinez-Frias et al. (2001), Keppler-Noreuil (2001), and Carey (2001) on cloacal exstrophy and the OEIS complex. These papers demonstrated the ongoing difficulties in terminology and delineation when fundamental causes are unknown. Martinez-Frias et al. (2001) had pointed out that bladder exstrophy and cloacal exstrophy seem to be distinct clinical entities. Exstrophy of the cloaca includes the persistence and exstrophy of a common cloaca that receives ureters, ileum, and a rudimentary hindgut, and is associated with failure of fusion of the genital tubercles and pubic rami, incomplete development of the lumbosacral vertebrae with spinal dysraphism, imperforate anus, cryptorchidism and epispadias in males and anomalies of the mullerian duct derivatives in females, and a wide range of urinary tract anomalies. Omphalocele is common and most patients have a single umbilical artery. In a review of 14 cases with presumptive OEIS complex, Keppler-Noreuil (2001) demonstrated the variability in this condition with the presumed minimal finding of OEIS complex without omphalocele or spine defects in 2 cases to the full spectrum of the complex. Cytogenetics El-Hattab et al. (2010) described an infant girl with OEIS complex and chromosome 1p36 deletion (see 607872) who displayed features of both disorders, including omphalocele, cloacal exstrophy, imperforate anus, sacral segmentation defects, renal malposition and malrotation, genital anomalies, diastasis of the symphysis pubis, microbrachycephaly, large anterior fontanel, cardiac septal defects, rib fusion, limb deformity, developmental delay, and typical facial features. At 12 months of age, the patient developed bowel obstruction which progressed to septic shock and multiorgan failure and she died. Chromosomal microarray analysis detected a 2.4-Mb terminal deletion of chromosome 1p. There was no evidence of uniparental disomy. El-Hattab et al. (2010) suggested that OEIS complex might be caused by recessive mutation of a gene located in the 1p36 region, with the deletion uncovering a mutation located on the intact homolog; however, they noted that this was the first reported case of OEIS complex in association with a 1p36 deletion and that it was also possible that this case represented the chance occurrence of 2 independent conditions. Inheritance Smith et al. (1992) described 2 cases in successive pregnancies. The karyotype of the first was 46,XY, whereas that of the second was 46,XX. Lee et al. (1999) reported an autopsy study of monozygotic twins concordant for the OEIS complex. They found reports of OEIS (cloacal exstrophy) in 18 pairs of twins (13 monozygotic, 1 dizygotic, and 4 of unknown zygosity). In the 13 monozygotic twins, the anomalies were concordant in 3 pairs and discordant in 5 pairs; concordancy was not mentioned in 5 pairs. The higher incidence of OEIS in monozygotic twins than in dizygotic twins suggested a possible genetic contribution to the occurrence of these defects. In a review, Schinzel et al. (1979) estimated that approximately 10% of all cases of cloacal exstrophy occur in like-sex twins and suggested that the 2 events, twinning and early malformations such as cloacal exstrophy, may be causally related. Population Genetics Feldkamp et al. (2011) performed an epidemiologic study of cloacal exstrophy to describe the prevalence, associated anomalies, and maternal characteristics. Feldkamp et al. (2011) used data from the International Clearinghouse Birth Defects Surveillance and Research submitted from 18 birth defect surveillance programs representing 24 countries. Cases were clinically evaluated locally and reviewed centrally by 2 authors. Cases of persistent cloaca were excluded. A total of 186 cases of cloacal exstrophy were identified for an overall prevalence of 1 in 131,579 births, ranging from 1 in 44,444 births in Wales to 1 in 269,464 births in South America. Live birth prevalence was 1 in 184,195 births. Prevalence ratios did not vary by maternal age. Forty-two (23%) cases met the criteria for the OEIS complex, whereas 60 (32%) were classified as OEI and 18 (10%) as EIS (one with suspected VATER, 192350, 0.5%). Other findings included 2 cases with trisomy 13, 1 with mosaic trisomy 12, 1 with mosaic 45,X, and 1 classified as having amnion band sequence (217100). Twenty-seven (14.5%) infants had other anomalies unrelated to cloacal exstrophy. Feldkamp et al. (2011) concluded that cloacal exstrophy is a rare anomaly with variability in prevalence by geographic location. The proportion of cases classified as OEIS complex was lower in this study than previously reported. Among all cases, 55% were reported to have an omphalocele. INHERITANCE \- Isolated cases CHEST Ribs Sternum Clavicles & Scapulae \- 11 pairs of ribs ABDOMEN External Features \- Omphalocele Gastrointestinal \- Imperforate anus \- Duplicated colon \- Intestinal malrotation \- Anal atresia \- Anteriorly placed anus \- Rectovaginal fistula GENITOURINARY External Genitalia (Male) \- Small penis \- Ambiguous genitalia \- Epispadias \- Abnormal or absent scrotum External Genitalia (Female) \- Ambiguous genitalia \- Hypoplastic labia \- Widely separated labioscrotal folds Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Bifid uterus Kidneys \- Hydronephrosis \- Renal agenesis \- Pelvic kidney Ureters \- Duplicated collecting system \- Hydroureter Bladder \- Cloacal exstrophy \- Vesicovaginal fistula SKELETAL Spine \- Hemivertebrae \- Absent sacrum \- Sacral segmentation defects Pelvis \- Symphysis pubis diastasis \- Congenital hip dislocation Feet \- Club feet NEUROLOGIC Central Nervous System \- Tethered cord \- Lipomyelocystoceles \- Meningomyelocele \- Chiari malformation \- Hydrocephalus MISCELLANEOUS \- OEIS is an acronym for Omphalocele, Exstrophy of the cloaca, Imperforate anus, and Spinal defects \- Majority of cases are sporadic ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	OEIS COMPLEX	c1838703	30,367	omim	https://www.omim.org/entry/258040	2019-09-22T16:24:08	{"doid": ["0080175", "0080173"], "mesh": ["C564009"], "omim": ["258040"], "orphanet": ["322", "93929"], "synonyms": ["Alternative titles", "OMPHALOCELE-EXSTROPHY-IMPERFORATE ANUS-SPINAL DEFECTS"]}
This article is about the schizophrenia symptom. For the mental disorders of self-awareness and personality in general, see personality disorder. Self-disorder Other namesIpseity disturbance Pronunciation * /ˌskɪtsəˈfriːniə, ˌskɪdz-, -oʊ-, -ˈfrɛniə/[1] SpecialtyPsychiatry A self-disorder, also called ipseity disturbance, is a psychological phenomenon of disruption or diminishing of a person's sense of minimal (or basic) self-awareness. The sense of minimal self refers to the very basic sense of having experiences that are one's own; it has no properties, unlike the more extended sense of self, the narrative self, which is characterized by the person's reflections on themselves as a person, things they like, their identity, and other aspects that are the result of reflection on one's self. Disturbances in the sense of minimal self, as measured by the Examination of Anomalous Self-Experience (EASE),[2] aggregate in the schizophrenia spectrum disorders, to include schizotypal personality disorder, and distinguish them from other conditions such as psychotic bipolar disorder and borderline personality disorder.[3] ## Contents * 1 Minimal self * 2 Disturbance * 3 Examination of Anomalous Self-Experience (EASE) * 3.1 EASE items * 4 Examination of Anomalous World Experience (EAWE) * 4.1 EAWE items * 5 Clinical relevance * 6 Future directions and controversy * 7 History of the concept * 8 See also * 9 References * 10 External links ## Minimal self[edit] The minimal self has been likened to a "flame that enlightens its surroundings and thereby itself." Unlike the extended self, which is composed of properties such as the person's identity, the person's narrative, and other aspects that can be gleaned from reflection, the minimal self has no properties, but refers to the "mine-ness" "given-ness" of experience, that the experiences are that of the person having them in that person's stream of consciousness. These experiences that are part of the minimal self are normally "tacit" and implied, requiring no reflection on the part of the person experiencing to know that the experience is theirs. The minimal self cannot be further elaborated and normally one cannot grasp it upon reflection.[3] The minimal self goes hand-in-hand with immersion in the shared social world, such that "[t]he world is always pregiven, ie, tacitly grasped as a self-evident background of all experiencing and meaning." This is the self-world structure.[4] De Warren gives an example of the minimal self combined with immersion in the shared social world: "When looking at this tree in my backyard, my consciousness is directed toward the tree and not toward my own act of perception. I am, however, aware of myself as perceiving this tree, yet this self-awareness (or self-consciousness) is not itself thematic."[5] The focus is normally on the tree itself, not on the person's own act of seeing the tree: to know that one is seeing the tree does not require an act of reflection. ## Disturbance[edit] In the schizophrenia spectrum disorders, the minimal self and the self-world structure are "constantly challenged, unstable, and oscillating," causing anomalous self-experiences known as self-disorders. These involve the person feeling as if they lack an identity, as if they are not really existing, that the sense of their experiences being their own (the "mine-ness" of their experiential world) is failing or diminishing, as if their inner experiences are no longer private, and that they don't really understand the world. These experiences lead to the person engaging in hyper-reflectivity, or abnormally prolonged and intense self-reflection, to attempt to gain a grasp on these experiences, but such intense reflection may further exacerbate the self-disorders. Self-disorders tend to be chronic, becoming incorporated into the person's way of being and affecting "how" they experience the world and not necessarily "what" they experience. This instability of the minimal self may provoke the onset of psychosis.[4][6] Similar phenomena can occur in other conditions, such as bipolar disorder and depersonalization disorder, but Sass's (2014) review of the literature comparing accounts of self-experience in various mental disorders shows that serious self-other confusion and "severe erosion of minimal self-experience" only occur in schizophrenia;[7] as an example of the latter, Sass cites the autobiographical account of Elyn Saks, who has schizophrenia, of her experience of "disorganization" in which she felt that thoughts, perceptions, sensations, and even the passage of time became incoherent, and that she had no longer "the solid center from which one experiences reality", which occurred when she was 7 or 8 years old.[8] This disturbance tends to fluctuate over time based on emotions and motivation, accounting for the phenomenon of dialipsis in schizophrenia, where neurocognitive performance tends to be inconsistent over time.[7] The disturbance of the minimal self may manifest in people in various ways, including as a tendency to inspect one's thoughts in order to know what they are thinking, like a person seeing an image, reading a message, or listening closely to someone talking (audible thoughts; or in German: Gedankenlautwerden). In normal thought, the "signifier" (the images or inner speech representing the thought) and the "meaning" are combined into the "expression", so that the person "inhabits" their thinking, or that both the signifier and the meaning implicitly come to mind together; the person does not need to reflect on their thoughts to understand what they are thinking. In people with self-disorder, however, it is frequently the case that many thoughts are experienced as more like external objects that are not implicitly comprehended. The person must turn their focus toward the thoughts to understand their thoughts because of that lack of implicit comprehension, a split of the signifier and the meaning from each other, where the signifier emerges automatically in the field of awareness but the meaning does not. This is an example of the failing "mine-ness" of the experiential field as the minimal self recedes from its own thoughts, which are consigned to an outer space. This is present chronically, both during and outside of psychosis, and may represent a middle point between normal inner speech and auditory hallucinations, as well as normal experience and first-rank symptoms.[9] They may also experience uncontrolled multiple trains of thought with different themes simultaneously coursing through one's head interfering with concentration (thought pressure) or often feel they must attend to things with their full attention in order to get done what most people can do without giving it much thought (hyper-reflectivity), which can lead to fatigue.[2][3] ## Examination of Anomalous Self-Experience (EASE)[edit] The EASE is a semi-structured interview that attempts to capture the extent of the mainly non-psychotic self-disorders experienced by the person. It is divided into 5 broad sections: Cognition and stream of consciousness, which covers disturbances in the flow of thoughts and experiences, and includes such self-disorders as "thought pressure", an experienced chaos of unrelated thoughts, "loss of thought ipseity", a sense as if the person does not own their thoughts (but not to the level of psychosis), and "spatialization of experience", which is where the person experiences their thoughts as if they occurred within a space; self-awareness and presence, which deals with dissociative experiences of the self and world as well as a tendency toward intense reflection, in addition to a declining understanding of how to interact with others and the world called "perplexity" or "lack of natural evidence"; bodily experiences, which deals with alienating experiences of the body as well as with "mimetic experiences", the sense of a person that if they move, pseudo-movements of other, unrelated objects are experienced; demarcation/transitivism, which covers specific disturbances in the person's ego boundaries such as the person confusing their own thoughts, ideas, and feelings for that of their interlocutor; and existential reorientation, which refers to changes in the person's experience of the world that reflect the effect of self-disorders on the person's worldview. A large number of these items have affinities with the basic symptoms[2] The EASE, and pre-EASE studies attempting to assess basic self-disturbance, has been found in studies to discriminate between people on the schizophrenia spectrum, and those with psychotic bipolar disorder or borderline personality disorder. The EASE has been found to have good reliability, meaning that when 2 clinicians do the assessment, they draw roughly the same conclusions.[3] The items on the EASE were compared against the accounted experiences of depersonalization disorder, finding many affinities, but also differences, reflecting namely the failing sense of "mine-ness" of the experiential world and a tendency to confuse the self with the world, others, or both.[10] ### EASE items[edit] Domain 1: Stream of consciousness Symptom Description 1.1 Thought interference Thoughts that are not semantically related to the main line of thinking pop up and interfere with it; these thoughts are generally irrelevant and unimportant. 1.2 Loss of thought ipseity Thoughts appear strange in that they do not seem as if they originate from the self; the person is rationally aware that these thoughts are theirs. 1.3 Thought pressure Many thoughts appearing simultaneously or in rapid succession that lack a common theme, which the person feels they cannot control. 1.4 Thought block The train of thought comes to a halt. 1.4.1 Blocking The thought becomes lost and inaccessible and no new thought appears in its place. 1.4.2 Fading The thought slowly fades away with no new thought appearing. 1.4.3 Fading combined with simultaneous or successive thought interference The thought slowly fades away while a new thought begins to appear. 1.5 Silent thought echo A thought which is not perceptualized is repeated or doubled. 1.6 Ruminations-obsessions Persistence or recurrence of thoughts. 1.6.1 Primary ruminations Tendency to ruminate with no underlying reason. 1.6.2 Secondary ruminations Tendency to ruminate secondary to another issue, such as perplexity. 1.6.3 True obsessions Recurring thoughts that are not macabre and which the person attempts to resist. 1.6.4 Pseudo-obsessions Recurring thoughts that tend to have violent, sexual, or otherwise aggressive content that are generally not resisted by the person. In the ICD-10's definition of schizotypal disorder these are called "obsessive ruminations", and they tend to play out like movies or series of projections in a space internal to the person's mind, located perhaps "on an inner screen" or "behind [their] eyes", that they passively watch and may also inspect.[11] 1.6.5 Compulsions Rituals in relation to ruminations or obsessions. 1.7 Perceptualization of inner speech or thought Thoughts acquire perceptual qualities, which may appear to occur in the head or outside the person (hallucinations). 1.7.1 Internal The person experiences these perceptions as occurring inside the head. 1.7.2 Equivalents Thoughts appear as written text. 1.7.3 Internal as a psychotic first-rank symptom Person believes the thoughts are so loud that they can be heard by others. 1.7.4 External Person experiences hallucinations, which may seem to repeat their thoughts. 1.8 Spatializaton of experience Internal experiences such as thoughts appear as if they occurred inside an internal space; the person may experience them as being like physical objects appearing in that space. 1.9 Ambivalence Difficulty deciding between 2 or more insignificant options. 1.10 Inability to discriminate modalities of intentionality Person has difficulty telling the difference between perceptions and imaginations and between true memories and dreams. 1.11 Disturbance of thought initiative or thought intentionality Difficulty initiating and organizing goal-directed activities. 1.12 Attentional disturbances (see subtypes) 1.12.1 Captivation of attention by a detail in the perceptual field Person is drawn to aspects of the environment which are hard to divert attention away from, even though the person has no particular interest in those details. 1.12.2 Inability to split attention The person cannot do 2 or more activities at the same time which use different senses. 1.13 Disorder of short-term memory Difficulty keeping things in mind for a short period of time experienced as a tendency to forget things from the beginning as the person continues, such as in reading a story. 1.14 Disturbance in experience of time Change in the flow of time, not including changes in flow speed caused by boredom or pleasure, or regarding past vs. future. 1.14.1 Disturbance in the subjective experience of time flow Time seems to speed up, slow down, stand still, or become fragmented. 1.14.2 Disturbance in the existential time The future is blocked and existence seems to be dominated by either the present or the past. 1.15 Discontinuous awareness of own action Break in awareness of own actions. 1.16 Discordance between intended expression and the expressed The person experiences their expression as being uncontrollable, distorting the meaning of what the person is actually trying to say. 1.17 Disturbance of expressive language function The person experiences difficulty in mobilizing the words needed to express themselves. Domain 2: Self-awareness and presence Symptom Description 2.1 Diminished sense of basic self Feelings as if one is, for example, ephemeral, non-existent, profoundly different from others (but unable to sufficiently elaborate on this), or that one must agree with others; this has occurred chronically since at least adolescence. 2.1.1 Childhood onset Onset was before puberty. 2.1.2 Adolescence onset Onset was in adolescence. 2.2 Distorted first-person perspective There are at least 3 subtypes. 2.2.1 Person feels as if their experiences aren't their own, at least briefly, or as if they were a mere inanimate object. 2.2.2 Person feels an incredible distance between the self and experience, resulting in intense and involuntary constant or recurring self-monitoring. 2.2.3 Person feels as if the self were located at a specific point in space, or perhaps as if it were a physical object, or both. 2.3 Other states of depersonalization Sense of alienation from self or one's own experience. 2.3.1 Melancholiform depersonalization Melancholic mood change from which the person feels alienated. 2.3.2 Unspecified depersonalizaton Other depersonalization 2.4 Diminished presence An increased distance from being affected by the world that is experienced by the person as originating from within the self; this is experienced as an affliction by the person. 2.4.1 Specified Increasing distance from the world experienced as apathy towards specific events. 2.4.2 Unspecified Sense of barrier between self and world that cannot be furthered specified by the person. 2.4.3 Including derealization or perceptual change Where the sense of barrier results in a change in world perception (e.g. sense of fogginess) or is accompanied by derealization. 2.5 Derealization The world appears as strange, alien, unreal, or changed. 2.5.1 Fluid (global) derealization The world seems to lose its color or become lifeless, or there is some other diminution of the qualities of the world. 2.5.2 Intrusive derealization Things in the world seem much more intrusive than normal, which strongly affect the person emotionally. 2.6 Hyperreflectivity; increased reflectivity Tendency to engage in excessive reflection of matters involving the self or other things hindering the sense of being able to live carefree or spontaneously; person will engage in intense reflection while engaged in activity (called also "simultaneous introspection" in Japanese psychopathology). 2.7 I-split Sense that the self does not exist as a unified whole beyond having a multifaceted personality. 2.7.1 I-split suspected When person's comments hint at I-split. 2.7.2 Person reports non-psychotic experience of I-split. 2.7.3 Person reports non-psychotic experience of I-split that is experienced in a way that the different pieces of self exist at different points in space like physical objects. 2.7.4 Person reports delusional experience of I-split. 2.8 Dissociative depersonalization (out of body experience) Person experiences the self as if it were outside the body. 2.8.1 Person feels as if this is occurring, without hallucinating. 2.8.2 Person experiences this as a dissociative hallucination. 2.9 Identity confusion Person feels as if they were another person. 2.10 Sense of change in relation to chronological age Feeling as if the person were very much younger or older than they really are. 2.11 Sense of change in relation to gender (see subtypes) 2.11.1 Person worries that they might be gay. 2.11.2 Person is confused about their sex or feels as if they were the opposite sex. 2.12 Loss of common sense/perplexity/lack of natural evidence Person is confused about the meaning of what people normally understand implicitly and may spend a lot of time wondering why, say, the sky is blue or 2+2=4; or person may follow extremely rigid schemas that come across as bizarre to others ("morbid rationalism") or may have a tendency to obsess about the spatial or geometric aspects of the world ("geometrism"). 2.13 Anxiety (see subtypes) 2.13.1 Panic attacks with autonomous symptoms Panic accompanied by multiple autonomic symptoms including labored breathing, heart racing, chest pain, or a sense of choking. 2.13.2 Psychic-mental anxiety Feeling of anxiety without autonomic symptoms. 2.13.3 Phobic anxiety Anxiety triggered by specific fears (e.g. agoraphobia). 2.13.4 Social anxiety Anxiety caused by social situations. 2.13.5 Diffuse, free-floating, and pervasive anxiety Intense, constant anxiety. 2.13.6 Paranoid anxiety Anxiety triggered by paranoid fears. 2.14 Ontological anxiety Pervasive anxiety experienced by person over their own existence that causes them to be more interested in survival than in self-realization; it can involve a sense as if something ominous were approaching, a sense of being exposed to others, or some other fear of violation of their own existence. 2.15 Diminished transparency of consciousness A sense that one is blocked from clearly perceiving the contents of consciousness which is not secondary to something else (e.g. thought pressure, organic brain disorder, or clinical depression). 2.16 Diminished initiative Pervasive difficulty initiating goal-directed activity that is not secondary to, for example, clinical depression. 2.17 Hypohedonia Pervasive and recurring diminished capacity for pleasure. 2.18 Diminished vitality Sense of diminishment of one's vital energy that is not secondary to, for example, clinical depression. 2.18.1 State-like Experienced only episodically. 2.18.1 Trait-like Experienced chronically. Domain 3: Bodily experiences Symptom Description 3.1 Morphological change Sensations or perceptions as if parts of the body or the entire body has changed size or shape. 3.1.1 Due to paroxysmal sensations. 3.1.2 Due to perception. 3.2 Mirror-related phenomena Frequently looking at mirrors or avoiding mirrors, or otherwise feeling as if the shape of the face has changed when looking in a mirror. 3.2.1 The person only looks in the mirror to see if their face has changed, but perceives no change. 3.2.2 Perceived change or distortion of the face. 3.2.3 Other mirror-related phenomena. 3.3 Somatic depersonalization (bodily estrangement) Feeling alienated from one's body or its parts. 3.4 Psychophysical misfit and psychophysical split The body feels as if it does not fit (but not simply because the person dislikes their appearance) or a feeling as if the body and mind do not go together. 3.5 Bodily disintegration Feeling as if the body is falling to pieces. 3.6 Spatialization of bodily experiences Feeling as if parts of the body were no longer a medium for action but as if they were simply standalone physical objects, or feeling as if one can feel body parts that one normally cannot feel. 3.7 Cenesthetic experiences Various unusual bodily sensations, including feelings of numbness, electrical sensations, and thermal sensations. 3.8 Motor disturbances (see subtypes) 3.8.1 Pseudo-movements of the body Person feels as if a part of the body is moving, but it actually is not. 3.8.2 Motor interference Movements of the body intended by the person are derailed, moving in a way not intended by the person. 3.8.3 Motor blocking Person feels unable to move a body part. 3.8.4 Sense of motor paresis Usually temporary sense of weakness in one or more limbs, which can interfere with the person's physical movements (such as grasping an object). 3.8.5 Desautomation of movement Normally automatic or partially automatic physical activities that are carried out on a daily basis or frequently, such as brushing one's hair or riding a bike, can no longer be so, causing the person to have to concentrate and guide each aspect of their movement. 3.9 Mimetic experiences Pseudo-movements of other objects and people are experienced as if there were a connection to the person's own actions. Domain 4: Transitivism/demarcation Symptom Description 4.1 Confusion with the other Person confuses their thoughts, feelings, and other aspects with their interlocutor, or otherwise feels invaded or intruded upon by their interlocutor (but cannot explain why this is so). 4.2 Confusion with one's own specular image Person confuses themselves with their reflection, such as when they are looking in a mirror. 4.3 Threatening bodily contact (see subtypes) 4.3.1 Person feels threatened by being close to or in contact with another person not because of paranoia or suspicion. 4.3.2 Person feels annihilated when in close contact with another person. 4.4 Passivity mood Mood-like feeling of being at the mercy of the world, with the person feeling restrained. 4.5 Other transitivistic phenomena Other feelings as if not properly demarcated from other people and the world. Domain 5: Existential reorientation Symptom Description 5.1 Primary self-reference phenomena Person feels as if outside events are connected to themselves which cannot be explained by any more primary psychopathology. 5.2 Feeling of centrality Brief feeling as if being at the center of all existence. 5.3 Feeling as if the subject's experiential field is the only extant reality Person feels as if only things they are perceiving exist, such that it feels as if things cease to exist when the person looks away, for example. 5.4 "As if" feelings of extraordinary creative power, extraordinary insight into hidden dimensions of reality, or extraordinary insight into own mind or the mind of others. person experiences a sense as if they possess insight most other people do not. 5.5 "As if" feeling that the experienced world is not truly real, existing, as if it was only somehow apparent, illusory, or deceptive An example includes feeling as if the person were in a movie. 5.6 Magical ideas (i.e. ideas implying nonphysical causality) Person feels that they can control things with their mind that they actually cannot, or to otherwise unrealistically control external events. 5.7 Existential or intellectual change Person experiences a major change in their worldview, such as joining a new religion, that does not occur as part of a manic or hypomanic episode. 5.8 Solipsistic grandiosity Person feels superior to other people and considers others to be beneath their notice or concern. ## Examination of Anomalous World Experience (EAWE)[edit] The EAWE is the companion interview to the EASE that focuses on the person's experiences with the world, rather than with the self. There are 6 domains: Space and objects, which deals with the person's experience with space and physical objects, with disorders including hallucinations, distortions of spatial relationships, and experiences of seeing the same object in multiple ways at the same time (called "contamination" on the Rorschach test); time and events, which deals with the person's experience with time, with disorders involving time speeding up or slowing down, time breaking up or becoming fragmented, and constant anticipation of something major about to happen; other persons, which deals with the person's experience of other people, with disorders including disruptions of the sense of ego boundaries with other people, referential ideation based on actions or words by other people, and loss or lack of the ability to naturally understand social situations and social cues leading to attempts to compensate through increased focus or concentration; language, which deals with reduced fluency and disruption of prose in one's native language, distortions in the person's expression which causes others to misunderstand the person, problems with concrete and abstract concepts, and distraction by individual words and phrases leading to the person having difficulty following what they are reading or listening to; atmosphere, which deals with the person's overall feeling-state of the world, with disorders including derealization (particularly The Truman Show-style derealization), objects no longer having normal meaning, hyper-awareness of things that normally stay in the background of awareness, apophanous mood, and a sense of radical changes in the very structure of the universe itself; and existential orientation, which deals with radical changes in a person's worldview, dealing with such things as rejecting society's conventions and rules, being extremely open to believing new ideas, and grandiosity which involves the person considering others to be inferior, like insects compared to them.[12] ### EAWE items[edit] Domain 1: Space and objects Symptom Description 1.1 Abnormal intensity or persistence of visual perceptions Visual stimuli appear more or less intense or take longer to leave perception after ending. 1.1.1 Increase in intensity of visual perceptions* Visual stimuli seem more intense, such as light being brighter or colors stronger. 1.1.2 Decrease in intensity of visual perceptions* Visual stimuli seem less intense. 1.1.3 Recurrence or prolongation of visual stimuli Even after visual stimuli are gone, person continues to see them. Also called palinopsia. 1.2 Blindness or partial blindness Vision is experienced as being blurry or partially or wholly absent. 1.2.1 Blurred vision* 1.2.2 Partial seeing Person sees only part of an object. 1.2.3 Transitory blindness Visual field is experienced as either partly or entirely absent. 1.3 Disturbances involving verticality (accuracy) of visual perceptions* Mis-seeing objects or perceiving visual stimuli that is actually absent. 1.3.1 Visual illusions* Person mis-sees something, mistaking it for something else. 1.3.2 Visual hallucinations* Person experiences seeing something when nothing is there. Can seem only partially external. 1.3.3 Visual pseudohallucinations* Like visual hallucinations, but person while experiencing it recognizes its lack of basis in reality. 1.4 Visual fragmentation Objects or scenes appear broken up. 1.4.1 Object fragmentation Cannot perceive objects as a whole. 1.4.2 Break-up of a scene The world becomes fragmented, with different things appearing disconnected or unrelated to one another. 1.4.3 Captivation of attention by isolated details Person attracted to certain details as if spellbound. 1.5 Disorganization or disturbed object stability Visual perception of things becomes fluid and unstable. 1.5.1 Disorganized object contours Object contours are distorted. 1.5.2 Loss of perceptual stability (fluidity or contamination) Things seem to change their form or nature before the person's very eyes. Multiple forms of a single object may be perceived simultaneously in the same place, like a "photographic double exposure". (See also the fluidity and contamination ratings on the Rorschach test.) 1.6 Changes in quality, size, or shape of visual perceptions 1.6.1 Changes in color of visual perceptions Things seem to be a different color from what they normally are. 1.6.2 Micropsia/macropsia Things seem bigger or smaller than they actually are. 1.6.3 Dysmegalopsia Things seem bigger on one side and smaller on the other than they actually are. 1.6.4 Metamorphopsia Objects have a different but stable form than how they actually are. 1.6.5 Other distortions 1.7 Disturbances of perceptual distance or object juxtaposition Distances and/or relative positioning of objects to each other is distored. 1.7.1 Objects seem closer or farther away* Objects are closer or farther than they appear. 1.7.2 Disturbance of relative spatial relationship (juxtaposition) of objects The relative positioning of objects is distorted, including in the perception of 2 objects one of which is closer, with the closer one appearing farther away and the farther away one appearing closer. May have difficulty determining what is in the background or foreground. 1.7.3 General disturbances in estimation of distance Person struggles to estimate how far away they are from something. 1.8 Distorted experiences of space Space itself seems distorted. 1.8.1 Diminished perspectival orientation Experiences space as isotropic, sees the world as if standing from nowhere in particular or everywhere at once. 1.8.2 Loss of topographical orientation Feels disoriented in familiar places. 1.8.3 Loss of spatial integrity or structure Feels as if space is inconsistent, as if pouring a jug of water down on the floor below results in the water falling onto the floor above or as if a path leads somewhere that should be geometrically impossible. 1.8.4 Loss of dimensionality Perceives the world in only 2 dimensions. 1.8.5 Experience of infinite space Person is overwhelmed by the magnitude of space in their location. 1.8.6 Figure/ground reversal Person sees the space between objects rather than the objects themselves. 1.8.7 Affective experience of space* Space feels threatening or strange, takes on a negative feel. 1.9 Abnormal intensity or persistence of auditory perceptions Sounds seem more or less intense or last longer than they should. 1.9.1 Increases in intensity of auditory perceptions* Sounds seem louder or more intense. 1.9.2 Decreases in intensity of auditory perceptions* Sounds seem quieter or less intense. 1.9.3 Heightened awareness of background auditory sensations Overly aware of sounds that should remain in the background, that are less relevant than other more important sounds. 1.9.4 Recurrence or prolongation of auditory stimuli Sounds last longer than they should or recur. 1.10 Disturbances involving veridicality (accuracy) of auditory perceptions* Mis-hearing sounds or hearing sounds that aren't there. 1.10.1 Auditory illusions* Mis-hears sounds as something else. 1.10.2 Auditory hallucinations* Hears sounds that aren't there, in a way that seems at least somewhat external to the person. 1.10.3 Auditory pseudohallucinations* Like auditory hallucinations, but person is aware during the experience that they are false. 1.11 Other changes in quality of auditory perceptions Experiences distortions in pitch, timbre, or other qualities of some or all sounds. 1.12 Problems localizing sounds Has trouble pinpointing where sounds are coming from. 1.13 Disturbances of other senses* Other senses, such as smell, taste, or touch, experience distortions. 1.13.1 Tactile disturbance* Distortions in the sense of touch. 1.13.2 Gustatory disturbance* Distortions in the sense of taste. 1.13.3 Olfactory disturbance* Distortions in the sense of smell. 1.14 Synesthesia or abnormal concommitant perception* Stimulus in one sense brings in involvement of another sense. 1.15 Splitting-off or isolation of sensory perceptions Stimulus is perceived as having nothing to do with what is producing the stimulus, like another person's voice seems to have nothing to do with the person who is speaking. 1.16 Disturbances in recognizing or identifying an object of perception Fails to recognize what they are seeing or hearing, even when it is familiar to them. 1.17 Loss of boundaries with, or demarcation from, the physical world Person experiences difficulty determining where their body ends and the rest of the world begins. Domain 2: Time and events Symptom Description 2.1 Time or movements appear to change speed This does not only occur when a person is bored, excited, or is engaged in activity. 2.1.1 Time or movements seem speeded up* 2.1.2 Time or movements seem slowed down* 2.1.3 Time or movements seem (somehow) both speeded up and slowed down 2.2 Discrepancy between internal and external time* Experiences discrepancy between the time that passes for their own actions versus the time for the rest of the world. 2.2.1 Internal time seems slower than external time* Feels as if they are moving or thinking very slowly relative to the rest of the world. 2.2.2 Internal time seems faster than external time* Feels as if they are moving or thinking much faster than others and the rest of the world. 2.3 Disruption of dynamic organization of time Seems like time no longer flows like it should. Here, there is a disruption of the unity of the present moment with the retention (immediate previous moment, "primary remembrance") and the protention (immediate next moment, "anticipation"), as described by philosopher Edmund Husserl. 2.3.1 Time feels as though completely stopped, static, infinite, disappeared Feels as if time has stopped or ceased to exist. 2.3.2 Time as disjointed or fragmented Each moment feels disconnected from the last and the next, as if time itself has become staccato, just a sequence of photographs, each having nothing to do with the next or last one. 2.3.3 Disorientation in time Person becomes confused about the passage of time, with difficulty understanding how time flows and when to engage in events, and even what time of day it is. 2.3.4 Feeling limited to or isolated in the present moment Person feels as if they newly come into being as a wholly different person with each passing moment of time. 2.3.5 Various bizarre experiences of time Feels as if time is going backward, as if they are stuck in a Groundhog Day loop, as if they control time, as if they are present in multiple periods of time at once, or other bizarre experiences. 2.4 Disturbed anticipation Disturbance of the expectation of the immediate next moment in time. 2.4.1 Perpetual anticipation Constantly feels as if something very big is imminent, right about to happen. Called also ante festum experience or trema ("stage fright"). 2.4.2 Constant surprise due to inability to anticipate future events Is constantly surprised by mundane events that would normally be expected immediately beforehand, due to the inability to anticipate. 2.4.3 Feeling that "anything could happen" Feeling that literally anything, from the probable through the highly unlikely to the impossible, could happen, while not caring what that is. 2.4.4 Protention (future directedness) collapses Feels as if they cannot move into the imminent next moments in a smooth, flowing way. 2.5 Disturbed awareness of the expected future* The conception of the future beyond the imminent is distorted or feared in some way. 2.5.1 Future seems nonexistent* 2.5.2 Future seems unimportant or irrelevant* 2.5.3 Future seems threatening* 2.5.4 Premonitions* 2.6 Disturbed experiences of memories or of the past 2.6.1 Past seems cut-off* 2.6.2 Past seems vague or obscure* 2.6.3 Past disappears or seems non-existent* 2.6.4 Past seems accelerated* Feels as if the memories are all condensed into a single moment. 2.6.5 Past seems slower* Feels as if memories are all drawn out and elongated in time. 2.6.6 Intrusiveness of the past* The past seems to limit the person, what they can do. 2.6.7 Erosion of distinction between past and present* Confused about whether the person is remembering something or if they're actually doing something right now. 2.6.8 Past seems disjointed What happened in the past seems all out of order, all disconnected from each other, or otherwise disjointed. Domain 3: Other persons Symptom Description 3.1 Lack of social understanding or interpersonal attunement (hypoattunement) Person feels they cannot smoothly engage with other people at all; may feel like they must study and follow explicit rules to interact successfully with other people. 3.1.1 Loss of social common sense Feels they cannot naturally grasp what other people do or how the conversation has gone. 3.1.2 Bodily/proprioceptive loss of attunement Feels they are outward and cannot time their mannerisms and other actions properly (e.g. may not know when to begin speaking after another person has finished, or when to greet a person as they walk past them). 3.1.3 Specific difficulty understanding non-verbal communication Has difficulty reading body language, tone of voice, and other forms of non-verbal communication. 3.2 Sense of remoteness from others* Feels cut off from other people. 3.3 Alienated strategies for understanding others Feels they have to engage in intellectual-style analysis of social situations to understand what they mean and what to do. 3.3.1 Alienated scrutinizing of others' behavior Aware they tend to analyze social situations to know what they mean, like a zoologist out in the field doing in situ study of animals. 3.3.2 Algorithmic approach to social understanding/interaction Person attempts to create algorithms, a set of formal rules, to use to guide them in social situations. 3.4 Sense of inferiority, criticism, or mistrust in relation to others* Tends to feel threatened and criticized in social situations, making it hard to interact comfortably. 3.4.1 Feelings of self-consciousness, self-criticism* Tends to be overly aware of flaws in their appearance, interaction, etc. 3.4.2 Feelings of social paranoia or social anxiety* Feels people they're interacting with or are around them are constantly focusing on and judging them. 3.4.3 Pervasive mistrust of others* Tends to feel other people are out to "get" them. 3.5 Torment or distress due to generalized social insecurity Mere presence of others feels extremely burdensome and unbearable, as if by their very presence they endanger the person's cold self. 3.6 Interference by voices* Feels like voices prevent them from interacting normally with people. 3.7 Disturbance of self-other demarcation Feels like they have a hard time telling what thoughts, ideas, actions, sayings are in them, and what are in other people. 3.7.1 Hyperattunement Feels like they can read minds. 3.7.2 Unusual influence over others Feels like they can mind control other people. 3.7.3 Pathological openness Feels like their innermost thoughts and feelings are open to being read by others. 3.7.4 Experiences of being controlled Feels like they're being mind-controlled. 3.7.5 Merging or fluid psychological boundaries They feel mixed up or confuse their thoughts and feelings with those of other people. May feel like there is no clear boundary between themselves and other people. 3.7.6 Universal merging with others* Feels like there are no individuals, but everyone is part of the same hive mind or other collective consciousness. 3.7.7 Uncertain personal identity/attitudes* Feels confused about their identity when around others. 3.7.8 Uncertain physical boundaries Has difficulty telling where their body ends and other people's bodies begin. 3.7.9 Experience of being imitated Feels like other people are imitating them deliberately to mess with them or make fun of them, in a way that seems strange to them. 3.8 Difficulties with the gaze Has trouble with eye contact 3.8.1 Intrusiveness of the gaze of the other Feels like other people's gazes are very intrusive and make them uncomfortable, often leading to avoidance of eye contact. 3.8.2 Feeling of exposure through one's own eyes Feels like eye contact exposes their innermost thoughts and feelings to the other person. 3.8.3 Intrusiveness of one's own gaze Feels like their own gaze is intrusive and unbearable for others. 3.8.4 Dehumanization of the eyes of others When making eye contact, the other person does not seem to be human or alive, with their eyes and body parts being seen as like inanimate objects. 3.8.5 Eyes as cosmic portals Feels like the eyes of others (or one's own in the mirror) are windows into another world or dimension. 3.8.6 Unspecific uneasigness with gaze Feels uneasy with eye contact without specifying the reason. 3.9 Depersonalization of others Depersonalization, but of other people rather than oneself. 3.9.1 People seem dead* Feels as if other people are dead (even though they're alive, up and moving around). 3.9.2 People seem unreal/false/illusory Other people seem like they don't really exist or are fraudulent copies of themselves, without objective reality. 3.9.3 People seem mechanical Other people seem like they are mere robots without a soul. 3.10 Persons dominated by a single characteristic Focuses on a single characteristic of other people, and feels as if it defines the other person's entire being, like the other person is nothing more than that characteristic. 3.11 Heightened intensity, aliveness, or reality of others* People seem more alive and energetic than normal, which feels fishy. 3.12 Changes in quality or tone of others' appearance Other people look or seem strangely different from how they normally are. 3.12.1 People seem familiar in a strange way Of people they've never met before, it strangely feels like they know the other person from somewhere. Like deja vu, but with people. 3.12.2 People seem unfamiliar in a strange way Of people they know well, it strangely feels like they don't know the other person at all. Like Jamais vu, but with people. 3.12.3 People seem disgusied* Feels like other people aren't actually those other people, but are people disguised as those other people. 3.12.4 People seem threatening in a strange way* There is something about other people that makes it seem like they are a threat. 3.12.5 General/unspecified changes in the physical appearance of others Something about how the other person looks, like maybe their eyes or face, seems strangely different from before. 3.13 People seem as if communicating something special or unusual (beyond the obvious) Other people seem to be dropping hints intended for the person, with the intent of the other people's speech being very different from what is said. 3.13.1 Paranoid significance* The hint seems to express dislike or threats toward the person. 3.13.2 Grandiose significance* The hint seems to signify the person's superiority or special powers. 3.13.3 Metaphysical significance The hint seems to signify impending Doomsday or perhaps a cataclysm that has fundamentally altered the universe. 3.13.4 Unknown/unsalatable significance The person cannot express the meaning of the hint. 3.14 Anomalous behavior/attitudinal responses to others Person is aware they are acting strangely differently toward other people, often due to paranoia or not understanding social situations like they used to. 3.14.1 Active withdrawal* Person tends to want to be alone and shut others out. 3.14.2 Oppositional/rebellious behavior* Person tends to want to act counter to other people. 3.14.3 Social disinhibition* Person aware they disregard social norms when they interact. 3.14.4 Compulsive interpersonal harmony* The person feels very eager to please and will do anything to avoid conflict with others. 3.14.5 Extreme compliance Automatic obedience or imitation of others, echopraxia. 3.14.6 Compulsive clownery/entertainment of others Feels like they must always crack jokes or clown around, in a way that turns out wooden or stilted to other people. Domain 4: Language Symptom Description 4.1 Basic disruptions of standard verbal comprehension Difficulty comprehending speech or writings 4.1.1 Meaning/sound dissociation Difficulty putting the representations of words with their meanings when heard or read 4.1.2 Distraction via semantic possibilities Gets caught up on all the different senses of a word or a statement that was just heard or read 4.1.3 Distraction by individual words Gets focused on individual words instead of the message as a whole 4.1.4 Unspecified difficulty understanding It's difficult to understand what they're hearing or reading 4.2 Difficulty understanding emotional/expressive aspects of speech* Has a hard time with understanding the intonations in what people say 4.3 Specific changes in standard feel or meaning of words Becomes focused on words because they feel different than they did before 4.3.1 Focus on sound or appearance of words/phrases* Very aware of how words sound or appear 4.3.2 Unconventional semantic determination via signifier or fragments of words Determines words' meanings by how they or parts of them look, rather than by the conventional meaning 4.3.3 Words seem arbitrary/absurd Is often so distracted by how arbitrary words seem that they do not attend to conversations 4.3.4 Words or language seems alive Words take on a life of their own or feel like physical objects 4.3.5 Egocentric linguistic reference Self-referencing ideas coming from the specific words or grammar that a person uses, but NOT the content of what they're saying. 4.4 Unconventional word choice, grammar, tone, or cryptic discourse Says things in an unusual manner that often confuses people, which may be at least somewhat willful. 4.4.1 Cryptic, telegraphic, or ungrammatical speech Speaks in a cryptic manner or using sentences structures that violate the grammar of the language they're speaking (even though they are a native speaker, for example), which may be experienced as intentional. 4.4.2 Stock words Tends to overuse a certain few words or phrases to the point where they acquire many meanings beyond the conventional, causing their speech to feel stilted. 4.4.3 Made-up words (neologisms) or unconventional usage Aware of using made-up words or using words in ways that differ greatly from their meanings. 4.4.4 Mannerisms and stilted speech Tends to use very formal registers to say things in situations that would normally call for more casual speech. 4.5 Disturbed fluency Has a hard time expressing self using language 4.5.1 Unavailability of words Cannot find the right words 4.5.2 Unfocused or disorganized thoughts preclude verbal expression Aware they have difficulty speaking because they cannot get their thoughts "straight", that is, their thinking has become so digressive or otherwise difficult to understand that they cannot express themselves 4.5.3 General discordance between the intended expression and the expressed Aware of inability to express themselves in a way that accurately expresses what they meant to say; little things in the expression keep being off to the point the listener or reader may be left with a different impression. 4.6 Disturbed relevance Aware of having a hard time remaining on a single line of thought while talking or writing 4.6.1 Derailment* Aware that they have a tendency to lose track of what they're saying or writing. 4.6.2 Tangential responding Aware that they make off-topic answers to questions 4.7 Disturbance of linguistic engagement or purposefulness Aware they speak in such a strange way that they are not engaging 4.7.1 Aprosody (lack of emotional intonation)* Aware their speech lacks the normal intonation 4.7.2 Echolalia Feels a need to repeat what the other person says 4.7.3 Speech feels autonomous Feels like they are not in control of their speaking or writing 4.8 Anomalous experience of the abstract and the concrete Has difficulty using the abstract and the concrete appropriately 4.8.1 Difficulty with or dislike of abstract concepts 4.8.2 Abstract rendered in unusually concrete terms 4.8.3 Specific or concrete meanings rendered in unusually abstract or general terminology 4.8.4 Hyperabstract or vague discourse 4.9 Ineffability: inability of language to describe or express (may include temptation to remain silent) Feels language cannot fully express what they mean to say 4.9.1 Language inadequate to express unusual circumstances* Feels their experiences are so unusual language becomes inadequate to describe them 4.9.2 General feeling of the inadequacy of the language Feels language is inadequate to describe even normal experiences, or otherwise sees the use of language as a waste of time 4.10 Alienation from self-description When they provide a narrative of one's life, they have difficulty with even recognizing the person back them as themselves. Domain 5: Atmosphere Symptom Description 5.1 Derealization of the world Sense of disconnection or unreality of the world 5.1.1 Remoteness or barrier (plate-glass feeling)* Feels cut off from the world 5.1.2 Decreased intensity or substantiality* The world seems flat 5.1.3 Deanimation* The world seems lifeless 5.1.4 Falseness The whole world feels like it is a stage 5.1.5 Loss of enticement quality* Nothing has any appeal 5.1.6 Static quality, stillness, or morbid intellectualism Looks at the world in a very static or geometric way 5.1.7 Nonspecific/other derealization* The world feels strange in some way 5.2 Loss of affordances Objects and events no longer have their normal meaning and are seen simply as fixtures on the world. 5.3 Inanimate things seem alive or intentional* 5.4 Heightened intensity/hyperrealization* The world feels somehow more alive, colorful, and intense than normal. 5.5 Deja vu experiences Things feel familiar somehow or like they've happened before. 5.6 Jamais vu experiences The familiar becomes unfamiliar and novel 5.7 Perplexity Reality becomes confusing 5.7.1 Confusion of realms Difficulty distinguishing the internal, mental realm and the physical realm. 5.7.2 Unreal interferes Delusions or imaginations interfere with the ability to live in the world. 5.7.3 World experienced as incoherent, disoriented The world is no longer a fixed stable place of meaning, but has become confusing and incoherent. 5.7.4 Perplexing hyperawareness of tacit dimension Things that would normally stay in the background of perception come to the foreground and are the focus of attention. 5.8 Anomalous manner of ascribing or perceiving meaning The way the person derives meaning from things changes greatly 5.8.1 Meaning imposed on object by subject Person tends to give their own idiosyncratic meaning to things 5.8.2 Meaning inherent in the object itself The idiosyncratic meaning is perceived as soon as the object comes into perspective and is seen as intrinsic to the object. 5.8.3 Proliferation of meanings from the object Perceiving the object causes an uncontrollable emergence of associations, that is, things that it reminds the person of. 5.9 Anomalous forms of meaning Meaning given to objects tend to be very atypical, often in terms of the concrete and the abstract 5.9.1 Physical or literalist instantiation of abstract meaning Things like thoughts and feelings become hard and concrete, like they were physical objects in themselves. 5.9.2 Anomalous classification Tends to classify different things together using unusual criteria 5.10 Intensified awareness of patterns or trends* Increased tendency to see patterns in things 5.11 Anomalous sense of causal relationships Cause and effect become distorted. 5.11.1 Actions or events seem controlled by an external force or will 5.11.2 Actions or events seem predetermined or planned 5.12 All-inclusive self-consciousness/ontological paranoia Keeps feeling like they are being watched, focused on 5.13 Diminished ontological independence of experienced world/subjectivism The world lacks independence from the mind. 5.13.1 Subjectivism/solipsism The person feels like they are the only mind in the universe and that they are the ones who build up the universe and bring things and people into being. 5.13.2 Double bookkeeping Aware of two different realities, one real and physical, the other imaginary and delusional. 5.13.3 Influencing physical reality Feels like their thoughts control the world 5.13.4 Pseudomovements of objects/persons When the person is moving, it feels like things or people are moving in conjunction with them. 5.14 Revelatory or pseudorelevatory (apophanous) mood There is something different, special, or unusual about the world, but the person cannot grasp it, filling them with wonder. 5.14.1 Uncanny particularity Something seems peculiar about various mundane happenings in the world, like they signify something bigger happening behind the scenes. 5.14.2 Self-referentiality Sees mundane things as referring back to themselves in one of various ways, listed below. 5.14.2.a Paranoid significance* Suggests someone is trying to harm them 5.14.2.b Grandiose significance Suggests they are superior or special in some way 5.14.2.c Metaphysical significance Suggests the entire universe has radically changed, with the implication that it is the person who is response, or the message is directed specifically toward them. 5.14.2.d Unknown/unsalatable significance The nature of the significance is unknown. 5.14.3 Unspecifiable strangeness Something has changed, the person can sense it, but they don't know exactly what. 5.15 Quasi-mystical experiences Amazed at the very existence of the world 5.15.1 Mystic union with the world* Feels especially connected and united with the world, but not in a way that suggests their ego boundaries have been compromised. 5.15.2 Mere being Struck by the sheer existence of everything 5.16 Experiences of the end of the world Feels like the world is ending. 5.17 Anomalies of mood or affect The person has entered into an unusual mood state 5.17.1 Emptiness, numbness, indifference, lack of spontaneous response to the world* 5.17.2 Feeling of emotional/affective blockage (in the sense of being unable to express)* 5.17.3 Pervasive, nameless anxiety with fear of annihilation* 5.17.4 Basic irritation, restlessness, anger (nonemotional dysphoria)* 5.17.5 Detached euphoria Feels euphoric, but in a way that is very disconnected, different than the euphoria in a manic state which tends to involve increased energy and actions toward goals. 5.17.6 Despair, demoralization, hopelessness* 5.17.7 Abnormalities of mood constancy* 5.17.7.a Mood or emotion is abnormally present* Feels like the mood lasts beyond the events or thoughts that triggered it. 5.17.7.b Mood or emotion is abnormally labile* Mood keeps changing 5.17.8 Incongruity of mood or emotion 5.17.8.a Mood or emotion inappropriate to the current situation Has moods or emotional reactions one would expect to what's going on 5.17.8.b Moods or emotions are mutually contradictory Very high level of ambivalence about how they feel about things Domain 6: Existential orientation Symptom Description 6.1 Rejection of society or convention The person generally chooses to live according to their rules in disregard of societal norms. 6.1.1 Disinclination for human society Person rejects society and would prefer to live as a misfit. 6.1.2 Antagonomia Tends to act in ways that directly oppose societal values. 6.1.3 Idionomia Person feels radically unique. 6.2 Extreme indifference or openness Person is very open to all possibilities in a way suggesting they are detached from the normal concerns of life. 6.2.1 Attitude of indifference, insouciance, lack of concern Expresses "callous indifference" and that nothing really matters, in a way suggesting cold detachment, different from the way indifference is typically expressed in mood disorders where there is a strong emotional component. 6.2.2 Conceptual freedom/anything goes Feels like anything could happen: as far as they're concerned, for example, apples could just as easily start falling up from trees rather than down. 6.3 Pervasive disbelief, skepticism, or curiosity re the obvious, taken-for-granted Constant tendency to question everything that society takes for granted. 6.4 Absolute certitude The person is absolutely sure about their unusual interpretation of the world, and does not believe that it will ever be refuted. 6.5 Feeling of being special or superior Person feels superior or like they have a special role to play in the universe. 6.5.1 Feeling of extraordinary insight* Person feels as if they and they alone understand the mysteries of the world. 6.5.2 Messianic duty* Person feels as if they are a savior the world is depending on. 6.5.3 Intellectual/spiritual grandiosity (with invidious comparison) Person feels as if they are much much more highly advanced and evolved than all other people, whom they view as vastly inferior. 6.6 Impossible responsibility or guilt* Person feels guilty over things they could not have done. 6.7 Sense of loss of freedom or individuality Feels as if they are controlled by outside forces. 6.8 Adherence to abstract, intellectualistic, and/or autonomous rules Person follows self-imposed "rational" rules that are quite idiosyncratic. 6.9 Existential or intellectual change* Person suddenly is absorbed by things like religion or philosophy. 6.10 Feeling of centrality Person feels as if the universe revolves around them. 6.11 Decentering of the self relative to universe Feels as if they are not really real, like they truly exist apart from the universe. Indicates experience that can also occur in other primary psychotic or mood disorders outside the schizophrenia spectrum, such as delusional disorder, major depressive disorder, or bipolar disorder. ## Clinical relevance[edit] The presence of self-disorders may have predictive power for whether those with an at risk mental state will develop psychosis;[13][14] the risk of suicidal ideation and suicide by people with schizophrenia, though depression would also be an important factor;[15] predicting initial social dysfunction in people with either schizophrenic or bipolar psychosis;[16] and whether a person will move to a schizophrenia spectrum diagnosis later.[17] The presence of self-disorders may cause reduced person insight into their illness through the alteration of the basic structures of consciousness.[3][4] Self-disorders are difficult for the people experiencing them to articulate spontaneously;[2][18] and are not well-known, by either the general public or professionals in the field. Because of this, people will often make vague, clichéd complaints that mimic the symptoms of other mental disorders, symptoms such as "fatigue" or "concentration difficulties". Were a knowledgeable clinician to probe deeper, however, the underlying self-disorders may be assessed and help clarify the nature of the person's illness. In their review, Parnas, et al. (2014) say, "The psychiatrist’s acquaintance with the phenomenon of 'non-specific specificity' is, in our view, extremely important in the context of early diagnostic assessment, especially of people presenting with a vague, unelaborated picture of maladjustment, underperformance, chronic malaise and dysphoria, negative symptoms, or hypochondriac preoccupations." People with schizophrenia often describe their self-disorders as causing more suffering for them than psychosis.[3] Self-disorders underlie most of the first-rank symptoms, those often termed passivity phenomena. There is a current proposal to list self-disorder as one of the symptoms of schizophrenia in the upcoming ICD-11.[19] ## Future directions and controversy[edit] In a 2014 review, Postmes, et al., suggested that self-disorders and psychosis may arise from attempts to compensate for perceptual incoherence and proposed a hypothesis for how the interaction among these phenomena and the person's attempts to resolve the incoherence give rise to schizophrenia. The problems with the integration of sensory information create problems for the person in keeping a grip on the world, and since the self-world interaction is fundamentally linked to the basic sense of self, the latter is also disrupted as a result.[20] Sass and Borda have studied the correlates of the dimensions of self-disorders, namely disturbed grip (perplexity, difficulty "getting" stuff most people can get), hyperreflexivity (where thoughts, feelings, sensations, and objects pop up uncontrollably in the field of awareness, as well dysfunctional reflecting on matters and the self), and diminished self-affection (where the person has difficulty being "affected" by aspects of the self, experiencing those aspects as if they existed in an outer space), and have proposed how both primary and secondary factors may arise from dysfunctions in perceptual organization and multisensory integration.[21][22] In a 2013 review, Mishara, et al., criticized the concept of the minimal self as an explanation for self-disorder, saying that it is unfalsifiable, and that self-disorder arises primarily from difficulty integrating different aspects of the self as well as having difficulty distinguishing self and other, as proposed by Lysaker and Lysaker: Ichstörung or ego disorder, as they say, in schizophrenia arises from disturbed relationships not from the "solipsistic" concept of the self as proposed by Sass, Parnas, and others.[23] In his review, Sass agrees that the focus of research into self-disorder has focused too much on the self, and mentions attempts to look at disturbances in the person's relationship with other people and the world, with work being done to create an Examination of Anomalous World Experience, which will look at the person's anomalous experiences regarding time, space, persons, language, and atmosphere; he suggests there are problems with both the self and the world in people with self-disorder, and that it may be better conceptualized as a "presence-disturbance".[7] Parnas acknowledges the Lysaker model, but says that it is not incompatible with the concept of the minimal self, as they deal with different levels of self-hood.[3] ## History of the concept[edit] See also: Basic symptoms of schizophrenia The concept of a basic self-disturbance in schizophrenia appears in all the foundational texts on the disease. However, the concept was difficult to operationalize and was criticized for being vague and too subjective; little systematic or empirical research was done on the concept in the 20th century. The publication of the DSM-III (1980) had unintended consequences, however, and led, in many instances, to focusing only on the signs and symptoms listed as criteria and generally ignoring the other signs and symptoms that can appear with each disorder; it privileged a behaviorist approach to diagnosis. The concept of this self-disturbance soon disappeared from training programs in the United States.[3][24] The Bonn Scale for the Assessment of Basic Symptoms was created to assess sub-clinical affective, cognitive and perceptual disturbances, as well as basic self-disturbance, in people, and in many studies basic symptoms were found to aggregate in people with schizophrenic and schizotypal disorders. Basic symptoms are subjective and difficult for the person to describe spontaneously, but the person will try to adapt and cope with them: functioning becomes impaired when people reach their adaptive capacity. In the period leading up to the first episode of schizophrenia, uncharacteristic basic symptoms first appear and are followed by the onset of more characteristic basic symptoms and, finally, psychosis.[18] To revive the concept of basic self-disturbance and to overcome the previous problems of a lack of a concrete definition of it, a group of researchers developed the EASE, based on phenomenological interviews with first-admission people with schizophrenia spectrum disorders, to enable empirical research of self-disorders.[2][3] ## See also[edit] Schizotypy * Early intervention in psychosis * Center for Subjectivity Research ## References[edit] 1. ^ Jones, Daniel (2003) [1917], Peter Roach; James Hartmann; Jane Setter (eds.), English Pronouncing Dictionary, Cambridge: Cambridge University Press, ISBN 978-3-12-539683-8 2. ^ a b c d e Josef Parnas, Paul Moller, Tilo Kircher, Jorgen Thalbitzer, Lennart Jansson, Peter Handest & Dan Zahavi (September 2005). "EASE: Examination of Anomalous Self-Experience". Psychopathology. 38 (5): 236–258. doi:10.1159/000088441. PMID 16179811.CS1 maint: multiple names: authors list (link) 3. ^ a b c d e f g h i Josef Parnas & Mads Gram Henriksen (September 2014). "Disordered self in the schizophrenia spectrum: a clinical and research perspective". Harvard Review of Psychiatry. 22 (5): 251–265. doi:10.1097/HRP.0000000000000040. PMC 4219858. PMID 25126763. 4. ^ a b c Mads G. Henriksen & Josef Parnas (May 2014). "Self-disorders and schizophrenia: a phenomenological reappraisal of poor insight and noncompliance". Schizophrenia Bulletin. 40 (3): 542–547. doi:10.1093/schbul/sbt087. PMC 3984518. PMID 23798710. 5. ^ De Warren, N. Husserl and the Promise of Time. New York: Cambridge University Press., cited in Brice Martin, Marc Wittmann, Nicolas Franck, Michel Cermolacce, Fabrice Berna & Anne Giersch (2014). "Temporal structure of consciousness and minimal self in schizophrenia". Frontiers in Psychology. 5: 1175. doi:10.3389/fpsyg.2014.01175. PMC 4212287. PMID 25400597.CS1 maint: multiple names: authors list (link) 6. ^ Louis A. Sass & Josef Parnas (2003). "Schizophrenia, consciousness, and the self". Schizophrenia Bulletin. 29 (3): 427–444. doi:10.1093/oxfordjournals.schbul.a007017. PMID 14609238. 7. ^ a b c Sass, Louis A. (2014). "Self-disturbance and schizophrenia: Structure, specificity, pathogenesis (Current issues, New directions)". Schizophrenia Research. 152 (1): 5–11. doi:10.1016/j.schres.2013.05.017. ISSN 1573-2509. PMID 23773296. 8. ^ Saks, Elyn (2007). The center cannot hold : my journey through madness. New York: Hyperion. ISBN 978-1-4013-0944-2. 9. ^ Kendler, K.S.; Parnas, J. (2012). Philosophical Issues in Psychiatry II: Nosology. International Perspectives in Philosophy & Psychiatry. OUP Oxford. pp. 242–243. ISBN 978-0-19-964220-5. Retrieved 2016-04-12. 10. ^ Louis Sass, Elizabeth Pienkos, Barnaby Nelson & Nick Medford (June 2013). "Anomalous self-experience in depersonalization and schizophrenia: a comparative investigation". Consciousness and Cognition. 22 (2): 430–441. doi:10.1016/j.concog.2013.01.009. PMID 23454432.CS1 maint: multiple names: authors list (link) 11. ^ Rasmussen, A. Rosen; Parnas, Josef (2015). "Pathologies of imagination in schizophrenia spectrum disorders". Acta Psychiatrica Scandinavica. 131 (3): 157–161. doi:10.1111/acps.12323. PMID 25098736. 12. ^ Sass, Louis; Pienkos, Elizabeth; Skodlar, Borut; Stanghellini, Giovanni; Fuchs, Thomas; Parnas, Josef; Jones, Nev (2017-01-01). "EAWE: Examination of Anomalous World Experience". Psychopathology. 50 (1): 10–54. doi:10.1159/000454928. ISSN 1423-033X. PMID 28268224. 13. ^ Andrea Raballo, Elena Pappagallo, Alice Dell' Erba, Nella Lo Cascio, Martina Patane', Eva Gebhardt, Tommaso Boldrini, Laura Terzariol, Massimiliano Angelone, Alberto Trisolini, Paolo Girardi & Paolo Fiori Nastro (January 2016). "Self-Disorders and Clinical High Risk for Psychosis: An Empirical Study in Help-Seeking Youth Attending Community Mental Health Facilities". Schizophrenia Bulletin. 42 (4): 926–32. doi:10.1093/schbul/sbv223. PMC 4903056. PMID 26757754.CS1 maint: multiple names: authors list (link) 14. ^ Barnaby Nelson, Andrew Thompson & Alison R. Yung (November 2012). "Basic self-disturbance predicts psychosis onset in the ultra high risk for psychosis "prodromal" population". Schizophrenia Bulletin. 38 (6): 1277–1287. doi:10.1093/schbul/sbs007. PMC 3494062. PMID 22349924. 15. ^ Elisabeth Haug, Ingrid Melle, Ole A. Andreassen, Andrea Raballo, Unni Bratlien, Merete Oie, Lars Lien & Paul Moller (July 2012). "The association between anomalous self-experience and suicidality in first-episode schizophrenia seems mediated by depression". Comprehensive Psychiatry. 53 (5): 456–460. doi:10.1016/j.comppsych.2011.07.005. PMID 21871617.CS1 maint: multiple names: authors list (link) 16. ^ Elisabeth Haug, Merete Oie, Ole A. Andreassen, Unni Bratlien, Andrea Raballo, Barnaby Nelson, Paul Moller & Ingrid Melle (April 2014). "Anomalous self-experiences contribute independently to social dysfunction in the early phases of schizophrenia and psychotic bipolar disorder". Comprehensive Psychiatry. 55 (3): 475–482. doi:10.1016/j.comppsych.2013.11.010. PMID 24378241.CS1 maint: multiple names: authors list (link) 17. ^ Josef Parnas, John Carter & Julie Nordgaard (February 2016). "Premorbid self-disorders and lifetime diagnosis in the schizophrenia spectrum: a prospective high-risk study". Early Intervention in Psychiatry. 10 (1): 45–53. doi:10.1111/eip.12140. PMID 24725282. 18. ^ a b Frauke Schultze-Lutter (January 2009). "Subjective symptoms of schizophrenia in research and the clinic: the basic symptom concept". Schizophrenia Bulletin. 35 (1): 5–8. doi:10.1093/schbul/sbn139. PMC 2643966. PMID 19074497. 19. ^ Heinz, A.; Voss, M.; Lawrie, S. M.; Mishara, A.; Bauer, M.; Gallinat, J.; Juckel, G.; Lang, U.; Rapp, M. (2016-07-15). "Shall we really say goodbye to first rank symptoms?". European Psychiatry. 37: 8–13. doi:10.1016/j.eurpsy.2016.04.010. ISSN 1778-3585. PMID 27429167. 20. ^ Postmes, L.; Sno, H.N.; Goedhart, S.; van der Stel, J.; Heering, H.D.; de Haan, L. (2014). "Schizophrenia as a self-disorder due to perceptual incoherence". Schizophrenia Research. 152 (1): 41–50. doi:10.1016/j.schres.2013.07.027. ISSN 1573-2509. PMID 23973319. 21. ^ Borda, Juan P.; Sass, Louis A. (2015). "Phenomenology and neurobiology of self disorder in schizophrenia: Primary factors". Schizophrenia Research. 169 (1–3): 464–473. doi:10.1016/j.schres.2015.09.024. ISSN 1573-2509. PMID 26516103. 22. ^ Sass, Louis A.; Borda, Juan P. (2015). "Phenomenology and neurobiology of self disorder in schizophrenia: Secondary factors". Schizophrenia Research. 169 (1–3): 474–482. doi:10.1016/j.schres.2015.09.025. ISSN 1573-2509. PMID 26603059. 23. ^ Mishara, A. L.; Lysaker, P. H.; Schwartz, M. A. (2013). "Self-disturbances in Schizophrenia: History, Phenomenology, and Relevant Findings From Research on Metacognition". Schizophrenia Bulletin. 40 (1): 5–12. doi:10.1093/schbul/sbt169. ISSN 0586-7614. PMC 3885311. PMID 24319117. 24. ^ Nancy C. Andreasen (January 2007). "DSM and the death of phenomenology in america: an example of unintended consequences". Schizophrenia Bulletin. 33 (1): 108–112. doi:10.1093/schbul/sbl054. PMC 2632284. 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[EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Self-disorder	None	30,368	wikipedia	https://en.wikipedia.org/wiki/Self-disorder	2021-01-18T18:33:28	{"wikidata": ["Q25230657"]}
Noma is a gangrenous disease that causes severe destruction of the soft and osseous tissues of the face. ## Epidemiology Its exact prevalence is unknown. The disease was present in the Western world up until the start of the 20th century, but it now mainly affects children between 2 and 6 years of age living in the poorest regions of the world. Rare cases of noma have been described in adults with severe immunodeficiency (individuals with AIDS or myelopathy, or those being treated with immunosuppressants) in Africa and in the Western world. ## Clinical description In addition to the severe facial destruction, children with noma often present with rhinolalia aperta, uncontrollable drooling, and socially handicapping halitosis. The most debilitating sequela is permanent jaw constriction. Spontaneous resolution of the disease is associated with the formation of extremely dense and fibrous scars that may lead to osseous ankylosis between the mandible and maxilla or the mandible and the malar bone. The buccal opening in these children is limited to between 0 and 10 mm making intake of solid foods problematic or impossible. The risk factors associated with noma are malnutrition, intercurrent disease such as rubella or malaria, poor oral hygiene, and the presence of a lesion of the gingival mucosa (an early sign of necrotising gingivitis). ## Etiology The aetiology remains unknown. A bacterial aetiology has long since been suggested but carrying out extensive studies in the regions most affected by the disease is problematic. The few studies reported have indicated that bacteria from the Prevotella and Fusobacteria groups may play a role in the disease. ## Management and treatment The management of acute noma is aimed at improving the health status (introduction of a balanced diet and vitamin supplements, and sufficient hydration) of affected individuals and providing topical care. Antibiotics are recommended to prevent the often lethal complications associated with infection and to help limit extension of the lesion. If the lesion is still intrabuccal and limited, antibiotics may also prevent progression of the disease in some cases. Once the cicatrisation stage is complete, stepwise reconstructive surgery (aimed at relieving the stricture of the mouth and then reconstruction of the mandible and maxilla, cheek, lips and nose) can be considered. In addition to reconstruction of the face of affected children, reconstructive surgery can be used to allow improvement of impaired function (elocution, salivary continence, buccal opening). ## Prognosis Noma is associated with significant morbidity and mortality, often due to complications such as generalised sepsis, intracerebral septic emboli, bronchial aspiration or inanition. The disease develops very rapidly and in isolated regions medical care is often only sought after the lesions are well established. Delayed treatment will not allow a return to status quo ante. The disease leads to social exclusion of affected children: they are rarely admitted into schools for fear of contamination (which in reality does not occur) and are often rejected by their families and village, who continue to view noma as a malediction. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Noma	c0028271	30,369	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2700	2021-01-23T18:56:22	{"gard": ["4001"], "mesh": ["D009625"], "umls": ["C0028271"], "icd-10": ["A69.0"], "synonyms": ["Cancrum oris"]}
## Summary ### Clinical characteristics. EFEMP2-related cutis laxa, or autosomal recessive cutis laxa type 1B (ARCL1B), is characterized by cutis laxa and systemic involvement, most commonly arterial tortuosity, aneurysms, and stenosis; retrognathia; joint laxity; and arachnodactyly. Severity ranges from perinatal lethality as a result of cardiopulmonary failure to manifestations limited to the vascular and craniofacial systems. ### Diagnosis/testing. The diagnosis of EFEMP2-related cutis laxa is established in a proband with suggestive findings and biallelic pathogenic variants in EFEMP2 identified by molecular genetic testing. ### Management. Treatment of manifestations: Treatment of aortic root dilatation with beta-blockers or angiotensin receptor inhibitors can be considered. Aortic aneurysm replacement has been performed successfully. Symptomatic treatment of pulmonary emphysema; muscle-reinforcing physical therapy for joint hypermobility; routine repair of hernias. Tracheostomy may be necessary when retrognathia leads to upper-airway obstruction. Surveillance: Follow-up evaluations with a cardiologist and pulmonologist at least annually starting from the time of diagnosis. Annual MR angiography from head to pelvis. Agents/circumstances to avoid: Sun tanning to avoid damaging the skin; cigarette smoking to avoid worsening of emphysema. ### Genetic counseling. EFEMP2-related cutis laxa is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an EFEMP2 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the EFEMP2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings The diagnosis of EFEMP2-related cutis laxa should be considered in individuals with the following clinical characteristics: * Vascular involvement * Arterial and aortic tortuosity * Aortic and arterial aneurysms. The ascending aorta and aortic arch are typically most dilated. * Aortic stenosis.The isthmus aorta in particular is often stenotic. * Stenosis and dilatation of pulmonary arteries * Pulmonary hypertension * Hemorrhagic stroke * Cutis laxa. Furrowing of the skin of the whole body that can be displaced more than normal skin and shows abnormal recoil; the skin has a "doughy" consistency. It does not display redundancy as in the Ehlers-Danlos syndromes. * Respiratory involvement. Diaphragmatic hernia or hypoplasia * Craniofacial involvement * Retrognathia * Widely spaced eyes * High palate * Long philtrum * Sagging cheeks * Dysplastic ears * Other evidence of a generalized connective disorder * Joint laxity or contractures * Arachnodactyly * Pectus excavatum * Inguinal hernias * Hypotonia * Bone fragility ### Establishing the Diagnosis The diagnosis of EFEMP2-related cutis laxa is established in a proband with suggestive findings and biallelic pathogenic variants in EFEMP2 identified by molecular genetic testing (see Table 1). Note: Identification of biallelic EFEMP2 variants of uncertain significance (or identification of one known EFEMP2 pathogenic variant and one EFEMP2 variant of uncertain significance) does not establish or rule out a diagnosis of this disorder. Because the phenotype of EFEMP2-related cutis laxa is indistinguishable from many other inherited disorders with cutis laxa and/or arterial abnormalities (tortuosity, aneurysm, and/or stenosis), recommended molecular genetic testing approaches include use of a multigene panel or comprehensive genomic testing. Note: Single-gene testing (sequence analysis of EFEMP2, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended. * A cutis laxa or arteriopathy multigene panel that includes EFEMP2 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. Note: To date such variants have not been identified as a cause of this disorder. 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 EFEMP2-Related Cutis Laxa View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method EFEMP2Sequence analysis 3~100% 4 Gene-targeted deletion/duplication analysis 5None reported 4 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. ## Clinical Characteristics ## Differential Diagnosis ### Table 3. Genes of Interest in the Differential Diagnosis of EFEMP2-Related Cutis Laxa (ARCL1B) View in own window Gene(s)DisorderMOIClinical FindingsComment CLEmphysemaIDGI & GU malformationCardiovascular ALDH18A1ARCL3A (OMIM 219150)AR+-+++--ARCL3A is not assoc w/cardiovascular & pulmonary involvement. ATP6V0A2ATP6V0A2-related cutis laxa (ARCL2A)AR++-++--ARCL2A is also assoc w/hip dislocation & delayed closure of fontanelle. Secondary effects of strokes (DD, structural brain defects) 1 may complicate distinction between ARCL2A & ARCL1B. ATP6V1AARCL2D (OMIM 617403)AR+++--+AneurysmProgeroid facial features ATP6V1E1ARCL2C (OMIM 617402)AR+++--+AneurysmProgeroid facial features; overlapping features wARCL2A ATP7AOccipital horn syndrome (OHS) (See ATP7A Copper Transport Disorders.)XL+-++Vascular tortuosity (mainly of cerebral vasculature) ELNELN-related cutis laxa (ADCL1) (OMIM 123700)AD++--Aortic root dilatation, aneurysmAbsence of arterial tortuosity, infantile aneurysms, infantile developmental emphysema, death in infancy/early childhood, arachnodactyly, & retrognathia in ADCL1 distinguish it from ARCL1B. FBLN5FBLN5-related cutis laxa (ARCL1A & ADCL2)AR AD++++++-+Peripheral pulmonary arterial stenosisNo aortic/arterial aneurysms GORABGerodermia osteodysplastica (GO) (OMIM 231070)AR++----GO is generally not assoc w/CV & pulmonary manifestations. LTBP4LTBP4-related cutis laxa (URDS, ARCL1C)AR+++++-+++Peripheral pulmonary artery stenosisURDS craniofacial & pulmonary phenotype is similar to ARCL1B. Relatively mild CV involvement & severe GI & urinary complications in URDS distinguish ARCL1C from ARCL1B. PYCR1ARCL3B (OMIM 614438)AR+-+-Arterial stenoses, intracranial artery malformation ARCL2B (OMIM 612940)AR+-+++-- SLC2A10Arterial tortuosity syndromeAR+\+ 2--Severe & widespread arterial tortuosity of aorta & middle-sized arteries (w/↑ risk of aneurysms & dissections); focal & widespread stenosis SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1 TGFBR2Loeys-Dietz syndromeAD+---Cerebral, thoracic, & abdominal arterial aneurysms &/or dissections; arterial tortuosity often present AD = autosomal dominant; ADCL = autosomal dominant cutis laxa; AR = autosomal recessive; ARCL = autosomal recessive cutis laxa; CL = cutis laxa; CV = cardiovascular; DD = developmental delay; GI = gastrointestinal; GU = genitourinary; ID = intellectual development; MOI = mode of inheritance; URDS = Urban-Rifkin-Davis syndrome 1\. Hoyer et al [2009], Renard et al [2010] 2\. Single case report of emphysema in arterial tortuosity syndrome reported by Takahashi et al [2013] ## Management No clinical practice guidelines for EFEMP2-related cutis laxa have been published. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with EFEMP2-related cutis laxa, 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 EFEMP2-Related Cutis Laxa View in own window System/ConcernEvaluationComment Arterial aneurysm, tortuosity, &/or stenosisEchocardiography, 3D CT scan, MRA from head to pelvisRecommend involvement of pediatric cardiologist Emphysema / Obstructive lung diseaseLung function test & bronchoscopyRecommend involvement of pediatric pulmonologist Bony abnormalitiesRadiographs Recurrent bone fracturesBone densitometry KeratoglobusOphthalmologic eval Genetic counselingBy genetics professionals 1To inform patients & their families re nature, MOI, & implications of EFEMP2-related cutis laxa to facilitate medical & personal decision making MOI = mode of inheritance; MRA = magnetic resonance angiography 1\. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse ### Treatment of Manifestations ### Table 5. Treatment of Manifestations in Individuals with EFEMP2-Related Cutis Laxa View in own window Manifestation/ ConcernTreatment Arterial dilatation/ aneurysm * Based on experience in related disorders (e.g., Marfan syndrome), treatment w/beta-blockers or angiotensin receptor blockers can be considered when aortic root dilatation is present. * Surgical repair of large aortic aneurysms (at risk for dissection) should be considered. * Aortic aneurysm replacement has been performed successfully. Pulmonary emphysemaTreated symptomatically MicrognathiaTracheostomy may be necessary when retrognathia leads to upper airway obstruction. Joint hypermobilityMuscle-strengthening PT HerniaRoutine surgical repair PT = physical therapy ### Surveillance ### Table 6. Recommended Surveillance for Individuals with EFEMP2-Related Cutis Laxa View in own window System/ConcernEvaluationFrequency Cardiovascular & pulmonary concernsFollow-up evals w/cardiologist & pulmonologistAt least annually from time of diagnosis Arterial abnormalitiesMRA from head to pelvisAnnually MRA = magnetic resonance angiography ### Agents/Circumstances to Avoid Avoid the following: * Sun tanning, which can damage skin * Cigarette smoking, which can worsen emphysema ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of older and younger sibs of an affected individual in order to identify as early as possible those who should undergo regular cardiovascular and pulmonary surveillance to allow prompt initiation of treatment and preventive measures. 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	EFEMP2-Related Cutis Laxa	None	30,370	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK54467/	2021-01-18T21:29:41	{"synonyms": ["Autosomal Recessive Cutis Laxa Type 1B (ARCL1B)"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "CAMFAK syndrome" – news · newspapers · books · scholar · JSTOR (April 2010) (Learn how and when to remove this template message) CAMFAK syndrome Other namesCataract-microcephaly-arthrogryposis-kyphosis syndrome, Cataract-microcephaly-failure to thrive-kyphoscoliosis syndrome CAMFAK syndrome has an autosomal recessive pattern of inheritance. CAMFAK syndrome (or CAMAK syndrome) is an acronym used to describe a rare inherited neurologic disease, characterized by peripheral and central demyelination of nerves, similar to that seen in Cockayne syndrome.[1] The name "CAMFAK" comes from the first letters of the characteristic findings of the disease: cataracts, microcephaly, failure to thrive, and kyphoscoliosis.[2] The disease may occur with or without failure to thrive and arthrogryposis. ## Contents * 1 Presentation * 2 Genetics * 3 Treatment * 4 References * 5 External links ## Presentation[edit] Low birth weight and a bird-like face may be the first signs. Severe intellectual deficit and death within the first decade are typical. ## Genetics[edit] CAMFAK syndrome is inherited in an autosomal recessive manner.[2] This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. ## Treatment[edit] This section is empty. You can help by adding to it. (July 2017) ## References[edit] 1. ^ Talwar D, Smith SA (October 1989). "CAMFAK syndrome: a demyelinating inherited disease similar to Cockayne syndrome". Am. J. Med. Genet. 34 (2): 194–8. doi:10.1002/ajmg.1320340212. PMID 2554729. 2. ^ a b Online Mendelian Inheritance in Man (OMIM): 212540 ## External links[edit] * Wiley InterScience Journal Classification D * OMIM: 212540 * MeSH: C566861 * DiseasesDB: 33725 External resources * Orphanet: 1317 * v * t * e Multiple sclerosis and other demyelinating diseases of the central nervous system Signs and symptoms * Ataxia * Depression * Diplopia * Dysarthria * Dysphagia * Fatigue * Incontinence * Nystagmus * Optic neuritis * Pain * Uhthoff's phenomenon Investigations and diagnosis * Multiple sclerosis diagnosis * McDonald criteria * Poser criteria * Clinical * Clinically isolated syndrome * Expanded Disability Status Scale * Serological and CSF * Oligoclonal bands * Radiological * Radiologically isolated syndrome * Lesional demyelinations of the central nervous system * Dawson's fingers Approved[by whom?] treatment * Management of multiple sclerosis * Alemtuzumab * Cladribine * Dimethyl fumarate * Fingolimod * Glatiramer acetate * Interferon beta-1a * Interferon beta-1b * Mitoxantrone * Natalizumab * Ocrelizumab * Ozanimod * Siponimod * Teriflunomide Other treatments * Former * Daclizumab * Multiple sclerosis research Demyleinating diseases Autoimmune * Multiple sclerosis * Neuromyelitis optica * Diffuse myelinoclastic sclerosis Inflammatory * Acute disseminated encephalomyelitis * MOG antibody disease * Balo concentric sclerosis * Marburg acute multiple sclerosis * Neuromyelitis optica * Diffuse myelinoclastic sclerosis * Tumefactive multiple sclerosis * Experimental autoimmune encephalomyelitis Hereditary * Adrenoleukodystrophy * Alexander disease * Canavan disease * Krabbe disease * Metachromatic leukodystrophy * Pelizaeus–Merzbacher disease * Leukoencephalopathy with vanishing white matter * Megalencephalic leukoencephalopathy with subcortical cysts * CAMFAK syndrome Other * Central pontine myelinolysis * Marchiafava–Bignami disease * Mitochondrial DNA depletion syndrome Other * List of multiple sclerosis organizations * List of people with multiple sclerosis * Multiple sclerosis drug pipeline * Pathophysiology This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	CAMFAK syndrome	c1859312	30,371	wikipedia	https://en.wikipedia.org/wiki/CAMFAK_syndrome	2021-01-18T19:03:03	{"mesh": ["C566861", "C537965"], "orphanet": ["1317"], "wikidata": ["Q5008650"]}
## Clinical Features Sellick et al. (2005) reported a large multigenerational family segregating symmetric cutaneous small vessel lymphocytic vasculitis affecting the cheeks, thighs, and hands. In all affected family members the disease presented in early infancy, and there was no evidence for an association with systemic disease and no abnormalities of hair, nails, or teeth. Symptoms had a relapsing course but no seasonal variation. Skin biopsy of the lesions revealed small vessel lymphocytic vasculitis of the superficial and deep dermis with red blood cell extravasation. Inheritance The pattern of transmission of the disorder in the family reported by Sellick et al. (2005) was consistent with autosomal dominant inheritance with incomplete penetrance. Mapping Haplotype construction and analysis of recombination events by Sellick et al. (2005) in a family segregating cutaneous small vessel lymphocytic vasculitis defined a 4.7-Mb minimal interval for the disease locus at chromosome 6q26-q27 with a multipoint lod score of 3.01. The CCR6 (601835) and GPR31 (602043) genes, which map to the linked region, were screened in 2 affected individuals, but no mutations were identified. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	VASCULITIS, LYMPHOCYTIC, CUTANEOUS SMALL VESSEL	c1853293	30,372	omim	https://www.omim.org/entry/609817	2019-09-22T16:05:32	{"mesh": ["C565222"], "omim": ["609817"]}
For the disease affecting humans sometimes known as "mud fever", see Leptospirosis. Dermatophilus congolensis, a causative agent of mud fever Mud fever, also known as scratches or pastern dermatitis, is a group of diseases of horses causing irritation and dermatitis in the lower limbs of horses. Often caused by a mixture of bacteria, typically Dermatophilus congolensis, and Staphylococcus spp, mud fever can also be caused by fungal organisms (dermatophytes). Photosensitization, chorioptic mange mites, contact dermatitis and other conditions also contribute to some cases. This condition is also known as dew poisoning, grease, grease heel, or greasy heel. ## Contents * 1 Cause * 2 See also * 3 References * 4 External links ## Cause[edit] Mud fever is caused by an infection of the skin by bacteria, including Dermatophilus congolensis, and often Staphylococcus spp. Dermatophytes (fungal organisms such as Malassezia or Trichophyton) can also contribute, as can chorioptic mange mites. Photosensitivity or irritant contact may contribute in certain cases. Rarely, vasculitis can cause continued inflammation.[1] ## See also[edit] * Rainscald ## References[edit] 1. ^ Pascoe, Reginald R.; Knottenbelt, Derek C. (1999). "Iatrogenic and Idiopathic Disorders". Manual of Equine Dermatology. Elsevier Health Sciences. p. 202. ISBN 0-7020-1968-2. Retrieved 2008-05-31. ## External links[edit] * VetSci – Mud Fever Infographic * ArcaNatura – Guide to Visually Diagnosing Clinical Signs of Scratches [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Mud fever	c0023364	30,373	wikipedia	https://en.wikipedia.org/wiki/Mud_fever	2021-01-18T18:53:57	{"mesh": ["D007922"], "wikidata": ["Q1753695"]}
A number sign (#) is used with this entry because a cardiac arrhythmia syndrome with variable manifestations can be caused by heterozygous mutation in the ankyrin-B gene (ANK2; 106410) on chromosome 4q25-q26. Long QT syndrome-4 can also be caused by mutation in the ANK2 gene. For a general phenotypic description and a discussion of genetic heterogeneity of long QT syndrome, see 192500. Description Loss-of-function mutations in ANK2 can result in a broad spectrum of clinical cardiac phenotypes. Carriers of some mutations (e.g., E1425G, 106410.0001) display QT interval prolongation, stress- and/or exercise-induced polymorphic ventricular arrhythmia, syncope, and sudden cardiac death. Patients with other variants show clinical phenotypes, sometimes mild, extending beyond LQTS, leading to the label 'ankyrin-B syndrome.' These phenotypes include bradycardia, sinus arrhythmia, delayed conduction/conduction block, idiopathic ventricular fibrillation, and catecholaminergic polymorphic ventricular tachycardia (Mohler et al., 2007). Clinical Features ### Long QT Syndrome 4 Schott et al. (1995) reported a large French family segregating a form of long QT syndrome. Among 25 affected members (21 adults and 4 children), the average rate-corrected QT interval was 490 ms (for adults) and 465 ms (for children) compared with 380 ms and 403 ms in unaffected individuals. Sinus node bradycardia or junctional escape rhythm was diagnosed in all patients with LQT4. Episodes of atrial fibrillation were diagnosed in 12 adult patients but were absent during childhood. Since the initial description, Mohler et al. (2003) reported that 8 additional individuals had been born, of whom 4 carried the LQT4 haplotype. Sinus node abnormalities were diagnosed in utero in all affected members from generation 4. ### Ankyrin-B Syndrome Mohler et al. (2004) expanded the phenotype of the disorder originally called LQT4 by Schott et al. (1995). They found that 8 unrelated patients with loss of ankyrin-B activity displayed varying degrees of cardiac dysfunction, including bradycardia, sinus arrhythmia, idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, and risk of sudden death. However, a prolonged rate-corrected QT interval was not a consistent feature, indicating that ankyrin-B dysfunction represents a clinical entity distinct from classic long QT syndromes. Mapping In a 65-member family in which the long QT syndrome was associated with more marked sinus bradycardia than usual, leading to sinus node dysfunction, Schott et al. (1995) excluded linkage to 3 previously mapped LQT loci on chromosomes 11 (LQT1; 192500), 7 (LQT2; 613688), and 3 (LQT3; 603830). Positive linkage was obtained for markers located on 4q25-q27, with a maximum lod score of 7.05 for marker D4S402. Molecular Genetics Mohler et al. (2003) sequenced the ankyrin-B gene, which was known to map to the 4q25-q27 region, and identified an A-to-G transition at position 4274 in exon 36, resulting in a glu1425-to-gly substitution (E1425G; 106410.0001), in a patient with long QT syndrome-4. Mohler et al. (2004) identified 8 unrelated probands harboring 5 different ankyrin-B loss-of-function mutations (106410.0001-106410.0005), 4 of which were previously undescribed, whose clinical features distinguished the cardiac phenotype from classic long QT syndromes. The mutations were localized in the ankyrin-B regulatory domain, which distinguishes function of ankyrin-B from ankyrin-G (ANK3; 600465) in cardiomyocytes. Mohler et al. (2007) identified 7 novel nonsynonymous variants in ANK2 in patients with a variety of cardiac phenotypes. Four of these variants displayed abnormal activity in cardiomyocytes. Nomenclature Splawski (2004) suggested the designation 'sick sinus syndrome associated with bradycardia' for this disorder. Animal Model Mohler et al. (2003) reported that mice heterozygous for a null mutation in ankyrin-B were haploinsufficient and displayed arrhythmia similar to humans. Analysis of ECGs and heart rates of unrestrained animals using implanted radiotransmitter electrodes revealed significant similarities in cardiac phenotype between humans with LQT4 and AnkB +/- mice. AnkB +/- mice displayed bradycardia, heart rate variability, and sudden cardiac death. The mutation in ankyrin-B resulted in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-triphosphate receptors (all ankyrin-B-binding proteins), which reduced the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also led to altered calcium ion signaling in adult cardiomyocytes that resulted in extrasystoles, and provided a rationale for the arrhythmia. Thus, Mohler et al. (2003) identified a novel mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters. Genotype/Phenotype Correlations In transfection assays in neonatal mouse cardiomyocytes, Mohler et al. (2007) found that disease-associated human ANK2 mutations caused a range of in vitro phenotypes, with those variants demonstrating the most severe loss of function correlating with the most severe human phenotype. They identified 3 distinct functional classes of ANK2 loss-of-function variants. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Prolong QT interval on EKG \- Sinus bradycardia \- Sinus nude dysfunction \- Atrial fibrillation \- Syncope \- Sudden cardiac death MISCELLANEOUS \- Genetic heterogeneity (see LQT1 192500 ) MOLECULAR BASIS \- Caused by mutation in the ankyrin 2 gene (ANK2, 106410.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	CARDIAC ARRHYTHMIA, ANKYRIN-B-RELATED	c1141890	30,374	omim	https://www.omim.org/entry/600919	2019-09-22T16:15:43	{"omim": ["600919"], "orphanet": ["768", "101016"], "synonyms": ["Alternative titles", "ANKYRIN-B SYNDROME"], "genereviews": ["NBK1129"]}
A number sign (#) is used with this entry because of evidence that vitamin D-dependent rickets type 2A (VDDR2A) is caused by mutation in the gene encoding the vitamin D receptor (VDR; 601769) on chromosome 12q. Description Vitamin D-dependent rickets type 2A (VDDR2A) is caused by a defect in the vitamin D receptor gene. This defect leads to an increase in the circulating ligand, 1,25-dihydroxyvitamin D3. Most patients have total alopecia in addition to rickets. VDDR2B (600785) is a form of vitamin D-dependent rickets with a phenotype similar to VDDR2A but a normal vitamin D receptor, in which end-organ resistance to vitamin D has been shown to be caused by a nuclear ribonucleoprotein that interferes with the vitamin D receptor-DNA interaction. For a general phenotypic description and discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700). Clinical Features Brooks et al. (1978) reported a 22-year-old African American woman with hypocalcemia, secondary hyperparathyroidism, osteomalacia, and osteitis fibrosa cystica in association with normal serum 25-hydroxyvitamin D and markedly increased serum 1,25-dihydroxyvitamin D. The patient also had increased serum alkaline phosphatase and generalized aminoaciduria. Treatment with large doses of vitamin D3 corrected the hypocalcemia and hyperparathyroidism. Radiographs showed prominent trabeculation of long bones, 'rugger-jersey' changes in the vertebrae, and increased density of the skull. Biopsy of the iliac crests showed wide osteoid seams. Secondary hyperparathyroidism was reflected by erosion of the clavicles, symphysis pubis, and sacroiliac joints. Brooks et al. (1978) concluded that the disorder was due to impaired end-organ response to 1,25(OH)2D3, and suggested the term 'vitamin D-dependent rickets type 2.' Marx et al. (1978) reported a brother and sister with vitamin D-dependent rickets type 2 observed at ages 20 and 5 months, respectively. Both patients had hypocalcemia with secondary hyperparathyroidism, hypophosphatemia, and high serum concentrations of 1,25-dihydroxyvitamin D3. The findings were consistent with decreased end-organ sensitivity to 1,25-dihydroxyvitamin D3. Chemical features of vitamin D deficiency could be corrected with administration of 1,25-dihydroxyvitamin D3. Rosen et al. (1979) described 2 sisters, aged 3 and 7 years, who had onset of rickets in the first year or so of life. The parents were healthy second cousins. The older child lost her hair at age 16 months, and soon thereafter, bony deformities and progressive loss of teeth occurred. Vitamin D in large doses and calcium had no effect. The authors referred to 2 other cases, both sporadic. The authors postulated absence of specific receptors for 1,25-(OH)2D3 in intestine and bone, or alternatively, a defect in the nuclear instrumentarium of the response to 1,25-(OH)2D3. Although treatment with 1,25-(OH)2D3 had no effect, oral phosphate had significant benefit. Liberman et al. (1980) described a 13-year-old girl with total alopecia and rickets unresponsive to large doses of vitamin D2. She had profound hypocalcemia, which was unresponsive to several agents including 1,25-dihydroxycholecalciferol. Serum concentrations of 25-hydroxyvitamin D were normal, but those of 1,25-(OH)2-cholecalciferol were markedly raised. In addition, 24,25-dihydroxyvitamin D was undetectable in the serum. Administration of synthetic 24,25-dihydroxycholecalciferol was followed by normocalcemia which persisted long after treatment was stopped. Her sister, who died at age 10 months, also had total alopecia, rickets, and hypocalcemia resistant to vitamin D2 treatment. Liberman et al. (1980) postulated that the defect was caused by changes in the receptor site. Studies by Liberman et al. (1986) suggested a defect in the DNA-binding domain of the receptor. Tsuchiya et al. (1980) observed vitamin D-dependent rickets type II in the daughter of first cousins, suggesting autosomal recessive inheritance. Kudoh et al. (1981) described a patient with end-organ unresponsiveness to vitamin D without alopecia. A daughter of unrelated parents suffered from bone pains beginning at age 12 years and was found at age 14 to have hypocalcemia, secondary hyperparathyroidism and osteomalacia. Serum 25-OH-vitamin D was normal; serum 1,25-dihydroxyvitamin D was elevated. Fraher et al. (1986) reported a 3-year-old boy with extreme end-organ resistance to vitamin D. Although he had classic features of the disease and did not respond to treatment with vitamin D metabolites, he nevertheless had normal hair growth. In vitro studies of skin fibroblasts from the patient showed an absence of hormone binding. He died at 39 months of age. Fraher et al. (1986) emphasized that the absence of alopecia is not predictive of responsiveness to treatment. A mutation was later found in the VDR gene (601769.0007) in tissue from this patient (Kristjansson et al., 1993). Hughes et al. (1988) studied 2 families: a black Haitian family with 2 affected sisters and an Arab family living in the Middle East with 2 affected brothers. In both families, the parents were consanguineous but phenotypically normal. It was stated that the patients had partial alopecia. Arita et al. (2008) reported a consanguineous Bedouin family in which the 6-year-old proband had alopecia and rickets in infancy and was diagnosed with mild sensorineural hearing loss at 1 year of age. He also had an asymptomatic papular eruption on the face and scalp from the age of 2 years, and was noted to have mild facial dysmorphism, with frontal bossing, wide and flat nasal bridge, and epicanthic folds. The proband was the youngest of 9 sibs, and had 2 brothers and 1 sister with similar features, including facial dysmorphism, alopecia, skin papules, and deafness with secondary speech defects. Arita et al. (2008) stated that this was the first familial case of VDDR associated with deafness. Biochemical Features Eil et al. (1981) demonstrated defective nuclear uptake of 1,25-dihydroxyvitamin D in cultured fibroblasts from patients with vitamin D-dependent rickets type 2. Renal and a variety of other tissues including those of intestine, bone cells, and cultured skin fibroblasts have the enzyme 24-hydroxylase (CYP24A1; 126065), which can be induced by 1,25(OH)2D3 via the VDR. Feldman et al. (1982) found that cultured fibroblasts from patients with vitamin D-dependent rickets type 2 failed to induce 24-hydroxylase activity. Other studies suggested that the cells had defective cytoplasmic vitamin D receptors. Observations of Pike et al. (1984) suggested that VDDR type 2 was due to changes in the vitamin D receptor molecule that prevent its normal function, rather than to absence of the vitamin D receptor. In cells derived from a patient with vitamin D-dependent rickets type 2, Griffin and Zerwekh (1983) found normal ligand-receptor binding, a normal-sized ligand-receptor complex, and normal nuclear localization of the complex. The findings were consistent with the 'receptor-positive' form of vitamin D-resistance. However, the patient's cells were not able to induce 24-hydroxylase activity, indicating a functional defect. Malloy et al. (1997) noted that many of the so-called 'receptor-positive' forms of VDDR2 were later shown to have mutations in the VDR gene resulting in decreased binding affinity of the mutant receptor for DNA. However, some of these cases may have normal VDR genes and be caused by abnormal protein interactions (see VDDR2B, 600785). Liberman et al. (1983) studied the interaction of tritium-labeled 1,25-dihydroxyvitamin D3 with skin fibroblasts cultured from patients in 6 kindreds with rickets and resistance to 1,25(OH)2D3. Evidence of heterogeneity was found, confirming the suspicions generated by clinical variability between affected kindreds, such as the variable presence of alopecia. For example, cells from 2 kindreds showed unmeasurable cytosol binding and nuclear uptake, whereas cells from another kindred showed normal cytosol binding, but absence of nuclear uptake. Liberman et al. (1983) concluded that 5 or 6 distinct mutations were represented by the 6 kindreds studied. Comparable clinical disorders are based on defects in the receptor for glucocorticoid (138040) and androgen (313700) hormones. Liberman et al. (1986) studied 4 families with hereditary resistance to 1,25-dihydroxyvitamin D. In vitro studies of cells derived from 2 kindreds of Middle Eastern origin (Gamblin et al., 1985; Liberman et al., 1980) showed mildly decreased localization of the hormone-receptor complex to the nucleus and abnormal interaction of the occupied receptor with DNA-cellulose, suggesting a defect in the DNA-binding domain of the receptor (see 601769.0002). In vitro studies of cells derived from 2 other kindreds (Marx et al., 1978; Rosen et al., 1979; Eil et al., 1981) showed unmeasurable nuclear localization of the hormone, but normal DNA binding. These kindreds appeared to have a defect in the ability of the hormone-receptor complex to localize to the nucleus. Paradoxically, the second type was more responsive to calciferol therapy than the first. At least one family of the second type (Rosen et al., 1979) had rickets with alopecia. In fibroblasts from 4 different families with hereditary resistance to 1,25-(OH)2D3, Barsony et al. (1989) studied each of the 3 actions of the vitamin: mitogenic effect, antimitogenic effect, and induction of 25-(OH)D3 24-hydroxylase. They found dissociation of the defects. One mutant cell line showed severe abnormality of all 3 actions. A second showed normal antimitogenic action, but the other 2 actions were undetectable. In 2 mutant cell lines, mitogenic action was normal, but the other 2 actions were undetectable or severely impaired. Diagnosis Gamblin et al. (1985) found that the measurement of 25-OHase induction by 1,25(OH)2D3 in cultured skin fibroblasts was a sensitive in vitro test for defective genes in the 1,25(OH)2D effector pathway. In 2 patients with detectable induction, a calcemic response to high doses of calciferol was observed in vivo, suggesting that the defect of the effector pathway could be overcome by very high levels of 1,25(OH)2D. Takeda et al. (1986) found that the receptor defect was demonstrable in phytohemagglutinin-stimulated lymphocytes and that a test of the effects of 1,25-(OH)2D3 on thymidine incorporation into PHA-stimulated lymphocytes was useful for the rapid diagnosis of VDDR II. Clinical Management Balsan et al. (1986) demonstrated healing of rickets by long-term calcium infusions. Marx et al. (1986) found that vitamin D-resistant rickets type II was diagnosed earlier in patients with alopecia than in patients without alopecia (0.9 vs 3.3 years, respectively). During calciferol therapy, patients with alopecia showed lower serum calcium levels than those with normal hair, suggesting that patients without alopecia had a better response to treatment. Cells from patients with alopecia showed no 24-hydroxylase response to 1,25-(OH)2D3, whereas cells from most patients with normal hair showed a 24-hydroxylase response. Marx et al. (1986) concluded that the presence of alopecia reflects a more severe resistance. Manandhar et al. (1989) reported a child with rickets and alopecia who did not respond to high doses of vitamin D3 but did respond to a small dose of 1-alpha-hydroxyvitamin D3. Treatment was continued for 2 years, and the patient did not show any signs of relapse 1 year after stopping treatment. However, the alopecia did not resolve, and she continued to have increased serum 1,25-dihydroxycholecalciferol. Molecular Genetics In 2 unrelated patients with end-organ resistance to 1,25-dihydroxyvitamin D3, Hughes et al. (1988) identified 2 different mutations in the vitamin D receptor gene (601769.0001; 601769.0002). Hughes et al. (1988) suggested that this was the first molecular identification of a disease-producing mutation in a steroid hormone receptor gene. (Mutations were found about the same time in the androgen receptor; see 313700.) Malloy et al. (1997) stated that 13 mutations in the VDR gene causing vitamin D-dependent rickets type 2A had been characterized. Most of the mutations had been found in the highly conserved N-terminal DNA-binding domain, a location that does not affect the ligand-binding properties of the receptor; hence, the resulting clinical picture obtained from fibroblast studies was earlier referred to as the 'receptor-positive' phenotype. In a 6-year-old boy from a consanguineous Bedouin family with alopecia and skin papules, vitamin D-dependent rickets, and deafness, Arita et al. (2008) identified homozygosity for a missense mutation in the VDR gene (601769.0015). The mutation was also present in homozygosity in 2 similarly affected sibs from whom DNA was available; the unaffected parents and 3 unaffected sibs were heterozygous for the change, which was not found in 100 ethnically matched control chromosomes. Genotype/Phenotype Correlations Arita et al. (2008) tabulated mutations reported to date in the VDR gene (see Figure 2, Arita et al., 2008) and noted that almost all have been found within the DNA-binding domain (DBA) and the ligand-binding domain (LBD). Arita et al. (2008) stated that all reported cases with mutations in the DBA (10 reported mutations) had been associated with alopecia, whereas one-third of mutations in the LBD (7 of 21 mutations) had not been associated with hair loss. History Koren (2006) reviewed the elucidation of the role of the vitamin D receptor in some forms of rickets. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive \- Poor growth \- Growth retardation HEAD & NECK Head \- Frontal bossing Ears \- Deafness, sensorineural, mild (rare) Teeth \- Delayed tooth eruption \- Enamel hypoplasia \- Dental caries by age 2 years CHEST Ribs Sternum Clavicles & Scapulae \- 'Bulging' of the costochondral junction \- Deformed rib cage ABDOMEN External Features \- Protuberant abdomen due to muscle weakness SKELETAL \- Rickets \- Increased fractures \- Bone pain \- Sparse bone trabeculae \- Thin bony cortex Skull \- Widened cranial sutures \- Posterior flattening of the skull Limbs \- Delayed opacification of the epiphyses \- Widened, distorted epiphyses \- 'Bulging' epiphyses \- Frayed, irregular metaphyses \- Lower limb deformities \- Bowing of the legs \- Curvatures of the femur, tibia, fibula \- Enlargement of the wrists \- Enlargement of the ankles \- Subperiosteal erosions due to secondary hyperparathyroidism SKIN, NAILS, & HAIR Skin \- Cutaneous 0.5 to 1.0 cm bluish and flesh-colored papules (rarely reported) \- Cutaneous cysts Skin Histology \- Absence of normal hair follicles \- Follicular remnants in cysts \- Cysts are similar to those seen in 'atrichia with papular lesions' ( 209500 ) Hair \- Alopecia, complete, in approximately 75% of patients \- Alopecia appears within 12 months of age and is permanent \- Eyelashes may be spared MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle weakness \- Difficulty walking \- Difficulty standing NEUROLOGIC Central Nervous System \- Delayed motor development \- Seizures due to hypocalcemia Behavioral Psychiatric Manifestations \- Irritability ENDOCRINE FEATURES \- Secondary hyperparathyroidism LABORATORY ABNORMALITIES \- Hypocalcemia \- Hypophosphatemia \- Increased serum alkaline phosphatase \- Increased serum 1,25-dihydroxyvitamin D3 \- Increased serum parathyroid hormone \- Resistance to 1,25-dihydroxyvitamin D3 MISCELLANEOUS \- Onset within first 6 months of life \- Some patients can be treated with large doses of vitamin D and calcium MOLECULAR BASIS \- Caused by mutations in the vitamin D receptor gene (VDR, 601769.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	VITAMIN D-DEPENDENT RICKETS, TYPE 2A	c3536983	30,375	omim	https://www.omim.org/entry/277440	2019-09-22T16:21:14	{"doid": ["10609"], "mesh": ["D053098"], "omim": ["277440"], "orphanet": ["93160"], "synonyms": ["Alternative titles", "VITAMIN D-DEPENDENT RICKETS, TYPE 2A, WITH OR WITHOUT ALOPECIA", "RICKETS, HEREDITARY VITAMIN D-RESISTANT", "GENERALIZED RESISTANCE TO 1,25-DIHYDROXYVITAMIN D", "VITAMIN D-RESISTANT RICKETS WITH END-ORGAN UNRESPONSIVENESS TO 1,25-DIHYDROXYCHOLECALCIFEROL", "PSEUDOVITAMIN D-DEFICIENCY, TYPE IIA", "PDDR IIA", "HYPOCALCEMIC VITAMIN D-RESISTANT RICKETS", "RICKETS-ALOPECIA SYNDROME"]}
A number sign (#) is used with this entry because mandibuloacral dysplasia with type B lipodystrophy can be caused by compound heterozygous mutation in the ZMPSTE24 gene (606480) on chromosome 1p34. For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370). Clinical Features Schrander-Stumpel et al. (1992) reported a girl who presented at birth with a small chin, small nose and mouth, retrognathia, and thin facial skin. By age 2 years, her skin was very thin and tense on her limbs, resulting in contractures and poor wound healing. She had several skeletal anomalies, including delayed closure of the fontanels and multiple wormian bones, hypoplastic clavicles, short terminal phalanges with acroosteolysis. Other features included poorly implanted teeth, scarce, brittle hair, mottled pigmentation, and broad, dysplastic nails. She also had multiple hard nodules consisting of sclerotic calcified tissue on the hands and feet and other areas of the body. In a follow-up report of the same patient, Agarwal et al. (2003) noted that the patient had generalized lipodystrophy affecting the extremities, the trunk, and the face, which contributed to the 'progeroid' appearance. Simha and Garg (2002) studied body fat distribution in 2 male and 2 female patients with MAD by anthropometry, dual energy x-ray absorptiometry, and magnetic resonance imaging. Three of the 4 subjects had loss of subcutaneous fat from the extremities with normal or slight excess in the neck and truncal regions (termed type A pattern). In contrast, 1 patient had generalized loss of subcutaneous fat involving the face, trunk, and extremities (type B pattern). All of the patients had normal glucose tolerance, but had fasting and postprandial hyperinsulinemia suggestive of insulin resistance. Elevated serum triglycerides with low high density lipoprotein cholesterol levels were noted in 3 subjects. The authors concluded that MAD presents with 2 types of body fat distribution patterns, both of which are associated with insulin resistance and its metabolic complications. Miyoshi et al. (2008) reported 2 Japanese sisters, aged 7 and 3 years, with MAD. Both had the classic facial phenotype with mandibular hypoplasia, prominent eyes, beaked nose, and dental overcrowding. Other classic features included atrophic skin, mottled hyperpigmentation, fractured clavicle in 1, acroosteolysis, joint contractures, and generalized loss of subcutaneous adipose tissue. The older sister had lipodystrophy affecting the chest and thighs, but sparing the abdomen. Endocrine studies were essentially normal. Ahmad et al. (2010) studied 2 brothers with early-onset MAD, aged 9 months and 4 years, who were negative for mutation in the LMNA gene but were found to be compound heterozygous for mutations in the ZMPSTE24 gene (606480.0005 and 606480.0009) and in whom thin skin was noted as early as 5 months of age. Features in common with previously reported MAD cases due to mutations in ZMPSTE24 included early onset of symptoms, postnatal growth retardation, feeding difficulty, delayed dentition, micrognathia, delayed closure of cranial sutures, joint stiffness, mottled hyperpigmentation, and thin skin with prominent superficial vasculature. The older brother also had small pinched nose, short clavicles, acroosteolysis, hair loss, wormian bones, dental overcrowding, and repeated fractures, whereas the younger brother did not have a small nose or hair loss. The brothers displayed little evidence of lipodystrophy, and there was no delay of mental development or evidence of renal disease. Compared to MAD patients with mutations in the LMNA gene, Ahmad et al. (2010) concluded that patients with mutations in ZMPSTE24 develop manifestations earlier in life, and suggested that distinguishing features might include premature birth, renal disease, calcified skin nodules, and lack of acanthosis nigricans. Molecular Genetics In a woman with MAD and generalized lipodystrophy first reported by Schrander-Stumpel et al. (1992), Agarwal et al. (2003) identified compound heterozygosity for 2 mutations in the ZMPSTE24 gene (606480.0001 and 606480.0002). The unaffected parents and 2 unaffected sibs of the patients were heterozygous for 1 of the mutations. In 2 Japanese sisters with severe MAD, Miyoshi et al. (2008) identified compound heterozygous mutations in the ZMPSTE24 gene (606480.0004 and 606480.0005). ### Exclusion Studies In 4 families with MAD and type B lipodystrophy, Simha et al. (2003) did not identify mutations in several genes associated with other forms of lipodystrophy, including LMNA (150330), AGPAT2 (603100), seipin (606158), and PPARG (601487). INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Mandibular hypoplasia \- Bird-like facies \- Loss of facial subcutaneous adipose tissue Eyes \- Prominent eyes Nose \- Pinched nose \- Pointed nose \- Beak nose Mouth \- Small mouth \- High-arched palate Teeth \- Dental overcrowding \- Loss of teeth \- Hypoplastic teeth Neck \- Decreased adipose tissue around neck CHEST Ribs Sternum Clavicles & Scapulae \- Clavicular hypoplasia \- Progressive acroosteolysis of the clavicle SKELETAL \- Joint contractures Skull \- Delayed closure of cranial sutures \- Wormian bones Hands \- Acroosteolysis of distal phalanges \- Shortened phalanges Feet \- Acroosteolysis of distal phalanges SKIN, NAILS, & HAIR Skin \- Mottled pigmentation \- Skin atrophy Hair \- Alopecia, partial \- Brittle hair \- Sparse hair MUSCLE, SOFT TISSUES \- Generalized lipodystrophy (abnormal distribution of subcutaneous fat) \- Loss of subcutaneous adipose tissue from extremities \- Loss of truncal adipose tissue \- Loss of adipose tissue around the neck \- Loss of facial adipose tissue ENDOCRINE FEATURES \- Insulin-resistant diabetes mellitus \- Glucose intolerance LABORATORY ABNORMALITIES \- Hyperglycemia \- Hyperlipidemia \- Hyperinsulinemia MISCELLANEOUS \- Onset in early childhood \- Genetic heterogeneity (see MADA, 248370 ) MOLECULAR BASIS \- Caused by mutation in the zinc metalloproteinase STE24 gene (ZMPSTE24, 606480.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	MANDIBULOACRAL DYSPLASIA WITH TYPE B LIPODYSTROPHY	c1837756	30,376	omim	https://www.omim.org/entry/608612	2019-09-22T16:07:34	{"mesh": ["C535706"], "omim": ["608612"], "orphanet": ["90154", "2457"], "synonyms": ["Alternative titles", "LIPODYSTROPHY, TYPE B, ASSOCIATED WITH MANDIBULOACRAL DYSPLASIA"]}
A rare benign eye tumor characterized by the presence of glial cells, vascular tissue, and sheets of pigment epithelial cells lacking the distribution and organization of the normal retina and retinal pigment epithelium. The lesion is most commonly found unilaterally as a slightly elevated mass in a peripapillary location but can also occur in the macula or the retinal periphery. It is sometimes associated with neurofibromatosis type 1 or 2, nevoid basal cell carcinoma syndrome, or branchio-oculo-facial syndrome. Patients may be asymptomatic or present with progressive loss of vision. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Combined hamartoma of the retina and retinal pigment epithelium	c1862062	30,377	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=440727	2021-01-23T17:47:47	{"synonyms": ["CHR-RPE", "Combined hamartoma of the retina and RPE"]}
Rare type of breast cancer Medullary carcinoma of the breast SpecialtyOncology, pathology Medullary breast carcinoma is a rare type of breast cancer[1] that often can be treated successfully. It is relatively circumscribed.[2] It involves infiltration by lymphocyte[3] (a type of white blood cell) in and around the tumor that can be seen when viewed under a microscope.[citation needed] This is the only breast cancer associated with a loss of function mutation in BRCA1, and thus the only form associated with a hereditary mutation. It is typically triple-negative and exhibits upregulation of p53.[citation needed] This is one of five types of epithelial breast cancer: ductal, lobular, medullary, colloid, and tubular.[citation needed] DCIS is less commonly present, and medullary breast cancer tends to have a pushing, rather than infiltrative, border. The tumour presents as a soft, fleshy mass with a pushing border. Tumours commonly possess mutations of E-cadherin, which results in its overexpression. Strengthened adhesions between tumour cells reduce the frequency of metastasis.[citation needed] On histopathology, medullary breast carcinoma is characterized by groups of tumor cells with syncytial appearance (that is, seemingly fused cytoplasms, at left). There is typically also a lymphocytic and plasma cell infiltrate (right).[4] ## References[edit] 1. ^ Tominaga J, Hama H, Kimura N, Takahashi S (March 2008). "MR imaging of medullary carcinoma of the breast". Eur J Radiol. 70 (3): 525–9. doi:10.1016/j.ejrad.2008.01.044. PMID 18353587. 2. ^ Bacus SS, Zelnick CR, Chin DM, et al. (December 1994). "Medullary carcinoma is associated with expression of intercellular adhesion molecule-1. Implication to its morphology and its clinical behavior". Am. J. Pathol. 145 (6): 1337–48. PMC 1887499. PMID 7992839. 3. ^ Kuroda H, Tamaru J, Sakamoto G, Ohnisi K, Itoyama S (January 2005). "Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast". Virchows Arch. 446 (1): 10–4. doi:10.1007/s00428-004-1143-9. PMID 15660281. 4. ^ Netra SM, Vani BR, Murthy VS (2018). "Cytomorphological Study of Medullary Carcinoma of Breast in Comparison to Infiltrating Ductal Carcinoma". J Cytol. 35 (4): 195–198. doi:10.4103/JOC.JOC_160_17. PMC 6210819. PMID 30498288.CS1 maint: multiple names: authors list (link) ## External links[edit] * Medullary breast carcinoma entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". Classification D * ICD-O: M8510/3 * v * t * e Breast cancer Types Ductal * Ductal carcinoma in situ (DCIS): Paget's disease of the breast * Comedocarcinoma * Invasive ductal carcinoma (IDC) * Intraductal papilloma Lobular * Lobular carcinoma in situ (LCIS) * Invasive lobular carcinoma (ILC) Fibroepithelial/stromal * Fibroadenoma * Phyllodes tumor Other * Medullary carcinoma * Male breast cancer * Inflammatory breast cancer * Precursor lesions * Atypical ductal hyperplasia * Nipple adenoma General * Breast cancer * Classification * Risk factors * Alcohol * Hereditary breast—ovarian cancer syndrome * BRCA mutation * Screening * Treatment Other * Breast cancer awareness * Pink ribbon * National Breast Cancer Awareness Month * List of people with breast cancer * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Medullary breast carcinoma	c0860580	30,378	wikipedia	https://en.wikipedia.org/wiki/Medullary_breast_carcinoma	2021-01-18T18:41:52	{"umls": ["C0860580"], "wikidata": ["Q3658397"]}
Trichothiodystrophy or TTD is a heterogeneous group disorders characterized by short, brittle hair with low-sulphur content (due to an abnormal synthesis of the sulphur containing keratins). ## Epidemiology The exact prevalence of TTD is unknown, but it appears to be rather uncommon. ## Clinical description Within the spectrum of the TTD syndromes are numerous syndromes affecting mainly organs derived from the neuroectoderm. The clinical appearance is always characterized by brittle and fragile hair, often combined with growth retardation and intellectual deficit, congenital ichthyosis and nail abnormalities, among other symptoms. The abnormalities are usually obvious at birth, with variable clinical expression. The variants of TTD, depending on their different associations, are: BIDS syndrome (or TTD type D or Amish Brittle Hair syndrome), IBIDS syndrome (or Tay syndrome or TTD typeE), PIBIDS syndrome (or TTD type F), Sabinas syndrome (TTD type B), SIBIDS syndrome, ONMRS (Itin syndrome) and Pollitt syndrome (TTD type C). ## Etiology About half of the patients with TTD exhibit marked photosensitivity, due to abnormalities in excision repair of ultraviolet (UV)-damaged DNA. In most cases, the deficiency in DNA excision repair is indistinguishable from that observed in Xeroderma Pigmentosum type D. In this photosensitive group of patients, the majority of cases (95% of patients) are due to mutations within the XPD (ERCC2) gene (localized to 19q13.2-q13.3). The remaining cases are caused by mutations within the XPB gene. These genes encode the DNA-dependent ATPase/helicase subunits of TFIIH (transcription factor). So far, no gene has been isolated for the nonphotosensitive group. ## Diagnostic methods The diagnostic findings of TTD are short, unruly, brittle hair, with alternating dark and light bands under polarizing microscopy (tiger-tail pattern), trichoschisis (or trichorrhexis), and an absent or defective cuticle visualized by scanning electron microscopy. ## Differential diagnosis TTD is a differential diagnosis in congenital alopecias. ## Antenatal diagnosis Prenatal diagnosis, based on measurement of DNA repair in trophoblasts or amniotic cells, is available. ## Genetic counseling TTD is an autosomal recessive disorder. ## Management and treatment There is no specific treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Trichothiodystrophy	c1955934	30,379	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33364	2021-01-23T17:22:33	{"gard": ["12109"], "mesh": ["D054463", "C536559"], "omim": ["234050", "300953", "601675", "616390", "616395", "616943", "618546"], "umls": ["C0740342", "C1955934"], "icd-10": ["L67.8"]}
A rare congenital disorder of glycosylation characterized by cerebral and portal vein thrombosis, portal hypertension, macrocephaly, and persistent absence seizures. Additional reported features include mild to moderate global developmental delay and intellectual disability, as well as thrombocytopenia. Brain imaging may show variable stages of infarction and cerebral and cerebellar 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	c1853205	30,380	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83639	2021-01-23T17:21:09	{"gard": ["9965"], "mesh": ["C537277"], "omim": ["610293"], "umls": ["C1853205"], "icd-10": ["E88.8"], "synonyms": ["Congenital disorder of glycosylation due to PIGM deficiency", "PIGM-CDG"]}
## Mapping Marsh et al. (1994) used sib-pair analysis of 170 individuals from 11 Amish families to demonstrate linkage of 5 markers located on 5q31.1 with a gene controlling total serum IgE concentration. No linkage was found between these markers and specific IgE antibody concentrations. Analysis of total IgE within a subset of 128 IgE antibody-negative sib pairs confirmed linkage to 5q31.1, especially to the interleukin-4 gene (IL4; 147780). A combination of segregation and maximum likelihood analyses provided further evidence for the linkage. Marsh et al. (1994) suggested that IL4 or a nearby gene in 5q31.1 regulated IgE production in a nonantigen-specific, i.e., noncognate, fashion. Meyers et al. (1994) performed genetic studies of total serum IgE levels in Dutch families ascertained through a parent with asthma. Families were genotyped for markers on 5q where there are multiple candidate genes that may influence the control of IgE and inflammation. Evidence for linkage of the IgE phenotype to 5q was obtained by both sib-pair and lod score analyses with evidence for recessive inheritance of high IgE levels from segregation analysis. In a note added in proof, Meyers et al. (1994) commented on the study by Marsh et al. (1994), which was also performed at Johns Hopkins. In the series of 92 Dutch families in which Meyers et al. (1994) found evidence for recessive inheritance of high IgE levels with linkage to 5q, there was significant residual familial correlation in the 1-locus segregation analysis. Consequently, 2-locus segregation and linkage analyses were performed by Xu et al. (1995). Segregation analyses provided evidence for a second major locus unlinked to the locus on 5q. Utilization of this 2-locus model corroborated the previous evidence for linkage between this trait and markers on 5q31-q33. The lod score for the most informative marker D5S436 increased from 3.00 at 10% recombination to 4.67 at 9% recombination, when the 2-locus model was used. Additional linkage studies were required to map the second locus. Molecular Genetics In Finland, Laitinen et al. (1997) found no evidence of genetic linkage between markers in 5q and either serum IgE levels or asthma. They concluded that allelic variation at 5q31 is not likely to contribute to inheritance of serum IgE levels or the development of asthma in this Finnish subpopulation. Extending their previous studies (Xu et al., 1995) of total serum IgE levels in 92 families, Xu et al. (2000) investigated 108 probands and their families, ascertained as in the previous study through a proband with asthma. Significant evidence for linkage was found for a novel locus on 7q, with a multipoint lod score of 3.36; a lod score of 3.65 was obtained after genotyping additional markers in this region. Evidence for linkage was also found for 2 previously reported regions, 5q and 12q, with lod scores of 2.73 and 2.46, respectively. These results suggested that several major genes, plus residual genetic effects, regulate total serum IgE levels. Moffatt et al. (2001) examined the association between the HLA-DRB1 locus (142857) and quantitative traits underlying asthma (600807) in a population sample consisting of 1,004 individuals from 230 families from the rural Australian town of Busselton. They detected strong associations between HLA-DRB1 alleles and the total serum IgE concentration and IgE titers against individual antigens, with the HLA-DRB1 locus accounting for 4% of the variation in total serum IgE level and 2 to 3% of the variation in specific IgE titers. Alleles associated with elevations of the total serum IgE were different from those associated with specific allergens, consistent with hypotheses that serum IgE is made up of cognate (specific) and noncognate components. Liang et al. (2015) surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genomewide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes, and validated positive results in additional families and in subjects from the general population. The authors showed replicated associations, with a metaanalysis false discovery rate less than 10(-4), between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors, and mitochondrial proteins. Liang et al. (2015) confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top 3 loci accounted for 13% of IgE variation in the primary subject panel, explaining the 10-fold higher variance found compared with that derived from large SNP genomewide association studies. Inheritance Using maximum likelihood analysis of variance components estimates in an Australian population-based sample of 232 Caucasian nuclear families, Palmer et al. (2000) found a narrow-sense heritability of total serum IgE levels of 47.3%, i.e., additive genetic effects contributed just under half of the total variance. Specific serum IgE levels against house dust mite and Timothy grass, measured as a combined RAST index, showed a narrow-sense heritability of 33.8% and with environmental effects common to sibs contributing approximately 15% of the total phenotypic variance, explained by childhood exposure to domestic allergens. The study suggested the presence of important genetic determinants of the pathophysiologic traits associated with asthma. The authors proposed that total and specific serum IgE levels are appropriate phenotypes for molecular investigations of the genetic susceptibility to asthma. Other Features Kermarrec et al. (1996) noted that between 2 and 10% of rheumatoid arthritis patients treated with gold salts developed immunologic manifestations such as membranous glomerulopathy, skin reactions, cytopenia, and in increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopropanolsulfonate (ATPS) also manifest an autoimmune glomerulonephritis and increased serum IgE concentration, whereas Lewis (LEW) rats are resistant to complications. Kermarrec et al. (1996) showed that linkage between responses to ATPS in a (BN x LEW) F2 cohort and the major histocompatibility complex on rat chromosome 20 and between markers in the region of interleukin-4 (147780) and other candidate genes on rat chromosome 10. Wooley et al. (1980) had suggested that certain HLA-DR alleles are associated with an increased frequency of adverse reactions. The authors stated that the finding that human serum IgE concentration is linked to the IL4 region, taken together with these findings in 2 different strains of rat, raise the possibility that homologous genes could be implicated in the ATPS manifestations in the rat and in the regulation of IgE levels in the human. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	IMMUNOGLOBULIN E CONCENTRATION, SERUM	c1840252	30,381	omim	https://www.omim.org/entry/147061	2019-09-22T16:39:33	{"omim": ["147061"]}
Spectrum of conditions caused by HIV infection "AIDS" and "Aids" redirect here. For other uses, see AIDS (disambiguation). HIV/AIDS Other namesHIV disease, HIV infection[1][2] The red ribbon is a symbol for solidarity with HIV-positive people and those living with AIDS.[3] SpecialtyInfectious disease, immunology SymptomsEarly: Flu-like illness[4] Later: Large lymph nodes, fever, weight loss[4] ComplicationsOpportunistic infections, tumors[4] DurationLifelong[4] CausesHuman immunodeficiency virus (HIV)[4] Risk factorsExposure to blood, breast milk, sex, men who have sex with men, drug users, prisoners, sex workers and their clients [4] Diagnostic methodBlood tests[4] PreventionSafe sex, needle exchange, male circumcision, pre-exposure prophylaxis, post-exposure prophylaxis[4] TreatmentAntiretroviral therapy[4] PrognosisNear normal life expectancy with treatment[5][6] 11 years life expectancy without treatment[7] Frequency55.9 million – 100 million total cases[8] 1.7 million new cases (2019)[8] 38 million living with HIV (2019)[8] Deaths32.7 million total deaths[8] 690,000 (2019)[8] Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV),[9][10][11] a retrovirus.[12] Following initial infection a person may not notice any symptoms, or may experience a brief period of influenza-like illness.[4] Typically, this is followed by a prolonged period with no symptoms.[5] If the infection progresses, it interferes more with the immune system, increasing the risk of developing common infections such as tuberculosis, as well as other opportunistic infections, and tumors which are otherwise rare in people who have normal immune function.[4] These late symptoms of infection are referred to as acquired immunodeficiency syndrome (AIDS).[5] This stage is often also associated with unintended weight loss.[5] HIV is spread primarily by unprotected sex (including anal and oral sex), contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding.[13] Some bodily fluids, such as saliva, sweat and tears, do not transmit the virus.[14] Methods of prevention include safe sex, needle exchange programs, treating those who are infected, and pre- & post-exposure prophylaxis.[4] Disease in a baby can often be prevented by giving both the mother and child antiretroviral medication.[4] There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy.[5][6] Treatment is recommended as soon as the diagnosis is made.[15] Without treatment, the average survival time after infection is 11 years.[7] In 2018, about 37.9 million people were living with HIV and it resulted in 770,000 deaths.[8] An estimated 20.6 million of these live in eastern and southern Africa.[16] Between the time that AIDS was identified (in the early 1980s) and 2018, the disease caused an estimated 32 million deaths worldwide.[8] HIV/AIDS is considered a pandemic—a disease outbreak which is present over a large area and is actively spreading.[17] HIV made the jump from other primates to humans in west-central Africa in the early-to-mid 20th century.[18] AIDS was first recognized by the United States Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade.[19] HIV/AIDS has had a large impact on society, both as an illness and as a source of discrimination.[20] The disease also has large economic impacts.[20] There are many misconceptions about HIV/AIDS, such as the belief that it can be transmitted by casual non-sexual contact.[21] The disease has become subject to many controversies involving religion, including the Catholic Church's position not to support condom use as prevention.[22] It has attracted international medical and political attention as well as large-scale funding since it was identified in the 1980s.[23] Play media Video summary (script) ## Contents * 1 Signs and symptoms * 1.1 Acute infection * 1.2 Clinical latency * 1.3 Acquired immunodeficiency syndrome * 2 Transmission * 2.1 Sexual * 2.2 Body fluids * 2.3 Mother-to-child * 3 Virology * 4 Pathophysiology * 5 Diagnosis * 5.1 HIV testing * 5.2 Classifications * 6 Prevention * 6.1 Sexual contact * 6.2 Pre-exposure * 6.3 Post-exposure * 6.4 Mother-to-child * 6.5 Vaccination * 7 Treatment * 7.1 Antiviral therapy * 7.2 Opportunistic infections * 7.3 Diet * 7.4 Alternative medicine * 8 Prognosis * 9 Epidemiology * 10 History * 10.1 Discovery * 10.2 Origins * 11 Society and culture * 11.1 Stigma * 11.2 Economic impact * 11.3 Religion and AIDS * 11.4 Media portrayal * 11.5 Criminal transmission * 11.6 Misconceptions * 12 Research * 13 References * 14 External links ## Signs and symptoms Main article: Signs and symptoms of HIV/AIDS There are three main stages of HIV infection: acute infection, clinical latency, and AIDS.[1][24] ### Acute infection Main symptoms of acute HIV infection The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral syndrome.[24][25] Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks after exposure while others have no significant symptoms.[26][27] Symptoms occur in 40–90% of cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash, headache, tiredness, and/or sores of the mouth and genitals.[25][27] The rash, which occurs in 20–50% of cases, presents itself on the trunk and is maculopapular, classically.[28] Some people also develop opportunistic infections at this stage.[25] Gastrointestinal symptoms, such as vomiting or diarrhea may occur.[27] Neurological symptoms of peripheral neuropathy or Guillain–Barré syndrome also occurs.[27] The duration of the symptoms varies, but is usually one or two weeks.[27] Owing to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be considered in people presenting with an unexplained fever who may have risk factors for the infection.[27] ### Clinical latency The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV.[1] Without treatment, this second stage of the natural history of HIV infection can last from about three years[29] to over 20 years[30] (on average, about eight years).[31] While typically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains.[1] Between 50% and 70% of people also develop persistent generalized lymphadenopathy, characterized by unexplained, non-painful enlargement of more than one group of lymph nodes (other than in the groin) for over three to six months.[24] Although most HIV-1 infected individuals have a detectable viral load and in the absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4+ T cells (T helper cells) without antiretroviral therapy for more than five years.[27][32] These individuals are classified as "HIV controllers" or long-term nonprogressors (LTNP).[32] Another group consists of those who maintain a low or undetectable viral load without anti-retroviral treatment, known as "elite controllers" or "elite suppressors". They represent approximately 1 in 300 infected persons.[33] ### Acquired immunodeficiency syndrome Main symptoms of AIDS. Acquired immunodeficiency syndrome (AIDS) is defined as an HIV infection with either a CD4+ T cell count below 200 cells per µL or the occurrence of specific diseases associated with HIV infection.[27] In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years.[27] The most common initial conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%), cachexia in the form of HIV wasting syndrome (20%), and esophageal candidiasis.[27] Other common signs include recurrent respiratory tract infections.[27] Opportunistic infections may be caused by bacteria, viruses, fungi, and parasites that are normally controlled by the immune system.[34] Which infections occur depends partly on what organisms are common in the person's environment.[27] These infections may affect nearly every organ system.[35] People with AIDS have an increased risk of developing various viral-induced cancers, including Kaposi's sarcoma, Burkitt's lymphoma, primary central nervous system lymphoma, and cervical cancer.[28] Kaposi's sarcoma is the most common cancer, occurring in 10% to 20% of people with HIV.[36] The second-most common cancer is lymphoma, which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3% to 4%.[36] Both these cancers are associated with human herpesvirus 8 (HHV-8).[36] Cervical cancer occurs more frequently in those with AIDS because of its association with human papillomavirus (HPV).[36] Conjunctival cancer (of the layer that lines the inner part of eyelids and the white part of the eye) is also more common in those with HIV.[37] Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and unintended weight loss.[38] Diarrhea is another common symptom, present in about 90% of people with AIDS.[39] They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers.[40] ## Transmission Average per act risk of getting HIV by exposure route to an infected source Exposure route Chance of infection Blood transfusion 90%[41] Childbirth (to child) 25%[42][clarification needed] Needle-sharing injection drug use 0.67%[43] Percutaneous needle stick 0.30%[44] Receptive anal intercourse* 0.04–3.0%[45] Insertive anal intercourse* 0.03%[46] Receptive penile-vaginal intercourse* 0.05–0.30%[45][47] Insertive penile-vaginal intercourse* 0.01–0.38%[45][47] Receptive oral intercourse§ 0–0.04%[45] Insertive oral intercourse§ 0–0.005%[48] * assuming no condom use § source refers to oral intercourse performed on a man HIV is spread by three main routes: sexual contact, significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission).[13] There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood.[49] It is also possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.[50] ### Sexual The most frequent mode of transmission of HIV is through sexual contact with an infected person.[13] However, an HIV-positive person who has an undetectable viral load as a result of long-term treatment has effectively no risk of transmitting HIV sexually.[51][52] The existence of functionally noncontagious HIV-positive people on antiretroviral therapy was controversially publicized in the 2008 Swiss Statement, and has since become accepted as medically sound.[53] Globally, the most common mode of HIV transmission is via sexual contacts between people of the opposite sex;[13] however, the pattern of transmission varies among countries. As of 2017[update], most HIV transmission in the United States occurred among men who had sex with men (82% of new HIV diagnoses among males aged 13 and older and 70% of total new diagnoses).[54][55] In the US, gay and bisexual men aged 13 to 24 accounted for an estimated 92% of new HIV diagnoses among all men in their age group and 27% of new diagnoses among all gay and bisexual men.[56] With regard to unprotected heterosexual contacts, estimates of the risk of HIV transmission per sexual act appear to be four to ten times higher in low-income countries than in high-income countries.[57] In low-income countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-to-female transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per act for female-to-male transmission, and 0.08% per act for male-to-female transmission.[57] The risk of transmission from anal intercourse is especially high, estimated as 1.4–1.7% per act in both heterosexual and homosexual contacts.[57][58] While the risk of transmission from oral sex is relatively low, it is still present.[59] The risk from receiving oral sex has been described as "nearly nil";[60] however, a few cases have been reported.[61] The per-act risk is estimated at 0–0.04% for receptive oral intercourse.[62] In settings involving prostitution in low-income countries, risk of female-to-male transmission has been estimated as 2.4% per act, and of male-to-female transmission as 0.05% per act.[57] Risk of transmission increases in the presence of many sexually transmitted infections[63] and genital ulcers.[57] Genital ulcers appear to increase the risk approximately fivefold.[57] Other sexually transmitted infections, such as gonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis, are associated with somewhat smaller increases in risk of transmission.[62] The viral load of an infected person is an important risk factor in both sexual and mother-to-child transmission.[64] During the first 2.5 months of an HIV infection a person's infectiousness is twelve times higher due to the high viral load associated with acute HIV.[62] If the person is in the late stages of infection, rates of transmission are approximately eightfold greater.[57] Commercial sex workers (including those in pornography) have an increased likelihood of contracting HIV.[65][66] Rough sex can be a factor associated with an increased risk of transmission.[67] Sexual assault is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted infections.[68] ### Body fluids CDC poster from 1989 highlighting the threat of AIDS associated with drug use The second-most frequent mode of HIV transmission is via blood and blood products.[13] Blood-borne transmission can be through needle-sharing during intravenous drug use, needle-stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilized equipment. The risk from sharing a needle during drug injection is between 0.63% and 2.4% per act, with an average of 0.8%.[69] The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucous membrane exposure to infected blood as 0.09% (about 1 in 1000) per act.[49] This risk may, however, be up to 5% if the introduced blood was from a person with a high viral load and the cut was deep.[70] In the United States intravenous drug users made up 12% of all new cases of HIV in 2009,[71] and in some areas more than 80% of people who inject drugs are HIV-positive.[13] HIV is transmitted in about 90% of blood transfusions using infected blood.[41] In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in half a million) where improved donor selection and HIV screening is performed;[13] for example, in the UK the risk is reported at one in five million[72] and in the United States it was one in 1.5 million in 2008.[73] In low-income countries, only half of transfusions may be appropriately screened (as of 2008),[74] and it is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing between 5% and 10% of global infections.[13][75] It is possible to acquire HIV from organ and tissue transplantation, although this is rare because of screening.[76] Unsafe medical injections play a role in HIV spread in sub-Saharan Africa. In 2007, between 12% and 17% of infections in this region were attributed to medical syringe use.[77] The World Health Organization estimates the risk of transmission as a result of a medical injection in Africa at 1.2%.[77] Risks are also associated with invasive procedures, assisted delivery, and dental care in this area of the world.[77] People giving or receiving tattoos, piercings, and scarification are theoretically at risk of infection but no confirmed cases have been documented.[78] It is not possible for mosquitoes or other insects to transmit HIV.[79] ### Mother-to-child Main articles: HIV and pregnancy and HIV and breastfeeding HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk, resulting in the baby also contracting HIV.[80][13] As of 2008, vertical transmission accounted for about 90% of cases of HIV in children.[81] In the absence of treatment, the risk of transmission before or during birth is around 20%, and in those who also breastfeed 35%.[81] Treatment decreases this risk to less than 5%.[82] Antiretrovirals when taken by either the mother or the baby decrease the risk of transmission in those who do breastfeed.[83] If blood contaminates food during pre-chewing it may pose a risk of transmission.[78] If a woman is untreated, two years of breastfeeding results in an HIV/AIDS risk in her baby of about 17%.[84] Due to the increased risk of death without breastfeeding in many areas in the developing world, the World Health Organization recommends either exclusive breastfeeding or the provision of safe formula.[84] All women known to be HIV-positive should be taking lifelong antiretroviral therapy.[84] ## Virology Main article: HIV Diagram of a HIV virion structure Scanning electron micrograph of HIV-1, colored green, budding from a cultured lymphocyte. HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells.[85] HIV is a member of the genus Lentivirus,[86] part of the family Retroviridae.[87] Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period.[88] Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors.[89] Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system.[90] Alternatively, the virus may be transcribed, producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin the replication cycle anew.[91] HIV is now known to spread between CD4+ T cells by two parallel routes: cell-free spread and cell-to-cell spread, i.e. it employs hybrid spreading mechanisms.[92] In the cell-free spread, virus particles bud from an infected T cell, enter the blood/extracellular fluid and then infect another T cell following a chance encounter.[92] HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread.[93][94] The hybrid spreading mechanisms of HIV contribute to the virus's ongoing replication against antiretroviral therapies.[92][95] Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered (and initially referred to also as LAV or HTLV-III). It is more virulent, more infective,[96] and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.[97] ## Pathophysiology Main article: Pathophysiology of HIV/AIDS Play media HIV/AIDS explained in a simple way HIV replication cycle After the virus enters the body there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood.[98] This response is accompanied by a marked drop in the number of circulating CD4+ T cells. The acute viremia is almost invariably associated with activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts recover. A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.[99] Ultimately, HIV causes AIDS by depleting CD4+ T cells. This weakens the immune system and allows opportunistic infections. T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases.[100] During the acute phase, HIV-induced cell lysis and killing of infected cells by CD8+ T cells accounts for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers.[101] Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body.[102] The reason for the preferential loss of mucosal CD4+ T cells is that the majority of mucosal CD4+ T cells express the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small fraction of CD4+ T cells in the bloodstream do so.[103] A specific genetic change that alters the CCR5 protein when present in both chromosomes very effectively prevents HIV-1 infection.[104] HIV seeks out and destroys CCR5 expressing CD4+ T cells during acute infection.[105] A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4+ T cells in mucosal tissues remain particularly affected.[105] Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase.[106] Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4+ T cells during the acute phase of disease.[107] ## Diagnosis Main article: Diagnosis of HIV/AIDS A generalized graph of the relationship between HIV copies (viral load) and CD4+ T cell counts over the average course of untreated HIV infection. CD4+ T Lymphocyte count (cells/mm³) HIV RNA copies per mL of plasma Days after exposure needed for the test to be accurate[108] Blood test Days Antibody test (rapid test, ELISA 3rd gen) 23–90 Antibody and p24 antigen test (ELISA 4th gen) 18–45 PCR 10–33 HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms.[25] HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age, including all pregnant women.[109] Additionally, testing is recommended for those at high risk, which includes anyone diagnosed with a sexually transmitted illness.[28][109] In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent.[28] ### HIV testing HIV Rapid Test being administered Oraquick Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks after the initial infection.[27] Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen.[27] Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR.[25] Antibody tests in children younger than 18 months are typically inaccurate, due to the continued presence of maternal antibodies.[110] Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen.[25] Much of the world lacks access to reliable PCR testing, and people in many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing.[110] In sub-Saharan Africa between 2007 and 2009, between 30% and 70% of the population were aware of their HIV status.[111] In 2009, between 3.6% and 42% of men and women in sub-Saharan countries were tested;[111] this represented a significant increase compared to previous years.[111] ### Classifications Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease,[25] and the CDC classification system for HIV infection.[112] The CDC's classification system is more frequently adopted in developed countries. Since the WHO's staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.[24][25][112] The World Health Organization first proposed a definition for AIDS in 1986.[25] Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007.[25] The WHO system uses the following categories: * Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome[25] * Stage I: HIV infection is asymptomatic with a CD4+ T cell count (also known as CD4 count) greater than 500 per microlitre (µl or cubic mm) of blood.[25] May include generalized lymph node enlargement.[25] * Stage II: Mild symptoms, which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl[25] * Stage III: Advanced symptoms, which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung, and a CD4 count of less than 350/µl[25] * Stage IV or AIDS: severe symptoms, which include toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi, or lungs, and Kaposi's sarcoma. A CD4 count of less than 200/µl[25] The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008 and 2014.[112][113] This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in five groups.[113] In those greater than six years of age it is:[113] * Stage 0: the time between a negative or indeterminate HIV test followed less than 180 days by a positive test. * Stage 1: CD4 count ≥ 500 cells/µl and no AIDS-defining conditions. * Stage 2: CD4 count 200 to 500 cells/µl and no AIDS-defining conditions. * Stage 3: CD4 count ≤ 200 cells/µl or AIDS-defining conditions. * Unknown: if insufficient information is available to make any of the above classifications. For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.[24] ## Prevention Main article: Prevention of HIV/AIDS AIDS Clinic, McLeod Ganj, Himachal Pradesh, India, 2010 ### Sexual contact People wearing AIDS awareness signs. on the left: "Facing AIDS a condom and a pill at a time"; on the right: "I am Facing AIDS because people I ♥ are infected." Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term.[114] When condoms are used consistently by a couple in which one person is infected, the rate of HIV infection is less than 1% per year.[115] There is some evidence to suggest that female condoms may provide an equivalent level of protection.[116] Application of a vaginal gel containing tenofovir (a reverse transcriptase inhibitor) immediately before sex seems to reduce infection rates by approximately 40% among African women.[117] By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation.[118] Circumcision in Sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months".[119] Owing to these studies, both the World Health Organization and UNAIDS recommended male circumcision in 2007 as a method of preventing female-to-male HIV transmission in areas with high rates of HIV.[120] However, whether it protects against male-to-female transmission is disputed,[121][122] and whether it is of benefit in developed countries and among men who have sex with men is undetermined.[123][124][125] The International Antiviral Society, however, does recommend it for all sexually active heterosexual males and that it be discussed as an option with men who have sex with men.[126] Some experts fear that a lower perception of vulnerability among circumcised men may cause more sexual risk-taking behavior, thus negating its preventive effects.[127] Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk.[128] Evidence of any benefit from peer education is equally poor.[129] Comprehensive sexual education provided at school may decrease high-risk behavior.[130][131] A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV.[132] Voluntary counseling and testing people for HIV does not affect risky behavior in those who test negative but does increase condom use in those who test positive.[133] Enhanced family planning services appear to increase the likelihood of women with HIV using contraception, compared to basic services.[134] It is not known whether treating other sexually transmitted infections is effective in preventing HIV.[63] ### Pre-exposure Antiretroviral treatment among people with HIV whose CD4 count ≤ 550 cells/µL is a very effective way to prevent HIV infection of their partner (a strategy known as treatment as prevention, or TASP).[135] TASP is associated with a 10- to 20-fold reduction in transmission risk.[135][136] Pre-exposure prophylaxis (PrEP) with a daily dose of the medications tenofovir, with or without emtricitabine, is effective in people at high risk including men who have sex with men, couples where one is HIV-positive, and young heterosexuals in Africa.[117][137] It may also be effective in intravenous drug users, with a study finding a decrease in risk of 0.7 to 0.4 per 100 person years.[138] The USPSTF, in 2019, recommended PrEP in those who are at high risk.[139] Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV.[140] Intravenous drug use is an important risk factor, and harm reduction strategies such as needle-exchange programs and opioid substitution therapy appear effective in decreasing this risk.[141][142] ### Post-exposure A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions is referred to as post-exposure prophylaxis (PEP).[143] The use of the single agent zidovudine reduces the risk of a HIV infection five-fold following a needle-stick injury.[143] As of 2013[update], the prevention regimen recommended in the United States consists of three medications—tenofovir, emtricitabine and raltegravir—as this may reduce the risk further.[144] PEP treatment is recommended after a sexual assault when the perpetrator is known to be HIV-positive, but is controversial when their HIV status is unknown.[145] The duration of treatment is usually four weeks[146] and is frequently associated with adverse effects—where zidovudine is used, about 70% of cases result in adverse effects such as nausea (24%), fatigue (22%), emotional distress (13%) and headaches (9%).[49] ### Mother-to-child Main article: HIV and pregnancy Programs to prevent the vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%.[81][141] This primarily involves the use of a combination of antiviral medications during pregnancy and after birth in the infant, and potentially includes bottle feeding rather than breastfeeding.[81][147] If replacement feeding is acceptable, feasible, affordable, sustainable and safe, mothers should avoid breastfeeding their infants; however, exclusive breastfeeding is recommended during the first months of life if this is not the case.[148] If exclusive breastfeeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.[149] In 2015, Cuba became the first country in the world to eradicate mother-to-child transmission of HIV.[150] ### Vaccination Main article: HIV vaccine Currently there is no licensed vaccine for HIV or AIDS.[6] The most effective vaccine trial to date, RV 144, was published in 2009; it found a partial reduction in the risk of transmission of roughly 30%, stimulating some hope in the research community of developing a truly effective vaccine.[151] Further trials of the RV 144 vaccine are ongoing.[152][153] ## Treatment Main article: Management of HIV/AIDS There is currently no cure, nor an effective HIV vaccine. Treatment consists of highly active antiretroviral therapy (HAART) which slows progression of the disease.[154] As of 2010[update] more than 6.6 million people were receiving this in low- and middle-income countries.[155] Treatment also includes preventive and active treatment of opportunistic infections. As of March 2020[update], two persons have been successfully cleared of HIV.[156] Rapid initiation of anti-retroviral therapy within one week of diagnosis appear to improve treatment outcomes in low and medium-income settings.[157] ### Antiviral therapy Stribild – a common once-daily ART regime consisting of elvitegravir, emtricitabine, tenofovir and the booster cobicistat Current HAART options are combinations (or "cocktails") consisting of at least three medications belonging to at least two types, or "classes", of antiretroviral agents.[158] Initially, treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analog reverse transcriptase inhibitors (NRTIs).[159] Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC).[159] As of 2019, dolutegravir/lamivudine/tenofovir is listed by the World Health Organization as the first-line treatment for adults, with tenofovir/lamivudine/efavirenz as an alternative.[160] Combinations of agents that include protease inhibitors (PI) are used if the above regimen loses effectiveness.[158] The World Health Organization and the United States recommend antiretrovirals in people of all ages (including pregnant women) as soon as the diagnosis is made, regardless of CD4 count.[15][126][161] Once treatment is begun, it is recommended that it is continued without breaks or "holidays".[28] Many people are diagnosed only after treatment ideally should have begun.[28] The desired outcome of treatment is a long-term plasma HIV-RNA count below 50 copies/mL.[28] Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate.[28] Inadequate control is deemed to be greater than 400 copies/mL.[28] Based on these criteria treatment is effective in more than 95% of people during the first year.[28] Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death.[162] In the developing world, treatment also improves physical and mental health.[163] With treatment, there is a 70% reduced risk of acquiring tuberculosis.[158] Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission.[158][164] The effectiveness of treatment depends to a large part on compliance.[28] Reasons for non-adherence to treatment include poor access to medical care,[165] inadequate social supports, mental illness and drug abuse.[166] The complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effects may reduce adherence.[167] Even though cost is an important issue with some medications,[168] 47% of those who needed them were taking them in low- and middle-income countries as of 2010[update],[155] and the rate of adherence is similar in low-income and high-income countries.[169] Specific adverse events are related to the antiretroviral agent taken.[170] Some relatively common adverse events include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus, especially with protease inhibitors.[24] Other common symptoms include diarrhea,[170][171] and an increased risk of cardiovascular disease.[172] Newer recommended treatments are associated with fewer adverse effects.[28] Certain medications may be associated with birth defects and therefore may be unsuitable for women hoping to have children.[28] Treatment recommendations for children are somewhat different from those for adults. The World Health Organization recommends treating all children less than five years of age; children above five are treated like adults.[173] The United States guidelines recommend treating all children less than 12 months of age and all those with HIV RNA counts greater than 100,000 copies/mL between one year and five years of age.[174] The European Medicines Agency (EMA) has recommended the granting of marketing authorizations for two new antiretroviral (ARV) medicines, rilpivirine (Rekambys) and cabotegravir (Vocabria), to be used together for the treatment of people with human immunodeficiency virus type 1 (HIV-1) infection.[175] The two medicines are the first ARVs that come in a long-acting injectable formulation.[175] This means that instead of daily pills, people receive intramuscular injections monthly or every two months.[175] The combination of Rekambys and Vocabria injection is intended for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/ml) with their current ARV treatment, and when the virus has not developed resistance to certain class of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INIs).[175] ### Opportunistic infections Measures to prevent opportunistic infections are effective in many people with HIV/AIDS. In addition to improving current disease, treatment with antiretrovirals reduces the risk of developing additional opportunistic infections.[170] Adults and adolescents who are living with HIV (even on anti-retroviral therapy) with no evidence of active tuberculosis in settings with high tuberculosis burden should receive isoniazid preventive therapy (IPT); the tuberculin skin test can be used to help decide if IPT is needed.[176] Vaccination against hepatitis A and B is advised for all people at risk of HIV before they become infected; however, it may also be given after infection.[177] Trimethoprim/sulfamethoxazole prophylaxis between four and six weeks of age, and ceasing breastfeeding of infants born to HIV-positive mothers, is recommended in resource-limited settings.[178] It is also recommended to prevent PCP when a person's CD4 count is below 200 cells/uL and in those who have or have previously had PCP.[179] People with substantial immunosuppression are also advised to receive prophylactic therapy for toxoplasmosis and MAC.[180] Appropriate preventive measures reduced the rate of these infections by 50% between 1992 and 1997.[181] Influenza vaccination and pneumococcal polysaccharide vaccine are often recommended in people with HIV/AIDS with some evidence of benefit.[182][183] ### Diet Main article: Nutrition and HIV/AIDS The World Health Organization (WHO) has issued recommendations regarding nutrient requirements in HIV/AIDS.[184] A generally healthy diet is promoted. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the WHO; higher intake of vitamin A, zinc, and iron can produce adverse effects in HIV-positive adults, and is not recommended unless there is documented deficiency.[184][185][186][187] Dietary supplementation for people who are infected with HIV and who have inadequate nutrition or dietary deficiencies may strengthen their immune systems or help them recover from infections; however, evidence indicating an overall benefit in morbidity or reduction in mortality is not consistent.[188] Evidence for supplementation with selenium is mixed with some tentative evidence of benefit.[189] For pregnant and lactating women with HIV, multivitamin supplement improves outcomes for both mothers and children.[190] If the pregnant or lactating mother has been advised to take anti-retroviral medication to prevent mother-to-child HIV transmission, multivitamin supplements should not replace these treatments.[190] There is some evidence that vitamin A supplementation in children with an HIV infection reduces mortality and improves growth.[191] ### Alternative medicine In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine,[192] whose effectiveness has not been established.[193] There is not enough evidence to support the use of herbal medicines.[194] There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.[195] ## Prognosis Deaths due to HIV/AIDS per million persons in 2012 0 1–4 5–12 13–34 35–61 62–134 135–215 216–458 459–1,402 1,403–5,828 HIV/AIDS has become a chronic rather than an acutely fatal disease in many areas of the world.[196] Prognosis varies between people, and both the CD4 count and viral load are useful for predicted outcomes.[27] Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.[7] After the diagnosis of AIDS, if treatment is not available, survival ranges between 6 and 19 months.[197][198] HAART and appropriate prevention of opportunistic infections reduces the death rate by 80%, and raises the life expectancy for a newly diagnosed young adult to 20–50 years.[196][199][200] This is between two thirds[199] and nearly that of the general population.[28][201] If treatment is started late in the infection, prognosis is not as good:[28] for example, if treatment is begun following the diagnosis of AIDS, life expectancy is ~10–40 years.[28][196] Half of infants born with HIV die before two years of age without treatment.[178] Disability-adjusted life year for HIV and AIDS per 100,000 inhabitants as of 2004. no data ≤ 10 10–25 25–50 50–100 100–500 500–1000 1,000–2,500 2,500–5,000 5,000–7500 7,500–10,000 10,000–50,000 ≥ 50,000 The primary causes of death from HIV/AIDS are opportunistic infections and cancer, both of which are frequently the result of the progressive failure of the immune system.[181][202] Risk of cancer appears to increase once the CD4 count is below 500/μL.[28] The rate of clinical disease progression varies widely between individuals and has been shown to be affected by a number of factors such as a person's susceptibility and immune function;[203] their access to health care, the presence of co-infections;[197][204] and the particular strain (or strains) of the virus involved.[205][206] Tuberculosis co-infection is one of the leading causes of sickness and death in those with HIV/AIDS being present in a third of all HIV-infected people and causing 25% of HIV-related deaths.[207] HIV is also one of the most important risk factors for tuberculosis.[208] Hepatitis C is another very common co-infection where each disease increases the progression of the other.[209] The two most common cancers associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma.[202] Other cancers that are more frequent include anal cancer, Burkitt's lymphoma, primary central nervous system lymphoma, and cervical cancer.[28][210] Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders,[211] osteoporosis,[212] neuropathy,[213] cancers,[214][215] nephropathy,[216] and cardiovascular disease.[171] Some conditions, such as lipodystrophy, may be caused both by HIV and its treatment.[171] ## Epidemiology Main article: Epidemiology of HIV/AIDS See or edit source data. Percentage of people with HIV/AIDS.[217] Trends in new cases and deaths per year from HIV/AIDS[217] HIV/AIDS is a global pandemic.[218] As of 2016[update] approximately 36.7 million people worldwide have HIV, the number of new infections that year being about 1.8 million.[219] This is down from 3.1 million new infections in 2001.[220] Slightly over half the infected population are women and 2.1 million are children.[219] It resulted in about 1 million deaths in 2016, down from a peak of 1.9 million in 2005.[219] Sub-Saharan Africa is the region most affected. In 2010, an estimated 68% (22.9 million) of all HIV cases and 66% of all deaths (1.2 million) occurred in this region.[221] This means that about 5% of the adult population is infected[222] and it is believed to be the cause of 10% of all deaths in children.[223] Here, in contrast to other regions, women comprise nearly 60% of cases.[221] South Africa has the largest population of people with HIV of any country in the world at 5.9 million.[221] Life expectancy has fallen in the worst-affected countries due to HIV/AIDS; for example, in 2006 it was estimated that it had dropped from 65 to 35 years in Botswana.[17] Mother-to-child transmission in Botswana and South Africa, as of 2013[update], has decreased to less than 5%, with improvement in many other African nations due to improved access to antiretroviral therapy.[224] South & South East Asia is the second most affected; in 2010 this region contained an estimated 4 million cases or 12% of all people living with HIV resulting in approximately 250,000 deaths.[222] Approximately 2.4 million of these cases are in India.[221] During 2008 in the United States approximately 1.2 million people were living with HIV, resulting in about 17,500 deaths. The US Centers for Disease Control and Prevention estimated that in that year, 20% of infected Americans were unaware of their infection.[225] As of 2016[update] about 675,000 people have died of HIV/AIDS in the US since the beginning of the HIV epidemic.[226] In the United Kingdom as of 2015[update], there were approximately 101,200 cases which resulted in 594 deaths.[227] In Canada as of 2008, there were about 65,000 cases causing 53 deaths.[228] Between the first recognition of AIDS (in 1981) and 2009, it has led to nearly 30 million deaths.[229] Rates of HIV are lowest in North Africa and the Middle East (0.1% or less), East Asia (0.1%), and Western and Central Europe (0.2%).[222] The worst-affected European countries, in 2009 and 2012 estimates, are Russia, Ukraine, Latvia, Moldova, Portugal and Belarus, in decreasing order of prevalence.[230] ## History Main article: History of HIV/AIDS Further information: Category:HIV/AIDS by country ### Discovery The Morbidity and Mortality Weekly Report reported in 1981 on what was later to be called "AIDS". The first news story on the disease appeared May 18, 1981 in the gay newspaper New York Native.[231][232] AIDS was first clinically reported on June 5, 1981, with five cases in the United States.[36][233] The initial cases were a cluster of injecting drug users and gay men with no known cause of impaired immunity who showed symptoms of Pneumocystis carinii pneumonia (PCP), a rare opportunistic infection that was known to occur in people with very compromised immune systems.[234] Soon thereafter, an unexpected number of homosexual men developed a previously rare skin cancer called Kaposi's sarcoma (KS).[235][236] Many more cases of PCP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak.[237] In the early days, the CDC did not have an official name for the disease, often referring to it by way of diseases associated with it, such as lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.[238][239] They also used Kaposi's sarcoma and opportunistic infections, the name by which a task force had been set up in 1981.[240] At one point the CDC coined it the "4H disease", as the syndrome seemed to affect heroin users, homosexuals, hemophiliacs, and Haitians.[241][242] In the general press the term GRID, which stood for gay-related immune deficiency, had been coined.[243] However, after determining that AIDS was not isolated to the gay community,[240] it was realized that the term GRID was misleading, and the term AIDS was introduced at a meeting in July 1982.[244] By September 1982 the CDC started referring to the disease as AIDS.[245] In 1983, two separate research groups led by Robert Gallo and Luc Montagnier declared that a novel retrovirus may have been infecting people with AIDS, and published their findings in the same issue of the journal Science.[246][247] Gallo claimed a virus which his group had isolated from a person with AIDS was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) that his group had been the first to isolate. Gallo's group called their newly isolated virus HTLV-III. At the same time, Montagnier's group isolated a virus from a person presenting with swelling of the lymph nodes of the neck and physical weakness, two characteristic symptoms of AIDS. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV).[237] As these two viruses turned out to be the same, in 1986, LAV and HTLV-III were renamed HIV.[248] ### Origins Left to right: the African green monkey source of SIV, the sooty mangabey source of HIV-2, and the chimpanzee source of HIV-1 Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa and were transferred to humans in the early 20th century.[18] HIV-1 appears to have originated in southern Cameroon through the evolution of SIV(cpz), a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes troglodytes).[249][250] The closest relative of HIV-2 is SIV (smm), a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in coastal West Africa (from southern Senegal to western Ivory Coast).[97] New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.[251] HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three groups of the virus, M, N, and O.[252] There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.[253] However, SIV is a weak virus which is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into HIV.[254] Furthermore, due to its relatively low person-to-person transmission rate, SIV can only spread throughout the population in the presence of one or more high-risk transmission channels, which are thought to have been absent in Africa before the 20th century. Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to c. 1910.[255] Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including a higher degree of sexual promiscuity, the spread of prostitution, and the accompanying high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.[256] While transmission rates of HIV during vaginal intercourse are low under regular circumstances, they are increased manyfold if one of the partners suffers from a sexually transmitted infection causing genital ulcers. Early 1900s colonial cities were notable for their high prevalence of prostitution and genital ulcers, to the degree that, as of 1928, as many as 45% of female residents of eastern Kinshasa were thought to have been prostitutes, and, as of 1933, around 15% of all residents of the same city had syphilis.[256] An alternative view holds that unsafe medical practices in Africa after World War II, such as unsterile reuse of single-use syringes during mass vaccination, antibiotic and anti-malaria treatment campaigns, were the initial vector that allowed the virus to adapt to humans and spread.[254][257][258] The earliest well-documented case of HIV in a human dates back to 1959 in the Congo.[259] The earliest retrospectively described case of AIDS is believed to have been in Norway beginning in 1966.[260] In July 1960, in the wake of Congo's independence, the United Nations recruited Francophone experts and technicians from all over the world to assist in filling administrative gaps left by Belgium, who did not leave behind an African elite to run the country. By 1962, Haitians made up the second-largest group of well-educated experts (out of the 48 national groups recruited), that totaled around 4500 in the country.[261][262] Dr. Jacques Pépin, a Quebecer author of The Origins of AIDS, stipulates that Haiti was one of HIV's entry points to the United States and that one of them may have carried HIV back across the Atlantic in the 1960s.[262] Although the virus may have been present in the United States as early as 1966,[263] the vast majority of infections occurring outside sub-Saharan Africa (including the U.S.) can be traced back to a single unknown individual who became infected with HIV in Haiti and then brought the infection to the United States at some time around 1969.[264] The epidemic then rapidly spread among high-risk groups (initially, sexually promiscuous men who have sex with men). By 1978, the prevalence of HIV-1 among gay male residents of New York City and San Francisco was estimated at 5%, suggesting that several thousand individuals in the country had been infected.[264] ## Society and culture ### Stigma Main article: Discrimination against people with HIV/AIDS Ryan White became a poster child for HIV after being expelled from school because he was infected.[265] AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV-infected people; compulsory HIV testing without prior consent or protection of confidentiality; violence against HIV-infected individuals or people who are perceived to be infected with HIV; and the quarantine of HIV-infected individuals.[20] Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of HIV.[266] AIDS stigma has been further divided into the following three categories: * Instrumental AIDS stigma—a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.[267] * Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.[267] * Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV-positive people.[268] Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those associated with homosexuality, bisexuality, promiscuity, prostitution, and intravenous drug use.[269] In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice, such as anti-homosexual or anti-bisexual attitudes.[270] There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.[267] However, the dominant mode of spread worldwide for HIV remains heterosexual transmission.[271] In 2003, as part of an overall reform of marriage and population legislation, it became legal for people with AIDS to marry in China.[272] In 2013, the U.S. National Library of Medicine developed a traveling exhibition titled Surviving and Thriving: AIDS, Politics, and Culture;[273] this covered medical research, the U.S. government's response, and personal stories from people with AIDS, caregivers, and activists.[274] ### Economic impact Main articles: Economic impact of HIV/AIDS and Cost of HIV treatment Changes in life expectancy in some African countries, 1960–2012 HIV/AIDS affects the economics of both individuals and countries.[223] The gross domestic product of the most affected countries has decreased due to the lack of human capital.[223][275] Without proper nutrition, health care and medicine, large numbers of people die from AIDS-related complications. Before death they will not only be unable to work, but will also require significant medical care. It is estimated that as of 2007 there were 12 million AIDS orphans.[223] Many are cared for by elderly grandparents.[276] Returning to work after beginning treatment for HIV/AIDS is difficult, and affected people often work less than the average worker. Unemployment in people with HIV/AIDS also is associated with suicidal ideation, memory problems, and social isolation. Employment increases self-esteem, sense of dignity, confidence, and quality of life for people with HIV/AIDS. Anti-retroviral treatment may help people with HIV/AIDS work more, and may increase the chance that a person with HIV/AIDS will be employed (low-quality evidence).[277] By affecting mainly young adults, AIDS reduces the taxable population, in turn reducing the resources available for public expenditures such as education and health services not related to AIDS, resulting in increasing pressure on the state's finances and slower growth of the economy. This causes a slower growth of the tax base, an effect that is reinforced if there are growing expenditures on treating the sick, training (to replace sick workers), sick pay and caring for AIDS orphans. This is especially true if the sharp increase in adult mortality shifts the responsibility from the family to the government in caring for these orphans.[276] At the household level, AIDS causes both loss of income and increased spending on healthcare. A study in Côte d'Ivoire showed that households having a person with HIV/AIDS spent twice as much on medical expenses as other households. This additional expenditure also leaves less income to spend on education and other personal or family investment.[278] ### Religion and AIDS Main article: Religion and HIV/AIDS The topic of religion and AIDS has become highly controversial, primarily because some religious authorities have publicly declared their opposition to the use of condoms.[279][280] The religious approach to prevent the spread of AIDS, according to a report by American health expert Matthew Hanley titled The Catholic Church and the Global AIDS Crisis, argues that cultural changes are needed, including a re-emphasis on fidelity within marriage and sexual abstinence outside of it.[280] Some religious organizations have claimed that prayer can cure HIV/AIDS. In 2011, the BBC reported that some churches in London were claiming that prayer would cure AIDS, and the Hackney-based Centre for the Study of Sexual Health and HIV reported that several people stopped taking their medication, sometimes on the direct advice of their pastor, leading to a number of deaths.[281] The Synagogue Church Of All Nations advertised an "anointing water" to promote God's healing, although the group denies advising people to stop taking medication.[281] ### Media portrayal Main article: Media portrayal of HIV/AIDS One of the first high-profile cases of AIDS was the American Rock Hudson, a gay actor who had been married and divorced earlier in life, who died on October 2, 1985, having announced that he was suffering from the virus on July 25 that year. He had been diagnosed during 1984.[282] A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime minister Anthony Eden.[283] On November 24, 1991, the virus claimed the life of British rock star Freddie Mercury, lead singer of the band Queen, who died from an AIDS-related illness having only revealed the diagnosis on the previous day.[284] However, he had been diagnosed as HIV-positive in 1987. Mercury had also begun to show signs of the virus as early as 1982.[285] One of the first high-profile heterosexual cases of the virus was American tennis player Arthur Ashe. He was diagnosed as HIV-positive on August 31, 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but he did not tell the public about his diagnosis until April 1992.[286] He died as a result on February 6, 1993, aged 49.[287] Therese Frare's photograph of gay activist David Kirby, as he lay dying from AIDS while surrounded by family, was taken in April 1990. Life magazine said the photo became the one image "most powerfully identified with the HIV/AIDS epidemic." The photo was displayed in Life, was the winner of the World Press Photo, and acquired worldwide notoriety after being used in a United Colors of Benetton advertising campaign in 1992.[288] ### Criminal transmission Main article: Criminal transmission of HIV Criminal transmission of HIV is the intentional or reckless infection of a person with the human immunodeficiency virus (HIV). Some countries or jurisdictions, including some areas of the United States, have laws that criminalize HIV transmission or exposure.[289] Others may charge the accused under laws enacted before the HIV pandemic. In 1996, Ugandan-born Canadian Johnson Aziga was diagnosed with HIV; he subsequently had unprotected sex with eleven women without disclosing his diagnosis. By 2003, seven had contracted HIV; two died from complications related to AIDS.[290][291] Aziga was convicted of first-degree murder and sentenced to life imprisonment.[292] ### Misconceptions Main articles: Misconceptions about HIV/AIDS and Discredited HIV/AIDS origins theories There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS,[293][294][295] and that HIV can infect only gay men and drug users. In 2014, some among the British public wrongly thought one could get HIV from kissing (16%), sharing a glass (5%), spitting (16%), a public toilet seat (4%), and coughing or sneezing (5%).[296] Other misconceptions are that any act of anal intercourse between two uninfected gay men can lead to HIV infection, and that open discussion of HIV and homosexuality in schools will lead to increased rates of AIDS.[297][298] A small group of individuals continue to dispute the connection between HIV and AIDS,[299] the existence of HIV itself, or the validity of HIV testing and treatment methods.[300][301] These claims, known as AIDS denialism, have been examined and rejected by the scientific community.[302] However, they have had a significant political impact, particularly in South Africa, where the government's official embrace of AIDS denialism (1999–2005) was responsible for its ineffective response to that country's AIDS epidemic, and has been blamed for hundreds of thousands of avoidable deaths and HIV infections.[303][304][305] Several discredited conspiracy theories have held that HIV was created by scientists, either inadvertently or deliberately. Operation INFEKTION was a worldwide Soviet active measures operation to spread the claim that the United States had created HIV/AIDS. Surveys show that a significant number of people believed—and continue to believe—in such claims.[306] ## Research Main article: HIV/AIDS research HIV/AIDS research includes all medical research which attempts to prevent, treat, or cure HIV/AIDS, along with fundamental research about the nature of HIV as an infectious agent, and about AIDS as the disease caused by HIV. Many governments and research institutions participate in HIV/AIDS research. This research includes behavioral health interventions such as sex education, and drug development, such as research into microbicides for sexually transmitted diseases, HIV vaccines, and antiretroviral drugs. Other medical research areas include the topics of pre-exposure prophylaxis, post-exposure prophylaxis, and circumcision and HIV. 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Retrieved August 24, 2018. ## External links Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app. HIV/AIDSat Wikipedia's sister projects * Definitions from Wiktionary * Media from Wikimedia Commons * News from Wikinews * Quotations from Wikiquote * Travel guide from Wikivoyage * Resources from Wikiversity * Taxonomy from Wikispecies * HIV/AIDS at Curlie * UNAIDS – Joint United Nations Program on HIV/AIDS. * AIDSinfo – Information on HIV/AIDS treatment, prevention, and research, U.S. Department of Health and Human Services. * 2018 Recommendations of the International Antiviral Society * Medicine portal * Viruses portal Classification D * ICD-10: B20 – B24 * ICD-9-CM: 042–044 * OMIM: 609423 * MeSH: D000163 * DiseasesDB: 5938 External resources * MedlinePlus: 000594 * eMedicine: emerg/253 * Patient UK: HIV/AIDS * v * t * e Diseases of poverty Diseases of poverty * AIDS * Malaria * Tuberculosis * Measles * Pneumonia * Diarrheal diseases * Plague Neglected 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X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency Authority control * BNE: XX527488 * BNF: cb11975352k (data) * GND: 4112470-4 * HDS: 025625 * LCCN: sh85002541 * NDL: 00575858 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	HIV/AIDS	c0001175	30,382	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS	2021-01-18T18:50:15	{"mesh": ["D000163"], "umls": ["C0001175"], "icd-9": ["044", "042", "043"], "icd-10": ["B2424."], "orphanet": ["310050", "319269"], "wikidata": ["Q12199"]}
Caudal regression syndrome Other namesSacral regression sequence, Sacral agenesis Sacral agenesis SpecialtyMedical genetics Caudal regression syndrome, or sacral agenesis (or hypoplasia of the sacrum), is a rare birth defect. It is a congenital disorder in which the fetal development of the lower spine—the caudal partition of the spine—is abnormal.[1] It occurs at a rate of approximately one per 60,000 live births.[2] Some babies are born with very small differences compared to typical development, and others have significant changes. Most grow up to be otherwise normal adults who have difficulty with walking and incontinence. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Prognosis * 4 Society * 4.1 Notable cases * 5 References * 6 External links ## Signs and symptoms[edit] This condition exists in a variety of forms, ranging from partial absence of the tail bone regions of the spine to absence of the lower vertebrae, pelvis and parts of the thoracic and/or lumbar areas of the spine. In some cases where only a small part of the spine is absent, there may be no outward sign of the condition. In cases where more substantial areas of the spine are absent, there may be fused, webbed or smaller lower extremities and paralysis. Bowel and bladder control is usually affected.[citation needed] ## Cause[edit] Antero-posterior radiographic view, showing missing ribs, absent lumbosacral vertebrae, hypoplastic pelvis and "frog-like" position of the lower extremities in a fetus with caudal regression syndrome The condition arises from some factor or set of factors present during approximately the 3rd week to 7th week of fetal development. Formation of the sacrum/lower back and corresponding nervous system is usually nearing completion by the 4th week of development. Due to abnormal gastrulation, the mesoderm migration is disturbed. This disturbance results in symptoms varying from minor lesions of the lower vertebrae to more severe symptoms such as complete fusion of the lower limbs. While the exact cause is unknown, it has been speculated that the condition has a combination of environmental and genetic causes, and that various types of the condition may have differing causes.[citation needed] Sacral agenesis syndrome (a type of caudal regression syndrome involving agenesis of the lumbar spine, sacrum, and coccyx, and hypoplasia of the lower extremities) is a well-established congenital anomaly associated with maternal diabetes mellitus.[3][4] However, other causes are presumably involved, as demonstrated by the rare overall incidence of caudal regression syndrome (1:60,000) compared to diabetes - however, the condition does have a greatly-increased incidence among infants born to mothers with diabetes, estimated at 1 in 350 newborns of mothers with diabetes.[2] The dominant inherited sacral agenesis (also referred to as Currarino syndrome) is very often correlated with a mutation in the Hb9 (also called HlxB9) gene (shown by Sally Ann Lynch, 1995, Nature Genetics).[citation needed] It was previously thought to be related to sirenomelia ("Mermaid syndrome") but has now been determined not to be related to this condition.[5] ## Prognosis[edit] There are four levels (or "types") of malformation. The least severe indicates partial deformation (unilateral) of the sacrum. The second level indicates a bilateral (uniform) deformation. The most severe types involve a total absence of the sacrum.[citation needed] Depending on the type of sacral agenesis, bowel or urinary bladder deficiencies may be present. A permanent colostomy may be necessary in the case of imperforate anus. Incontinence may also require some type of continence control system (e.g., self-catheterization) be utilized. The condition often impacts the formation of the knees, legs or feet that is sometimes addressed through surgery. For some with tightly webbed, bent knees or knees that are fused straight, disarticulation surgery at the knee may be a viable option to maximize mobility options.[citation needed] Before more comprehensive medical treatment was available, full amputation of the legs at the hip was often performed. More recently, the 'amputation' (actually a disarticulation because no cutting of the bone is involved) is done at the knee for those who have bent knee positions and webbing between thigh and calf to enable more ease of mobility and better seating. Some children with knee disarticulation use prosthetic legs to walk. Prosthetics for children without substantial hip and trunk control is usually abandoned in favor of faster and easier wheelchair mobility as the child's weight and age increases. Children may 'walk' on their hands and generally are able to climb and move about to accomplish whatever they need and want to accomplish. Children more mildly affected may have normal gait and no need for assistive devices for walking. Others may walk with bracing or crutches.[citation needed] There is typically no cognitive impairment associated with this disability. Adults with this disability live independently, attend college, and have careers in various fields. In 2012, Spencer West, a man with sacral agenesis and both legs amputated, climbed Mount Kilimanjaro using only his hands.[6] ## Society[edit] ### Notable cases[edit] * Johnny Eck, American freak show performer * Kenny Easterday, played a fictionalized version of himself in the film Kenny * Kurt Fearnley, Australian wheelchair racer * Bobby Martin, American footballer * Jessica Rogers, American wheelchair racer and swimmer, founder and President of iSACRA (International Caudal Regression Syndrome Association) * Rose Siggins, actress (American Horror Story: Freak Show)[7] * Victoria Pendergast, first female Australian sit-skier at Winter Paralympics * Rebecca Dubber, New Zealand para-swimmer and Rio 2016 Paralympic bronze medalist * Kevin McKee, two-times olympic champion and two-times world champion in sledge hockey ## References[edit] 1. ^ Sonek JD, Gabbe SG, Landon MB, Stempel LE, Foley MR, Shubert-Moell K (March 1990). "Antenatal diagnosis of sacral agenesis syndrome in a pregnancy complicated by diabetes mellitus". Am. J. Obstet. Gynecol. 162 (3): 806–8. doi:10.1016/0002-9378(90)91015-5. PMID 2180307. 2. ^ a b Medline Plus. Caudal Regression Syndrome.https://medlineplus.gov/genetics/condition/caudal-regression-syndrome/#frequency 3. ^ Al Kaissi, Ali; Klaushofer, Klaus; Grill, Franz (19 December 2008). "Caudal regression syndrome and popliteal webbing in connection with maternal diabetes mellitus: a case report and literature review". Cases Journal. 1: 407. doi:10.1186/1757-1626-1-407. PMC 2614953. PMID 19099562. 4. ^ Zaw, Win; Stone, David G. (March 2002). "Caudal Regression Syndrome in Twin Pregnancy With Type II Diabetes". Journal of Perinatology. 22 (2): 171–174. doi:10.1038/sj.jp.7210614. PMID 11896527. S2CID 10374738. 5. ^ https://rarediseases.org/rare-diseases/sirenomelia/ 6. ^ "Man Climbs Mt. Kilimanjaro On Hands". ABC News. 22 June 2012. 7. ^ Karimi, Faith; Sutton, Joe (13 December 2015). "'American Horror Story' actress Rose Siggins dead at 43". CNN. ## External links[edit] Classification D * ICD-10: Q89.8 * OMIM: 600145 * DiseasesDB: 31157 External resources * eMedicine: orthoped/618 * Orphanet: 3027 * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Caudal regression syndrome	c0344490	30,383	wikipedia	https://en.wikipedia.org/wiki/Caudal_regression_syndrome	2021-01-18T18:30:18	{"gard": ["6007"], "mesh": ["C537221"], "umls": ["C0344490", "C0300948"], "icd-10": ["Q76.4"], "orphanet": ["3027"], "wikidata": ["Q1129947"]}
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe skin reaction most often triggered by particular medications. Although Stevens-Johnson syndrome and toxic epidermal necrolysis were once thought to be separate conditions, they are now considered part of a continuum. Stevens-Johnson syndrome represents the less severe end of the disease spectrum, and toxic epidermal necrolysis represents the more severe end. SJS/TEN often begins with a fever and flu-like symptoms. Within a few days, the skin begins to blister and peel, forming very painful raw areas called erosions that resemble a severe hot-water burn. The skin erosions usually start on the face and chest before spreading to other parts of the body. In most affected individuals, the condition also damages the mucous membranes, including the lining of the mouth and the airways, which can cause trouble with swallowing and breathing. The painful blistering can also affect the urinary tract and genitals. SJS/TEN often affects the eyes as well, causing irritation and redness of the conjunctiva, which are the mucous membranes that protect the white part of the eye and line the eyelids, and damage to the clear front covering of the eye (the cornea). Severe damage to the skin and mucous membranes makes SJS/TEN a life-threatening disease. Because the skin normally acts as a protective barrier, extensive skin damage can lead to a dangerous loss of fluids and allow infections to develop. Serious complications can include pneumonia, overwhelming bacterial infections (sepsis), shock, multiple organ failure, and death. About 10 percent of people with Stevens-Johnson syndrome die from the disease, while the condition is fatal in up to 50 percent of those with toxic epidermal necrolysis. Among people who survive, long-term effects of SJS/TEN can include changes in skin coloring (pigmentation), dryness of the skin and mucous membranes (xerosis), excess sweating (hyperhidrosis), hair loss (alopecia), and abnormal growth or loss of the fingernails and toenails. Other long-term problems can include impaired taste, difficulty urinating, and genital abnormalities. A small percentage of affected individuals develop chronic dryness or inflammation of the eyes, which can lead to increased sensitivity to light (photophobia) and vision impairment. ## Frequency SJS/TEN is a rare disease, affecting 1 to 2 per million people each year. Stevens-Johnson syndrome (the less severe form of the condition) is more common than toxic epidermal necrolysis. People who are HIV-positive and those with a chronic inflammatory disease called systemic lupus erythematosus are more likely to develop SJS/TEN than the general population. The reason for the increased risk is unclear, but immune system factors and exposure to multiple medications may play a role. ## Causes Several genetic changes have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. Most of these changes occur in genes that are involved in the normal function of the immune system. The genetic variations most strongly associated with SJS/TEN occur in the HLA-B gene. This gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Certain variations in this gene occur much more often in people with SJS/TEN than in people without the condition. Studies suggest that the HLA-B gene variations associated with SJS/TEN cause the immune system to react abnormally to certain medications. In a process that is not well understood, the drug causes immune cells called cytotoxic T cells and natural killer (NK) cells to release a substance called granulysin that destroys cells in the skin and mucous membranes. The death of these cells causes the blistering and peeling that is characteristic of SJS/TEN. Variations in several other HLA and non-HLA genes have also been studied as potential risk factors for SJS/TEN. However, most people with genetic variations that increase the risk of SJS/TEN never develop the disease, even if they are exposed to drugs that can trigger it. Researchers believe that additional genetic and nongenetic factors, many of which are unknown, likely play a role in whether a particular individual develops SJS/TEN. The drugs most frequently associated with SJS/TEN include several medications that are used to treat seizures (particularly carbamazepine, lamotrigine, and phenytoin); allopurinol, which is used to treat kidney stones and a form of arthritis called gout; a class of antibiotic drugs called sulfonamides; nevirapine, which is used to treat HIV infection; and a type of non-steroidal anti-inflammatory drugs (NSAIDs) called oxicams. Other factors may also trigger SJS/TEN. In particular, these skin reactions have occurred in people with an unusual form of pneumonia caused by infection with Mycoplasma pneumoniae and in people with viral infections, including cytomegalovirus. Researchers suspect that a combination of infections and drugs could contribute to the disease in some individuals. In many cases, no definitive trigger for an individual's SJS/TEN is ever discovered. ### Learn more about the gene associated with Stevens-Johnson syndrome/toxic epidermal necrolysis * HLA-B ## Inheritance Pattern SJS/TEN is not an inherited condition. However, the genetic changes that increase the risk of developing SJS/TEN can be passed from one generation to the next. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Stevens-Johnson syndrome/toxic epidermal necrolysis	c1840548	30,384	medlineplus	https://medlineplus.gov/genetics/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis/	2021-01-27T08:24:50	{"gard": ["7700"], "omim": ["608579"], "synonyms": []}
A rare, life-threatening, mitochondrial DNA depletion syndrome disease characterized by severe, progressive sensorimotor neuropathy associated with corneal ulceration, scarring or anesthesia, acral mutilation, metabolic and immunologic derangement, and hepatopathy (which can manifest with fulminant hepatic failure, a Reye-like syndrome or indolent progression to liver cirrhosis, depending on clinical form involved), present in the Navajo Native American population. Clinical presentation includes failure to thrive, distal limb weakness with reduced sensation, limb contractures with loss of funtion, areflexia, recurrent metabolic acidosis with intercurrent illness, immunologic anomalies manifesting with severe systemic infections, and sexual infantilism. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Navajo neurohepatopathy	c1850406	30,385	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=255229	2021-01-23T18:24:10	{"gard": ["3972"], "mesh": ["C538344"], "omim": ["256810"], "umls": ["C1850406"], "synonyms": ["Navajo neuropathy"]}
2018 attempted murder in Salisbury, England Poisoning of Sergei and Yulia Skripal A forensics tent covers the bench where Sergei and Yulia Skripal fell unconscious LocationSalisbury, Wiltshire, United Kingdom Date4 March 2018 TargetSergei Viktorovich Skripal Yulia Sergeevna Skripal WeaponsA-234 (suspected chemical weapon used) Victims3 admitted to hospital (subsequently discharged): The Skripals Det Sgt Nick Bailey, Wilts Police. Two other people were poisoned later, one died AccusedRussian nationals "Alexander Petrov" (alleged alias of Dr. Alexander Mishkin[1]) and "Ruslan Boshirov"[2] (alleged alias of Colonel Anatoliy Chepiga)[3] The poisoning of Sergei and Yulia Skripal was the poisoning of Sergei Skripal, a former Russian military officer and double agent for the British intelligence agencies, and his daughter, Yulia Skripal, on 4 March 2018 in the city of Salisbury, England. According to UK sources[4][5] and the Organisation for the Prohibition of Chemical Weapons (OPCW),[6] the poisoning was by means of a Novichok nerve agent. Each spent some weeks in hospital in a critical condition, before being discharged. A police officer, Nick Bailey, was also taken into intensive care after attending the incident, and was later discharged.[7][8][9][a] The British government accused Russia of attempted murder and announced a series of punitive measures against Russia, including the expulsion of diplomats. The UK's official assessment of the incident was supported by 28 other countries which responded similarly. Altogether, an unprecedented 153 Russian diplomats were expelled by the end of March 2018.[11] Russia denied the accusations and responded similarly to the expulsions and "accused Britain of the poisoning."[12] On 30 June 2018, a similar poisoning of two British nationals in Amesbury, seven miles north of Salisbury, involved the same nerve agent.[13][14] A man found a perfume bottle, later discovered to contain the agent, in a litter bin somewhere in Salisbury and gave it to a woman who sprayed it on her wrist.[15][16] The woman, Dawn Sturgess, fell ill within 15 minutes and died on 8 July, but the man, Charlie Rowley, who also came into contact with the poison, survived.[17] British police believe this incident was not a targeted attack, but a result of the way the nerve agent was disposed of after the poisoning in Salisbury.[18] On 5 September 2018, British authorities identified two Russian nationals, using the names Alexander Petrov and Ruslan Boshirov, as suspected of the Skripals' poisoning,[2] and alleged that they were active officers in Russian military intelligence.[19] Later, investigative website Bellingcat stated that it had positively identified Ruslan Boshirov as being the highly decorated GRU Colonel Anatoliy Chepiga,[20] that Alexander Petrov was Dr. Alexander Mishkin, also of the GRU,[21][22] and that a third GRU officer present in the UK at the time was identified as Denis Vyacheslavovich Sergeev,[23][24] believed to hold the rank of major general in the GRU. The pattern of his communications while in the UK indicates that he liaised with superior officers in Moscow.[25] The attempted assassination was allegedly organized by a secret Unit 29155 of the Russian GRU under command of Maj. Gen. Andrei V. Averyanov. The unit is allegedly responsible for destabilizing European countries and organized the Montenegrin coup attempt.[26] On 27 November 2019, the OPCW global chemical weapons watchdog added Novichok, the Soviet-era nerve agent used in the attack, to its list of banned toxins.[27] ## Contents * 1 Chronology of events * 2 Investigation * 2.1 Suspects and attack timeline * 3 Response of the United Kingdom * 4 Response of Russia * 4.1 Russian government * 4.2 Russian state media * 5 Chemical weapons experts and intelligence * 5.1 Porton Down * 5.2 Former Russian scientists and intelligence officers * 5.3 Spiez Laboratory in Switzerland * 6 Response from other countries and organisations * 6.1 US government * 6.2 European Union and member states * 6.3 Other non-EU countries * 6.4 NATO * 6.5 Joint responses * 7 Expulsion of diplomats * 8 Aftermath * 8.1 Russian public opinion * 9 Recovery money * 10 Recognition of responders * 11 Media depictions * 12 See also * 13 Notes * 14 References * 15 External links ## Chronology of events[edit] * At 14:40 GMT on 3 March 2018, Yulia Skripal, the 33-year-old daughter of Sergei Skripal, a 66-year-old resident of Salisbury, flew to Heathrow Airport from Russia. * At 09:15 on 4 March Sergei Skripal's burgundy 2009 BMW 320d was seen in the area of London Road, Churchill Way North and Wilton Road at Salisbury. * At 13:30 Skripal's car was seen on Devizes Road on the way towards the town centre. * At 13:40 the Skripals arrived in the upper level car park at the Maltings, Salisbury and then went to the Bishop's Mill pub in the town centre. * At 14:20 they dined at Zizzi on Castle Street, leaving at 15:35.[28] * At 16:15 an emergency services call reported that a man and woman, later identified as Sergei and Yulia, had been found unconscious on a public bench in the centre of Salisbury by the passing Chief Nursing Officer for the British Army and her daughter.[b][31][32][33] An eyewitness saw the woman foaming at the mouth with her eyes wide open but completely white.[34] According to a later British government statement they were "slipping in and out of consciousness on a public bench".[35] * At 17:10, they were taken separately to Salisbury District Hospital by an ambulance and an air ambulance.[36] At 09:03 the following morning, Salisbury NHS Foundation Trust declared a major incident in response to concerns raised by medical staff; shortly afterwards this became a multi-agency incident named Operation Fairline.[37][38] Health authorities checked 21 members of the emergency services and the public for possible symptoms;[39][40] two police officers were treated for minor symptoms, said to be itchy eyes and wheezing, while one, Detective Sergeant Nick Bailey, who had been sent to Skripal's house, was in a serious condition.[41][42] On 22 March, Bailey was discharged from the hospital. In a statement he said "normal life for me will probably never be the same" and thanked the hospital staff.[8] On 26 March, Skripal and his daughter were reported to still be critically ill.[43][44] On 29 March it was announced that Yulia's condition was improving and she was no longer in a critical condition.[45] After three weeks in a critical condition, Yulia regained consciousness and was able to speak.[46][47] Sergei was also in a critical condition until he regained consciousness one month after the attack.[48][49] On 5 April, doctors said that Sergei was no longer in critical condition and was responding well to treatment.[50] On 9 April, Yulia was discharged from hospital and taken to a secure location.[51][52] On 18 May, Sergei Skripal was discharged from the hospital too.[53] On 23 May, a handwritten letter and a video statement by Yulia were released to the Reuters news agency for the first time after the poisoning. She stated that she was lucky to be alive after the poisoning and thanked the staff of the Salisbury hospital. She described her treatment as slow, heavy and extremely painful and mentioned a scar on her neck, apparently from a tracheotomy. She expressed hope that someday she would return to Russia. She thanked the Russian embassy for its offer of assistance but said she and her father were "not ready to take it".[54] On 5 April, British authorities said that inside Skripal's house, which had been sealed by the police, two guinea pigs were found dead by vets, when they were allowed in, along with a cat in a distressed state, which had to be put down.[55] On 22 November the first interview with DS Bailey was released, in which he reported that he had been poisoned, despite the fact that he inspected the Skripals' house wearing a forensic suit. In addition to the poisoning, Bailey and his family had lost their home and all their possessions, because of contamination. Investigators said that the perfume bottle containing Novichok, which was later found in a bin, had contained enough of the nerve agent to potentially kill thousands of people.[56] In early 2019, building contractors built a scaffolding "sealed frame" over the house and the garage of Skripal's home. A military team then dismantled and removed the roofs on both buildings over the course of two weeks. Cleaning and decontamination was followed by rebuilding over a period of four months.[57][58] On 22 February 2019, Government officials announced that the last of the 12 sites that had been undergoing an intense and hazardous clean-up – Skripal's house – had been judged safe.[59] In May 2019, Sergei Skripal made a phone call and left a voice message to his niece Viktoria living in Russia. This was the first time after the poisoning that his voice had been heard by the public.[60] In August 2019 it was confirmed that a second police officer had been poisoned while investigating, but only in trace amounts.[61] ## Investigation[edit] The first public response to the poisoning came on 6 March. It was agreed under the National Counter Terrorism Policing Network that the Counter Terrorism Command based within the Metropolitan Police would take over the investigation from Wiltshire Police. Assistant Commissioner Mark Rowley, head of Counter Terrorism Policing, appealed for witnesses to the incident following a COBR meeting chaired by Home Secretary Amber Rudd.[62] Samples of the nerve agent used in the attack tested positive at the Defence Science and Technology Laboratory at Porton Down for a "very rare" nerve agent, according to the UK Home Secretary.[63] 180 military experts in chemical warfare defence and decontamination, as well as 18 vehicles, were deployed on 9 March to assist the Metropolitan Police to remove vehicles and objects from the scene and look for any further traces of the nerve agent. The personnel were drawn mostly from the Army, including instructors from the Defence CBRN Centre and the 29 Explosive Ordnance Disposal and Search Group, as well as from the Royal Marines and Royal Air Force. The vehicles included TPz Fuchs operated by Falcon Squadron from the Royal Tank Regiment.[64] On 11 March, the UK government advised those present at either The Mill pub or the Zizzi restaurant in Salisbury on 4 and 5 March to wash or wipe their possessions, emphasising that the risk to the general public was low.[65][66] Several days later, on 12 March, Prime Minister Theresa May said the agent had been identified as one of the Novichok family of agents, believed to have been developed in the 1980s by the Soviet Union.[67][68] According to the Russian ambassador to the UK, Alexander Yakovenko, the British authorities identified the agent as A-234,[69] derived from an earlier version known as A-232.[70] By 14 March, the investigation was focused on Skripal's home and car, a bench where the two fell unconscious, a restaurant in which they dined and a pub where they had drinks.[71] A recovery vehicle was removed by the military from Gillingham in Dorset on 14 March, in connection with the poisoning.[72][73] Subsequently, there was speculation within the British media that the nerve agent had been planted in one of the personal items in Yulia Skripal's suitcase before she left Moscow for London,[74] and in US media that it had been planted in their car.[75][76] Ahmet Üzümcü, Director-General of the Organisation for the Prohibition of Chemical Weapons (OPCW), said on 20 March that it will take "another two to three weeks to finalise the analysis" of samples taken from the poisoning of Skripal.[77] On 22 March, the Court of Protection gave permission for new blood samples to be obtained from Yulia and Sergei Skripal for use by the OPCW.[78][79] By 28 March, the police investigation concluded that the Skripals were poisoned at Sergei's home, with the highest concentration being found on the handle of his front door.[80] On 12 April the OPCW confirmed the UK's analysis of the type of nerve agent and reported it was of a "high purity", stating that the "name and structure of the identified toxic chemical are contained in the full classified report of the Secretariat, available to States Parties."[81][82][83] A declassified letter from the UK's national security adviser, Sir Mark Sedwill, to NATO Secretary General Jens Stoltenberg, stated Russian military intelligence hacked Yulia Skripal's email account since at least 2013 and tested methods for delivering nerve agents including on door handles.[84] The Department for Environment confirmed the nerve agent was delivered "in a liquid form". They said eight sites require decontamination, which will take several months to complete and cost millions of pounds. The BBC reported experts said the nerve agent does not evaporate or disappear over time. Intense cleaning with caustic chemicals is required to get rid of it.[85][86] The Skripals' survival was possibly due to the weather – there had been heavy fog and high humidity, and according to its inventor and other scientists, moisture weakens the potency of this type of toxin.[87][88][89] On 22 April 2018, it was reported that British counter-terror police had identified a suspect in the poisoning: a former FSB officer (reportedly[citation needed] a 54-year-old former FSB captain) who acted under several code names including "Gordon" and "Mihails Savickis". According to detectives, he led a team of six Russian assassins who organized the chemical weapons attack.[90] Sedwill reported on 1 May 2018 however that UK intelligence and police agencies had failed to identify the individual or individuals who carried out the attack.[91] On 3 May 2018, the head of the OPCW, Ahmet Üzümcü, informed the New York Times that he had been told that about 50–100 grams of the nerve agent was thought to have been used in the attack, which indicated it was likely created for use as a weapon and was enough to kill a large number of people.[92] The next day however the OPCW made a correcting statement that the "quantity should probably be characterised in milligrams", though "the OPCW would not be able to estimate or determine the amount of the nerve agent that was used".[93][94] On 19 July the Press Association reported that police believed they had identified "several Russians" as the suspected perpetrators of the attack. They had been identified through CCTV, cross-checked with border entry data.[95] On 6 August 2018, it was reported that the British government was "poised to submit an extradition request to Moscow for two Russians suspected of carrying out the Salisbury nerve agent attack". The Metropolitan Police used two super recognisers to identify the suspects after trawling through up to 5,000 hours of CCTV footage from Salisbury and numerous airports across the country.[96][97] ### Suspects and attack timeline[edit] On 5 September 2018, the Crown Prosecution Service (CPS) announced charges in absentia against two alleged Russian agents.[citation needed] The two Russian nationals were believed to have been travelling under aliases, although they had genuine Russian passports with the identities of Alexander Petrov and Ruslan Boshirov when applying for visas and entering the UK. The CPS said there was enough evidence to charge the men, but it was not applying to Russia for the extradition of the two suspects. Interpol Red Notices and domestic and European Arrest Warrants were issued in case the suspects travel to the EU.[2] As part of the announcement Scotland Yard and the Counter Terrorism Command released a detailed track of the individuals' 48 hours in the UK.[98] This covered their arrival from Moscow at Gatwick Airport, a trip to Salisbury by train the day before the attack, stated by police to be for reconnaissance, a trip to Salisbury by train on the day of the attack, and return to Moscow via Heathrow Airport.[99][19] The two spent both nights at the City Stay Hotel, next to Bow Church DLR station in Bow, East London. Novichok was found in their hotel room after police sealed it off on 4 May 2018. Neil Basu, National Lead for Counter Terrorism Policing said that tests were carried out on their hotel room and it was "deemed safe".[100][101] British Prime Minister Theresa May announced in the Commons the same day that British intelligence services had identified the two suspects as officers in the G. U. Intelligence Service (formerly known as GRU) and the assassination attempt was not a rogue operation and was "almost certainly" approved at a senior level of the Russian government.[2][102] May also said Britain would push for the EU to agree new sanctions against Russia. On 5 September 2018, the Russian news site Fontanka reported that the numbers on leaked passport files for Petrov and Boshirov are only three digits apart, and fall in a range that includes the passport files for a Russian military official expelled from Poland for spying.[103][104] It is not known how the passport files were obtained, but Andrew Roth, the Moscow correspondent for The Guardian, commented that "If the reporting is confirmed, it would be a major blunder by the intelligence agency, allowing any country to check passport data for Russians requesting visas or entering the country against a list of nearly 40 passport files of suspected GRU officers."[105] On 14 September 2018, the online platforms Bellingcat and the Russian publication Russia Insider noted that in Petrov's leaked passport files, there is no record of a residential address or any identification papers prior to 2009, suggesting that the name is an alias created that year; the analysis also noted that Petrov's dossier is stamped "Do not provide any information" and has the handwritten annotation "S.S.," a common abbreviation in Russian for "top secret."[106] On 15 September 2018, the Russian opposition newspaper Novaya Gazeta reported finding in Petrov's passport files a cryptic number that seems to be a telephone number associated with the Russian Defence Ministry, most likely the Military Intelligence Directorate.[107] On 26 September 2018, the real identity of the suspect named by police as Ruslan Boshirov was revealed as Colonel Anatoliy Vladimirovich Chepiga by The Daily Telegraph, citing reporting by itself and Bellingcat, with Petrov having a more junior rank in the GRU.[108] The 39-year-old was made a Hero of the Russian Federation by decree of the President in 2014. Two European security sources confirmed that the details were accurate.[109][110] The BBC commented: "The BBC understands there is no dispute over the identification."[111] The British defence minister Gavin Williamson wrote: "The true identity of one of the Salisbury suspects has been revealed to be a Russian Colonel. I want to thank all the people who are working so tirelessly on this case."[112] However, that statement was subsequently deleted from Twitter.[113] On 8 October 2018, the real identity of the suspect named by police as Alexander Petrov was revealed as Alexander Mishkin.[1][114][115][116] On 22 November 2018, more CCTV footage, with the two suspects walking in Salisbury, was published by the police.[117] On 19 December 2018, Mishkin (a.k.a. Petrov) and Chepiga (a.k.a. Boshirov) were added to the sanctions list of USA Treasury Department along with other 13 members of the GRU agency.[118][119][120] On 6 January 2019, the Telegraph reported that the British authorities had established all the essential details of the assassination attempt, including the chain of command that leads up to Vladimir Putin.[121] ## Response of the United Kingdom[edit] Within days of the attack, political pressure began to mount on Theresa May's government to take action against the perpetrators, and most senior politicians appeared to believe that the Russian government was behind the attack.[122][123] The situation was additionally sensitive for Russia as Russian president Vladimir Putin was facing his fourth presidential election in mid-March, and Russia was to host the 2018 FIFA World Cup football competition in June.[123][124] When giving a response to an urgent question from Tom Tugendhat, the chairman of the Foreign Affairs Select Committee of the House of Commons, who suggested that Moscow was conducting "a form of soft war against the West", Foreign Secretary Boris Johnson on 6 March said the government would "respond appropriately and robustly" if the Russian state was found to have been involved in the poisoning.[125][126] UK Home Secretary Amber Rudd said on 8 March 2018 that the use of a nerve agent on UK soil was a "brazen and reckless act" of attempted murder "in the most cruel and public way".[127] Prime Minister Theresa May said in the House of Commons on 12 March: > It is now clear that Mr Skripal and his daughter were poisoned with a military-grade nerve agent of a type developed by Russia. This is part of a group of nerve agents known as 'Novichok'. Based on the positive identification of this chemical agent by world-leading experts at the Defence Science and Technology Laboratory at Porton Down; our knowledge that Russia has previously produced this agent and would still be capable of doing so; Russia's record of conducting state-sponsored assassinations; and our assessment that Russia views some defectors as legitimate targets for assassinations; the Government has concluded that it is highly likely that Russia was responsible for the act against Sergei and Yulia Skripal. Mr Speaker, there are therefore only two plausible explanations for what happened in Salisbury on 4 March. Either this was a direct act by the Russian State against our country. Or the Russian government lost control of this potentially catastrophically damaging nerve agent and allowed it to get into the hands of others.[67] May also said that the UK government requested that Russia explain which of these two possibilities it was by the end of 13 March 2018.[67] She also said: "[T]he extra-judicial killing of terrorists and dissidents outside Russia were given legal sanction by the Russian Parliament in 2006. And of course Russia used radiological substances in its barbaric assault on Mr Litvinenko." She said that the UK government would "consider in detail the response from the Russian State" and in the event that there was no credible response, the government would "conclude that this action amounts to an unlawful use of force by the Russian State against the United Kingdom" and measures would follow.[67] British media billed the statement as "Theresa May's ultimatum to Putin."[4][128] On 13 March 2018, UK Home Secretary Amber Rudd ordered an inquiry by the police and security services into alleged Russian state involvement in 14 previous suspicious deaths of Russian exiles and businessmen in the UK.[129] May unveiled a series of measures on 14 March 2018 in retaliation for the poisoning attack, after the Russian government refused to meet the UK's request for an account of the incident. One of the chief measures was the expulsion of 23 Russian diplomats which she presented as "actions to dismantle the Russian espionage network in the UK", as these diplomats had been identified by the UK as "undeclared intelligence agents".[130][131] The BBC reported other responses, including:[132][133] * Increasing checks on private flights, customs and freight * Freezing Russian state assets where there is evidence that they may be used to threaten the life or property of UK nationals or residents * Plans to consider new laws to increase defences against "hostile state activity" * Ministers and the British royal family boycotting the 2018 FIFA World Cup in Russia * Suspending all high-level bilateral contacts between the UK and Russia * Retraction of the state invitation to Russian's foreign minister Sergey Lavrov[9] * A new £48-million chemical weapons defence centre[134] * Offering voluntary vaccinations against anthrax to British troops who are held at high readiness so that they are ready to deploy to areas where there is risk of this type of attack[135] May said that some measures which the government planned could "not be shared publicly for reasons of national security".[130] Jeremy Corbyn cast doubt in his parliamentary response to May's statement concerning blaming the attack on Russia prior to the results of an independent investigation, which provoked criticism from some MPs, including members of his own party.[136][137] A few days later, Corbyn was satisfied that the evidence pointed to Russia.[138] He supported the expulsion but argued that a crackdown on money laundering by UK financial firms on behalf of Russian oligarchs would be a more effective measure against "the Putin regime" than the Tory government's plans.[139] Corbyn pointed to the pre-Iraq War judgements about Iraq and weapons of mass destruction as reason to be suspicious.[140] The United Nations Security Council called an urgent meeting on 14 March 2018 on the initiative of the UK to discuss the Salisbury incident.[141][35] According to the Russian mission's press secretary, the draft press statement introduced by Russia at the United Nations Security Council meeting was blocked by the UK.[142] The UK and the US blamed Russia for the incident during the meeting, with the UK accusing Russia of breaking its obligations under the Chemical Weapons Convention.[143] Separately, the White House fully supported the UK in attributing the attack to Russia, as well as the punitive measures taken against Russia. The White House also accused Russia of undermining the security of countries worldwide.[144][145] The UK, and subsequently NATO, requested Russia provide "full and complete disclosure" of the Novichok programme to the Organisation for the Prohibition of Chemical Weapons.[146][147][148] On 14 March 2018, the government stated it would supply a sample of the substance used to the Organisation for the Prohibition of Chemical Weapons once UK legal obligations from the criminal investigation permitted.[149] Boris Johnson said on 16 March that it was "overwhelmingly likely" that the poisoning had been ordered directly by Russian president Vladimir Putin, which marked the first time the British government accused Putin of personally ordering the poisoning.[150] According to the UK Foreign Office, the UK attributed the attack to Russia based on Porton Down's determination that the chemical was Novichok, additional intelligence, and a lack of alternative explanations from Russia.[151] The Defence Science and Technology Laboratory announced that it was "completely confident" that the agent used was Novichok, but they still did not know the "precise source" of the agent.[152][153] The UK had held an intelligence briefing with its allies in which it stated that the Novichok chemical used in the Salisbury poisoning was produced at a chemical facility in the town of Shikhany, Saratov Oblast, Russia.[154] ## Response of Russia[edit] ### Russian government[edit] On 6 March 2018 Andrey Lugovoy, deputy of Russia's State Duma (the Liberal Democratic Party of Russia) and alleged killer of Alexander Litvinenko, in his interview with the Echo of Moscow said: "Something constantly happens to Russian citizens who either run away from Russian justice, or for some reason choose for themselves a way of life they call a change of their Motherland. So the more Britain accepts on its territory every good-for-nothing, every scum from all over the world, the more problems they will have."[155][156] Russian Foreign Minister Sergey Lavrov on 9 March rejected Britain's claim of Russia's involvement in Skripal's poisoning and accused the United Kingdom of spreading "propaganda".[157][158] Lavrov said that Russia was "ready to cooperate" and demanded access to the samples of the nerve-agent which was used to poison Skripal. The request was rejected by the British government.[159] Following Theresa May's 12 March statement in Parliament – in which she gave President Putin's administration until midnight of the following day to explain how a former spy was poisoned in Salisbury, otherwise she would conclude it was an "unlawful use of force" by the Russian state against the UK,[4] Lavrov, talking to the Russian press on 13 March, referred to the statement as "an ultimatum from London" and endorsed remarks made by the ministry's spokesperson the day prior, who called May's statement "a circus show in the British parliament";[160][161][162] he added that the procedure stipulated by the Chemical Weapons Convention should be followed whereunder Russia was entitled to have access to the substance in question and 10 days to respond.[160][163][164] He called allegations about Russia's complicity "balderdash".[165] The Russian foreign ministry spokesperson, speaking on a Russian state television channel on the evening of 13 March, said that no one had the right to present Russia with 24-hour ultimatums.[166][167][168] On 17 March, Russia announced that it was expelling 23 British diplomats and ordered the closure of the UK's consulate in St Petersburg and the British Council office in Moscow, stopping all British Council activities in Russia.[169] The poisoning has been officially declared to be a fabrication and a "grotesque provocation rudely staged by the British and U.S. intelligence agencies" to undermine Russia.[170][171] The Russian government and embassy of Russia in the United Kingdom repeatedly requested access to the Skripals, and sought to offer consular assistance. These requests and offers were denied or declined.[172][173][174][175][176] In September, Russia described the Skripals' situation as "de-facto deprivation of liberty", claiming that several diplomatic and human rights conventions were violated.[172] On 5 September the Russian government rejected the accusations "against Russia and two allegedly Russian citizens."[177] On 5 September 2018 Putin's Press Secretary, Dmitry Peskov, stated that May's accusations from that day were "unacceptable". Peskov asserted Russia had not received any official request from Britain for assistance in identifying the two suspected Russian GRU military intelligence officers that Scotland Yard believes carried out the Skripal attack. The same day, the Foreign Ministry of Russia asserted that UK ambassador in Moscow, Laurie Bristow, had said that London would not provide Russia with the suspects' fingerprints, passport numbers, visa numbers, or any extra data.[178] On 12 September 2018, Putin, while answering questions at the plenary meeting of the 4th Eastern Economic Forum in Russia's Far Eastern port city of Vladivostok said that the identities of both men London suspected of involvement in the Skripal case were known to the Russian authorities and that both were civilians, who had done nothing criminal. He also said he would like the men to come forward to tell their story.[179][180][181] In a 13 September 2018 interview on the state-funded television channel RT, the accused claimed to be sports nutritionists who had gone to Salisbury merely to see the sights and look for nutrition products, saying that they took a second day-trip to Salisbury because slush had dampened their first one.[182] On 14 September, Lavrov stated: "Our proposal of putting into operation existing mechanisms between London and Moscow on the legal assistance in criminal cases is still in force. Since there is no response to our proposal, we have all grounds to believe that there had been no crime, which these ladies and gentlemen are trying to attribute to our citizens."[183] On 26 September, the same day one of the suspects was identified as the Colonel of GRU, Lavrov once again urged the British authorities to cooperate in the investigation of the case, said Britain had given no proof of Russia's guilt and suggested that Britain had something to hide.[184][185] On 25 September, the Russian FSB began searching for Ministry of Internal Affairs (MVD) officers who had provided journalists with foreign passport and flight information about the suspects[needs update].[186] ### Russian state media[edit] For a few days following the poisoning, the story was discussed by web sites, radio stations and newspapers, but Russian state-run main national TV channels largely ignored the incident.[187][188] Eventually, on 7 March, anchor Kirill Kleimyonov of the state television station Channel One Russia's current affairs programme Vremya mentioned the incident by attributing the allegation to foreign secretary Boris Johnson.[189] After speaking of Johnson disparagingly, Kleimyonov said that being "a traitor to the motherland" was one of the most hazardous professions and warned: "Don't choose England as a next country to live in. Whatever the reasons, whether you're a professional traitor to the motherland or you just hate your country in your spare time, I repeat, no matter, don't move to England. Something is not right there. Maybe it's the climate, but in recent years there have been too many strange incidents with a grave outcome. People get hanged, poisoned, they die in helicopter crashes and fall out of windows in industrial quantities."[125][187][189][190][191] Kleimyonov's commentary was accompanied by a report highlighting previous suspicious Russia-related deaths in the UK, namely those of financier Alexander Perepilichny, businessman Boris Berezovsky, ex-FSB officer Alexander Litvinenko and radiation expert Matthew Puncher.[189] Puncher discovered that Litvinenko was poisoned by polonium; he died in 2006, five months after a trip to Russia.[192] The host of the Vesti Nedeli on Russian state television (Russia-1 channel of VGTRK), Dmitry Kiselyov, said on 11 March that the poisoning of Sergei Skripal, who was "completely wrung out and of little interest" as a source, was only advantageous to the British to "nourish their Russophobia" and organise the boycott of the FIFA World Cup scheduled for June 2018. Kiselyov referred to London as a "pernicious place for Russian exiles".[193][194][195][196] The prominent Russian television hosts' warnings to Russians living in the UK were echoed by a similar direct warning from a senior member of the Russian Federation Council, Andrey Klimov, who said: "It's going to be very unsafe for you."[164] Claims made by Russian media were fact-checked by UK media organisations.[197][198] An interview with two men claiming to be the suspects named by the UK was aired on RT on 13 September 2018 with RT editor Margarita Simonyan.[199] They said they were ordinary tourists who had wished to see Stonehenge, Old Sarum, and the "famous ... 123-metre spire" of Salisbury Cathedral. They also said that they "maybe approached Skripal's house, but we didn't know where it was located," and denied using Novichok, which they had allegedly transported in a fake perfume bottle, saying, "Is it silly for decent lads to have women's perfume? The customs are checking everything, they would have questions as to why men have women's perfume in their luggage."[200] Although Simonyan avoided most questions about the two men's backgrounds, she hinted that they might be gay by asking, "All footage features you two together ... What do you have in common that you spend so much time together?"[200] The New York Times interpreted the hint by noting that "The possibility that Mr. Petrov and Mr. Boshirov could be gay would, for a Russian audience, immediately rule out the possibility that they serve as military intelligence officers."[182] ## Chemical weapons experts and intelligence[edit] ### Porton Down[edit] On 3 April 2018 Gary Aitkenhead, the chief executive of the Government's Defence Science and Technology Laboratory (Dstl) at Porton Down responsible for testing the substance involved in the case, said they had established the agent was Novichok or from that family but had been unable to verify the "precise source" of the nerve agent and that they had "provided the scientific info to Government who have then used a number of other sources to piece together the conclusions you have come to."[201][202] Aitkenhead refused to comment on whether the laboratory had developed or maintains stocks of Novichok.[202] He also dismissed speculations the substance could have come from Porton Down: "There is no way anything like that could have come from us or left the four walls of our facility."[202] Aitkenhead stated the creation of the nerve agent was "probably only within the capabilities of a state actor" and there was no known antidote.[201][153] ### Former Russian scientists and intelligence officers[edit] Vil Mirzayanov, a former Soviet Union scientist who worked at the research institute that developed the Novichok class of nerve agents and lives in the United States, believes that hundreds of people could have been affected by residual contamination in Salisbury. He said that Sergei and Yulia Skripal, if poisoned with a Novichok, would be left with debilitating health issues for the rest of their lives. He also criticised the response of Public Health England, saying that washing personal belongings was insufficient to remove traces of the chemical.[203][204] Two other Russian scientists who now live in Russia and have been involved in Soviet-era chemical weapons development, Vladimir Uglev and Leonid Rink, were quoted as saying that Novichok agents had been developed in the 1970s–1980s within the programme that was officially titled FOLIANT and the term Novichok referred to a whole system of chemical weapons use; they, as well as Mirzayanov, who published Novichok's formula in 2008, also noted that Novichok-type agents might be synthesised in other countries.[205][206][207][208] In 1995, Leonid Rink received a one-year suspended sentence for selling Novichok agents to unnamed buyers, soon after the fatal poisoning of Russian banker Ivan Kivilidi by Novichok.[209][210][211][212] A former KGB and FSB officer, Boris Karpichkov, who operated in Latvia in the 1990s and fled to the UK in 1998,[213] told ITV's Good Morning Britain that on 12 February 2018, three weeks before the Salisbury attack and exactly on his birthday, he received a message over the burner phone from "a very reliable source" in the FSB telling Karpichkov that "something bad [wa]s going to happen with [him] and seven other people, including Mr. Skripal", whom he then knew nothing about.[214] Karpichkov said he disregarded the message at the time, thinking it was not serious, as he had previously received such messages.[214] According to Karpichkov, the FSB's list includes the names of Oleg Gordievsky and William Browder.[213][215] ### Spiez Laboratory in Switzerland[edit] The Swiss Federal Intelligence Service asserted on 14 September 2018 that two Russian spies had been caught in the Netherlands and expelled, earlier in the year, for attempting to hack into the Spiez Laboratory in the Swiss town of Spiez, a designated lab of the OPCW that had been tasked with confirming that the samples of poison collected in Salisbury were Novichok. The spies were discovered through a joint investigation by the Swiss, Dutch, and British intelligence services. The two men expelled were not the same as the Salisbury suspects.[216][217] ## Response from other countries and organisations[edit] ### US government[edit] Following Theresa May's statement in Parliament, the US Secretary of State Rex Tillerson released a statement on 12 March that fully supported the stance of the UK government on the poisoning attack, including "its assessment that Russia was likely responsible for the nerve agent attack that took place in Salisbury".[218] The following day, US President Donald Trump said that Russia was likely responsible.[219] United States Ambassador to the United Nations Nikki Haley at the Security Council briefing on 14 March 2018 stated: "The United States believes that Russia is responsible for the attack on two people in the United Kingdom using a military-grade nerve agent".[220] Following the United States National Security Council's recommendation,[221] President Trump, on 26 March, ordered the expulsion of sixty Russian diplomats (referred to by the White House as "Russian intelligence officers"[222]) and the closure of the Russian consulate in Seattle.[223][224] The action was cast as being "in response to Russia's use of a military-grade chemical weapon on the soil of the United Kingdom, the latest in its ongoing pattern of destabilising activities around the world."[222] On 8 August,[225] five months after the poisoning,[226] the US government agreed to place sanctions on Russian banks and exports.[227][228][229][226] On 6 August,[225] the US State Department concluded that Russia was behind the poisoning.[225] The sanctions, which are enforced under the Chemical and Biological Weapons Control and Warfare Elimination Act of 1991 (CBW Act),[225] were planned to come into effect on 27 August.[230] However, these sanctions were not implemented by the Trump administration.[231] ### European Union and member states[edit] European Commission Vice-President Frans Timmermans argued for "unequivocal, unwavering and very strong" European solidarity with the United Kingdom when speaking to lawmakers in Strasburg on 13 March.[232] Federica Mogherini, the High Representative of the Union for Foreign Affairs and Security Policy, expressed shock and offered the bloc's support.[233] MEP and leader of the Alliance of Liberals and Democrats for Europe in the European Parliament Guy Verhofstadt proclaimed solidarity with the British people.[234] During a meeting in the Foreign Affairs Council on 19 March, all foreign ministers of the European Union declared in a joint statement that the "European Union expresses its unqualified solidarity with the UK and its support, including for the UK's efforts to bring those responsible for this crime to justice." In addition, the statement also pointed out that "The European Union takes extremely seriously the UK Government's assessment that it is highly likely that the Russian Federation is responsible."[235] Norbert Röttgen, a former federal minister in Angela Merkel's government and current chairman of Germany's parliamentary foreign affairs committee, said the incident demonstrated the need for Britain to review its open-door policy towards Russian capital of dubious origin.[236] Sixteen EU countries expelled 33 Russian diplomats on 26 March.[237][238] The European Union officially sanctioned 4 Russians that were suspected of carrying out the attack on 21 January 2019. The head of the GRU Igor Kostyukov and the deputy head Vladimir Alexseyev were both sanctioned along with Mishkin and Chepiga. The sanctions banned them from traveling to the EU and froze any assets they may have there along with banning any person or company in the EU providing any financial support to those sanctioned.[239] ### Other non-EU countries[edit] Albania, Australia, Canada, Georgia, North Macedonia, Moldova, Norway and Ukraine expelled a total of 27 Russian diplomats who were believed to have been intelligence officers.[240] The New Zealand Government also issued a statement supporting the actions, noting that it would have expelled any Russian intelligence agents who had been detected in the country.[241] ### NATO[edit] NATO issued an official response to the attack on 14 March. The alliance expressed its deep concern over the first offensive use of a nerve agent on its territory since its foundation and said that the attack was in breach of international treaties. It called on Russia to fully disclose its research of the Novichok agent to the Organisation for the Prohibition of Chemical Weapons.[242] Jens Stoltenberg, NATO Secretary General, announced on 27 March that NATO would be expelling seven Russian diplomats from the Russian mission to NATO in Brussels. In addition, 3 unfilled positions at the mission have been denied accreditation from NATO. Russia blamed the US for the NATO response.[243] ### Joint responses[edit] The leaders of France, Germany, the United States and the United Kingdom released a joint statement on 15 March which supported the UK's stance on the incident, stating that it was "highly likely that Russia was responsible" and calling on Russia to provide complete disclosure to the Organisation for the Prohibition of Chemical Weapons concerning its Novichok nerve agent program.[244][245] On 19 March, the European Union also issued a statement strongly condemning the attack and stating it "takes extremely seriously the UK Government's assessment that it is highly likely that the Russian Federation is responsible".[235] On 6 September 2018, Canada, France, Germany and the United States issued a joint statement saying they had "full confidence" that the Salisbury attack was orchestrated by Russia's Main Intelligence Directorate and "almost certainly approved at a senior government level" and urged Russia to provide full disclosure of its Novichok programme to the OPCW.[246] ## Expulsion of diplomats[edit] Expelled Russian diplomats By the end of March 2018 a number of countries and other organisations expelled a total of more than 150 Russian diplomats in a show of solidarity with the UK. According to the BBC it was "the largest collective expulsion of Russian intelligence officers in history".[247][243][248] The UK expelled 23 Russian diplomats on 14 March 2018. Three days later, Russia expelled an equal number of British diplomats and ordered closure of the UK consulate in St. Petersburg and closure of the British Council in Russia.[169] Nine countries expelled Russian diplomats on 26 March: along with 6 other EU nations, the US, Canada, Ukraine and Albania. The following day, several nations inside and outside of the EU, and NATO responded similarly. By 30 March, Russia expelled an equal number of diplomats of most nations who had expelled Russian diplomats. By that time, Belgium, Montenegro, Hungary and Georgia had also expelled one or more Russian diplomats. Additionally on 30 March, Russia reduced the size of the total UK mission's personnel in Russia to match that of the Russian mission to the UK. Bulgaria, Luxembourg, Malta, Portugal, Slovakia, Slovenia and the European Union itself have not expelled any Russian diplomats but have recalled their ambassadors from Russia for consultations.[249][250][251][252][253][254] Furthermore, Iceland decided to diplomatically boycott the 2018 FIFA World Cup held in Russia.[255] Country or organisation Diplomats expelled Date announced Response by Russia Date announced Albania 2 26 March 2 diplomats expelled by Russia.[256] 30 March Australia 2 27 March 2 diplomats expelled by Russia.[256] 30 March Belgium 1 27 March 1 diplomat expelled (the economic attaché).[257] 4 April Canada 4[a][258] 26 March 4 diplomats expelled by Russia.[256] 30 March Croatia 1 26 March 1 diplomat based in Zagreb declared PNG.[259] 30 March Czech Republic 3 26 March 3 diplomats expelled by Russia.[256] 30 March Denmark 2 26 March 2 diplomats expelled by Russia.[256] 30 March Estonia 1 26 March 1 diplomat expelled by Russia.[256] 30 March Finland 1 26 March 1 diplomat expelled by Russia.[256] 30 March France 4 26 March 4 diplomats expelled by Russia.[256] 30 March Germany 4 26 March 4 diplomats expelled by Russia.[256] 30 March Georgia 1[260] 30 March 1 diplomat expelled by Russia.[261] 13 April Hungary 1 26 March 1 diplomat expelled by Russia.[262] 4 April Ireland 1 27 March 1 diplomat expelled by Russia.[256] 30 March Italy 2 26 March 2 diplomats expelled by Russia.[256] 30 March Latvia 1 26 March 1 diplomat expelled by Russia.[256] 30 March Lithuania 3 26 March 3 diplomats expelled by Russia.[256] 30 March Macedonia 1 26 March 1 diplomat expelled by Russia.[256] 30 March Moldova 3 27 March 3 diplomats expelled by Russia.[256] 30 March Montenegro 1[263] 28 March 1 diplomat expelled by Russia.[264] 2 April NATO 7[b][243] 27 March Netherlands 2 26 March 2 diplomats expelled by Russia.[256] 30 March Norway 1 26 March 1 diplomat expelled by Russia.[256] 30 March Poland 4 26 March 4 diplomats expelled by Russia.[256] 30 March Romania 1 26 March 1 diplomat expelled by Russia.[256] 30 March Spain 2 26 March 2 diplomats expelled by Russia.[256] 30 March Sweden 1 26 March 1 diplomat expelled by Russia.[256] 30 March Ukraine 13 26 March 13 diplomats expelled by Russia.[256] 30 March United Kingdom 23 14 March 23 UK diplomats expelled by Russia. British consulate in St Petersburg closed. Russian office of the British Council closed. 17 March UK diplomatic mission to Russia reduced in size to match Russian mission to UK. Requires the UK to recall a further 27 officials. 30 March United States 60,[c] Russian consulates in San Francisco and Seattle closed. 26 March 60 US diplomats expelled by Russia. US consulate in St Petersburg closed. 30 March Notes * ^[a] 4 diplomats expelled. 3 pending applications declined. * ^[b] 7 expelled and 3 pending applications declined. Maximum delegation reduced by 10 (from 30 to 20). * ^[c] 48 Russian diplomats expelled from Washington D.C. and 12 expelled from New York. ## Aftermath[edit] Some of the emergency vehicles used in the response to the poisoning have been buried in a landfill site near Cheltenham.[265] On 13 September, Chris Busby, a retired research scientist, who is a regular expert on the Russian government controlled RT television network, was arrested after his home in Bideford was raided by police.[266][267] Busby was an outspoken critic of the British Government's handling of the Salisbury poisoning.[268] In one video he stated: "Just to make it perfectly clear, there's no way that there's any proof that the material that poisoned the Skripals came from Russia." Busby was held for 19 hours under the Explosive Substances Act 1883,[269] before being released with no further action.[270] Following his release, Busby told the BBC he believed that the fact that two of the officers who had raided his property had felt unwell was explained by "psychological problems associated with their knowledge of the Skripal poisoning".[271] On 16 September, fears of Novichok contamination flared up again after two people fell ill at a Prezzo restaurant, 300 metres (980 ft) from the Zizzi location where the Skripals had eaten before collapsing. The restaurant, a nearby pub, and surrounding streets were cordoned off, with some patrons under observation or unable to leave the area.[272] The next day, the police said there was "nothing to suggest that Novichok" was the cause of the two people falling ill.[273] However, on 19 September, one of the apparent victims, Anna Shapiro, claimed in The Sun newspaper that the incident had been an attempted assassination against her and her husband by Russia.[274] This article was later removed from The Sun "for legal reasons"[274] and the police began to investigate the incident as a "possible hoax" after the couple were discharged from hospital.[275] In April 2019, The New York Times reported that then deputy CIA director Gina Haspel advised Donald Trump in a discussion that young children had been hospitalised and ducks killed after exposure to the Novichok nerve agent that poisoned the Skripals. She showed him photos of these victims which the New York Times reported had been provided by British officials.[276] The incident was cited as an example of the "persuasive skills" of the then CIA director Gina Haspel. In response Tracy Daszkiewicz, the director of public health for Wiltshire, said: "There were no other casualties other than those previously stated. No wildlife were impacted by the incident and no children were exposed to or became ill as a result of either incident".[277][278] ### Russian public opinion[edit] The Moscow Times reported later in the year of the poisonings "The results of the survey published by the independent Levada Center pollster [in October 2018] say that 28 percent of Russians believe that British intelligence services were behind Skripals' poisoning, with only 3 percent saying they believe their own intelligence officers carried out the attack. Another 56 percent said that "it could have been anyone." Meanwhile, 37 percent of respondents said they knew about the case in detail and 33 percent said they had "heard something" about it, with another 20 percent saying they had heard nothing about the poisoning."[279] ## Recovery money[edit] As of 17 October 2018, a total of £7.5 million had been pledged by government in support of the city and to support businesses, boost tourism and to cover unexpected costs. Wiltshire Council had spent or pledged £7,338,974 on recovery, and a further half million "was in the pipeline": * £733,381 towards unexpected closure and loss of footfall to businesses * £404,024 in revenue grants for 74 businesses * £99,891 in capital grants * £229,446 in business rate relief for 56 businesses * £210,491 on events to boost tourism * £500,000 from the Department of Digital, Culture, Media and Sport * £4,000 on dry cleaning or disposal of clothes believed to be contaminated by Novichock * £1 million towards keeping contaminated sites safe * £570,000 recovery money to cover costs of free parking, and free park and ride services * £4.1 million of the money pledged by the Home Office to cover Wiltshire Police's costs. A council commissioner said total policing cost had exceeded £10 million. Having £6.6 million allocated for funding the police force, he said he hoped to "recoup the full amount from central government".[280] ## Recognition of responders[edit] Deputy Chief Constable Paul Mills and Superintendent Dave Minty of Wiltshire Police were each awarded the Queen's Police Medal in the 2020 New Year Honours for their roles in responding to the incident.[281][282] The combined Wiltshire Emergency Services received Wiltshire Life's 2019 "Pride of Wiltshire" award.[283] ## Media depictions[edit] The Salisbury Poisonings, a three-part dramatisation of the events with a focus on the response of local officials and the local community, was broadcast on BBC One in June 2020.[284] ## See also[edit] * Intelligence agencies of Russia * Assassination of Kim Jong-nam by North Korea with VX nerve agent * Poisoning of Alexander Litvinenko putatively by Russian intelligence agents with Polonium-210 * Poisoning of Alexei Navalny, Russian politician poisoned with Novichok * Bulgarian umbrella used to assassinate Georgi Markov in London * List of poisonings * Biography portal * Russia portal ## Notes[edit] 1. ^ Stephen Davies of Salisbury NHS Foundation Trust wrote an open letter to The Times, published on 16 March 2018, clarifying that contrary to reports, no members of the public were affected: "Sir, Further to your report ("Poison exposure leaves almost 40 needing treatment", 14 March), may I clarify that no patients have experienced symptoms of nerve agent poisoning in Salisbury and there have only ever been three patients with significant poisoning. Several people have attended the emergency department concerned that they may have been exposed. None has had symptoms of poisoning and none has needed treatment. Any blood tests performed have shown no abnormality. No member of the public has been contaminated by the agent involved."[10] 2. ^ The nurse was the Chief Nursing Officer for the Army and the commanding officer of the Queen Alexandra's Royal Army Nursing Corps, Colonel Alison L McCourt OBE ARRC QHN; her teenage daughter later received an award for alerting her mother and assisting in first aid.[29][30] ## References[edit] 1. ^ a b Second Skripal Poisoning Suspect Identified as Dr. Alexander Mishkin. 2018. Bellingcat. 8 Oct. https://www.bellingcat.com/news/uk-and-europe/2018/10/08/second-skripal-poisoning-suspect-identified-as-dr-alexander-mishkin/. Retrieved: 9 October 2018. 2. ^ a b c d "Salisbury Novichok poisoning: Two Russian nationals named as suspects". BBC News. 5 September 2018. 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"Russians Planned Attack on Lab Testing Salisbury Nerve Agent, Swiss Say". New York Times. Retrieved 15 September 2018. 218. ^ "Attributing Responsibility for the Nerve Agent Attack in the U.K." U.S. Department of State. Retrieved 15 March 2018. 219. ^ Vonberg, Judith. "Trump: Russia likely poisoned ex-spy, 'based on all the evidence'". CNN. Retrieved 15 March 2018. 220. ^ Haley, Nikki (14 March 2018). "Remarks at an Emergency UN Security Council Briefing on Chemical Weapons Use by Russia in the United Kingdom". United States Mission to the United Nations. Department of State. 221. ^ Kosinski, Michelle. "Trump's National Security Council recommends expelling Russian diplomats". CNN. Retrieved 24 March 2018. 222. ^ a b Statement from the Press Secretary on the Expulsion of Russian Intelligence Officers The White House, 26 March 2018. 223. ^ Rucker, Philip; Nakashima, Ellen (26 March 2018). "Trump administration expels 60 Russian officers, shuts Seattle consulate in response to attack on former spy in Britain". The Washington Post. ISSN 0190-8286. Retrieved 26 March 2018. 224. ^ США высылают из страны 60 российских дипломатов TASS, 26 March 2018. 225. ^ a b c d "Imposition of Chemical and Biological Weapons Control and Warfare Elimination Act Sanctions on Russia". 226. ^ a b Serhan, Yasmeen (9 August 2018). "The U.S. Sanctions Russia for Skripal Poisoning—Five Months Later". 227. ^ Axelrod, Tal (10 August 2018). "Russia: New US sanctions a 'declaration of economic war'". 228. ^ "Russia Warns U.S. Against Ramping Up Sanctions". Time. 229. ^ "As U.S. sanctions Russia for ex-spy, Moscow adds to list of critics found poisoned or dead". 230. ^ "U.S. sanctions tied to nerve agent attack in effect Monday: federal notice". Reuters. 24 August 2018. Retrieved 24 August 2018. 231. ^ "U.S. has not imposed new Russia sanctions sparked by Skripal poisoning". NBC News. 232. ^ "The Latest: Trump, May agree on consequences for poison use". Associated Press. 13 March 2018. Archived from the original on 13 March 2018. Retrieved 13 March 2018. 233. ^ "Despite Brexit, Britain wins EU support on nerve agent attack". Reuters. 13 March 2018. Archived from the original on 13 March 2018. Retrieved 13 March 2018. 234. ^ "UK's effort to rally allies over Sergei Skripal poisoning may fall short". The Guardian. 13 March 2018. Archived from the original on 13 March 2018. Retrieved 13 March 2018. 235. ^ a b "Statement by the Foreign Affairs Council on the Salisbury attack" (Press release). Council of the European Union. 19 March 2018. Retrieved 19 March 2018. 236. ^ Wintour, Patrick (13 March 2018). "UK's effort to rally allies over Sergei Skripal poisoning may fall short". The Guardian. Retrieved 23 March 2018. 237. ^ "Spy poisoning: Russian diplomats expelled across US and Europe". BBC News. 26 March 2017. Retrieved 26 March 2018. 238. ^ Borger, Julian; Wintour, Patrick; Stewart, Heather (26 March 2018). "US and EU expel scores of Russian diplomats over Skripal attack". The Guardian. Retrieved 26 March 2018. 239. ^ "EU sanctions Russian suspects over Salisbury". 21 January 2019. Retrieved 21 January 2019. 240. ^ Dewan, Angela (27 March 2018). "These are all the countries that are expelling Russian diplomats". CNN. Retrieved 27 March 2018. 241. ^ "PM Jacinda Ardern: Why NZ is not expelling Russia diplomats". The New Zealand Herald. 27 March 2018. Retrieved 28 March 2018. 242. ^ "Statement by the North Atlantic Council on the use of a nerve agent in Salisbury". nato.int. 14 March 2018. Retrieved 23 March 2018. 243. ^ a b c "Nato slashes Russia staff after poisoning". BBC News. 27 March 2018. Retrieved 27 March 2018. 244. ^ Walker, Peter; Roth, Andrew (15 March 2018). "UK, US, Germany and France unite to condemn spy attack". The Guardian. London. Retrieved 15 March 2018. 245. ^ "Salisbury attack: Joint statement from the leaders of France, Germany, the United States and the United Kingdom". Government of the United Kingdom. Retrieved 15 March 2018. 246. ^ Henry Mance; Michael Peel; Guy Chazan (6 September 2018). "Key western allies back UK over Salisbury attack". Financial Times. Retrieved 6 September 2018. 247. ^ "Russia faces wave of diplomatic expulsions". BBC News. 26 March 2018. Retrieved 27 March 2018. 248. ^ "Montenegro to expel Russian diplomat over UK nerve gas attack". Reuters. 28 March 2018. Retrieved 28 March 2018. 249. ^ Bulgaria Recalls Ambassador From Russia to Discuss Nerve Agent Attack. Reuters via US News. 27 March 2018. 250. ^ Slovakia to Call Ambassador to Russia Back Home for Consultation. TASR.sk. 28 March 2018. 251. ^ Luxembourg recalls ambassador from Russia over Salisbury attack. Reuters. 28 March 2018. 252. ^ Diacono, Tim. Malta Has Just Recalled Its Ambassador To Russia. Lovin Malta. Retrieved on 18 May 2018. 253. ^ State of play over Russian envoy expulsions. Finance.yahoo.com (28 March 2018). Retrieved on 18 May 2018. 254. ^ Slovenia recalling its ambassador to Russia for consultations. Tass. 29 March 2018. 255. ^ Iceland's leaders to boycott Russia World Cup over Salisbury attack. Reuters.com. 26 March 2018. 256. ^ a b c d e f g h i j k l m n o p q r s t u v "Spy poisoning: Russia expels more UK diplomats". BBC. 31 March 2018. 257. ^ "Deze diplomaat wijst Rusland uit" (in Dutch). VTM. 4 April 2018. Retrieved 4 April 2018. 258. ^ "Canada expels Russian diplomats in solidarity with United Kingdom". www.canada.ca. 26 March 2018. 259. ^ Nepoželjna šefica ureda ministrice, kćer počasnog konzula Moskve Večernji list, 30 March 2018. 260. ^ "Georgia expels one Russian diplomat over UK nerve agent attack". Reuters. 30 March 2018. 261. ^ "Россия объявила грузинского дипломата персоной нон грата" (in Russian). РИА Новости. 13 April 2018. Retrieved 15 April 2018. 262. ^ "Russia says expels one Hungarian diplomat over Skripal case". Reuters. 4 April 2018. Retrieved 20 April 2018. 263. ^ "Montenegro to expel Russian diplomat over UK nerve gas attack". Reuters. 28 March 2018. 264. ^ Россия вышлет черногорского дипломата (in Russian). РИА Новости. 2 April 2018. Retrieved 15 April 2018. 265. ^ "Novichok 999 vehicles buried in landfill". BBC News. 31 August 2018. 266. ^ Narwan, Gurpreet (14 September 2018). "Police fall ill at chemical expert's home". The Times. Retrieved 20 September 2018. 267. ^ "Dr Chris Busby: Police become unwell at chemical weapons expert's Devon home". Sky News. Retrieved 20 September 2018. 268. ^ "Alternative Fakten und nationale Alleingänge – Großbritannien und Deutschland blamieren sich im Fall Skripal bis auf die Knochen". 6 April 2018. Retrieved 20 September 2018 – via www.nachdenkseiten.de. 269. ^ Cooper, Joel (14 September 2018). "Inside the bomb scare lab that belongs to Russia Today nuclear expert". Retrieved 20 September 2018. 270. ^ Reporters, Telegraph (13 September 2018). "Chemical weapons expert arrested after police 'taken ill' at Devon home". The Telegraph. Retrieved 20 September 2018. 271. ^ "Bideford radiation expert held over home chemicals". BBC News. 13 September 2018. Retrieved 20 September 2018. 272. ^ "Roads shut after 2 fall ill in UK city where ex-spy poisoned". CBS8 News. Associated Press. 273. ^ "'No Novichok link' to Salisbury incident". BBC News. 17 September 2018. Retrieved 17 September 2018. 274. ^ a b "Rat poison, Prezzo and the Russian model: odd Salisbury subplot begins to unravel". The Guardian. Retrieved 20 September 2018. 275. ^ "Salisbury Prezzo novichok poisoning scare may be a hoax, say police". The Independent. Retrieved 20 September 2018. 276. ^ Barnes, Julian E.; Goldman, Adam (16 April 2019). "Gina Haspel Relies on Spy Skills to Connect With Trump. He Doesn't Always Listen". New York Times. Retrieved 20 April 2019. 277. ^ Morris, Steven; Bannock, Caroline (18 April 2019). "No children or ducks harmed by novichok, say health officials". The Guardian. ISSN 0261-3077. Retrieved 21 April 2019. 278. ^ Trump wrote off novichok attack of defector as 'spy games' – report, The Guardian, 16 April 2019 279. ^ "Only 3% of Russians Believe Moscow Was Behind Skripal Attack, Poll Says". The Moscow Times. 25 October 2018. 280. ^ Hudson, Rebecca (17 October 2018). "Breakdown of Wiltshire Council spend on Salisbury recovery". Salisbury Journal. Retrieved 27 March 2019. 281. ^ "No. 62866". The London Gazette (Supplement). 28 December 2019. p. N33. 282. ^ "Deputy Chief Constable Paul Mills and Superintendent Dave Minty recognised in New Year Honours list". Police Federation of England and Wales. 28 December 2019. Retrieved 15 June 2020. 283. ^ "Winners". Wiltshire Life Awards. Retrieved 15 June 2020. 284. ^ McIntosh, Steven (14 June 2020). "TV drama revisits Salisbury poison attack 'horror'". BBC News. ## External links[edit] Wikimedia Commons has media related to Nerve agent attack 2018. * Report from the Russian Embassy to the UK, "Salisbury Unanswered Questions," 4 March 2019 * "Salisbury & Amesbury Investigation –UK Counter Terrorism Policing", 5 September 2018 * "Russian spy: What we know so far", BBC, 19 March 2018 * "Amanda Erickson: The long, terrifying history of Russian dissidents being poisoned abroad", The Washington Post, 7 March 2018 * "Joel Gunter: Sergei Skripal and the 14 deaths under scrutiny", bbc.com, 7 March 2018 * Bellingcat's investigative page for the Chepiga identification – Skripal Suspect Boshirov Identified as GRU Colonel Anatoliy Chepiga [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Poisoning of Sergei and Yulia Skripal	None	30,386	wikipedia	https://en.wikipedia.org/wiki/Poisoning_of_Sergei_and_Yulia_Skripal	2021-01-18T18:33:49	{"wikidata": ["Q50415393"]}
Hereditary elliptocytosis Other namesOvalocytosis, elliptocytes, ovalocytes Peripheral blood smear showing an abundant number of elliptocytes SpecialtyHematology Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive erythrocytes are sometimes referred to as elliptocytes or ovalocytes. It is one of many red-cell membrane defects. In its severe forms, this disorder predisposes to haemolytic anaemia. Although pathological in humans, elliptocytosis is normal in camelids. ## Contents * 1 Pathophysiology * 1.1 Common hereditary elliptocytosis * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 External links ## Pathophysiology[edit] ### Common hereditary elliptocytosis[edit] A number of genes have been linked to common hereditary elliptocytosis (many involve the same gene as forms of Hereditary spherocytosis, or HS): Type OMIM Gene EL1 or HS5 611804 EPB41 EL2 or HS3 130600 SPTA1 EL3 or HS2 182870 SPTB EL4 or HS4 or SEO 109270 SLC4A1 These mutations have a common end result; they destabilise the cytoskeletal scaffold of cells. This stability is especially important in erythrocytes as they are constantly under the influence of deforming shear forces. As disc-shaped erythrocytes pass through capillaries, which can be 2-3 micrometres wide, they are forced to assume an elliptical shape in order to fit through. Normally, this deformation lasts only as long as a cell is present in a capillary, but in hereditary elliptocytosis the instability of the cytoskeleton means that erythrocytes deformed by passing through a capillary are forever rendered elliptical. These elliptical cells are taken up by the spleen and removed from circulation when they are younger than they would normally be, meaning that the erythrocytes of people with hereditary elliptocytosis have a shorter than average life-span (a normal person's erythrocytes average 120 days or more). Figure 2 - A schematic diagram representing the relationships between cytoskeletal molecules as relevant to hereditary elliptocytosis. * EL2 and EL3: The most common genetic defects (present in two-thirds of all cases of hereditary elliptocytosis) are in genes for the polypeptides α-spectrin or β-spectrin. These two polypeptides combine with one another in vivo to form an αβ heterodimer. These αβ heterodimers then combine to form spectrin tetramers. These spectrin tetramers are among the basic structural subunits of the cytoskeleton of all cells in the body. Although there is much interindividual variability, it is generally true that α-spectrin mutations result in an inability of α-spectrin to interact properly with β-spectrin to form a heterodimer. In contrast, it is generally true that β-spectrin mutations lead to αβ heterodimers being incapable of combining to form spectrin tetramers.[1] In both cases the end result is a weakness in the cytoskeleton of the cell. Individuals with a single mutation in one of the spectrin genes are usually asymptomatic, but those who are homozygotes or are compound heterozygotes (i.e. they are heterozygous for two different elliptocytosis-causing mutations) have sufficient cell membrane instability to have a clinically significant haemolytic anaemia. * EL1: Less common than spectrin mutations are band 4.1 mutations. Spectrin tetramers must bind to actin in order to create a proper cytoskeleton scaffold, and band 4.1 is an important protein involved in the stabilisation of the link between spectrin and actin. Similarly to the spectrin mutations, band 4.1 mutations cause a mild haemolytic anaemia in the heterozygous state, and a severe haemolytic disease in the homozygous state. * EL4: Southeast Asian ovalocytosis is associated with the Band 3 protein. * Another group of mutations that lead to elliptocytosis are those that cause glycophorin C deficiencies. There are three phenotypes caused by abnormal glycophorin C, these are named Gerbich, Yus and Leach (see glycophorin C for more information). Only the rarest of the three, the Leach phenotype, causes elliptocytosis. Glycophorin C has the function of holding band 4.1 to the cell membrane. It is thought that elliptocytosis in glycophorin C deficiency is actually the consequence of a band 4.1 deficit, as glycophorin C deficient individuals also have reduced intracellular band 4.1 (probably due to the reduced number of binding sites for band 4.1 in the absence of glycoprotein C). Inheritance of multiple mutations tends to infer more serious disease. For instance, the most common genotype responsible for HPP occurs when the affected individual inherits an α-spectrin mutation from one parent (i.e. one parent has hereditary elliptocytosis) and the other parent passes on an as-yet-undefined defect that causes the affected individual's cells to preferentially produce the defective α-spectrin rather than normal α-spectrin. ## Diagnosis[edit] The diagnosis of hereditary elliptocytosis is usually made by coupling a family history of the condition with an appropriate clinical presentation and confirmation on a blood smear. In general it requires that at least 25% of erythrocytes in the specimen are abnormally elliptical in shape, though the observed percentage of elliptocytes can be 100%. This is in contrast to the rest of the population, in which it is common for up to 15% of erythrocytes to be elliptical.[2] If some doubt remains regarding the diagnosis, definitive diagnosis can involve osmotic fragility testing, an autohaemolysis test, and direct protein assaying by gel electrophoresis.[3] ## Treatment[edit] The vast majority of those with hereditary elliptocytosis require no treatment whatsoever. They have a mildly increased risk of developing gallstones, which is treated surgically with a cholecystectomy if pain becomes problematic. This risk is relative to the severity of the disease. Folate helps to reduce the extent of haemolysis in those with significant haemolysis due to hereditary elliptocytosis. Because the spleen breaks down old and worn-out blood cells, those individuals with more severe forms of hereditary elliptocytosis can have splenomegaly. Symptoms of splenomegaly can include: * Vague, poorly localised abdominal pain * Fatigue and dyspnoea * Growth failure * Leg ulcers * Gallstones. Removal of the spleen (splenectomy) is effective in reducing the severity of these complications, but is associated with an increased risk of overwhelming bacterial septicaemia, and is only performed on those with significant complications. Because many neonates with severe elliptocytosis progress to have only a mild disease, and because this age group is particularly susceptible to pneumococcal infections, a splenectomy is only performed on those under 5 years old when it is absolutely necessary. ## Prognosis[edit] Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy. ## Epidemiology[edit] The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention.[4] Around 90% of those with this disorder are thought to fall into the asymptomatic population. It is estimated that its incidence is between 3 and 5 per 10,000 in the United States,[5] and that those of African and Mediterranean descent are of higher risk. Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic. For example, in equatorial Africa its incidence is estimated at 60-160 per 10,000,[6] and in Malayan natives its incidence is 1500-2000 per 10,000.[7] Almost all forms of hereditary elliptocytosis are autosomal dominant, and both sexes are therefore at equal risk of having the condition. The most important exception to this rule of autosomal dominance is for a subtype of hereditary elliptocytosis called hereditary pyropoikilocytosis (HPP), which is autosomal recessive.[8] There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis. Common hereditary elliptocytosis is the most common form of elliptocytosis, and the form most extensively researched. Even when looking only at this form of elliptocytosis, there is a high degree of variability in the clinical severity of its subtypes. A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder. Southeast Asian ovalocytosis and spherocytic elliptocytosis are less common subtypes predominantly affecting those of south-east Asian and European ethnic groups, respectively. The following categorisation of the disorder demonstrates its heterogeneity:[9] * Common hereditary elliptocytosis (in approximate order from least severe to most severe) * With asymptomatic carrier status - individuals have no symptoms of disease and diagnosis is only able to be made on blood film * With mild disease - individuals have no symptoms, with a mild and compensated haemolytic anaemia * With sporadic haemolysis \- individuals are at risk of haemolysis in the presence of particular comorbidities, including infections, and vitamin B12 deficiency * With neonatal poikilocytosis \- individuals have a symptomatic haemolytic anaemia with poikilocytosis that resolves in the first year of life * With chronic haemolysis - individual has a moderate to severe symptomatic haemolytic anaemia (this subtype has variable penetrance in some pedigrees) * With homozygosity or compound heterozygosity \- depending on the exact mutations involved, individuals may lie anywhere in the spectrum between having a mild haemolytic anaemia and having a life-threatening haemolytic anaemia with symptoms mimicking those of HPP (see below) * With pyropoikilocytosis (HPP) - individuals are typically of African descent and have a life-threateningly severe haemolytic anaemia with micropoikilocytosis (small and misshapen erythrocytes) that is compounded by a marked instability of erythrocytes in even mildly elevated temperatures (pyropoikilocytosis is often found in burns victims and is the term is commonly used in reference to such people) * South-east Asian ovalocytosis (SAO) (also called stomatocytic elliptocytosis) - individuals are of South-East Asian descent (typically Malaysian, Indonesian, Melanesian, New Guinean or Filipino, have a mild haemolytic anaemia, and has increased resistance to malaria * Spherocytic elliptocytosis (also called hereditary haemolytic ovalocytosis) - individuals are of European descent and elliptocytes and spherocytes are simultaneously present in their blood ## History[edit] Elliptocytosis was first described in 1904,[10] and was first recognised as a hereditary condition in 1932.[11] More recently it has become clear that the severity of the condition is highly variable,[12] and there is much genetic variability amongst those affected.[13] ## See also[edit] * AMMECR1 * List of hematologic conditions ## References[edit] 1. ^ McMullin MF (1999). "The molecular basis of disorders of the red cell membrane". J. Clin. Pathol. 52 (4): 245–8. doi:10.1136/jcp.52.4.245. PMC 501324. PMID 10474512. 2. ^ Gerard M. Doherty (2010). Current Diagnosis & Treatment - Surgery (13th ed.). McGraw Hill Professional. pp. 204–5. ISBN 978-0-07-163515-8. Retrieved 5 May 2011. 3. ^ Robert S. Hillman; Kenneth A. Ault; Henry M. Rinder (2005). Hematology in clinical practice: a guide to diagnosis and management (4th ed.). McGraw-Hill Professional. p. 147. ISBN 978-0-07-144035-6. Retrieved 5 May 2011. 4. ^ Kim, D (24 May 2006). "Elliptocytosis, Hereditary". Medscape. WebMD LLC. Retrieved 12 August 2013. 5. ^ Bannerman, Rm; Renwick, Jh (July 1962). "The hereditary elliptocytoses: clinical and linkage data". Annals of Human Genetics. 26 (1): 23–38. doi:10.1111/j.1469-1809.1962.tb01306.x. ISSN 0003-4800. PMID 13864689. 6. ^ Hoffman, R; Benz, E; Shattil, S; Furie, B; Cohen, H (2005). Hoffman Hematology: Basic Principles and Practice (4th ed.). Philadelphia: Churchill Livingstone. ISBN 978-0-443-06628-3. 7. ^ Cattani, Ja; Gibson, Fd; Alpers, Mp; Crane, Gg (1987). "Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea" (Free full text). Transactions of the Royal Society of Tropical Medicine and Hygiene. 81 (5): 705–9. doi:10.1016/0035-9203(87)90001-0. ISSN 0035-9203. PMID 3329776. 8. ^ Kutlar, A (22 October 2013). "Hereditary Pyropoikilocytosis". Medscape. WebMD LLC. Retrieved 29 January 2015. 9. ^ Coetzer T, Lawler J, Prchal JT, Palek J (1 September 1987). "Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis". Blood. 70 (3): 766–72. doi:10.1182/blood.V70.3.766.766. PMID 3620700. 10. ^ Dresbach M (1904). "Elliptical human red corpuscles". Science. 19 (481): 469–470. Bibcode:1904Sci....19..469D. doi:10.1126/science.19.481.469. PMID 17730874. 11. ^ Hunter, WC (1932). "Further study of a white family showing elliptical erythrocytes". Ann Intern Med. 6 (6): 775–781. doi:10.7326/0003-4819-6-6-775. 12. ^ Gallagher, Pg (2005). "Red Cell Membrane Disorders". Hematology. 2005 (1): 13–8. doi:10.1182/asheducation-2005.1.13. PMID 16304353. 13. ^ Tse, Wt; Lux, Se (January 1999). "Red blood cell membrane disorders". British Journal of Haematology. 104 (1): 2–13. doi:10.1111/j.1365-2141.1999.01130.x. ISSN 0007-1048. PMID 10027705. ## External links[edit] Classification D * ICD-10: D58.1 * ICD-9-CM: 282.1 * OMIM: 611804 * MeSH: D004612 * DiseasesDB: 4172 External resources * MedlinePlus: 000563 * eMedicine: ped/987 med/648 * Hereditary Elliptocytosis Image of hereditary elliptocytosis * MedlinePlus Entry * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia * v * t * e Genetic disorder, membrane: Solute carrier disorders 1-10 * SLC1A3 * Episodic ataxia 6 * SLC2A1 * De Vivo disease * SLC2A5 * Fructose malabsorption * SLC2A10 * Arterial tortuosity syndrome * SLC3A1 * Cystinuria * SLC4A1 * Hereditary spherocytosis 4/Hereditary elliptocytosis 4 * SLC4A11 * Congenital endothelial dystrophy type 2 * Fuchs' dystrophy 4 * SLC5A1 * Glucose-galactose malabsorption * SLC5A2 * Renal glycosuria * SLC5A5 * Thyroid dyshormonogenesis type 1 * SLC6A19 * Hartnup disease * SLC7A7 * Lysinuric protein intolerance * SLC7A9 * Cystinuria 11-20 * SLC11A1 * Crohn's disease * SLC12A3 * Gitelman syndrome * SLC16A1 * HHF7 * SLC16A2 * Allan–Herndon–Dudley syndrome * SLC17A5 * Salla disease * SLC17A8 * DFNA25 21-40 * SLC26A2 * Multiple epiphyseal dysplasia 4 * Achondrogenesis type 1B * Recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia * SLC26A4 * Pendred syndrome * SLC35C1 * CDOG 2C * SLC39A4 * Acrodermatitis enteropathica * SLC40A1 * African iron overload see also solute carrier family * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hereditary elliptocytosis	c0013902	30,387	wikipedia	https://en.wikipedia.org/wiki/Hereditary_elliptocytosis	2021-01-18T18:35:14	{"gard": ["6621"], "mesh": ["D004612"], "umls": ["C0013902"], "orphanet": ["288"], "wikidata": ["Q2298020"]}
## Summary ### Clinical characteristics. DFNX1 nonsyndromic hearing loss and deafness is part of the spectrum of PRPS1-related disorders. Hearing loss in hemizygous males is bilateral, sensorineural, and moderate to profound; prelingual or postlingual in onset; and progressive or non-progressive. The audiogram shape is variable. Hearing in female carriers can be normal or abnormal. ### Diagnosis/testing. Diagnosis relies on the presence of characteristic hearing loss in males and detection of a hemizygous PRPS1 pathogenic variant. ### Management. Treatment of manifestations: Routine management of sensorineural hearing loss. Cochlear implantation can improve auditory and oral communication skills in affected males. Surveillance: Regular audiologic evaluation to assess hearing status and progression of hearing loss. Evaluation of relatives at risk: Evaluate at-risk males at birth with detailed audiometry to assure early diagnosis and treatment of hearing loss. ### Genetic counseling. DFNX1 is inherited in an X-linked manner. The father of an affected male will not have the disorder nor will he be a carrier of the pathogenic variant. If the mother of an affected male has a pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the variant will be affected; females who inherit the variant will be carriers and may have hearing loss. Carrier testing for at-risk female relatives, prenatal diagnosis for pregnancies at increased risk, and preimplantation genetic diagnosis are possible if the PRPS1 pathogenic variant in the family has been identified. ## Diagnosis ### Suggestive Findings DFNX1 nonsyndromic hearing loss and deafness, part of the spectrum of PRPS1-related disorders, should be considered in a male proband with the following clinical, laboratory, and imaging findings and family history. Clinical findings * Sensorineural hearing loss is: * Bilateral moderate to profound; * Prelingual or postlingual in onset; * Progressive or non-progressive. * Audiograms are usually flat across all frequencies. However, some individuals have severe hearing loss in the low frequencies and some have residual hearing in the high frequencies. * Vestibular function is normal. Imagining. Temporal bone imaging is normal. Family history consistent with X-linked inheritance. In heterozygous females hearing can be normal or abnormal. ### Establishing the Diagnosis Male proband. The diagnosis of DFNX1 is established in a male proband with sensorineural hearing loss and a hemizygous pathogenic variant in PRPS1 identified by molecular genetic testing [Liu et al 2010, Kim et al 2016] (see Table 1). Female carrier. The diagnosis of DFNX1 is usually established in a female carrier who may have normal hearing or sensorineural hearing loss and a heterozygous pathogenic variant in PRPS1 identified by molecular genetic testing [Liu et al 2010] (see Table 1). Molecular genetic testing. Because the phenotype of DFNX1 is indistinguishable from many other inherited disorders with hearing loss, recommended molecular genetic testing approaches include use of a multigene panel (see Option 1) or comprehensive genomic testing (see Option 2). Note: Single-gene testing (sequence analysis of PRPS1 followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended. #### Option 1 A multigene panel that includes PRPS1 and other genes of interest (see Hereditary Hearing Loss and Deafness Overview) 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. Of note, given the rarity of DFNX1 nonsyndromic hearing loss and deafness some panels for hearing loss 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. #### Option 2 Comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is another good option. Exome sequencing is most commonly used; genome sequencing is also possible. Exome array (when clinically available) may be considered if exome sequencing is not diagnostic. 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 DFNX1 View in own window Gene 1Test MethodProportion of Pathogenic Variants 2 Detectable by This Method PRPS1Sequence analysis 3, 45/5 5 Gene-targeted deletion/duplication analysis 6Unknown 7 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\. 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\. Sequencing of the seven exons of the coding region and the intron/exon boundaries of PRPS1 in the five families reported to date with DFNX1 nonsyndromic hearing loss and deafness identified five different pathogenic missense variants [Liu et al 2010, Kim et al 2016]. To date no intragenic deletions or duplications have been observed. 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. 7\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description Hearing loss in individuals with DFNX1 nonsyndromic hearing loss and deafness can be prelingual or postlingual (in which onset ranges from 3 years to 20 years), progressive or non-progressive, and severe to profound [Liu et al 2010, Liu et al 2013, Kim et al 2016]. Synofzik et al [2014] concluded that the three PRPS1-related phenotypes (CMTX5, Arts syndrome, and DFNX1) constitute a continuum after observing all three phenotypes in one family with a loss-of-function pathogenic variant: a male with CMT and Arts syndrome and a heterozygous female with hearing loss due to skewing of X-chromosome inactivation. On detailed clinical and neurophysiologic examination manifestations of peripheral neuropathy that range from a subclinical axonal motor neuropathy to an axonal sensory-motor neuropathy were found in males with PRPS1-related hearing loss [Robusto et al 2015]. In addition, optic atrophy and retinitis pigmentosa have been described in females heterozygous for a PRPS1 pathogenic variant [Almoguera et al 2014]. Heterozygous females. Hearing in heterozygous females can be normal or abnormal. When hearing is abnormal, hearing loss can be either symmetric or asymmetric and ranges from mild to moderate [Liu et al 2013]. In the family described by Almoguera et al [2014], both the proband and her mother have peripheral neuropathy and ophthalmologic manifestations, whereas the phenotype of the affected sister is milder and confined to eye, with no hearing loss. ### Genotype-Phenotype Correlations The established PRPS1-related disorders are not distinct entities, but rather clusters on a phenotypic continuum as evidenced by overlap of the features of CMTX5 / Arts syndrome / DFNX1 both in affected individuals and within families. A wide and continuous spectrum of clinical manifestations has been associated with PRPS1 missense variants (see Genetically Related Disorders). A relationship between the type (location) of PRS-I disruption and phenotype has been suggested, with the most severe phenotypes caused by variants predicted to affect allosteric and active sites and the milder phenotypes caused by variants predicted to disrupt the structure locally [de Brouwer et al 2010]. In females, who predictably have a less severe presentation, the ratio of X chromosome inactivation adds an additional variable in predicting clinical outcome [Synofzik et al 2014]. ### Prevalence Prevalence has not been determined. Five families with DFNX1 have been reported [Liu et al 2010, Kim et al 2016]. ## Differential Diagnosis See Deafness and Hereditary Hearing Loss Overview for complete differential diagnosis of hereditary hearing loss. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with DFNX1 nonsyndromic hearing loss and deafness, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Pure tone audiograms, auditory brain stem response testing * Evaluation for peripheral neuropathy and ophthalmologic findings (optic atrophy and retinitis pigmentosa) * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Sensorineural hearing loss. Cochlear implantation in affected males can improve auditory and oral communication skills. See Deafness and Hereditary Hearing Loss Overview. ### Surveillance Hearing loss in DFNX1 is prelingual or postlingual and progressive; regular audiologic evaluation is recommended to assess hearing status and progression of hearing loss. Periodic reevaluation of clinical findings by a neurologist is indicated for males with clinical evidence of peripheral neuropathy. ### Evaluation of Relatives at Risk Determining in infancy whether at-risk male and female relatives of a person with DFNX1 nonsyndromic hearing loss and deafness have inherited the PRPS1 pathogenic variant allows for early support and management of the child and the family. Evaluations may include: * Molecular genetic testing if the pathogenic PRPS1 variant in the family is known. * Audiometry if molecular genetic testing for the at-risk relative is not available. 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 www.ClinicalTrialsRegister.eu 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	DFNX1 Nonsyndromic Hearing Loss and Deafness	None	30,388	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK57098/	2021-01-18T21:31:26	{"synonyms": ["DFN2 Nonsyndromic Hearing Loss and Deafness"]}
## Clinical Features Kaitila et al. (1982) described a brother and sister with a previously unrecognized form of disproportionate short stature. The brother had tracheobronchial malacia and progressive scoliosis. The trachea and bronchi were reinforced with surrounding acrylate mesh before surgical treatment of the scoliosis. (Tracheobronchial malacia occurs in infants with chondrodysplasias, e.g., diastrophic dysplasia (222600), but is rare in adults with skeletal dysplasias. Bronchomalacia occurs as an apparently isolated genetic disorder (211450).) The sister was less severely affected. Bone x-rays showed progression from marked metaphyseal dysplasia of tubular bones in childhood to short and broad bones with mild dysplasia of the joints in adulthood. The vertebrae and intervertebral plates were only mildly affected, despite marked scoliosis. Cartilage-hair hypoplasia (250250), a relatively frequent disorder in Finland, was carefully ruled out. Possibly the sibs represent a genetic compound of the CHH gene and another allele. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, disproportionate short-limb HEAD & NECK Nose \- Narrow, beaked nose Mouth \- Narrow palate RESPIRATORY Airways \- Tracheobronchial malacia CHEST External Features \- Shallow, narrow chest SKELETAL \- Metaphyseal dysplasia Spine \- Progressive scoliosis \- Thoracolumbar scoliosis Pelvis \- Small iliac bones \- Irregular proximal femoral metaphyses \- Delayed ossification proximal femoral epiphyses Limbs \- Short limbs \- Limited elbow extension \- Enlarged joints \- Short, broad tibiae and fibulae \- Irregular, widened metaphyses Hands \- Short fingers \- Finger joint hypermobility \- Short phalanges (especially distal phalanges) \- Short metacarpals \- Cone-shaped epiphyses Feet \- Short phalanges \- Short metatarsals SKIN, NAILS, & HAIR Skin \- Wrinkled skin over fingers Nails \- Short, broad nails NEUROLOGIC Central Nervous System \- Delayed motor development \- Normal intelligence ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	METAPHYSEAL CHONDRODYSPLASIA, KAITILA TYPE	c1855217	30,389	omim	https://www.omim.org/entry/250230	2019-09-22T16:25:26	{"mesh": ["C565400"], "omim": ["250230"], "orphanet": ["166038"]}
## Summary ### Clinical characteristics. Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy. ### Diagnosis/testing. The diagnosis of Perrault syndrome is based on the clinical findings of SNHL in men and women and ovarian dysfunction in women with a 46,XX karyotype. The diagnosis is confirmed by the presence of biallelic pathogenic variants in one of six genes (CLPP, ERAL1, HARS2, HSD17B4, LARS2, or TWNK); however, in approximately 60% of individuals with Perrault syndrome identified to date, a molecular diagnosis cannot be established. ### Management. Treatment of manifestations: Hearing loss should be assessed and treated by a multidisciplinary team including an audiologist and otolaryngologist. Possible interventions for those with hearing loss include special educational resources, hearing aids, vibrotactile devices, and cochlear implantation. Cochlear implantation is an option for children older than 12 months with severe-to-profound hearing loss. Primary amenorrhea is treated in adolescents in collaboration with a pediatric endocrinologist in the usual manner, first to induce puberty and then to mimic the menstrual cycle and maintain bone health. Assisted reproduction through in vitro fertilization using donor eggs is a consideration for women with gonadal dysgenesis; oocyte cryopreservation can be considered in women at risk for POI. Surveillance: Routine audiologic assessments when hearing loss is mild to moderate; no follow up or audiologic assessments when hearing loss is profound. For children with hearing impairment: monitor development For women with primary amenorrhea: during induction of puberty, follow up every three months for staging of pubertal development and adjustment of estrogen dose. For women on maintenance estrogen replacement therapy: annual follow up as well as assessment of bone density approximately every five years. Agents/circumstances to avoid: Avoid: ototoxic medication (e.g., aminoglycosides) if alternative medications are available; exposure to loud noise, which can exacerbate hearing loss. Evaluation of relatives at risk: It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early interventions (e.g., in young children with profound hearing loss; estrogen replacement to facilitate pubertal development in females with ovarian involvement; and potential oocyte cryopreservation if POI is an issue). ### Genetic counseling. Perrault syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. When the pathogenic variants in the family are known, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible. ## Diagnosis No formal diagnostic criteria have been published for Perrault syndrome. ### Suggestive Findings Perrault syndrome should be suspected in individuals with the following clinical findings and family history. Clinical findings * Sensorineural hearing loss (SNHL) in men and women. SNHL is bilateral and ranges in severity from moderate with early-childhood onset to profound with prelingual (congenital) onset. The hearing threshold increase can be variable. When presenting in early childhood, hearing loss can be progressive. * SNHL may be apparent from birth in infants who fail neonatal screening tests. * In older children SNHL can be demonstrated on an audiogram, which will show similar hearing thresholds for both bone and air conduction. * Ovarian dysfunction in women with a 46,XX karyotype. The spectrum of ovarian dysfunction extends across a continuum from primary ovarian insufficiency (POI) to ovarian dysgenesis. * POI is defined as cessation of menses before age 40 years, with raised levels of follicle stimulating hormone (FSH) and reduced serum estrogen concentration. * Ovarian dysgenesis is a developmental disorder characterized by loss of germ and supportive cells (e.g., granulosa and theca cells, respectively) in the gonads. The ovaries are dysplastic, streak, or absent. Serum concentration of estrogen is decreased with a consequent elevation in serum concentration of the two gonadotropins, lutenizing hormone (LH) and follicle stimulating hormone (FSH) (i.e., with hypergonadotropic hypogonadism). The uterus is rudimentary and prepubertal on ultrasound examination. Family history is consistent with autosomal recessive inheritance including the possibility of parental consanguinity. ### Establishing the Diagnosis The diagnosis of Perrault syndrome is established: * Either by clinical findings, family history, and exclusion of other possible diagnoses with findings similar to Perrault syndrome (see Differential Diagnosis); * Or by identification of biallelic pathogenic variants in one of the six associated genes (see Table 1) in a person with Suggestive Findings. #### Clinical Findings and Family History * SNHL that is bilateral and ranges in severity from moderate with early-childhood onset to profound with prelingual (congenital) onset * Ovarian dysfunction in women with a 46,XX karyotype Note: Sensorineural hearing loss is usually the initial manifestation of Perrault syndrome. The diagnosis will not be considered, based on clinical findings alone, in males who do not have an affected sister. The initial diagnosis will not be made in females based on clinical findings alone until delayed pubertal development is noted, usually in the teenage years. #### Molecular Genetic Testing The diagnosis of Perrault syndrome is molecularly confirmed by the presence of biallelic pathogenic variants in one of six genes: CLPP, ERAL1, HARS2, HSD17B4, LARS2, and TWNK (see Table 1). Note: To date biallelic pathogenic variants in these six genes do not account for all individuals with clinically confirmed Perrault syndrome (Table 1) [Demain et al 2017]. Due to the heterogeneous nature of this disorder, molecular genetic testing approaches can include gene-targeted testing (through a multigene panel) or comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved). * A multigene panel that includes CLPP, ERAL1, HARS2, HSD17B4, LARS2, and TWNK and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Comprehensive genomic testing is the best option when the diagnosis of Perrault syndrome has not been considered because an individual has atypical phenotypic features. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Perrault Syndrome View in own window Gene 1, 2Proportion of Perrault Syndrome Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 CLPP7/427/7None reported ERAL13/423/3None reported HARS23/423/3None reported HSD17B43/423/3None reported LARS28/428/8None reported TWNK5/425/5None reported Unknown 613/42NA 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. When multigene panel testing that includes most/all of the known genes is used, approximately 60% of individuals with Perrault syndrome have not had pathogenic variants [Lerat et al 2016, Demain et al 2017]. Failure to detect pathogenic variants in one of these genes suggests either the presence of a variant in a gene region not sequenced (e.g., enhancer, promoter, intron), pathogenic variants in an as-yet-unidentified gene, or inaccurate clinical diagnosis (see Differential Diagnosis). ## Clinical Characteristics ### Clinical Description Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. Significant inter- and intrafamilial phenotypic variability has been observed [Jenkinson et al 2012]. Of note, the variable age of onset and degree of deafness do not depend on the sex of the affected individual. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. There is no evidence of impaired vestibular function. Affected females have gonadal dysfunction. Although the ovarian findings in Perrault syndrome were originally described as primary ovarian failure due to absent or streak gonads, subsequent reports identified a spectrum of ovarian dysfunction ranging from gonadal dysgenesis presenting as primary amenorrhea (also known as primary ovarian failure) to primary ovarian insufficiency (POI) (presenting as secondary amenorrhea) which is defined as cessation of menses before age 40 years. One woman with Perrault syndrome had children prior to the onset of ovarian insufficiency [Jenkinson et al 2013]. Fertility in affected males is usually reported as normal, although the number of reported affected males is limited. Males with variants in CLPP have been noted to be azoospermic [Demain et al 2017]. Other features. Some individuals have been reported to have additional clinical features. No consistent pattern has been observed with these additional features, which have been reported in more than one individual [Jenkinson et al 2012]. Neurologic features are present in some individuals with Perrault syndrome. Members of families with CLPP-related Perrault syndrome and LARS2-related Perrault syndrome have been reported with or without neurologic features [Jenkinson et al 2013, Pierce et al 2013, Kosaki et al 2018]: * Learning difficulties and developmental delay [Jenkinson et al 2012, Lerat et al 2016, Demain et al 2017] * Cerebellar ataxia [Jenkinson et al 2012, Lerat et al 2016, Demain et al 2017] * Motor and sensory peripheral neuropathy [Jenkinson et al 2012, Lerat et al 2016, Demain et al 2017] Skeletal features reported in some individuals include high-arched palate, positive thumb and wrist signs, and marfanoid habitus [Zerkaoui et al 2017] ### Phenotype Correlations by Gene Sensorineural hearing loss (SNHL) in Perrault syndrome resulting from biallelic pathogenic variants in ERAL1, HARS2, HSD17B4, or LARS2 can be congenital and profound or progressive with varying degrees of severity; onset is usually in early childhood and a range of frequencies are affected. CLPP. In families reported to date with biallelic CLPP pathogenic variants, SNHL is severe to profound with congenital or early childhood onset [Jenkinson et al 2013, Ahmed et al 2015, Lerat et al 2016, Demain et al 2017]. TWNK. All individuals reported to date with biallelic TWNK variants have had associated neurologic features including ataxia and peripheral neuropathy [Morino et al 2014, Lerat et al 2016, Demain et al 2017, Ołdak et al 2017]. ### Genotype-Phenotype Correlations Low-frequency SNHL resulting in an upsloping audiogram has been associated with the LARS2 pathogenic variant c.1565C>A in either the homozygous state or in a heterozygous state in trans to another pathogenic LARS2 variant. Other variants in LARS2 have not been associated with low-frequency SNHL [Pierce et al 2013, Demain et al 2017]. ### Nomenclature Perrault syndrome has also been referred to as ovarian dysgenesis with sensorineural deafness or XX gonadal dysgenesis with deafness. ### Prevalence Perrault syndrome is rare; approximately 100 affected individuals have been reported to date [Lerat et al 2016]. However, underascertainment is likely as males without an affected sister will be diagnosed with nonsyndromic deafness rather than Perrault syndrome. For example, the authors are aware of males with SNHL and prepubertal girls with SNHL with variants in Perrault syndrome-related genes. ## Differential Diagnosis For individuals with a clinical diagnosis of Perrault syndrome in whom a molecular basis has not been identified, other causes of sensorineural hearing loss and ovarian dysfunction need to be excluded before a clinical diagnosis of Perrault syndrome can made with confidence. Sensorineural hearing loss (SNHL) is genetically heterogeneous. See Hereditary Hearing Loss and Deafness Overview for a detailed differential diagnosis. XX gonadal dysgenesis and primary ovarian insufficiency are genetically heterogeneous. * XX gonadal dysgenesis. For individuals with primary ovarian failure, defined by primary amenorrhea with low estrogen and raised gonadotropins, Turner syndrome (45, X) or other abnormalities of the X chromosome should be excluded by karyotype analysis or chromosomal microarray (also known as array CGH). Hearing loss is present in approximately 50% of women with Turner syndrome [King et al 2007], but tends to be mild to moderate at higher frequencies [Oliveira et al 2013]. * Testing of genes in which pathogenic variants have been reported to cause ovarian dysgenesis (including BMP15, FSHR, MCM9, PSMC3IP, and SOHLH1) is appropriate (OMIM PS233300). * Other causes of primary ovarian failure include 17α-hydroxylase deficiency and 17,20-lysase deficiency (OMIM 202110); which can be excluded by measurement of 11-deoxycorticosterone and androstenedione levels. * Primary ovarian insufficiency (POI). Multiple genetic causes of POI are known. Analysis of a limited number of genes is available by routine clinical testing. * Premutation carriers of an expanded FMR1 allele are at increased risk for ovarian insufficiency; see FMR1-Related Disorders. * Many females with BPES (blepharophimosis, ptosis, epicanthus inversus syndrome), caused by pathogenic variants or deletions of FOXL2, have POI. BPES can be distinguished from Perrault syndrome by the presence of marked blepharophimosis and ptosis in BPES. * Ovarian antibodies are increased in polyglandular autoimmune syndrome type 1 (OMIM 240300) and type 2 (OMIM 269200). SNHL and POI * RMND1-associated mitochondrial disease, which has a wide phenotypic range including SNHL, hypotonia, developmental delay, lactic acidemia, and renal dysfunction [Ng et al 2016] can present with features consistent with a diagnosis of Perrault syndrome [Demain et al 2018]. * The authors described a novel and likely rare cause of Perrault syndrome in a female who did not have pathogenic variants in any of the known Perrault syndrome-related genes [Faridi et al 2017]. She manifested SNHL and POI as a result of inheriting homozygous pathogenic variants in each of two distinct unlinked genes: CLDN14 and SGO2. CLDN14 is a well-known cause of autosomal recessive SNHL. Her POI was attributed to inactivating variants in SGO2, a gene not known to cause any human disorder but essential for meiosis and strongly implicated in infertility by studies in murine models. The variants of both CLDN14 and SGO2 were segregating in her multigenerational family; her parents were documented to be heterozygous for variants in both genes. Although relatives either manifested SNHL or were heterozygous for the CLDN14 variant, she was the only female who had both SNHL and POI. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Perrault syndrome, 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 Perrault Syndrome View in own window System/ConcernEvaluationComment ENT 1Audiologic assessmentTo define the degree & frequency range of hearing impairment by audiometry & physiologic tests (summarized in Hereditary Hearing Loss and Deafness Overview) Neurologic 1Neurologic assessmentDetermine if ataxia, peripheral neuropathy, &/or learning disability is present. Endocrine 2Serum estrogen & gonadotropin (LH & FSH) concentrationsIn women w/relatively intact ovarian function, serum anti-müllerian hormone concentrations may provide evidence of incipient ovarian failure. 3 Pelvic imagingUltrasound scan or magnetic resonance imaging to define the presence of ovaries & antral follicle count Miscellaneous/ Other 1Consultation w/clinical geneticist &/or genetic counselor 1\. Men and women 2\. Women only 3\. De Vos et al [2010] ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with Perrault Syndrome View in own window Manifestation/ ConcernTreatmentConsiderations/Other Hearing lossPossible interventions: * Hearing aids * Vibrotactile devices * Cochlear implantation 1 * Assessment & treatment by multidisciplinary team incl: audiologist, otolaryngologist, speech therapist * Provide for any special educational needs. * Early intervention in young children w/profound hearing loss improves cognitive & language development. Ovarian insufficiencyIn adolescents presenting w/primary amenorrhea, induction of puberty w/incremental doses of estrogen * In consultation w/pediatric endocrinologist * If puberty is complete, administer cyclic estrogen & progesterone to mimic menstrual cycle & trigger withdrawal bleeding. * Estrogen replacement therapy (if no contraindications) until age ≥50 yrs to ↓ risks of cardiovascular disease & osteoporosis Assisted reproduction through in vitro fertilization * For women w/gonadal dysgenesis: consider assisted reproduction through in vitro fertilization using donor eggs. * For women at risk for ovarian insufficiency: consider oocyte cryopreservation if ovarian function is sufficiently well preserved to allow for successful harvesting of oocytes. * Consider use of donor eggs. * Before considering pregnancy, assess uterine size. 1\. Cochlear implantation can be considered in children age >12 months with severe-to-profound hearing loss. ### Surveillance ### Table 5. Recommended Surveillance for Individuals with Perrault Syndrome View in own window System/ConcernEvaluationFrequency Hearing * Routine audiologic assessment for possible progressive hearing impairment * Audiologic surveillance not required for persons w/profound hearing loss Annually MusculoskeletalAssess bone density in women on maintenance estrogen replacement therapy.Every ~5 yrs Endocrine * Before puberty: clinical staging of puberty * During induction of puberty: adjustment of estrogen dose Every 3 mos Women on maintenance estrogen replacement therapy: assessment of withdrawal bleeding & well beingAnnually ### Agents/Circumstances to Avoid For individuals with hearing loss, avoid: * Ototoxic medication such as aminoglycosides if alternatives are available; * Exposure to loud noise, which may contribute to deterioration of hearing. ### Evaluation of Relatives at Risk It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early interventions (e.g., in young children with profound hearing loss, estrogen replacement to facilitate pubertal development in females with ovarian involvement, and potential oocyte cryopreservation if primary ovarian insufficiency is an issue). See Treatment of Manifestations. * If the pathogenic variants in the family are known, molecular genetic testing can be used to clarify the genetic status of at-risk sibs. * If the pathogenic variants in the family are not known, screening of sibs should include audiologic assessment in males and females and baseline measurements of serum LH and FSH in females. 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 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Perrault Syndrome	c0685838	30,390	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK242617/	2021-01-18T21:03:59	{"mesh": ["C537286"], "synonyms": []}
A number sign (#) is used with this entry because combined pituitary hormone deficiency-1 (CPHD1) is caused by homozygous or compound heterozygous mutation in the POU1F1 gene (173110) on chromosome 3p11. Description Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH; 139250) and one or more of the other 5 anterior pituitary hormones. Mutations of the POU1F1 gene in the human and Pit1 in the mouse are responsible for pleiotropic deficiencies of GH, prolactin (PRL; 176760), and thyroid-stimulating hormone (TSH; see 188540), while the production of adrenocorticotrophic hormone (ACTH; see 176830), luteinizing hormone (LH; 152780), and follicle-stimulating hormone (FSH; 136530) are preserved (Wu et al., 1998). In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen (Aarskog et al., 1997). Some cases present with severe mental retardation along with short stature (Radovick et al., 1992). ### Genetic Heterogeneity of Combined Pituitary Hormone Deficiency CPHD2 (262600), associated with hypogonadism, is caused by mutation in the PROP1 gene (601538). CPHD3 (221750), which is associated with rigid cervical spine and variable sensorineural deafness, is caused by mutation in the LHX3 gene (600577). CPHD4 (262700) is caused by mutation in the LHX4 gene (602146). CPHD5 (see septooptic dysplasia, 182230) is caused by mutation in the HESX1 gene (601802). CPHD6 (613986) is caused by mutation in the OTX2 gene (600037). Clinical Features Wit et al. (1989) described 2 unrelated Dutch families in which 4 of 10 children presented with total pituitary growth hormone (GH; 139250) and prolactin (PRL; 176760) deficiency and a partial thyrotropin (TSH; see 188540) deficiency. The GH gene was intact in 'family I.' The pituitaries were normal by MRI. All children responded well to GH and L-thyroxine therapy. Baseline plasma somatostatin and its peak response to arginine infusion were elevated in the 2 affected sibs in 'family I,' and they had a milder TSH deficiency than the 2 affected sibs in 'family II;' plasma insulin showed a poor response to arginine infusion. Wit et al. (1989) suggested that this hereditary combination of pituitary deficiencies was due to deficiency of a common positive transcription factor. Tatsumi et al. (1992) reported 2 sisters, born of consanguineous parents, who had cretinism due to deficiency of thyrotropin, growth hormone, and prolactin. Both patients showed typical clinical features of cretinism, such as puffy face and saddle nose, hoarse voice, and myxedema. The younger sister died of aspiration pneumonia 2 months after birth. The parents and 5 brothers were unaffected. Radovick et al. (1992) studied a patient with a deficiency of GH, PRL, and TSH, previously reported by Rogol and Kahn (1976), who had severe mental retardation and short stature. The patient's mother was of normal stature and had normal pituitary hormone levels; other family members were unavailable for study. Okamoto et al. (1994) described a Japanese girl who had prolonged neonatal jaundice, severely retarded postnatal growth, and protruding forehead with retracted nasal bridge. Hormone evaluation revealed complete deficiency of PRL and GH, with decreased TSH. Her serum cortisol level was normal and she had no symptoms associated with adrenal insufficiency. The anterior pituitary was normal in size by MRI. An older brother, who also had severe neonatal jaundice, died of hypoplastic left heart syndrome at 10 days of age; no endocrinologic evaluation or postmortem examination was done. There was also an unaffected older sister. De Zegher et al. (1995) reported a mother-infant pair with CPHD. Growth failure was noted in the mother from early infancy, and she was more than 7 standard deviations below the normal mean at 7 years of age; pulmonary valve stenosis was also noted. She was hypothyroid with a good response to thyroid therapy, and initiation of GH therapy was followed by catch-up growth. Spontaneous puberty occurred at age 15 years and menarche at 17 years. Low prolactin levels were found. A final height of 149.5 cm (-2.1 SD) was reached at age 19 years; 7 molars had not developed. MRI showed hypoplasia of the anterior pituitary; the pituitary stalk and the intrasellar neurohypophysis were normal. She became pregnant at age 29 years; ultrasound examinations after 33 weeks showed fetal femoral growth retardation and polyhydramnios was present in increasing amounts after 35 weeks. The fetus was delivered by cesarean section at 38 weeks. Preoperatively the mother was found to be severely hypothyroid; prolactin concentrations were undetectable in the mother's serum after delivery and lactogenesis failed. At birth, the infant girl was hypotonic with a widely open sagittal suture, depressed nasal bridge, enlarged tongue, and scalp and thoracic edema as well as ascites. Correction of severe neonatal hypotension necessitated prolonged administration of dopamine and/or dobutamine; the ductus arteriosus failed to close despite cyclooxygenase inhibitor therapy, and was surgically transected on day 10. Despite thyroid replacement therapy and recombinant human GH administration, neurologic development of the infant was impaired. At 1 year of age, the infant had a normal size but was hypotonic, had severe strabismus, and presented a 'chaotic behavior,' with short attention span and poor visual and auditory contact. Pellegrini-Bouiller et al. (1996) studied 4 sibs with CPHD, born of consanguineous unaffected parents, who had complete GH deficiency diagnosed in early childhood and later developed hypothyroidism and were found to have undetectable PRL levels. MRI in 1 of the sibs showed a hypoplastic pituitary. Voss and Rosenfeld (1992) reviewed the development and differentiation of the 5 pituitary cell types: galactotropes, gonadotropes, corticotropes, thyrotropes, and somatotropes. As indicated by the mutations in PIT1 described later, combined pituitary hormone deficiency can have either autosomal dominant or autosomal recessive inheritance, depending on the part of the PIT1 molecule affected by the mutation. Some mutations have a dominant-negative effect. Clinical Management Individuals with POU1F1 mutations that cause GH and TSH deficiencies respond to GH and thyroid hormone replacement (Wit et al., 1989). Molecular Genetics Noting that a combined pituitary hormone deficiency (CPHD) in 2 strains of mice, Snell dwarf and dwarf Jackson, was caused by mutation in the Pit1 gene, Tatsumi et al. (1992) analyzed the PIT1 gene (POU1F1; 173110) in a female patient with CPHD and identified homozygosity for a nonsense mutation (R172X; 173110.0001). The mutation was found in heterozygosity in her unaffected consanguineous parents. In a patient with CPHD, previously reported by Rogol and Kahn (1976), Radovick et al. (1992) identified a heterozygous missense mutation in the PIT1 gene (R271W; 173110.0002) that was not found in the unaffected mother. Functional analysis demonstrated that the mutant protein bound DNA normally, but acted as a dominant inhibitor of the action of the gene in the pituitary. In 3 unrelated Japanese children with CPHD, Ohta et al. (1992) identified 2 different missense mutations in heterozygous state in the PIT1 gene (173110.0002 and 173110.0004, respectively) and 1 in homozygous state (173110.0005). Ohta et al. (1992) suggested that mutant PIT1 proteins may act as dominant-negative mutants or recessive mutants depending on the location of the mutation, and as a result, hormonal kinetics and the formation of the anterior pituitary are affected. Pfaffle et al. (1992) analyzed the PIT1 gene in 2 unrelated Dutch families segregating apparently autosomal recessive CPHD, previously reported by Wit et al. (1989), and identified a homozygous missense mutation in the PIT1 gene (A158P; 173110.0003) in affected members of 'family II,' whereas affected members of 'family I' were compound heterozygous for A158P and a maternally inherited deletion of the PIT1 gene. In a Japanese girl with CPHD involving PRL, GH, and TSH, Okamoto et al. (1994) identified heterozygosity for the R271W mutation in the PIT1 gene. Her unaffected father and paternal grandmother and 2 aunts also carried the mutation, as did an older brother who had died at 10 days of age of hypoplastic left heart syndrome. RT-PCR analysis in peripheral lymphocytes revealed monoallelic expression of the normal allele in the father and grandmother and a skewed pattern of biallelic expression in the proband, suggesting epigenetic control of expression of the PIT1 gene. In a mother and infant with CPHD, de Zegher et al. (1995) identified heterozygosity for the R271W mutation in the PIT1 gene. At birth, serum T4 was undetectable in mother and infant, and the newborn presented with a striking delay of respiratory, cardiovascular, neurologic, and bone maturation. De Zegher et al. (1995) concluded that fetomaternal PIT1 deficiency resulted in unmitigated fetal hypothyroidism, unmasking thyroid hormone as a potent endogenous drive of fetal maturation and revealing placental transfer of maternal T4 as a rescue mechanism for infants with congenital hypothyroidism that prevents fetal and neonatal symptoms of thyroid deficiency and safeguards developmental potential. In a patient with combined deficiency of TSH, GH, and PRL, Irie et al. (1995) identified homozygosity for a nonsense mutation in the PIT1 gene (173110.0006); the unaffected parents were heterozygous for the mutation. In 4 sibs with CPHD, born of unaffected consanguineous parents, Pellegrini-Bouiller et al. (1996) identified homozygosity for a missense mutation in the PIT1 gene (F135C; 173110.0007); their healthy mother was heterozygous for the mutation, indicating recessive inheritance. Vallette-Kasic et al. (2001) analyzed the functional effects of the F135C mutation and demonstrated that the mutant had decreased transactivation capacity on the PRL, GH, and PIT1 genes; structural modeling indicated that interaction with other transcription factors might be prevented. Aarskog et al. (1997) reported a Norwegian patient with the R271W mutation and found reports of 9 other cases in different populations, suggesting that codon 271 in exon 6 is a 'hotspot' for PIT1 mutations. Pernasetti et al. (1998) analyzed the PIT1 gene in 3 reportedly unrelated consanguineous Saudi Arabian families in which there was a total of 7 children who were deficient in GH, PRL, and TSH, with an empty sella turcica on CT scan. Homozygosity for a missense mutation (P239S; 173110.0008) was identified in all affected individuals; the unaffected parents were heterozygous for the mutation. Hendriks-Stegeman et al. (2001) reported an Indian boy who was found to be hypothyroid on neonatal screening after arrival in The Netherlands at 4 months of age. He showed typical signs of congenital hypothyroidism, including low nasal bridge, macroglossia, facial myxedema, and wide open fontanels, and also exhibited generalized hypotonia, slight peripheral myxedema, constipation, and hypothermia. He was subsequently found to have undetectable PRL and GH and a hypoplastic anterior pituitary by MRI, and analysis of the POU1F1 (formerly 'PIT1') gene revealed compound heterozygosity for a 1-bp deletion and a missense mutation (173110.0009 and 173110.0010, respectively). The phenotypically normal mother, who had a normal hormonal profile, was heterozygous for the missense mutation, indicating that it was unlikely to have a dominant-negative effect; the unaffected father was heterozygous for the deletion. Hendriks-Stegeman et al. (2001) stated that the majority of patients with a POU1F1 defect present with growth failure, whereas less than half present with hypothyroidism as the first clinical manifestation. Hashimoto et al. (2003) studied a 15-year-old Italian girl with a history of neonatal jaundice and failure to thrive, who had presented at 2 months of age with signs of hypothyroidism, including large tongue, myxedema, umbilical hernia, jaundice, and widely open anterior and posterior fontanels. TRH stimulation revealed undetectable basal and stimulated TSH and PRL levels, whereas cortisol and ACTH levels were normal; peak GH responses to arginine, glucagon, and GHRH were extremely low. CT scan revealed hypoplasia of the anterior pituitary gland, which was confirmed by MRI at age 7 years. Analysis of the POU1F1 gene revealed homozygosity for a nonsense mutation (K145X; 173110.0011). Her parents, who were heterozygous for K145X, both showed evidence of mild endocrine dysfunction, with low normal TSH and PRL levels; in addition, the mother had hypogalactorrhea and had difficulties with breast feeding. Hashimoto et al. (2003) concluded that 2 normal copies of the POU1F1 gene appear necessary for full POU1F1 gene function. Turton et al. (2005) screened the POU1F1 gene in 80 patients with CPHD, 48 with isolated GH deficiency, and 1 with isolated TSH deficiency, and identified mutations in 10 (7.8%) of the 129 patients (see 173110.0002 and 173110.0012-173110.0014). All but 1 of the mutation-positive individuals had profound GH, TSH, and PRL deficiency: at age 20.5 years, 1 patient continued to have a free T4 in the normal range without hormone replacement therapy. Of 8 patients in whom MRI scans had been performed, 7 had a hypoplastic anterior pituitary and 1 had a normal-appearing pituitary gland. Citing the variable age of onset of TSH deficiency (9 years to 15 years) in the sibs described by Pellegrini-Bouiller et al. (1996), Turton et al. (2005) suggested that the phenotype associated with POU1F1 mutations may be variable, with occasional preservation of TSH secretion. Dattani (2005) reviewed the genetic causes and phenotypic features of IGHD and combined pituitary hormone deficiency (CPHD). The author noted that hormone abnormalities may evolve over time, necessitating frequent reevaluation, and that establishing the genotype can aid in management. In a 20-year-old Japanese man who was diagnosed with CPHD in infancy, with undetectable serum basal levels of GH, PRL, and TSH and a hypoplastic anterior pituitary on MRI, Miyata et al. (2006) identified homozygosity for a novel missense mutation in the POU1F1 gene (S179R; 173110.0015). His mother was heterozygous for the S179R allele; his father did not participate in the study. Heterogeneity Sloop et al. (2000) studied 7 children with CPHD and 2 with isolated GH deficiency, all of whom displayed abnormal pituitary gland development with ectopic posterior lobe location and frequently hypoplastic anterior lobes by magnetic resonance imaging. Noting that embryonic development of the pituitary requires the coordinated expression of specific transcription factors, and that mutations of the PIT1 and PROP1 transcription factors are responsible for CPHD in some patients with normally positioned posterior pituitaries, the authors hypothesized that mutations in 1 or both of the 2 human LHX3 isoforms might be responsible for posterior pituitary ectopia associated with anterior pituitary hypopituitarism. Comprehensive molecular analysis of the LHX3 isoforms was performed to test this hypothesis, but no loss-of-function mutations in the LHX3 gene were detected. In addition, analysis of PROP1 did not reveal mutations that might cause this phenotype. The authors concluded that the abnormal processes leading to the development of CPHD or GH deficiency associated with posterior pituitary ectopia are not a result of aberrant LHX3 or PROP1 function, but may be caused by defects at other gene loci. INHERITANCE \- Autosomal dominant \- Autosomal recessive GROWTH Height \- Short stature (if untreated) Other \- Severe growth retardation in infancy HEAD & NECK Head \- Prominent forehead Face \- Midface hypoplasia Eyes \- Deep-set eyes Nose \- Depressed nasal bridge \- Short nose with anteverted nostrils Mouth \- Macroglossia (untreated hypothyroidism) SKELETAL Skull \- Open sutures (untreated hypothyroidism) \- Open fontanelles (untreated hypothyroidism) SKIN, NAILS, & HAIR Skin \- Jaundice, neonatal \- Myxedema (untreated hypothyroidism) MUSCLE, SOFT TISSUES \- Hypotonia (untreated hypothyroidism) NEUROLOGIC Central Nervous System \- Hypoplasia of anterior or entire pituitary gland (frequent) \- Mental retardation (untreated hypothyroidism) ENDOCRINE FEATURES \- Hypothyroidism LABORATORY ABNORMALITIES \- Low or absent growth hormone (GH) \- Low or absent thyroid-stimulating hormone (TSH) \- Low or absent prolactin (PL) MOLECULAR BASIS \- Caused by mutation in the POU domain, class 1, transcription factor 1 gene (POU1F1, 173110.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	PITUITARY HORMONE DEFICIENCY, COMBINED, 1	c2751608	30,391	omim	https://www.omim.org/entry/613038	2019-09-22T15:59:54	{"doid": ["9406"], "mesh": ["C567803"], "omim": ["613038"], "orphanet": ["95494"], "synonyms": ["Familial congenital hypopituitarism", "Multiple pituitary hormone deficiencies, genetic forms"]}
Thiopurine S-methyltransferase deficiency is an autosomal recessive disorder that affects the body's ability to metabolize thiopurine drugs. Thiopurine S-methyltransferase (TPMT) is an enzyme that the body uses to break down thiopurine drugs. Thiopurine S-methyltransferase deficiency patients have a mutation in either one or both copies of the TPMT gene that causes reduced enzyme activity and difficulties breaking down thiopurine drugs. Affected individuals are at a high risk of experiencing bone marrow damage if they take thiopurine drugs. Many patients recover from the bone marrow damage once thiopurine drug use is stopped. However when the bone marrow is damaged, infections can cause serious health problems and may be life-threatening. To reduce the risk of bone marrow damage, thiopurine therapy should be lowered based on how many mutations a patient has in the TPMT gene. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Thiopurine S methyltranferase deficiency	c0342801	30,392	gard	https://rarediseases.info.nih.gov/diseases/5173/thiopurine-s-methyltranferase-deficiency	2021-01-18T17:57:22	{"mesh": ["C536512"], "omim": ["610460"], "orphanet": ["3315"], "synonyms": ["TPMT deficiency", "Thiopurines, poor metabolism of", "Thiopurine methyltransferase deficiency", "6-mercaptopurine sensitivity"]}
Queen bee syndrome was first defined by G.L. Staines, T.E. Jayaratne, and C. Tavris in 1973.[1] It describes a woman in a position of authority who views or treats subordinates more critically if they are female. This phenomenon has been documented by several studies.[2][3] In another study, scientists from the University of Toronto speculated that the queen bee syndrome may be the reason that women find it more stressful to work for female managers; no difference was found in stress levels for male workers.[4] An alternate, though closely related, definition describes a queen bee as one who has succeeded in her career, but refuses to help other women do the same.[5] ## Contents * 1 In adolescence * 2 Notable cases * 3 In the workplace * 4 Criticisms of the theory * 5 See also * 6 References * 7 Further reading * 8 External links ## In adolescence[edit] In recent years, research has shown that adolescent girls form (often small) groups called cliques, which are often created based on a shared characteristic or quality of the members such as attractiveness or popularity. Association with such a group is often wanted by those who are part of the larger, all encompassing group, such as a class or school. It is the association with these groups that brings an individual similar treatment.[6] ## Notable cases[edit] A popular example of a movie based on girls with queen bee syndrome is the 2004 film, Mean Girls. The authorized biographer of Margaret Thatcher, Charles Moore, stated in an interview his belief that the former British prime minister had herself suffered from the syndrome.[7] ## In the workplace[edit] Recent research has postulated that queen bee syndrome may be a product of certain cultural influences,[8][9] especially those related to the modern workplace.[10][11] Researchers have hypothesized[9] that queen bee behavior may be developed by women who have achieved high workplace positions within their respective fields as a way to defend against any gender bias found in their cultures. By opposing attempts of subordinates of their own sex to advance in career paths, women displaying queen bee behavior try to fit in with their male counterparts by adhering to the cultural stigmas placed on gender in the workplace. Distancing themselves from female subordinates can allow for the opportunity to show more masculine qualities, stereotypically seen as more culturally valuable and professional. By showing these supposedly important masculine qualities, women displaying queen bee behavior seek to further legitimize their right to be in important professional positions as well as attaining job security by showing commitment to their professional roles.[8][9] ## Criticisms of the theory[edit] Recent research, that uses a robust causal identification mechanism (i.e., regression discontinuity design), strongly contests the existence of the queen bee phenomenon;[12] the results of this study suggest that previous research was biased either by eliciting confirming cases (as is often done in qualitative research) or that observational data based on questionnaire measures was biased because of endogeneity issues. There are also doubts as to whether Queen Bee Syndrome is still in effect in academia.[13] Queen Bee Syndrome was first widely discussed 15 years ago so it seems fair to question whether it is still an issue that women face in the workplace and academia. ## See also[edit] * Feminism * Narcissistic leadership * Queen bee * Queen bee (sociology) * Toxic leader * Workplace bullying ## References[edit] 1. ^ Francine D. Blau and Jed DeVaro (2007). "New Evidence on Gender Differences in Promotion Rates: An Empirical Analysis of a Sample of New Hires". Cornell University ILR School. p. 16. Archived from the original on 2011-07-18. Retrieved 26 May 2010. 2. ^ Roger Dobson and Will Iredale (31 December 2006). "Office queen bees hold back women's careers". The Sunday Times. Archived from the original on 2011-06-04. Retrieved 2010-05-26. 3. ^ Ellemers, N.; van den Heuvel, H. (2004). "The underrepresentation of women in science: differential commitment or the queen bee syndrome?" (PDF). British Journal of Social Psychology. 43 (September): 313–338. doi:10.1348/0144666042037999. PMID 15479533. 4. ^ Chris Irvine (23 September 2008). "Women find working for female bosses more stressful". telegraph.co.uk. Archived from the original on 2018-07-13. Retrieved 2018-04-03. 5. ^ Judy Klemensrud (13 April 1981). "WOMEN IN MEDICINE FIND A NEED FOR SUPPORT". New York Times. 6. ^ Closson, L. M. (2009). Aggressive and Prosocial Behaviors Within Early Adolescent Friendship Cliques 7. ^ Somerset, Guy (6 June 2013). "Charles Moore interview". New Zealand Listener. Archived from the original on 2017-02-27. Retrieved 26 February 2017. "Partly there was a genuine problem about the talent within the Tory Party at that time – it was not great. But I think also she did suffer, as her critics say, from what they call the queen bee syndrome: she thought, 'I can do it, why can't others? It's not for me to fish around to find the right women, I'm just going to get the nearest good person to hand' ... All her comments, even as a young woman about other women in letters to [her sister] Muriel, tend to be competitive and sometimes quite critical. She didn't have much personal solidarity with women if they were also ambitious. She was very close to some women who were in subsidiary positions, such as her diary secretaries – she's extremely fond of them and very nice to them - but I don't think you'll find much closeness to any female equal." 8. ^ a b Derks, Belle; Ellemers, Naomi; Van Laar, Colette; De Groot, Kim (2011). "Do sexist organizational cultures create the Queen Bee?". British Journal of Social Psychology. 50 (3): 519–535. doi:10.1348/014466610X525280. PMID 21884548. 9. ^ a b c Derks, Belle; Van Laar, Colette; Ellemers, Naomi; De Groot, Kim (2011). "Gender-Bias Primes Elicit Queen-Bee Responses Among Senior Policewomen". Psychological Science (Submitted manuscript). 22 (10): 1243–1249. doi:10.1177/0956797611417258. PMID 21873568. 10. ^ Cooper, Virginia W. (November 1997). "Homophily or the Queen Bee Syndrome: Female Evaluation of Female Leadership". Small Group Research. 28 (4): 483–499. doi:10.1177/1046496497284001. ISSN 1046-4964. 11. ^ Sterk, Naomi; Meeussen, Loes; Van Laar, Colette (2018-09-20). "Perpetuating Inequality: Junior Women Do Not See Queen Bee Behavior as Negative but Are Nonetheless Negatively Affected by It". Frontiers in Psychology. 9: 1690. doi:10.3389/fpsyg.2018.01690. ISSN 1664-1078. PMC 6159757. PMID 30294289. 12. ^ Arvate, Paulo Roberto; Galilea, Gisele Walczak; Todescat, Isabela (2018-10-01). "The queen bee: A myth? The effect of top-level female leadership on subordinate females". The Leadership Quarterly. 29 (5): 533–548. doi:10.1016/j.leaqua.2018.03.002. ISSN 1048-9843. 13. ^ Faniko, Klea; Ellemers, Naomi; Derks, Belle (2020-07-22). "The Queen Bee phenomenon in Academia 15 years after: Does it still exist, and if so, why?". British Journal of Social Psychology. doi:10.1111/bjso.12408. ISSN 0144-6665. ## Further reading[edit] * Maume DJ Meet the new boss…same as the old boss? Female supervisors and subordinate career prospects Social Science Research Volume 40, Issue 1, January 2011, Pages 287-298 ## External links[edit] * Office queen bees hold back women’s careers * v * t * e Aspects of workplaces Topics * Absenteeism * Abusive supervision * Aggression * Bullying * Conflict * Control freak * Counterproductive behaviour * Coworker backstabbing * Culture of fear * Cyber-aggression * Democracy * Deviance * Discrimination * Diversity * Divide and rule * Emotions * Employee engagement * Employee monitoring * Employee morale * Employee silence * Employee surveys * Empowerment * Evaluation * Feminisation * Fit in or fuck off * Friendship * Gender inequality * Gossip * Happiness * Harassment * Health surveillance * Humor * Incivility * Intervention * Jargon * Kick the cat * Kiss up kick down * Listening * Machiavellianism * Micromanagement * Mobbing * Narcissism * Office politics * Performance appraisal * Personality clash * Phobia * Positive psychology * Privacy * Probation * Profanity * Psychopathy * Queen bee syndrome * Rat race * Relationships * Revenge * Role conflict * Romance * Sabotage * Safety and health * Spirituality * Staff turnover * Strategy * Stress * Toxic workplace * Toxic leader * Training * Undermining * Violence * Wellness * Work–family conflict * Workload See also * Corporation * Employment * Factory * Job * Office * Organization * Whistleblower Templates * Aspects of corporations * Aspects of jobs * Aspects of occupations * Aspects of organizations * Employment [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Queen bee syndrome	None	30,393	wikipedia	https://en.wikipedia.org/wiki/Queen_bee_syndrome	2021-01-18T18:51:08	{"wikidata": ["Q7270562"]}
Parental alienation syndrome (PAS) is a term introduced by child psychiatrist Richard Gardner in 1985[1] to describe a distinctive suite of behaviors in children that includes showing extreme but unwarranted fear, disrespect or hostility towards a parent.[2] Gardner believed that a set of behaviors that he observed in some families involved in child custody litigation could be used to diagnose psychological manipulation or undue influence of a child by a parent, typically by the other parent who may be attempting to prevent an ongoing relationship between a child and other family members after family separation or divorce.[3] Use of the term "syndrome" has not been accepted by either the medical or legal communities and Gardner's research has been broadly criticized by legal and mental health scholars for lacking scientific validity and reliability.[4][5][6][7] While remaining controversial, the derivative term parental alienation is sometimes used to describe a similar family dynamic.[8][9][10][11] ## Contents * 1 Initial description * 2 Characteristics * 3 Reception * 3.1 Exclusion from the DSM * 3.2 Scientific status * 3.3 Clinical status * 4 In courts * 4.1 Canada * 4.2 United Kingdom * 4.3 United States * 4.3.1 Richard Gardner's claims * 4.3.2 Case law * 5 See also * 6 References * 7 External links ## Initial description[edit] Parental alienation syndrome is a term coined by child psychiatrist Richard A. Gardner drawing upon his clinical experiences in the early 1980s.[2][3] The concept of one parent attempting to separate their child from the other parent as punishment or part of a divorce have been described since at least the 1940s,[8][11] but Gardner was the first to define a specific syndrome. In his 1985 paper,[2] he defined PAS as > ...a disorder that arises primarily in the context of child-custody disputes. Its primary manifestation is the child's campaign of denigration against the parent, a campaign that has no justification. The disorder results from the combination of indoctrinations by the alienating parent and the child's own contributions to the vilification of the alienated parent.[3] He also stated that the indoctrination may be deliberate or unconscious on the part of the alienating parent.[12][13] Gardner initially believed that parents (usually mothers) made false accusations of child abuse and sexual abuse against the other parent (usually fathers) in order to prevent further contact between them.[14][15] While Gardner initially described the mother as the alienator in 90% of PAS cases, he later stated both parents were equally likely to alienate.[16][17][18] He also later stated that in his experience accusations of sexual abuse were not present in the vast majority of cases of PAS.[19] ## Characteristics[edit] Gardner described PAS as a preoccupation by the child with criticism and deprecation of a parent.[20] Gardner stated that PAS occurs when, in the context of child custody disputes, one parent deliberately or unconsciously attempts to alienate a child from the other parent.[21] According to Gardner, PAS is characterized by a cluster of eight symptoms that appear in the child. These include a campaign of denigration and hatred against the targeted parent; weak, absurd, or frivolous rationalizations for this deprecation and hatred; lack of the usual ambivalence about the targeted parent; strong assertions that the decision to reject the parent is theirs alone (the "independent-thinker phenomenon"); reflexive support of the favored parent in the conflict; lack of guilt over the treatment of the alienated parent; use of borrowed scenarios and phrases from the alienating parent; and the denigration not just of the targeted parent but also to that parent's extended family and friends.[13][17][22] Despite frequent citations of these factors in scientific literature, the value ascribed to these factors has not been explored with professionals in the field.[23] Gardner and others divided PAS into mild, moderate and severe levels. The number and severity of the eight symptoms included in the syndrome were hypothesized to increase through the different levels. Recommendations for management differed according to the severity level of the child's symptoms. While a diagnosis of PAS is made based on the child's symptoms, Gardner stated that any change in custody should be based primarily on the symptom level of the alienating parent.[24] In mild cases, it was alleged that there was some parental programming against the targeted parent, but little or no disruption of visitation, and Gardner did not recommend court-ordered visitation. In moderate cases, it was alleged that more parental programming occurred resulting in greater resistance to visits with the targeted parent. Gardner recommended that primary custody remain with the programming parent if the brainwashing was expected to be discontinued, but if not, that custody should be transferred to the targeted parent. In addition, therapy with the child to stop alienation and remediate the damaged relationship with the targeted parent was recommended. In severe cases, in which children were found to display most or all of the eight symptoms and refused to visit the targeted parent, possibly threatening to run away or engage in self-harm if forced to visit the other parent, Gardner recommended that the child be removed from the alienating parent's home into a transition home before moving into the home of the targeted parent. In addition to modification of custody, Gardner recommended therapy for the child.[22][24] Gardner's proposed intervention for moderate and severe PAS, which include court-ordered transfer to the alienated parent, fines, house arrest, and incarceration, have been critiqued for their punitive nature towards the alienating parent and alienated child, and for the risk of abuse of power and violation of their civil rights.[25][26] With time, Gardner revised his views and expressed less support for the most aggressive management strategies.[25] ## Reception[edit] Gardner's original formulation, which labeled mothers almost exclusively as the alienating parent, was endorsed by fathers' rights groups, as it allowed fathers to explain the reluctance of their children to visit them and assign blame to their former wives.[25][27] In contrast, women's groups criticized the syndrome, concerned that it permitted abusers to claim that allegations of abuse by mother or child were reflective of brainwashing.[25] Gardner himself emphasized that PAS only applied in situations where there was no actual abuse or neglect had not occurred,[7][28] but by 1998, noted an increase in the awareness of PAS had led to an increase in its misapplication as an exculpatory legal maneuver.[29] PAS has been cited in high-conflict divorce and child custody cases, particularly as a defense against accusations of domestic violence or sexual abuse.[5][22] The status of the syndrome, and thus its admissibility in the testimony of experts, has been the subject of dispute, with challenges raised about its acceptance by professionals in the field, whether it follows a scientific methodology that is testable, whether it has been tested and has a known error rate, and the extent to which the theory has been published and peer-reviewed.[22] PAS has not been accepted by experts in psychology, child advocacy or the study of child abuse[6] or legal scholars.[7] PAS has been extensively criticized by members of the legal and mental health community, who state that PAS should not be admissible in child custody hearings based on both science and law.[5][6][7][22][30] No professional association has recognized PAS as a relevant medical syndrome or mental disorder. PAS is not listed in the International Statistical Classification of Diseases and Related Health Problems of the WHO. It is not recognized by the American Medical Association or the American Psychiatric Association.[7][31][32][33] The American Psychological Association declined to give a position on PAS, but raised concerns over its lack of supporting data and how the term is used.[34] The APA's 1996 Presidential Task Force on Violence and the Family expressed concern that custody evaluators use PAS as a means of giving custody to fathers despite a history of violence, a concern shared by other commentators.[5][35][36] The United States National Council of Juvenile and Family Court Judges rejected PAS, recommending it not be used for the consideration of child-custody issues.[27] The admissibility of PAS was rejected by an expert review panel and the Court of Appeal of England and Wales in the United Kingdom[37][38] and Canada's Department of Justice recommends against its use. PAS has been mentioned in some family court cases in the United States. Gardner portrayed PAS as well accepted by the judiciary and having set a variety of precedents, but legal analysis of the actual cases indicates that as of 2006 this claim was incorrect. ### Exclusion from the DSM[edit] PAS is not included in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).[7][31][32][33] Gardner and others lobbied for its inclusion in the DSM-V revision.[39][40] In 2001, Gardner argued that when the DSM-IV was released, there was insufficient research to include PAS, but since then, there have been enough scientific articles and attention to PAS that it merited being taken seriously.[39] A survey of American custody evaluators, published in 2007, found that half of the respondents disagreed with its inclusion, while a third thought it should be.[13] A related formulation, named parental alienation disorder, has been proposed, suggesting that inclusion of PAS in the DSM-5 would promote research and appropriate treatment, as well as reduce misuse of a valid and reliable construct.[8] In December 2012, the American Psychiatric Association announced that PAS would not be included in the DSM-V revision.[41] However, there are now diagnoses included in DSM-V that reflect the impact of parental behavior upon children, in particular parent-child relational problem and child affected by parental relationship distress.[42] The key distinction is that the diagnoses listed in the DSM relate to the mental health of the diagnosed individual, as opposed to attempting to describe a disorder of the relationship between different people, whether parent-child or parent-parent.[43] ### Scientific status[edit] Gardner's formulation of PAS is critiqued as lacking a scientific basis,[44][45][46] and as a hypothesis whose proponents have failed to meet the scientific burden of proof to merit acceptance.[7][44][46][47][48] The first publications about PAS were self-published and not peer reviewed,[11] and though subsequent articles have been published in peer reviewed journals, most have consisted of anecdotal evidence in the form of case studies;[20][49] in addition, the limited research into PAS has lacked evidence of its validity and reliability.[5][6] The lack of objective research and replication, falsifiability, and independent publication has led to claims that PAS is pseudoscience or junk science.[4][44][45] Proponents of PAS concur that large scale systematic controlled studies into PAS's validity and reliability are required,[11][13][50] supplementing a single small study in 2004 which suggested practitioners could come to a consensus based on written reports.[30] The theoretical foundation of PAS has been described as incomplete, simplistic and erroneous for ignoring the multiple factors (including the behaviors of the child, parents and other family members) that may contribute to parental alienation, family dysfunction and a breakdown in attachment between a parent and a child.[11][16][35][20][51] In this view, PAS confuses a child's developmental reaction to a divorce with psychosis, vastly overstates the number of false allegations of child sexual abuse, ignores the scientific literature suggesting most allegations of child sexual abuse are well founded and thus well-meaning efforts to protect a child from an abusive parent, exaggerates the damaging effects of parental alienation on children and proposes an unsupported and endangering remedy for PAS.[5][30] Concern has been expressed that PAS lacks adequate scientific support to be considered a syndrome and that Gardner has promoted PAS as a syndrome based on a vague clustering of behaviors.[11][32] Despite concerns about the validity of testimony regarding PAS, it has been inappropriately viewed as reliable by family court judges.[7] Proponents of PAS and others agree that using the designation of syndrome may be inappropriate as it implies more scientific legitimacy than it currently deserves.[20][25][50] While PAS is not accepted as a syndrome, parental alienation is a somewhat less controversial dynamic that has also appeared in the mental health and legal literature.[23][25] Since Gardner proposed PAS, other researchers in the field have suggested focusing less on diagnosing a syndrome and more on what has been described as the "alienated child," and the dynamics of the situation that have contributed to the alienation.[16][25] ### Clinical status[edit] PAS has been criticized for making clinical work with children who are alienated more confusing[11] and for labeling children with a mental diagnosis who may react angrily to their parents' separation or divorce.[52] Gardner's analysis has been criticized for inappropriately assigning all responsibility of the child's behavior to one parent when the child's behavior is oftentimes, but not always, the result of a dynamic in which both parents and the child play a role.[26][51] Gardner disagreed with criticism of PAS as overly simplistic, stating that while there are a wide variety of causes on why a child may become alienated from a parent, the primary etiological factor in cases of PAS is the brainwashing parent, and that otherwise, there is no PAS.[29] Gardner also stated that those initially critical of PAS for being a caricature were not directly involved with families in custody disputes and that criticisms of this nature faded by the late 1980s because the disorder was widespread.[3] However, no scientific study has yet demonstrated that the elements of PAS are unique to alleged parental alienation such that they are useful for diagnosis.[53] PAS has been criticized by for being sexist, being used by fathers to marginalize legitimate fears and concerns about abuse, and women's groups and others oppose the legitimacy of PAS as a danger to children.[35] After his initial publications, Gardner revised his theory to make fathers and mothers equally likely to alienate or be indoctrinators and disagreed that recognition of PAS is sexist. Gardner later indicated he believed men were equally likely to be PAS indoctrinators.[29] Studies of children and adults labelled as suffering from PAS have suggested that mothers were more likely than fathers to be the alienator.[13] ## In courts[edit] ### Canada[edit] Early Canadian court cases accepted expert opinions about PAS, used the term "syndrome" and concurred with Gardner's theory that only one parent was fully responsible for it. Gardner testified in one case (Fortin v. Major, 1996) but the court did not accept his opinion, concluding that the child was not alienated based on the evaluation of a court-appointed expert who, unlike Gardner, had met with the family members.[25] More recent cases, while accepting the concept of alienation, have noted the lack of recognition in the DSM-IV, and have generally avoided "syndrome" terminology, emphasizing that changes in custody are stressful for the child and should only occur in the most severe cases.[25] A 2006 research report by the Canadian Department of Justice described PAS as "empirically unsupported" and favored a different framework for dealing with issues of alienation that has more research support.[54] Decisions about possible parental alienation are considered a legal decision, to be determined by the judge based on the facts of the case, rather than a diagnosis made by a mental health professional. There is recognition that rejection of a parent is a complex issue, and that a distinction must be made between pathological alienation and reasonable estrangement.[25] ### United Kingdom[edit] In the United Kingdom, the admissibility concerning the evaluation of PAS was rejected both in an expert review,[55] and by the Court of Appeal.[37][38] ### United States[edit] On occasion, PAS has been cited as part of the child custody determination process in the United States,[37] and some courts have awarded sole custody to fathers based upon findings of PAS.[7] In some cases a custody court's acceptance of allegations of parental alienation have resulted in children being placed in the custody of an abusive parent.[56][57][58] The admissibility of testimony alleging PAS has been challenged under the Frye test and Daubert standard, to evaluate if it has sufficient scientific basis and acceptance within the scientific community.[7][59] #### Richard Gardner's claims[edit] Although Gardner claimed that PAS was generally accepted by the scholarly community and had passed the Frye test in two states,[29] a 2006 analysis of court cases involving PAS and cited by Gardner concluded that these decisions did not set legal precedent, that PAS is viewed negatively in most legal scholarship, and that Gardner's writings do not support the existence of PAS. Of sixty-four precedent-bearing cases reviewed at that time, only two decisions, both in New York State and both in criminal courts actually set precedents. Both held that the theory of PAS was inadmissible. One of the cases, subsequently upheld on appeal, found that PAS failed the Frye test as the appropriate professional community did not generally accept. At the time, Gardner listed fifty cases on his website that he claimed set precedents that made PAS admissible. Upon review it was determined that none of the cases set precedents for the admissibility of PAS. forty-six set no precedents or did not discuss admissibility and the remaining four were problematic. In the first the trial court found that PAS passed the Frye test, but that finding was not reviewed on appeal so as to become precedential as the trial court "[threw] out the words 'parental alienation syndrome'" and focused instead on the "willingness and ability of each parent to facilitate and encourage a close and continuing relationship between the parents and the child" under the state's child custody best interest factors.[60] In the second case, the appellate court did not discuss PAS. The third case specifically chose not to discuss the admissibility of PAS and the fourth made no decision on PAS.[7] #### Case law[edit] In one New York case, Matter of Robert Coull v. Pamela Rottman, 15 N.Y.S.3d 834, 131 AD 3d 964 (2015), child support was suspended based upon a trial court's finding of a parent's alienating behaviors. The court found that the father was prevented from seeing his son by the child's mother through a "pattern of alienation", and child support was suspended on that basis.[61][62] The decision was not based upon a psychological diagnosis, but was instead based upon a pattern of alienation actions and behaviors by the mother and her conduct during court proceedings.[61] A focus on parental behavior allows a court to base its decision "upon accepted psychological concepts and diagnoses... without mention of the controversial and potentially inflammatory concept of PAS"[63] New York has followed this approach, with a court explaining,[64] > PAS, essentially dismissed as "junk science", is not generally accepted in the scientific community, as it is not an approved term or diagnosis in the field of psychiatry and no New York court has allowed the admission of testimony concerning PAS.... However, New York Courts have embraced parental alienation as a concept. In recognizing that parental alienation can exist, some courts have loosely defined it as a custodial parent's active interference with or deliberate and unjustified frustration of the non-custodial parents' reasonable right of access to the child. That approach treats parental alienation as a descriptive concept, allowing a court to consider parental behavior without the need to determine whether parental alienation is a valid psychological construct.[65] ## See also[edit] * Child abuse * Family estrangement * Gatekeeper parent * Parental alienation * Parentification * Flying monkeys (popular psychology) * Richard A. Gardner * Triangulation (psychology) ## References[edit] 1. ^ Clemente, Miguel; Padilla-Racero, Dolores (April 2015). "Are children susceptible to manipulation? The best interest of children and their testimony". Children and Youth Services Review. 51: 101–107. doi:10.1016/j.childyouth.2015.02.003. 2. ^ a b c Gardner, Richard (Summer 1985). "Recent Trends in Divorce and Custody Litigation" (PDF). Academy Forum. 29 (2): 3–7. 3. ^ a b c d Gardner, RA (2001). "Parental Alienation Syndrome (PAS): Sixteen Years Later". Academy Forum. 45 (1): 10–12. Retrieved 2009-03-31. 4. ^ a b Faller, KC (1998). "The parental alienation syndrome: What is it and what data support it?" (PDF). Child Maltreatment. 3 (2): 100–115. doi:10.1177/1077559598003002005. 5. ^ a b c d e f Bruch, CS (2001). "Parental Alienation Syndrome and Parental Alienation: Getting It Wrong in Child Custody Cases" (PDF). Family Law Quarterly. 35 (527): 527–552. 6. ^ a b c d Wood, CL (1994). "The parental alienation syndrome: a dangerous aura of reliability". Loyola of Los Angeles Law Review. 29: 1367–1415. Retrieved 2008-04-12. 7. ^ a b c d e f g h i j k Hoult, JA (2006). "The Evidentiary Admissibility of Parental Alienation Syndrome: Science, Law, and Policy". Children's Legal Rights Journal. 26 (1). SSRN 910267. 8. ^ a b c Bernet, W (2008). "Parental Alienation Disorder and DSM-V". The American Journal of Family Therapy. 36 (5): 349–366. doi:10.1080/01926180802405513. 9. ^ Bala, N; Hunt, S; McCarney, C (2010). "Parental alienation: Canadian court cases 1989-2008". Family Court Review. 48 (1): 164–179. doi:10.1111/j.1744-1617.2009.01296.x. 10. ^ Rohrbaugh, Joanna Bunker (2008). A comprehensive guide to child custody evaluations: mental health and legal perspectives. Berlin: Springer. pp. 399–438. ISBN 978-0-387-71893-4. 11. ^ a b c d e f g Warshak, RA (2001). "Current controversies regarding parental alienation syndrome" (PDF). American Journal of Forensic Psychology. 19 (3): 29–59. Archived from the original (PDF) on 2007-08-29. 12. ^ Gardner, Richard (2004). "Commentary on Kelly and Johnston's The Alienated Child: A Reformulation of Parental Alienation Syndrome" (PDF). Family Court Review. 42 (4): 611–21. doi:10.1177/1531244504268711. 13. ^ a b c d e Baker, AJL (2007). "Knowledge and Attitudes About the Parental Alienation Syndrome: A Survey of Custody Evaluators". American Journal of Family Therapy. 35 (1): 1–19. doi:10.1080/01926180600698368. 14. ^ Caplan, PJ (2004). "What is it that's being called Parental Alienation Syndrome". In Caplan PJ; Cosgrove L (eds.). Bias in psychiatric diagnosis. Rowman & Littlefield. pp. 62. ISBN 9780765700018. 15. ^ Brown, T; Renata A (2007). Child Abuse and Family Law: Understanding the Issues Facing Human Service and Legal Professionals. Allen & Unwin. pp. 11–12. ISBN 9781865087313. 16. ^ a b c Jaffe, PG; Lemon NKD; Poisson SE (2002). Child Custody & Domestic Violence. SAGE Publications. pp. 52–54. ISBN 9780761918264. 17. ^ a b Gardner, RA (2002). "Denial of the Parental Alienation Syndrome Also Harms Women". American Journal of Family Therapy. 30 (3): 191–202. doi:10.1080/019261802753577520. 18. ^ Baker AJL (2007). Adult children of parental alienation syndrome: breaking the ties that bind. New York: W. W. Norton & Company. ISBN 978-0-393-70519-5. 19. ^ Dallam, SJ (1999). "The Parental Alienation Syndrome: Is It Scientific?". In St. Charles E; Crook L (eds.). Expose: The failure of family courts to protect children from abuse in custody disputes. Our Children Our Children Charitable Foundation. 20. ^ a b c d Ackerman, Ph.D, Marc J. (2002). Clinician's Guide to Child Custody Evaluations. John Wiley and Sons. pp. 73–82. ISBN 9780471150916. 21. ^ Jaffe, Peter G.; Lemon, Nancy K. D.; Poisson, Samantha E. (2002). Child Custody & Domestic Violence. SAGE Publications. pp. 52–54. ISBN 9780761918264. 22. ^ a b c d e Walker, LEA; Brantley KL; Rigsbee JA (2004). "A Critical Analysis of Parental Alienation Syndrome and Its Admissibility in the Family Court". Journal of Child Custody. 1 (2): 47–74. doi:10.1300/J190v01n02_03. 23. ^ a b Bow, JN; Gould JW; Flens JR (2009). "Examining Parental Alienation in Child Custody Cases: A Survey of Mental Health and Legal Professionals". The American Journal of Family Therapy. 37 (2): 127–145. doi:10.1080/01926180801960658. 24. ^ a b Gardner, Richard A. (2006). "Introduction". In Gardner, Richard A.; Sauber, S. Richard; Lorandos, Demosthenes (eds.). The International Handbook of Parental Alienation Syndrome: Conceptual, Clinical And Legal Considerations. Charles C. Thomas. pp. 5–11. ISBN 978-0398076474. 25. ^ a b c d e f g h i j Bala, Nicholas; Fidler, Barbara-Jo; Goldberg, Dan; Houston, Claire (2007). "Alienated Children and Parental Separation: Legal Responses in Canada's Family Courts". Queen's Law Journal. 38: 79–138. 26. ^ a b Johnston, JR; Kelly JB (2004). "Rejoinder to Gardner's Commentary on Kelly and Johnston's 'The Alienated Child: A Reformulation of Parental Alienation Syndrome'". Family Court Review. 42 (4): 622–628. doi:10.1111/j.174-1617.2004.tb01328.x. Archived from the original on 2013-01-05. 27. ^ a b Ottman, A; Lee R (2008). "Fathers' rights movement". In Edleson JL; Renzetti, CM (eds.). Encyclopedia of Interpersonal Violence. SAGE Publications. pp. 252. ISBN 978-1412918008. 28. ^ Gardner, RA (1998). "Recommendations for Dealing with Parents who Induce a Parental Alienation Syndrome in their Children". Journal of Divorce & Remarriage. 28 (3/4): 1–21. doi:10.1300/J087v28n03_01. 29. ^ a b c d Gardner, Richard (2004). "Commentary on Kelly and Johnston's The Alienated Child: A Reformulation of Parental Alienation Syndrome" (PDF). Family Court Review. 42 (4): 611–21. doi:10.1177/1531244504268711. 30. ^ a b c Drozd, L (2009). "Rejection in cases of abuse or alienation in divorcing families". In Galatzer-Levy RM; Kraus L; Galatzer-Levy J (eds.). The Scientific Basis of Child Custody Decisions, 2nd Edition. John Wiley & Sons. pp. 403–416. ISBN 9780470038581. 31. ^ a b Dallam, SJ (1999). "The Parental Alienation Syndrome: Is It Scientific?". In St. Charles E; Crook L (eds.). Expose: The failure of family courts to protect children from abuse in custody disputes. Our Children Our Children Charitable Foundation. 32. ^ a b c Caplan, PJ (2004). "What is it that's being called Parental Alienation Syndrome". In Caplan PJ; Cosgrove L (eds.). Bias in psychiatric diagnosis. Rowman & Littlefield. pp. 62. ISBN 9780765700018. 33. ^ a b Comeford, L (2009). "Fatherhood Movements". In O'Brien J (ed.). Encyclopedia of Gender and Society. 1. SAGE Publications. pp. 285. ISBN 9781412909167. 34. ^ "APA Statement on Parental Alienation Syndrome". Washington, DC: American Psychological Association. 1996. Retrieved 2009-03-31. 35. ^ a b c Sparta, SN; Koocher GP (2006). Forensic Mental Health Assessment of Children and Adolescents. Oxford University Press. pp. 83, 219–221. ISBN 9780195145847. 36. ^ "American Psychological Association Presidential Task Force on Violence And The Family". American Psychological Association. 1996. Archived from the original on 2000-03-07. 37. ^ a b c Fortin, Jane (2003). Children's Rights and the Developing Law. Cambridge University Press. pp. 263. ISBN 9780521606486. 38. ^ a b Bainham, Andrew (2005). Children: The Modern Law. Jordans. pp. 161. ISBN 9780853089391. 39. ^ a b Gardner, RA (2002-10-06). PAS and the DSM-5: A Call for Action. Men's News Daily. Archived from the original on 2003-12-20. Retrieved 2010-03-20. 40. ^ Rotstein, Gary (February 15, 2010). "Mental health professionals getting update on definitions". Pittsburgh Post-Gazette. Retrieved 2 March 2010. 41. ^ "American Psychiatric Association Board of Trustees Approves DSM-5-Diagnostic manual passes major milestone before May 2013 publication". American Psychiatric Association. 1 December 2012. Archived from the original on 5 October 2013. 42. ^ Slatton, Traci (May 26, 2015). "Lost Parents: When High Conflict Divorce Leads to Parental Alienation". Huffington Post. Retrieved 2015-06-06. 43. ^ Grohol, John M. "Parental Alienation: Disorder or Not?". PsychCentral. Psych Central. Retrieved 4 May 2017. 44. ^ a b c Emery, RE (2005). "Parental Alienation Syndrome: Proponents bear the burden of proof" (PDF). Family Court Review. 43 (1): 8–13. CiteSeerX 10.1.1.636.2641. doi:10.1111/j.1744-1617.2005.00002.x. 45. ^ a b Bond, Richard (2008). "The Lingering Debate Over the Parental Alienation Syndrome Phenomenon". 4 (1). Journal of Child Custody: 37–54. Cite journal requires `\|journal=` (help) 46. ^ a b Martindale, David; Gould, Jonathan W. (2007). The Art and Science of Child Custody Evaluations. New York: The Guilford Press. ISBN 978-1-59385-488-1. 47. ^ Houchin, TM; Ranseen, J; Hash, PAK; Bartnicki, DJ (2012). "The Parental Alienation Debate Belongs in the Courtroom, Not in DSM-5". Journal of the American Academy of Psychiatry and the Law. 40 (1): 127–131. PMID 22396350. 48. ^ Pepitona, M. Brianna; Alvis, Lindsey J.; Allen, Kenneth; Logid, Gregory (2012). "Is Parental Alienation Disorder a Valid Concept? Not According to Scientific Evidence. A Review of Parental Alienation, DSM-5 and ICD-11 by William Bernet". Journal of Child Sexual Abuse. 21 (12): 244–253. doi:10.1080/10538712.2011.628272. 49. ^ Ragland, ER; Fields H (2003). "Parental Alienation Syndrome: What Professionals Need to Know Part 1 of 2 Update". American Prosecutors Research Institute Newsletter. 16 (6). Archived from the original on 2009-04-25. 50. ^ a b Warshak, Richard A. "Bringing sense to Parental Alienation: A Look at the Disputes and the Evidence]" (PDF). Family Law Quarterly. 37 (2): 273–301. 51. ^ a b Waldron, KH; Joanis DE (1996). "Understanding and Collaboratively Treating Parental Alienation Syndrome". American Journal of Family Law. 10: 121–133. 52. ^ Walker, Lenore E.; Shapiro, David L. (2010). "Parental Alienation Disorder: Why Label Children with a Mental Diagnosis?". Journal of Child Custody. 7 (4): 266–286. doi:10.1080/15379418.2010.521041. 53. ^ Lubit, Roy (29 June 2019). "Valid and invalid ways to assess the reason a child rejects a parent: The continued malignant role of "parental alienation syndrome"". Journal of Child Custody. 16 (1): 42–66. doi:10.1080/15379418.2019.1590284. 54. ^ Jaffe, PG; Crooks CV; Bala N (2006). Making Appropriate Parenting Arrangements in Family Violence Cases: Applying the Literature to Identify Promising Practices (PDF). Department of Justice. Retrieved 2009-05-05.[permanent dead link] 55. ^ Sturge, C; Glaser D (2000). "Contact and domestic violence – the experts' court report". Family Law. 615. 56. ^ Silberg, Joyanna; Dallam, Stephanie (2 Jul 2019). "Abusers gaining custody in family courts: A case series of over turned decisions". Journal of Child Custody. 16 (2): 140–169. doi:10.1080/15379418.2019.1613204. 57. ^ Hoult, Jennifer (2006). "The Evidentiary Admissibility of Parental Alienation Syndrome: Science, Law, and Policy". Children's Legal Rights Journal. 26 (1): 1–61. 58. ^ Brown, Andraé L. (November 2008). "Criminal Rewards". Affilia. 23 (4): 388–396. doi:10.1177/0886109908323999. 59. ^ Myers, John E. B. (2005). Myers on evidence in child, domestic, and elder abuse cases. Gaithersburg, Md: Aspen Publishers. pp. 415. ISBN 0-7355-5668-7. 60. ^ "In re Marriage of Bates, 212 Ill.2d 489, 289 Ill.Dec. 218, 819 NE 2d 714 (2004)". Google Scholar. Retrieved 4 May 2017. 61. ^ a b "Matter of Coull v Rottman". Google Scholar. Retrieved 4 May 2017. 62. ^ Denney, Andrew (9 September 2015). "Father Not Obligated to Pay Child Support, Panel Finds". New York Law Journal. 63. ^ Larson, Aaron (4 Feb 2016). "Parental Alienation in Child Custody Cases". ExpertLaw.Com. ExpertLaw. Retrieved 4 May 2017. 64. ^ "Matter of E.S. v S.S., 2019 NY Slip Op 50948(U)". Google Scholar. Retrieved 2 August 2019. 65. ^ Simring Milchman, Madelyn (2 July 2019). "How far has parental alienation research progressed toward achieving scientific validity?". Journal of Child Custody. 16 (2): 115–139. doi:10.1080/15379418.2019.1614511. ## External links[edit] * Parental alienation syndrome at Curlie * National Coalition Against Parental Alienation [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Parental alienation syndrome	None	30,394	wikipedia	https://en.wikipedia.org/wiki/Parental_alienation_syndrome	2021-01-18T18:49:35	{"wikidata": ["Q1334131"]}
Presence of virus in the blood Viremia Other namesViraemia SpecialtyInfectious disease Viremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to bacteremia, a condition where bacteria enter the bloodstream.[1] The name comes from combining the word "virus" with the Greek word for "blood" (haima). It usually lasts for 4 to 5 days in the primary condition. ## Contents * 1 Primary versus secondary * 2 Active versus passive * 3 See also * 4 References * 5 External links ## Primary versus secondary[edit] Primary viremia refers to the initial spread of virus in the blood from the first site of infection. Secondary viremia occurs when primary viremia has resulted in infection of additional tissues via bloodstream, in which the virus has replicated and once more entered the circulation. Usually secondary viremia results in higher viral shedding and viral loads within the bloodstream due to the possibility that the virus is able to reach its natural host cell from the bloodstream and replicate more efficiently than the initial site.[2] An excellent example to profile this distinction is the rabies virus.[3] Usually the virus will replicate briefly within the first site of infection, within the muscle tissues. Viral replication then leads to viremia and the virus spreads to its secondary site of infection, the central nervous system (CNS). Upon infection of the CNS, secondary viremia results and symptoms usually begin.[4] Vaccination at this point is useless, as the spread to the brain is unstoppable. Vaccination must be done before secondary viremia takes place for the individual to avoid brain damage or death. ## Active versus passive[edit] Active viremia is caused by the replication of viruses which results in viruses being introduced into the bloodstream. Examples include the measles, in which primary viremia occurs in the epithelial lining of the respiratory tract before replicating and budding out of the cell basal layer (viral shedding), resulting in viruses budding into capillaries and blood vessels.[5] Passive viremia is the introduction of viruses in the bloodstream without the need of active viral replication. Examples include direct inoculation from mosquitoes, through physical breaches or via blood transfusions.[6] ## See also[edit] * Septicemia ## References[edit] 1. ^ Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. p. 881. ISBN 978-0-8385-8529-0. 2. ^ Cerino A, Bissolati M, Cividini A, Nicosia A, Esumi M, Hayashi N, Mizuno K, Slobbe R, Oudshoorn P, Silini E, Asti M, Mondelli MU (Jan 1997). "Antibody responses to the hepatitis C virus E2 protein: relationship to viraemia and prevalence in anti-HCV seronegative subjects". J Med Virol. 51 (1): 1–5. doi:10.1002/(sici)1096-9071(199701)51:1<1::aid-jmv1>3.3.co;2-3. PMID 8986942. 3. ^ Lodmell DL, Dimcheff DE, Ewalt LC (Mar 2006). "Viral RNA in the bloodstream suggests viremia occurs in clinically ill rabies-infected mice". Virus Res. (Submitted manuscript). 116 (1–2): 114–8. doi:10.1016/j.virusres.2005.09.004. PMID 16242805. 4. ^ Gribencha SV, Barinsky IF (Jul 1982). "Viraemia in rabies". Acta Virol. 26 (4): 301. 5. ^ Mulupuri, P.; Zimmerman, J. J.; Hermann, J.; Johnson, C. R.; Cano, J. P.; Yu, W.; Dee, S. A.; Murtaugh, M. P. (2007-12-10). "Antigen-Specific B-Cell Responses to Porcine Reproductive and Respiratory Syndrome Virus Infection". Journal of Virology. 82 (1): 358–370. doi:10.1128/JVI.01023-07. ISSN 0022-538X. PMC 2224379. PMID 17942527. 6. ^ Lai CJ, Goncalvez AP, Men R, Wernly C, Donau O, Engle RE, Purcell RH (Dec 2007). "Epitope determinants of a chimpanzee dengue virus type 4 (DENV-4)-neutralizing antibody and protection against DENV-4 challenge in mice and rhesus monkeys by passively transferred humanized antibody". J Virol. 81 (23): 12766–74. doi:10.1128/jvi.01420-07. PMC 2169078. PMID 17881450. ## External links[edit] Classification D * ICD-10: B34.9 * ICD-9-CM: 790.8 * MeSH: D014766 * v * t * e Blood tests for infectious disease Bacterial infection * syphilis * Venereal Disease Research Laboratory test * rapid plasma reagin * Wassermann test * Fluorescent treponemal antibody absorption test * Abelin reaction * Rickettsia * Weil–Felix test * Helicobacter * HelicoCARE direct * Streptococcus * Anti-streptolysin O Viral infection * HIV testing * Branched DNA assay * mChip * Epstein–Barr virus * Heterophile antibody test * Dengue fever * NS1 antigen test * measles * Warthin–Finkeldey cell * Inclusion bodies * Downie bodies * B type inclusion * Orthopoxvirus inclusion bodies * rabies * Negri bodies * Cowdry bodies * yellow fever * Councilman body * Tzanck test Protozoan infection * toxoplasmosis * Sabin–Feldman dye test * malaria * Diagnosis of malaria * Schüffner's dots Bloodstream infections * Blood culture * Viremia * Fungemia * Parasitemia * Algaemia General * C-reactive protein * Procalcitonin [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Viremia	c0042749	30,395	wikipedia	https://en.wikipedia.org/wiki/Viremia	2021-01-18T18:47:18	{"mesh": ["D014766"], "wikidata": ["Q1425304"]}
Schinzel Giedion syndrome (SGS) is a rare, severe condition that is present from birth and affects many parts of the body. Features of SGS include severe intellectual disability; a distinctive facial appearance; excessive hair growth (hypertrichosis); and various birth defects that may affect the skeletal system, genitourinary system; kidneys; and heart. Affected children usually do not survive beyond a few years after birth. SGS is caused by a mutation in the SETBP1 gene. The mutation is not inherited from a parent, but occurs for the first time in the affected child (a de novo mutation). Treatment is based on symptoms and consists of palliative care. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Schinzel Giedion syndrome	c0265227	30,396	gard	https://rarediseases.info.nih.gov/diseases/117/schinzel-giedion-syndrome	2021-01-18T17:57:49	{"mesh": ["C536632"], "omim": ["269150"], "orphanet": ["798"], "synonyms": ["Schinzel Giedion midface-retraction syndrome", "SGS", "Schinzel-Giedion syndrome"]}
Grain itch Other namesBarley itch, Mattress itch, Prairie itch, Straw itch SpecialtyDermatology Grain itch is a cutaneous condition caused by several types of mites, and characterized by intense pruritus.[1]:454 ## See also[edit] * Grocer's itch * List of cutaneous conditions * List of mites associated with cutaneous reactions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. * v * t * e Mite-borne diseases and infestations Infestations * Acariasis * Baker's itch * Cheyletiellosis * Demodicosis * Feather pillow dermatitis * Gamasoidosis * Grain itch * Grocer's itch * Rodent mite dermatitis * Scabies * Trombiculosis Other diseases * House dust mite allergy * Oral mite anaphylaxis * List of mites associated with cutaneous reactions Species and bites Trombidiformes * Demodex brevis / Demodex folliculorum * demodicosis * Demodex mite bite * Trombicula * trombiculosis * Pyemotes herfsi * Cheyletiella (cheyletiellosis) * Leptotrombidium deliense Sarcoptiformes * Sarcoptes scabiei * scabies Mesostigmata * Dermanyssus gallinae * gamasoidosis * Liponyssoides sanguineus * rickettsialpox Other * House dust mite This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Grain itch	c0344070	30,397	wikipedia	https://en.wikipedia.org/wiki/Grain_itch	2021-01-18T19:09:59	{"umls": ["C0344070", "C0344074"], "wikidata": ["Q4191607"]}
A rare, severe, circulatory system disease characterized by premature, diffuse, severe atherosclerosis (including the aorta and renal, coronary, and cerebral arteries), sensorineural deafness, diabetes mellitus, progressive neurological deterioration with cerebellar symptoms and photomyoclonic seizures, and progressive nephropathy. Partial deficiency of mitochondrial complexes III and IV in the kidney and fibroblasts (but not in muscle) may be associated. There have been no further descriptions in the literature since 1994. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Atherosclerosis-deafness-diabetes-epilepsy-nephropathy syndrome	c2931125	30,398	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1192	2021-01-23T18:32:14	{"gard": ["2279"], "mesh": ["C536178"], "omim": ["209010"], "umls": ["C2931125"], "icd-10": ["I70.9"], "synonyms": ["Atherosclerosis-hearing loss-diabetes-epilepsy-nephropathy syndrome", "Feigenbaum-Bergeron-Richardson syndrome"]}
A rare systemic amyloidosis characterized by combination of various symptoms, depending on the organ involved. Common clinical features are cardiac failure, cardiac conduction anomalies or arrhythmia, renal dysfunction, carpal tunnel syndrome and spinal canal stenosis. Histology reveals fibrillary amyloid deposition of wild type transthyretin mostly in the kidneys, heart, gastrointestinal tract, skin and tenosynovial tissue. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Wild type ATTR amyloidosis	c2732618	30,399	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=330001	2021-01-23T17:12:58	{"icd-10": ["E85.8"], "synonyms": ["ATTRwt amyloidosis", "ATTRwt-related amyloidosis", "SSA", "Senile systemic amyloidosis", "Wild type ATTR-related amyloidosis"]}

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