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N-acetylglutamate synthase (NAGS) deficiency is a urea cycle disorder leading to hyperammonaemia. ## Epidemiology The disorder is very rare but the prevalence is unknown. ## Clinical description Onset occurs at any age, but neonatal presentation appears to be the most frequent. The clinical manifestations are variable but common features include vomiting, hyperactivity or lethargy, diarrhoea, poor feeding, seizures, hypotonia, delayed psychomotor development and respiratory distress. The hyperammonaemia is often severe and may lead to hyperammonaemic coma. ## Etiology The primary disorder is caused by mutations in the NAGS gene (17q21.31), leading to a total or partial lack of NAGS activity. The product of NAGS, N-acetylglutamate (NAG), is an allosteric activator of carbamylphosphate synthetase I (CPSI), the enzyme catalysing the first step in ureagenesis. NAGS deficiency may also be secondary to certain organic acid disorders, defects in fatty acid metabolism or valproic acid treatment. ## Diagnostic methods Diagnosis may be suspected by demonstration of decreased liver NAGS activity and can be confirmed by DNA analysis. ## Differential diagnosis The principle differential diagnosis is carbamoylphosphate synthetase deficiency (see this term). ## Genetic counseling The primary disorder is transmitted as an autosomal recessive trait. ## Management and treatment The established treatment for patients with NAGS activity is daily administration of N-carbamyl-L-glutamate (NCLG), a structural analogue of NAG that activates CPSI. NCLG has held EU marketing authorisation as an orphan drug treatment for NAGS deficiency since 2003. ## Prognosis In most cases, early treatment with NCLG (i.e. before the onset of permanent neurological sequelae) allows normal psychomotor development and an excellent quality of life. Although the severity of the disorder is variable, the prognosis without treatment may be poor with neurological deficit and a potentially fatal outcome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Hyperammonemia due to N-acetylglutamate synthase deficiency	c0268543	30,100	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=927	2021-01-23T18:30:16	{"gard": ["7158"], "mesh": ["C536109"], "omim": ["237310"], "umls": ["C0268543"], "icd-10": ["E72.2"], "synonyms": ["NAGS deficiency"]}
This article is about skin changes that occur in hypothyroidism. The word myxedema was historically used to refer hypothyroidism in general. For the related medical emergency, see myxedema coma. Myxedema Other namesMyxoedema Hyaluronan, an example of a mucopolysaccharide SpecialtyEndocrinology Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hyperthyroidism and (rare) paradoxical cases of hypothyroidism. In this latter sense, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area. One manifestation of myxedema occurring in the lower limb is pretibial myxedema, a hallmark of Graves disease, an autoimmune form of hyperthyroidism. Myxedema can also occur in Hashimoto thyroiditis and other long-standing forms of hypothyroidism. The word myxedema originates from μύξα, taken from ancient Greek to convey 'mucus' or 'slimy substance', and ὁοίδημα for "swelling". It can also be thought as nonpitting edema, in contrast to pitting edema. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 5 Management * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor Additional finding include swelling of the arms and legs and significant ascites. Woman with myxedema, Bulgaria, 1930s. Myxedema can occur in the lower leg (pretibial myxedema) and behind the eyes (exophthalmos). Severe cases, requiring hospitalization can exhibit signs of hypothermia, hypoglycemia, hypotension, respiratory depression, and coma. ## Cause[edit] Myxedema is known to occur in various forms of hyperthyroidism, including Graves disease. One of the hallmarks of Grave's disease is pretibial myxedema, myxedema of the lower limb.[1] Myxedema is more common in women than in men.[2] Myxedema can occur in: * Hyperthyroidism, associated with pretibial myxedema and exophthalmos. Pretibial myxedema can occur in 1–4% of patients with Graves' disease, a cause of hyperthyroidism.[3] * Hypothyroidism, including Hashimoto's thyroiditis.[citation needed] ## Pathophysiology[edit] Myxedema describes a specific form of cutaneous and dermal edema secondary to increased deposition of connective tissue components. The connective fibres are separated by an increased amount of protein and mucopolysaccharides. These can include glycosaminoglycans, such as hyaluronic acid, chondroitin sulfate and other mucopolysaccharides.[1] This protein-mucopolysaccharide complex binds water, producing non-pitting boggy edema, in particular around eyes, hands, feet and in the supraclavicular fossae. Myxoedema is responsible for the thickening of the tongue and the laryngeal and pharyngeal mucous membranes, which results in thick slurred speech and hoarseness, both of which are seen commonly in hypothyroidism. The increased deposition of glycosaminoglycan is not fully understood, however two mechanisms predominate: * Fibroblast stimulation. It is thought that fibroblast stimulation by the thyroid stimulating hormone (TSH) receptor increases the deposition of glycosaminoglycan, which results in an osmotic edema and fluid retention. It is thought that many cells responsible for forming connective tissue react to increases in TSH levels.[citation needed] * Lymphocyte stimulation. In Graves' thyroid disease, lymphocytes react against the TSH receptor by inappropriately producing thyroid-stimulating immunoglobulin (IgG; type II hypersensitivity). Lymphocytes react not only against thyroid receptors, but also any tissue with cells expressing the receptor. This can lead to tissue damage and scar tissue formation, explaining the deposition of glycosaminoglycans.[citation needed] ## Diagnosis[edit] It is often possible to diagnose myxedema on clinical grounds alone. Characteristic symptoms are weakness, cold intolerance, mental and physical slowness, dry skin, typical facies, and hoarse voice. Results of the total serum thyroxine and free thyroxine index tests usually will confirm the diagnosis.[4] ## Management[edit] Primary treatment is prompted by the administration of adequate doses of either the thyroid hormone L-thyroxine given intravenously or by giving liothyronine via a nasogastric tube. It is essential to identify and treat the condition precipitating the coma.[4] Myxedema coma is rare but often fatal. It occurs most often in elderly women and may be mistaken for one of the chronic debilitating diseases common to this age group.[4] Though the exact cause of myxedema is still unclear, a wealth of research has demonstrated the importance of iodine.[5] In an important study[6] the researchers showed that in the myxedematous type of cretinism treatment with iodine normalizes thyroid function provided that the treatment is begun early in the postnatal period. If not, the prognosis remains dismal.[5] ## History[edit] Myxedema was first treated successfully in 1891, when George Redmayne Murray diagnosed a 46-year-old woman with the disease. He prescribed an extract from sheep thyroid. The patient improved significantly within a few weeks and lived another 28 years while taking the sheep thyroid extract.[7] ## References[edit] 1. ^ a b Berger, William D. James, Dirk M. Elston, Timothy G. (2011). Andrews' Diseases of the skin : clinical dermatology (11th ed.). [London]: Saunders/ Elsevier. ISBN 978-1-4377-0314-6. 2. ^ Schneider, Arthur S.; Kim, Philip A. Szanto; with special contributions by Sandra I.; Swanson, Todd A. (2009). Pathology (4th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 314. ISBN 978-1451109061. 3. ^ "Pretibial Myxedema". Archived from the original on 2016-03-04. Retrieved 2009-03-27. 4. ^ a b c McConahey, W. M. (March 1978). "Diagnosing and treating myxedema and myxedema coma". Geriatrics. 33 (3): 61–66. ISSN 0016-867X. PMID 624451. 5. ^ a b Lindholm, J.; Laurberg, P. (2011). "Hypothyroidism and Thyroid Substitution: Historical Aspects". Journal of Thyroid Research. 2011: 809341. doi:10.4061/2011/809341. PMC 3134382. PMID 21760981. 6. ^ Vanderpas, Jean B.; Rivera-Vanderpas, Maria T.; Bourdoux, Pierre; Luvivila, Kapata; Lagasse, Raphael; Perlmutter-Cremer, Noémi; Delange, François; Lanoie, Leo; Ermans, André M. (1986-09-25). "Reversibility of Severe Hypothyroidism with Supplementary Iodine in Patients with Endemic Cretinism". New England Journal of Medicine. 315 (13): 791–795. doi:10.1056/NEJM198609253151302. ISSN 0028-4793. PMID 3018564. 7. ^ "Eating Organs to Cure Disease". Tacomed.com. Archived from the original on 6 September 2017. Retrieved 15 June 2017. ## External links[edit] Classification D * ICD-10: E03.9 * ICD-9-CM: 244.9 * MeSH: D009230 * DiseasesDB: 6558 External resources * MedlinePlus: 000353 * eMedicine: med/1581 derm/347 * v * t * e Thyroid disease Hypothyroidism * Iodine deficiency * Cretinism * Congenital hypothyroidism * Myxedema * Myxedema coma * Euthyroid sick syndrome * Signs and symptoms * Queen Anne's sign * Woltman sign * Thyroid dyshormonogenesis * Pickardt syndrome Hyperthyroidism * Hyperthyroxinemia * Thyroid hormone resistance * Familial dysalbuminemic hyperthyroxinemia * Hashitoxicosis * Thyrotoxicosis factitia * Thyroid storm Graves' disease * Signs and symptoms * Abadie's sign of exophthalmic goiter * Boston's sign * Dalrymple's sign * Stellwag's sign * lid lag * Griffith's sign * Möbius sign * Pretibial myxedema * Graves' ophthalmopathy Thyroiditis * Acute infectious * Subacute * De Quervain's * Subacute lymphocytic * Palpation * Autoimmune/chronic * Hashimoto's * Postpartum * Riedel's Enlargement * Goitre * Endemic goitre * Toxic nodular goitre * Toxic multinodular goiter * Thyroid nodule * Colloid nodule [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Myxedema	c0027145	30,101	wikipedia	https://en.wikipedia.org/wiki/Myxedema	2021-01-18T18:35:51	{"mesh": ["D009230"], "umls": ["C0027145"], "icd-9": ["244.9"], "wikidata": ["Q966229"]}
Pulmonary artery coming from patent ductus arteriosus is a rare, congenital, non-syndromic heart malformation characterized by the presence of a single (or a double) patent ductus arteriosus which associates one or both pulmonary arteries originating from it. Manifestations are variable, frequently presenting with neonatal cyanosis, severe progressive hypoxia, persistent pulmonary hypertension, increased susceptibility to pulmonary infections, and thoracic asymmetry resulting from asymmetric lung volumes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Pulmonary artery coming from patent ductus arteriosus	None	30,102	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99049	2021-01-23T16:53:38	{"icd-10": ["Q25.7"]}
Temtamy and McKusick (1978) described mother and son. See 129900. Limbs \- Ectrodactyly \- Split hand \- Split foot Inheritance \- Autosomal dominant Teeth \- Hypodontia ▲ 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	SPLIT-HAND AND SPLIT-FOOT WITH HYPODONTIA	c1866742	30,103	omim	https://www.omim.org/entry/183500	2019-09-22T16:34:29	{"mesh": ["C566665"], "omim": ["183500"]}
Chronic inflammatory demyelinating polyneuropathy Other namesCIDP SpecialtyNeurology Chronic inflammatory demyelinating polyneuropathy is an acquired immune-mediated inflammatory disorder of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms.[1] The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots).[2] CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease.[3] Its symptoms are also similar to progressive inflammatory neuropathy. ## Contents * 1 Types * 2 Signs and Symptoms * 3 Causes * 3.1 Variants with paranodal autoantibodies * 3.2 Autoantibodies of the IgG3 Subclass in CIDP * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 Vaccine Injury Compensation for CIDP * 9 See also * 10 References * 11 External links ## Types[edit] Several variants have been reported. Specially important are: * An asymmetrical variant of CIDP is known as Lewis-Sumner Syndrome.[4] * A variant with CNS involvement named combined central and peripheral demyelination (CCPD)[5] Currently there is one special variant in which the CNS is also affected. It is termed "combined central and peripheral demyelination" (CCPD) and is special because it belongs at the same time to the CDIP syndrome and to the multiple sclerosis spectrum.[5] These cases seem to be related to the presence of anti-neurofascin autoantibodies.[citation needed] ## Signs and Symptoms[edit] Diagnosis is typically made on the basis of presenting symptoms in tandem with electrodiagnostic testing or a nerve biopsy. Doctors may use a lumbar puncture to verify the presence of increased cerebrospinal fluid protein. Symptoms such as diminished or absent deep-tendon reflexes and sensory ataxia are common. Other symptoms include proximal and distal muscle weakness in the limbs.[citation needed] ## Causes[edit] Structure of a typical neuron Neuron Dendrite Soma Axon Nucleus Node of Ranvier Axon terminal Schwann cell Myelin sheath Chronic inflammatory demyelinating polyneuropathy (or polyradiculoneuropathy) is considered an autoimmune disorder destroying myelin, the protective covering of the nerves. Typical early symptoms are "tingling" (sort of electrified vibration or paresthesia) or numbness in the extremities, frequent (night) leg cramps, loss of reflexes (in knees), muscle fasciculations, "vibration" feelings, loss of balance, general muscle cramping and nerve pain.[6][7] CIDP is extremely rare but under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is favoured in preventing irreversible axonal loss and improving functional recovery.[8] There is a lack of awareness and treatment of CIDP. Although there are stringent research criteria for selecting patients for clinical trials, there are no generally agreed-upon clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of the present research criteria to routine clinical practice often misses the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease.[9] CIDP has been associated with diabetes mellitus, HIV infection, and paraproteinemias.[citation needed] ### Variants with paranodal autoantibodies[edit] Main article: Anti-neurofascin demyelinating diseases Some variants of CIDP present autoimmunity against proteins of the node of Ranvier. These variants comprise a subgroup of inflammatory neuropathies with IgG4 autoantibodies against the paranodal proteins neurofascin-155, contactin-1 and caspr-1.[10] These cases are special not only because of their pathology, but also because they are non-responsive to the standard treatment. They are responsive to Rituximab instead.[10] Also some cases of combined central and peripheral demyelination (CCPD) could be produced by neurofascins.[11] ### Autoantibodies of the IgG3 Subclass in CIDP[edit] Autoantibodies to components of the Ranvier nodes, specially autoantibodies the Contactin-associated protein 1 (CASPR), cause a form of CIDP with an acute "Guillain-Barre-like" phase, followed by a chronic phase with progressive symptoms. Different IgG subclasses are associated with the different phases of the disease. IgG3 Caspr autoantibodies were found during the acute GBS-like phase, while IgG4 Caspr autoantibodies were present during the chronic phase of disease.[12] ## Diagnosis[edit] There are several types of immune-mediated neuropathies recognised.[13][14] These include: * Chronic inflammatory demyelinating polyneuropathy (CIDP) with subtypes: * Classical CIDP * CIDP with diabetes * CIDP/monoclonal gammopathy of undetermined significance * Sensory CIDP * Multifocal motor neuropathy * Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome) * Multifocal acquired sensory and motor neuropathy * Distal acquired demyelinating sensory neuropathy * Guillain–Barré syndrome with subtypes: * Acute inflammatory demyelinating polyradiculoneuropathy * Acute motor axonal neuropathy * Acute motor and sensory axonal neuropathy * Acute pandysautonomia * Miller Fisher syndrome * IgM monoclonal gammopathies with subtypes: * Waldenström's macroglobulinemia * Mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome * Myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS) For this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations.The diagnosis is usually provisionally made through a clinical neurological examination. Patients usually present with a history of weakness, numbness, tingling, pain and difficulty in walking. They may additionally present with fainting spells while standing up or burning pain in extremities. Some patients may have sudden onset of back pain or neck pain radiating down the extremities, usually diagnosed as radicular pain. These symptoms are usually progressive and may be intermittent.[citation needed] Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems breathing, eye, bowel, bladder and cardiac problems. The patient may also present with a single cranial nerve or peripheral nerve dysfunction.[citation needed] On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy (shrinkage) of muscles, fasciculations (twitching) and loss of sensation. Patients may have multi-focal motor neuropathy, as they have no sensory loss.[citation needed] Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made. Typical diagnostic tests include: * Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include: 1. a reduction in nerve conduction velocities; 2. the presence of conduction block or abnormal temporal dispersion in at least one motor nerve; 3. prolonged distal latencies in at least two nerves; 4. absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal). * Serum test to exclude other autoimmune diseases. * Lumbar puncture and serum test for anti-ganglioside antibodies. These antibodies are present in the branch of CIDP diseases comprised by anti-GM1, anti-GD1a, and anti-GQ1b. * Sural nerve biopsy; biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG. * Ultrasound of the peripheral nerves may show swelling of the affected nerves[15][16][17] * Magnetic resonance imaging can also be used in the diagnostic workup[18][19] In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy.[20] ### Differential diagnosis[edit] * Bickerstaff brainstem encephalitis * Fisher syndrome * Guillain–Barré syndrome ## Treatment[edit] First-line treatment for CIDP is currently intravenous immunoglobulin and other treatments include corticosteroids (e.g., prednisone), and plasmapheresis (plasma exchange) which may be prescribed alone or in combination with an immunosuppressant drug.[21] Recent controlled studies show subcutaneous immunoglobulin appears to be as effective for CIDP treatment as intravenous immunoglobulin in most patients, and with fewer systemic side effects.[22] Intravenous immunoglobulin and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. Despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use and cost effectiveness. Intravenous immunoglobulin is probably the first-line CIDP treatment, but is extremely expensive. For example, in the U.S., a single 65 g dose of Gamunex brand in 2010 might be billed at the rate of $8,000 just for the immunoglobulin—not including other charges such as nurse administration.[citation needed] Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including rituximab (Rituxan) which targets B cells, and cyclophosphamide, a drug which reduces the function of the immune system. Ciclosporin has also been used in CIDP but with less frequency as it is a newer approach.[23] Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes. Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine (Imuran/Azoran) and mycophenolate mofetil (Cellcept). In the U.S., these drugs are used "off-label", meaning that they do not have an indication for the treatment of CIDP in their package inserts. Before azathioprine is used, the patient should first have a blood test that ensures that azathioprine can safely be used.[citation needed] Anti-thymocyte globulin, an immunosuppressive agent that selectively destroys T lymphocytes is being studied for use in CIDP. Anti-thymocyte globulin is the gamma globulin fraction of antiserum from animals that have been immunized against human thymocytes. It is a polyclonal antibody.Although chemotherapeutic and immunosuppressive agents have shown to be effective in treating CIDP, significant evidence is lacking, mostly due to the heterogeneous nature of the disease in the patient population in addition to the lack of controlled trials.[citation needed] A review of several treatments found that azathioprine, interferon alpha and methotrexate were not effective.[24] Cyclophosphamide and rituximab seem to have some response. Mycophenolate mofetil may be of use in milder cases. Immunoglobulin and steroids are the first line choices for treatment. In severe cases of CIDP, when second-line immunomodulatory drugs are not efficient, autologous hematopoietic stem cell transplantation is sometimes performed. The treatment may induce long-term remission even in severe treatment-refractory cases of CIDP. To improve outcome, it has been suggested that it should be initiated before irreversible axonal damage has occurred. However, a precise estimation of its clinical efficacy for CIDP is not available, as randomized controlled trials have not been performed.[25] Physical therapy and occupational therapy may improve muscle strength, activities of daily living, mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints. ## Prognosis[edit] As in multiple sclerosis, another demyelinating condition, it is not possible to predict with certainty how CIDP will affect patients over time. The pattern of relapses and remissions varies greatly with each patient. A period of relapse can be very disturbing, but many patients make significant recoveries.[citation needed] If diagnosed early, initiation of early treatment to prevent loss of nerve axons is recommended. However, many individuals are left with residual numbness, weakness, tremors, fatigue and other symptoms which can lead to long-term morbidity and diminished quality of life.[2] It is important to build a good relationship with doctors, both primary care and specialist. Because of the rarity of the illness, many doctors will not have encountered it before. Each case of CIDP is different, and relapses, if they occur, may bring new symptoms and problems. Because of the variability in severity and progression of the disease, doctors will not be able to give a definite prognosis. A period of experimentation with different treatment regimens is likely to be necessary in order to discover the most appropriate treatment regimen for a given patient.[citation needed] ## Epidemiology[edit] In 1982 Lewis et al. reported a group of patients with a chronic asymmetrical sensorimotor neuropathy mostly affecting the arms with multifocal involvement of peripheral nerves.[26] Also in 1982 Dyck et al reported a response to prednisolone to a condition they referred to as chronic inflammatory demyelinating polyradiculoneuropathy.[27] Parry and Clarke in 1988 described a neuropathy which was later found to be associated with IgM autoantibodies directed against GM1 gangliosides.[28][29] This latter condition was later termed multifocal motor neuropathy[30] This distinction is important because multifocal motor neuropathy responds to intravenous globulin alone while chronic inflammatory demyelinating polyneuropathy responds to intravenous globulin, steroids and plasma exchanges.[31] It has been suggested that multifocal motor neuropathy is distinct from chronic inflammatory demyelinating polyneuropathy and that Lewis-Sumner syndrome is a distinct variant type of chronic inflammatory demyelinating polyneuropathy.[32] The Lewis-Sumner form of this condition is considered a rare disease with only 50 cases reported up to 2004.[33] A total of 90 cases had been reported by 2009.[34] ## Vaccine Injury Compensation for CIDP[edit] The National Vaccine Injury Compensation Program has awarded money damages to patients who came down with CIDP after receiving one of the childhood vaccines listed on the Federal Government's vaccine injury table. These Vaccine Court awards often come with language stating that the Court denies that the specific vaccine "caused petitioner to suffer CIDP or any other injury. Nevertheless, the parties agree to the joint stipulation, attached hereto as Appendix A. The undersigned finds said stipulation reasonable and adopts it as the decision of the Court in awarding damages, on the terms set forth therein."[35] A keyword search on the Court of Federal Claims "Opinions/Orders" database for the term "CIDP" returns 202 opinions related to CIDP and vaccine injury compensation.[36] ## See also[edit] * Autoimmune disease * Neurology ## References[edit] 1. ^ "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Information Page". ninds.nih.gov. Retrieved 2020-12-31. 2. ^ a b Kissel JT (2003). "The treatment of chronic inflammatory demyelinating polyradiculoneuropathy". Seminars in Neurology. 23 (2): 169–80. doi:10.1055/s-2003-41130. PMID 12894382. 3. ^ "GBS (Guillain-Barré Syndrome) - CIDP Neuropathy". cidpneuropathysupport.com. Retrieved 2017-12-14. 4. ^ "Lewis summer syndrome GUIDE". 5. ^ a b Jun-ichi Kira, Ryo Yamasaki, Hidenori Ogata, Anti-neurofascin autoantibody and demyelination, Neurochemistry international, Dec. 2018, doi: https://doi.org/10.1016/j.neuint.2018.12.011 6. ^ "C.I.D.P. Log". cidplog.com. Retrieved 2018-09-27. 7. ^ Latov, Norman (2014-07-01). "Diagnosis and treatment of chronic acquired demyelinating polyneuropathies". Nature Reviews Neurology. 10 (8): 435–446. doi:10.1038/nrneurol.2014.117. PMID 24980070. S2CID 23639113. 8. ^ Toothaker TB, Brannagan TH (2007). "Chronic inflammatory demyelinating polyneuropathies: current treatment strategies". Current Neurology and Neuroscience Reports. 7 (1): 63–70. doi:10.1007/s11910-007-0023-5. PMID 17217856. S2CID 46426663. 9. ^ Latov, Norman (2002). "Diagnosis of CIDP". Neurology. 59 (12 Suppl 6): S2–6. doi:10.1212/wnl.59.12_suppl_6.s2. PMID 12499464. S2CID 25742148. 10. ^ a b Doppler, Kathrin; Sommer, Claudia (March 2017). "The New Entity of Paranodopathies: A Target Structure with Therapeutic Consequences". Neurology International Open. 01 (1): E56–E60. doi:10.1055/s-0043-102455. 11. ^ Ciron, Jonathan; Carra-Dallière, Clarisse; Ayrignac, Xavier; Neau, Jean-Philippe; Maubeuge, Nicolas; Labauge, Pierre (January 2019). "The coexistence of recurrent cerebral tumefactive demyelinating lesions with longitudinally extensive transverse myelitis and demyelinating neuropathy". Multiple Sclerosis and Related Disorders. 27: 223–225. doi:10.1016/j.msard.2018.11.002. PMID 30414563. 12. ^ Hampe, Christiane S. (2019). "Significance of Autoantibodies". Neuroimmune Diseases: 109–142. doi:10.1007/978-3-030-19515-1_4. ISBN 978-3-030-19514-4. 13. ^ Finsterer, J. (August 2005). "Treatment of immune-mediated, dysimmune neuropathies". Acta Neurologica Scandinavica. 112 (2): 115–125. doi:10.1111/j.1600-0404.2005.00448.x. PMID 16008538. S2CID 10651959. 14. ^ Ensrud, Erik R.; Krivickas, Lisa S. (May 2001). "Acquired Inflammatory Demyelinating Neuropathies". Physical Medicine and Rehabilitation Clinics of North America. 12 (2): 321–334. doi:10.1016/S1047-9651(18)30072-X. PMID 11345010. 15. ^ Herraets, Ingrid J.T.; Goedee, H. Stephan; Telleman, Johan A.; van Asseldonk, Jan-Thies H.; Visser, Leo H.; van der Pol, W. Ludo; van den Berg, Leonard H. (January 2018). "High-resolution ultrasound in patients with Wartenberg's migrant sensory neuritis, a case-control study". Clinical Neurophysiology. 129 (1): 232–237. doi:10.1016/j.clinph.2017.10.040. PMID 29202391. S2CID 24416887. 16. ^ Goedee, H. Stephan; van der Pol, W. Ludo; van Asseldonk, Jan-Thies H.; Franssen, Hessel; Notermans, Nicolette C.; Vrancken, Alexander J.F.E.; van Es, Michael A.; Nikolakopoulos, Stavros; Visser, Leo H.; van den Berg, Leonard H. (10 January 2017). "Diagnostic value of sonography in treatment-naive chronic inflammatory neuropathies". Neurology. 88 (2): 143–151. doi:10.1212/WNL.0000000000003483. PMID 27927940. S2CID 5466514. 17. ^ Décard, Bernhard F.; Pham, Mirko; Grimm, Alexander (January 2018). "Ultrasound and MRI of nerves for monitoring disease activity and treatment effects in chronic dysimmune neuropathies – Current concepts and future directions". Clinical Neurophysiology. 129 (1): 155–167. doi:10.1016/j.clinph.2017.10.028. PMID 29190522. S2CID 37585666. 18. ^ Shibuya, Kazumoto; Sugiyama, Atsuhiko; Ito, Sho-ichi; Misawa, Sonoko; Sekiguchi, Yukari; Mitsuma, Satsuki; Iwai, Yuta; Watanabe, Keisuke; Shimada, Hitoshi; Kawaguchi, Hiroshi; Suhara, Tetsuya; Yokota, Hajime; Matsumoto, Hiroshi; Kuwabara, Satoshi (February 2015). "Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy: MR Neurography in CIDP". Annals of Neurology. 77 (2): 333–337. doi:10.1002/ana.24314. PMID 25425460. S2CID 39436370. 19. ^ Rajabally, Yusuf A.; Knopp, Michael J.; Martin-Lamb, Darren; Morlese, John (July 2014). "Diagnostic value of MR imaging in the Lewis–Sumner syndrome: A case series". Journal of the Neurological Sciences. 342 (1–2): 182–185. doi:10.1016/j.jns.2014.04.033. PMID 24825730. S2CID 44981467. 20. ^ Azulay JP (2006). "[The diagnosis of chronic axonal polyneuropathy: the poorly understood chronic polyradiculoneuritides]". Revue Neurologique (Paris) (in French). 162 (12): 1292–5. doi:10.1016/S0035-3787(06)75150-5. PMID 17151528. 21. ^ Hughes RA (2002). "Systematic reviews of treatment for inflammatory demyelinating neuropathy". Journal of Anatomy. 200 (4): 331–9. doi:10.1046/j.1469-7580.2002.00041.x. PMC 1570692. PMID 12090400. 22. ^ Hadden, Robert D. M.; Marreno, Fabrizio (2016-12-28). "Switch from intravenous to subcutaneous immunoglobulin in CIDP and MMN: improved tolerability and patient satisfaction". Therapeutic Advances in Neurological Disorders. 8 (1): 14–19. doi:10.1177/1756285614563056. ISSN 1756-2856. PMC 4286942. PMID 25584070. 23. ^ Odaka M, Tatsumoto M, Susuki K, Hirata K, Yuki N (2005). "Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin". Journal of Neurology, Neurosurgery, and Psychiatry. 76 (8): 1115–20. doi:10.1136/jnnp.2003.035428. PMC 1739743. PMID 16024890. 24. ^ Rajabally, Yusuf A. (2017). "Unconventional treatments for chronic inflammatory demyelinating polyneuropathy". Neurodegenerative Disease Management. 7 (5): 331–342. doi:10.2217/nmt-2017-0017. PMID 29043889. 25. ^ Burman, Joachim; Tolf, Andreas; Hägglund, Hans; Askmark, Håkan (2018-02-01). "Autologous haematopoietic stem cell transplantation for neurological diseases". Journal of Neurology, Neurosurgery, and Psychiatry. 89 (2): 147–155. doi:10.1136/jnnp-2017-316271. ISSN 0022-3050. PMC 5800332. PMID 28866625. 26. ^ Lewis, RA; Sumner, AJ; Brown, MJ; Asbury, AK (September 1982). "Multifocal demyelinating neuropathy with persistent conduction block". Neurology. 32 (9): 958–64. doi:10.1212/wnl.32.9.958. PMID 7202168. S2CID 40027684. 27. ^ Dyck, Peter James; O'Brien, Peter C.; Oviatt, Karen F.; Dinapoli, Robert P.; Daube, Jasper R.; Bartleson, John D.; Mokri, Bahram; Swift, Thomas; Low, Phillip A.; Windebank, Anthony J. (February 1982). "Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment". Annals of Neurology. 11 (2): 136–141. doi:10.1002/ana.410110205. PMID 7041788. S2CID 24567176. 28. ^ Parry, Gareth J.; Clarke, Stephen (February 1988). "Multifocal acquired demyelinating neuropathy masqurading as motor neuron disease". Muscle & Nerve. 11 (2): 103–107. doi:10.1002/mus.880110203. PMID 3343985. S2CID 21481288. 29. ^ Pestronk, A; Cornblath, DR; Ilyas, AA; Baba, H; Quarles, RH; Griffin, JW; Alderson, K; Adams, RN (July 1988). "A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside". Annals of Neurology. 24 (1): 73–8. doi:10.1002/ana.410240113. PMID 2843079. S2CID 44845902. 30. ^ Nobile-Orazio, Eduardo (April 2001). "Multifocal motor neuropathy". Journal of Neuroimmunology. 115 (1–2): 4–18. doi:10.1016/S0165-5728(01)00266-1. PMC 1073940. PMID 11282149. 31. ^ van Doorn, Pieter A.; Garssen, Marcel P.J. (October 2002). "Treatment of immune neuropathies". Current Opinion in Neurology. 15 (5): 623–631. doi:10.1097/00019052-200210000-00014. PMID 12352007. S2CID 29950514. 32. ^ Lewis, Richard Alan (October 2007). "Neuropathies associated with conduction block". Current Opinion in Neurology. 20 (5): 525–530. doi:10.1097/WCO.0b013e3282efa143. PMID 17885439. S2CID 32166227. 33. ^ Viala, K; Renié, L; Maisonobe, T; Béhin, A; Neil, J; Léger, JM; Bouche, P (September 2004). "Follow-up study and response to treatment in 23 patients with Lewis-Sumner syndrome". Brain : A Journal of Neurology. 127 (Pt 9): 2010–7. doi:10.1093/brain/awh222. PMID 15289267. 34. ^ Rajabally, Yusuf A.; Chavada, Govindsinh (February 2009). "Lewis-sumner syndrome of pure upper-limb onset: Diagnostic, prognostic, and therapeutic features". Muscle & Nerve. 39 (2): 206–220. doi:10.1002/mus.21199. PMID 19145651. S2CID 43478826. 35. ^ "Riley v. Secretary of Health and Human Services, Case No. 16-262V". United States Court of Federal Claims. July 30, 2019. 36. ^ "United States Court of Federal Claims Opinions/Orders". United States Court of Federal Claims. October 24, 2019. Retrieved October 24, 2019. ## External links[edit] Classification D * ICD-10: G61.8 * ICD-9-CM: 357.81 * OMIM: 139393 * MeSH: D020277 * DiseasesDB: 30084 External resources * eMedicine: neuro/467 * CIDP at NINDS * 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	Chronic inflammatory demyelinating polyneuropathy	c0393819	30,104	wikipedia	https://en.wikipedia.org/wiki/Chronic_inflammatory_demyelinating_polyneuropathy	2021-01-18T19:04:40	{"gard": ["6102"], "mesh": ["D020277"], "umls": ["C0393819"], "orphanet": ["2932"], "wikidata": ["Q1088030"]}
A number sign (#) is used with this entry because diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMSMFH) is caused by heterozygous mutation in the MTAP gene (156540) on chromosome 9p21. Description Diaphyseal medullary stenosis with malignant fibrous histiocytoma is an autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. In 2 families, affected individuals also showed a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma. Thus, the disorder may be considered a tumor predisposition syndrome (summary by Camacho-Vanegas et al., 2012). Clinical Features Arnold (1973) described several generations of a Vermont and New York kindred demonstrating multiple areas of necrosis in the diaphyses of the large tubular bones. The radiographic appearance of this skeletal condition resembled radiation osteitis, a highly premalignant condition; however, no source of radiation exposure was found in this family. Medullary fibrosarcoma, an uncommon bone tumor, was noted in 4 of the 12 affected members. Death had occurred from widespread metastases at ages varying from 23 to 48 years. Occurrence of fibrosarcoma in idiopathic bone infarcts (Furey et al., 1960) and in an infarct in a caisson worker (Dorfman et al., 1966) has been reported. Camacho-Vanegas et al. (2012) noted that 2 affected male individuals in the family reported by Arnold (1973) died of heart disease in their early forties without other known risk factors, and suggested that this may be a manifestation of the disorder. Hardcastle et al. (1986) gave follow-up information on the original American family and reported 2 other families, one English and the other Australian. They could find no reports of any hereditary or acquired condition similar to that in these 3 families. They suggested that the malignant change should be labeled 'malignant fibrous histiocytoma' rather than fibrosarcoma because the tumors were markedly aggressive. The malignancy occurred generally in the second to fifth decades of life. They defined the skeletal dysplasia as a diaphyseal medullary stenosis with overlying cortical bone thickening. The occurrence of fracture with minimal trauma was emphasized. Norton et al. (1996) reported a 19-year-old boy who presented with a nontender mass on the left tibia that proved to be a pleiomorphic spindle cell sarcoma. Radiographs of the affected leg showed extensive diaphyseal cortical thickening and a medullary permeative pattern in the diaphysis. Radiographs of the patient's mother and maternal grandmother showed a similar bony dysplasia, with areas of infarction and medullary sclerosis. The lower extremities were more affected than the upper extremities in all 3 cases. Family history was significant for the death of the maternal great-grandmother at age 32 from 'metastatic osteosarcoma.' Norton et al. (1996) commented on the similarities to the families reported by Hardcastle et al. (1986) and noted that the malignant fibrous histiocytomas in this condition presumably begin at the sites of infarction within the affected bone. Henry et al. (1958) reported a Canadian family in which 6 men had delayed healing of fractures of the long bones and later developed myopathy. Mehta et al. (2006) provided follow-up on the family reported by Henry et al. (1958); features of 8 living and 8 deceased family members with the disorder were evaluated. In this family, fractures preceded myopathy: the average age at onset of limb-girdle myopathy was 31 years, whereas that of fractures was 24 years. Fractures were primarily of the long bones of the lower limbs and were associated with poor healing and osteomyelitis, leading to amputation in some cases. Serum creatine kinase was mildly increased, and alkaline phosphatase was normal. Radiographs showed coarse trabeculation, patchy sclerosis, cortical thickening, and narrowing of the medullary cavities of the long bones. The findings were not consistent with Paget disease (see 167250). Muscle biopsies showed nonspecific myopathic changes without necrotic fibers, regenerating fibers, inflammatory infiltrates, or structural abnormalities. Many affected family members had premature graying of the hair and soft, thin skin, and 3 affected members had a clotting disorder. Inheritance The transmission patterns in the families with DMSMFH reported by Arnold (1973), Hardcastle et al. (1986), Norton et al. (1996), and Mehta et al. (2006) were all consistent with autosomal dominant inheritance. Mapping Martignetti et al. (1997, 1999) used microsatellite markers in a genome screen for the gene locus in diaphyseal medullary stenosis with malignant fibrous histiocytoma in 3 unrelated families. They linked the syndrome to a region of approximately 3 cM on 9p22-p21, with a maximum 2-point lod score of 5.49 with marker D9S171 at recombination fraction (theta) 0.05. This region of chromosome 9 is the site of chromosomal abnormalities in several other malignancies and contains a number of genes whose protein products are involved in growth regulation. Identification of the gene responsible for this rare familial sarcoma would be expected to define as well the cause of the more common nonfamilial, or sporadic, form of malignant fibrous histiocytoma, a tumor that constitutes approximately 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma. To determine whether the hereditary and sporadic forms of bone dysplasia with malignant fibrous histiocytoma are genetically linked, Martignetti et al. (2000) performed loss of heterozygosity (LOH) studies of the 9p22-9p21 region and found that 71% (5/7) of informative sporadic DMSMFH specimens displayed LOH for markers within that same region. Definition of the minimal region of LOH overlap effectively limited the DMSMFH gene to a 2-cM region between markers D9S736 and D9S171. By genomewide linkage analysis of the family reported by Henry et al. (1958) and Mehta et al. (2006), Watts et al. (2005) identified a candidate disease locus on chromosome 9p22-p21 (maximum lod score of 3.74 at marker D9S1121). Haplotype analysis refined the locus to a 15-Mb region. Genetic analysis excluded mutations in the ADAMTSL1 (609198) and TYRP1 (115501) genes. Watts et al. (2005) noted that the clinical phenotype in this family and the identified locus overlap with diaphyseal medullary stenosis with malignant fibrous histiocytoma. Molecular Genetics Camacho-Vanegas et al. (2012) identified 2 different heterozygous mutations affecting exon 9 of the MTAP gene (156540.0001 and 156540.0002) in affected members of 5 unrelated families with diaphyseal medullary stenosis with malignant fibrous histiocytoma. Four of the families had previously been reported by Arnold (1973), Hardcastle et al. (1986), Norton et al. (1996), and Watts et al. (2005). The mutations were found by positional cloning and examination of putative open reading frames within the candidate region. The analysis identified previously unrecognized exons in the MTAP gene, including exon 9. Both mutations affected splicing, with altered expression of MTAP isoforms. Serum samples from 2 patients showed accumulation of methylthioadenosine (MTA), whereas MTA was not present in serum from 3 controls. These findings implicated a defect in MTAP enzyme activity in the patients with mutations. DNA analysis of tumor tissue from an osteosarcoma of 1 patient showed homozygosity for the mutation with loss of heterozygosity of the wildtype allele. The findings of the study suggested that MTAP can also act as a tumor suppressor gene. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Presenile cataracts SKELETAL \- Osteopenia \- Radiolucency of the bones Limbs \- Bony dysplasia \- Pathologic fractures of the long bones \- Osteomyelitis leading to amputation due to slow healing fractures \- Patchy sclerotic changes to the long bones \- Coarse, sclerotic trabeculae \- Diaphyseal cortical thickening \- Diaphyseal medullary stenosis \- Metaphyseal striations \- Necrosis in large tubular bone diaphyses \- Narrow medullary cavities \- Marrow necrosis \- Marrow infarctions \- Bowing of the lower extremities SKIN, NAILS, & HAIR Skin \- Soft, thin skin (1 family) \- Easy bruising (1 family) Hair \- Premature graying (1 family) MUSCLE, SOFT TISSUES \- Limb-girdle muscle weakness (2 families) \- Proximal muscle weakness \- Proximal and distal muscle atrophy \- Distal limb muscle weakness occurs later \- Myopathic changes seen on EMG and muscle biopsy NEOPLASIA \- Malignant fibrous histiocytoma (in about 35% of patients) \- Osteosarcoma \- Fibrosarcoma LABORATORY ABNORMALITIES \- Serum alkaline phosphatase normal or mildly increased \- Serum creatine kinase normal or mildly increased MISCELLANEOUS \- Mean age at onset of bone fractures, 24 years \- Mean age at onset of proximal muscle weakness, 31 years \- Progressive disorder \- Not all patients have a myopathy \- Most become wheelchair-bound late in life MOLECULAR BASIS \- Caused by mutation in the methylthioadenosine phosphorylase gene (MTAP, 156540.0001 ) ▲ 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	DIAPHYSEAL MEDULLARY STENOSIS WITH MALIGNANT FIBROUS HISTIOCYTOMA	c1300202	30,105	omim	https://www.omim.org/entry/112250	2019-09-22T16:44:10	{"omim": ["112250"], "orphanet": ["85182"], "synonyms": ["Alternative titles", "BONE DYSPLASIA WITH MEDULLARY FIBROSARCOMA", "BONE DYSPLASIA WITH MALIGNANT FIBROUS HISTIOCYTOMA", "MYOPATHY, LIMB-GIRDLE, WITH BONE FRAGILITY"]}
Adenomatoid odontogenic tumor SpecialtyDentistry The adenomatoid odontogenic tumor is an odontogenic tumor[1] arising from the enamel organ or dental lamina. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 References * 6 External links ## Signs and symptoms[edit] Two thirds of cases are located in the anterior maxilla, and one third are present in the anterior mandible.[2] Two thirds of the cases are associated with an impacted tooth (usually being the canine). ## Diagnosis[edit] On radiographs, the adenomatoid odontogenic tumor presents as a radiolucency (dark area) around an unerupted tooth extending past the cementoenamel junction. It should be differentially diagnosed from a dentigerous cyst and the main difference is that the radiolucency in case of AOT extends apically beyond the cementoenamel junction. Radiographs will exhibit faint flecks of radiopacities surrounded by a radiolucent zone. It is sometimes misdiagnosed as a cyst.[3] ## Treatment[edit] Treatment can involve enucleation.[4] ## Epidemiology[edit] It is fairly uncommon, but it is seen more in young people. Two thirds of the cases are found in females.[5] ## References[edit] 1. ^ Nigam S, Gupta SK, Chaturvedi KU (2005). "Adenomatoid odontogenic tumor - a rare cause of jaw swelling". Braz Dent J. 16 (3): 251–3. doi:10.1590/S0103-64402005000300015. PMID 16429194. 2. ^ Nonaka CF, de Souza LB, Quinderé LB (2007). "Adenomatoid odontogenic tumour associated with dentigerous cyst--unusual case report". Rev Bras Otorrinolaringol (Engl Ed). 73 (1): 129–31. doi:10.1016/s1808-8694(15)31135-6. PMID 17505612. 3. ^ Handschel JG, Depprich RA, Zimmermann AC, Braunstein S, Kübler NR (August 2005). "Adenomatoid odontogenic tumor of the mandible: review of the literature and report of a rare case". Head Face Med. 1: 3. doi:10.1186/1746-160X-1-3. PMC 1266042. PMID 16270916. 4. ^ Vasconcelos BC, Frota R, Cardoso AB, Porto GG, Carneiro SC (2008). "Adenomatoid odontogenic tumor". Braz J Otorhinolaryngol. 74 (2): 315. doi:10.1016/s1808-8694(15)31107-1. PMID 18568215. 5. ^ "Odontogenic tumors". Archived from the original on 2011-07-20. Retrieved 2009-01-04. ## External links[edit] Classification D * ICD-O: M9300/0 * MeSH: C538229 * v * t * e Dental tumors Cementoblast * Cementoblastoma * Cementoma Ameloblast * Ameloblastoma Mixed/hamartoma * Odontoma Other * Adenomatoid odontogenic tumor * Keratocystic odontogenic tumour [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Adenomatoid odontogenic tumor	c0334565	30,106	wikipedia	https://en.wikipedia.org/wiki/Adenomatoid_odontogenic_tumor	2021-01-18T18:40:18	{"mesh": ["C538229"], "umls": ["C0334565"], "wikidata": ["Q4682247"]}
Constipation in children SpecialtyPediatrics Constipation in children refers to the medical condition of constipation in children. It is a functional gastrointestinal disorder. ## Contents * 1 Presentation * 2 Causes * 2.1 Congenital causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 Society and culture * 7 References ## Presentation[edit] Children have different bowel movement patterns than adults. In addition, there is a wide spectrum of normalcy when considering children’s bowel habits.[1] On average, infants have 3-4 bowel movements/day, and toddlers have 2-3 bowel movements per day. At around age 4, children develop an adult-like pattern of bowel movements (1-2 stools/day). Children benefit from scheduled toilet breaks, once early in the morning and 30 minutes after meals.[2][3] The Rome III Criteria for constipation in children helps to define constipation for various age groups.[citation needed] ## Causes[edit] While it is difficult to assess an exact age at which constipation most commonly arises, children frequently suffer from constipation in conjunction with life-changes. Examples include: toilet training, starting or transferring to a new school, and changes in diet.[1] Especially in infants, changes in formula or transitioning from breast milk to formula can cause constipation. Fortunately, the majority of constipation cases are not tied to a medical disease, and treatment can be focused on simply relieving the symptoms.[4] ### Congenital causes[edit] A number of diseases present at birth can result in constipation. They are as a group uncommon with Hirschsprung’s disease (HD) being the most common.[5] HD is more common in males than females, affecting 1 out of 5000 babies. In people with HD, specific types of cells called ‘neural crest cells’ fail to migrate to parts of the colon. This causes the affected portion of the colon to be unable to contract and relax to help push out a bowel movement. The affected portion of the colon remains contracted, making it difficult for stool to pass through.[6] Concern for HD should be raised in a child who has not passed stool during the first 48 hours of life. Milder forms of HD, in which only a small portion of the colon is affected, can present later in childhood as constipation, abdominal pain, and bloating.[6] Similar disorders to HD include anal achalasia and hypoganglionosis. In hypoganglionosis, there is a low number of neural crest cells, so the colon remains contracted. In anal achalasia, the internal anal sphincter remains contracted, making it difficult for stool to pass. However, there is a normal number of neural crest cells present.[4] There are also congenital structural anomalies that can lead to constipation, including anterior displacement of the anus, imperforate anus, strictures, and small left colon syndrome.[4] Anterior displacement of the anus can be diagnosed on physical exam.[7] The disease causes constipation because the inappropriate positioning of the anus which make it difficult to pass a bowel movement. Imperforate anus is an anus that ends in a blind pouch and does not connect to the rest of the person's intestines. Small left colon syndrome is a rare disease in which the left side of the babies colon has a small diameter, which makes it difficult for stool to pass. A risk factor for small left colon syndrome is having a mother with diabetes.[4] Some symptoms that may indicate an underlying disease include:[1] * Bowel movements that contain blood. * Severe abdominal bloating. * Peri-anal fistula * Absent anal wink reflex * Sacral dimple * Failure to thrive ## Diagnosis[edit] The diameters of different segments of the large intestine can be compared to the width of lumbar vertebra 2 for more consistent reference ranges on abdominal x-rays.[8] Ratios of large intestinal segments compared to lumbar vertebra 2, as 75th percentile, meaning that 25% of children normally have a ratio higher than this.[8] The Rome process suggests a diagnosis of constipation in children fewer than 4 years old when the child has 2 or more of the following complaints for at least 1 month.[4] For children older than 4 years, there must be 2 of these complaints for at least 2 months. * 2 or fewer bowel movements per week * Passing large bowel movements * On physical exam, a doctor may find large amounts of feces within the child’s rectum. * A child who is already toilet trained has at least 1 accident per week involving a bowel movement. * Child demonstrates withholding behavior in which he or she actively tries not to pass a bowel movement. * Hard stools * Pain with defecation. For children, the degree of constipation may be scored by the Leech or the Barr systems: Areas used for the Leech system of constipation grading. * The Leech system assigns a score of 0 to 5 based on the amount of feces:[9] * 0: no visible feces * 1: scanty feces visible * 2: mild fecal loading * 3: moderate fecal loading * 4: severe fecal loading * 5: severe fecal loading with bowel dilatation These score are assigned separately for the right colon, the left colon and the rectosigmoid colon, resulting in a maximum score of 15. A Leech score of 9 or greater is regarded as positive for constipation.[9] * The Barr system rates both the amount and consistency of the faeces, and assigns a score separately for the ascending colon, transverse colon, descending colon and rectum. Its maximum score is 22, and a score of 10 or greater is regarded as positive for constipation.[10] ## Treatment[edit] Lactulose and milk of magnesia have been compared with polyethylene glycol (PEG) in children. All had similar side effects, but PEG was more effective at treating constipation.[11][12] Osmotic laxatives are recommended over stimulant laxatives.[13] ## Epidemiology[edit] There is wide variation in the rates of constipation as reported by research in various countries.[14] The variation in research data makes it challenging to describe the true global situation.[14] Approximately 3% of children have constipation, with girls and boys being equally affected.[4] With constipation accounting for approximately 5% of general pediatrician visits and 25% of pediatric gastroenterologist visits, the symptom carries a significant financial impact upon our healthcare system.[1] ## Society and culture[edit] Constipation is often emotionally stressful for children and their caregivers.[15] It is common for parents to bring their children to doctors for this condition.[15] The experience of going to a doctor for this can be stressful.[15] Too often, children at doctors receive unnecessary health care when they get medical imaging for constipation.[16] Children should only get tests when there is an indication.[16] ## References[edit] 1. ^ a b c d Colombo, Jennifer M.; Wassom, Matthew C.; Rosen, John M. (2015-09-01). "Constipation and Encopresis in Childhood". Pediatrics in Review. 36 (9): 392–401, quiz 402. doi:10.1542/pir.36-9-392. ISSN 1526-3347. PMID 26330473. 2. ^ Walia R, Mahajan L, Steffen R (October 2009). "Recent advances in chronic constipation". Curr Opin Pediatr. 21 (5): 661–6. doi:10.1097/MOP.0b013e32832ff241. PMID 19606041. S2CID 11606786. 3. ^ Bharucha AE (2007). "Constipation". Best Practice & Research Clinical Gastroenterology. 21 (4): 709–31. doi:10.1016/j.bpg.2007.07.001. PMID 17643910. 4. ^ a b c d e f Tabbers, M.M.; DiLorenzo, C.; Berger, M.Y.; Faure, C.; Langendam, M.W.; Nurko, S.; Staiano, A.; Vandenplas, Y.; Benninga, M.A. (2014). "Evaluation and Treatment of Functional Constipation in Infants and Children". Journal of Pediatric Gastroenterology and Nutrition. 58 (2): 265–281. doi:10.1097/mpg.0000000000000266. PMID 24345831. S2CID 13834963. 5. ^ Wexner, Steven (2006). Constipation: etiology, evaluation and management. New York: Springer. 6. ^ a b Wesson, David (November 9, 2016). "UpToDate: Constipation". UpToDate. Retrieved March 15, 2017. 7. ^ Pediatrics, American Academy of (1986-08-01). "Congenital Anterior Displacement of Anus". Pediatrics in Review. 8 (2): 38–62. doi:10.1542/pir.8-2-38. ISSN 0191-9601. 8. ^ a b Koppen, Ilan J. N.; Yacob, Desale; Di Lorenzo, Carlo; Saps, Miguel; Benninga, Marc A.; Cooper, Jennifer N.; Minneci, Peter C.; Deans, Katherine J.; Bates, D. Gregory; Thompson, Benjamin P. (2016). "Assessing colonic anatomy normal values based on air contrast enemas in children younger than 6 years". Pediatric Radiology. 47 (3): 306–312. doi:10.1007/s00247-016-3746-0. ISSN 0301-0449. PMC 5316394. PMID 27896373. 9. ^ a b Leech, Susan C.; McHugh, Kieran; Sullivan, P. B. (1999). "Evaluation of a method of assessing faecal loading on plain abdominal radiographs in children". Pediatric Radiology. 29 (4): 255–258. doi:10.1007/s002470050583. ISSN 0301-0449. PMID 10199902. S2CID 9542750. 10. ^ G., Anthony; H., Kathleen (2012). "The Role of Diagnostic Tests in Constipation in Children". Constipation - Causes, Diagnosis and Treatment. doi:10.5772/29213. ISBN 978-953-51-0237-3. 11. ^ "Is PEG (Polyethylene Glycol) a more effective laxative than Lactulose in the treatment of a child who is constipated?". BestBETs. 16 July 2007. 12. ^ Candy D, Belsey J (February 2009). "Macrogol (polyethylene glycol) laxatives in children with functional constipation and faecal impaction: a systematic review". Arch. Dis. Child. 94 (2): 156–60. doi:10.1136/adc.2007.128769. PMC 2614562. PMID 19019885. 13. ^ "Osmotic laxative are preferable to the use of stimulant laxatives in the constipated child". BestBETs. 9 November 2007. 14. ^ a b Boronat, Alexandre Canon; Ferreira-Maia, Ana Paula; Matijasevich, Alicia; Wang, Yuan-Pang (2017). "Epidemiology of functional gastrointestinal disorders in children and adolescents: A systematic review". World Journal of Gastroenterology. 23 (21): 3915–3927. doi:10.3748/wjg.v23.i21.3915. PMC 5467078. PMID 28638232. 15. ^ a b c Ferrara, Lucille R.; Saccomano, Scott J. (July 2017). "Constipation in children". The Nurse Practitioner. 42 (7): 30–34. doi:10.1097/01.NPR.0000520418.32331.6e. PMID 28622255. 16. ^ a b Ferguson, Catherine Craun; Gray, Matthew P.; Diaz, Melissa; Boyd, Kevin P. (July 2017). "Reducing Unnecessary Imaging for Patients With Constipation in the Pediatric Emergency Department". Pediatrics. 140 (1): e20162290. doi:10.1542/peds.2016-2290. PMID 28615355. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Constipation in children	c3826517	30,107	wikipedia	https://en.wikipedia.org/wiki/Constipation_in_children	2021-01-18T18:39:28	{"wikidata": ["Q39054873"]}
For other uses, see Ptosis (disambiguation). This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Visceroptosis" – news · newspapers · books · scholar · JSTOR (August 2007) (Learn how and when to remove this template message) Visceroptosis (Glénard's disease) Other namesEnteroptosis, splanchnoptosis, abdominal ptosis SpecialtyGastroenterology, general surgery Visceroptosis is a prolapse or a sinking of the abdominal viscera (internal organs) below their natural position. "Ptosis" being the defining term, any or all of the organs may be displaced downward. When only the intestines are involved, the condition is known as enteroptosis. When the stomach is found below its normal position, the term gastroptosis is used. The condition exists in all degrees of severity and may not give rise to any adverse symptoms. Generally, when adverse symptoms are associated with the condition, however, there may be loss of appetite, heartburn, nervous indigestion, constipation, diarrhea, abdominal distention, headache, vertigo, emaciation, and loss of sleep. Any or all of these symptoms may be present. The condition may be brought about by loss of muscular tone, particularly of the abdominal muscles, with relaxation of the ligaments that typically hold the viscera in place. Tightlacing has been held to be a cause as well. Corsets to reduce the circumference of women's waists have been used to enable fashionable styles occurring during several historical periods, such as the late 1800s and early 1900s, when these symptoms were described for treatment by physicians. Adverse symptoms may be alleviated by supporting the organs with a properly applied bandage, or other similar device. Rest in bed, attention to diet, hygiene, exercise, and general muscular strengthening will cure the majority of cases.[citation needed] In some cases, surgical intervention may become necessary.[citation needed] Dr. Frantz Glénard (1848–1920) Visceroptosis is a known risk factor for the development of Superior mesenteric artery syndrome. Visceroptosis also is known as Glénard's disease (after French physician Frantz Glénard [1848–1920]). * Glénard's theory – the theory that abdominal ptosis is a nutritional disease with atrophy and prolapse of the intestine * Glénard's test (also called girdle test) – while standing behind the patient, the examiner places his arms around the patient, so that his hands meet in front of the patient's abdomen; he squeezes, raising the viscera, and then allows them to fall suddenly; Glénard's theory suggests that if the patient feels relieved by the raising pressure and experiences distress on the release, the condition is probably one of splanchnoptosis[1] * Stiller's theory – the theory that gastroptosis is due to universal asthenia characterized by weakness and laxity of the viscera ## References[edit] 1. ^ Dorland's Medical Dictionary ## External links[edit] Classification D * ICD-10: K63.4 * ICD-9-CM: 569.89 * MeSH: D014782 Wikimedia Commons has media related to Visceroptosis. * This article incorporates text from a publication now in the public domain: Gilman, D. C.; Peck, H. T.; Colby, F. M., eds. (1905). New International Encyclopedia (1st ed.). New York: Dodd, Mead. Missing or empty `\|title=` (help) * v * t * e Corsets and corsetmaking Types of corset * Basque * Corsage * Corselet * Girdle * Waist cincher Corsetmaking * Bone (corsetry) * Busk * Spoon busk History * Corset controversy * Metal corset * Hourglass corset * Roxey Ann Caplin Corset fetishism * Body modification * Bondage corset * Neck corset * Tightlacing * Training corset * Wasp waist Corset manufacturers * Baystate * Frederick's of Hollywood * Kraus * Spirella * Strouse, Adler * Vollers * The Warner Brothers Corset Co. * Worcester Categories * Corsetry * Fashion * Foundation garments * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Visceroptosis	c0042783	30,108	wikipedia	https://en.wikipedia.org/wiki/Visceroptosis	2021-01-18T19:02:38	{"mesh": ["D014782"], "icd-9": ["569.89"], "icd-10": ["K63.4"], "wikidata": ["Q5420556"]}
High leather boots worn in an overt sexual context. Man wearing high boots over jeans Typical pair of modern women's fashion boots in black leather. Knee-high ballet boots, impractical boots made expressly for their sexual appeal. A model wearing boots. Boot fetishism is a sexual fetish focused on boots. Boots have become the object of sexual attraction amounting to fetishism for some people and they have become a standard accessory in BDSM scenes (where leather, latex and PVC boots are favoured) and a fashion accessory in music videos.[1][2] Boots are seen as perhaps the most fetishistic of all footwear and boots may be the most popular fetish clothing attire.[3] ## Contents * 1 History * 2 Causes * 3 Popular culture * 4 See also * 5 References ## History[edit] One of the earliest descriptions of boots as a fetishistic object can be found in Émile Zola's 1868 novel Thérèse Raquin.[4] Actual boot fetishism is described in the diaries of 19th century British woman Hannah Cullwick, of which parts have been published.[5] Hermine Hug-Hellmuth described boot fetishism scientifically in 1915.[6] This article has also been published in English with comments by Arlene K. Richards in 1990, as Female fetishes and female perversions: Hermine Hug-Hellmuth's "A case of female foot or more properly boot fetishism" reconsidered.[7] Boots were used by Stanley Rachman as a subject for research on conditioning as a cause for fetishism in the 1960s, making men sexually aroused by seeing pictures of boots,[8] but the results have been put into question later, as boots already were very much en vogue for sexually attractive women at the time.[9] Unlike shoes, boot styles have often appeared as street wear before they inspire fashion designers.[10] Boots are usually seen as a sign of empowerment for the wearer, especially when worn by women.[11] This may be a reason for the connection to BDSM, where boots usually are seen as a statement of dominance. So called boot worship became a common subcultural practice among sadomasochists and related fetishists in the early 20th century.[12] High heeled boots help to elongate the calf, creating a longer legged appearance which is generally considered to be more sexually attractive. The length of the boot shafts also adds to this impression. Boots have been displayed in magazines such as Leg Show, and there are also magazines and websites aimed directly at this fetish.[citation needed] Boot fetishism may be accompanied by a fetish for the material from which it is made, such as leather, rubber, or latex. Boot fetishism is often targeted at fashion boots and riding boots but there are also boots expressly made for fetish purposes, such as ballet boots and some forms of thigh-high boots.[citation needed] There is also a very prominent subsection of mostly gay men who fetishize men's boots, with "boot worship" being a common practice in this group, to the point where there is a yearly contest to see who is the best bootblack.[13] The types of boots favored by men differ from those worn by women, with men typically preferring more sturdy, rugged boots, such as combat boots, jump boots, motorcycle boots, or riding boots.[citation needed] These boots feature prominently in outfits worn by leather enthusiasts in competitions such as International Mr. Leather.[citation needed] ## Causes[edit] Hsu and J. Michael Bailey (2019) argue that there is little evidence for "sexual conditioning" explanations of boot fetishism, since only a small minority of men who have seen attractive women in boots develop boot fetishes. They also say that "boot fetishes would not occur in a world without boots, and in a world where men and women switched boots, different patterns of fetishes would likely develop". They argue that random developmental processes which are still poorly understood make some men more prone to developing paraphilias and fetishes.[14] ## Popular culture[edit] The television series The Avengers, which ran in the 1960s, often featured fetishistic clothing, with Emma Peel, played by Diana Rigg, wearing thigh-high boots as a characteristic sign of her as a sexy and strong woman.[15] Patrick Macnee and Rigg's predecessor Honor Blackman (as Cathy Gale) released a 45 RPM single in 1964 titled "Kinky Boots".[16] Female comic book super heroines and villains, like Wonder Woman and Catwoman, also often wear boots as a sign of combined female power and sex appeal.[17] Jill, protagonist of the video game Mighty Jill Off, is a sexual submissive with a fetish for boots.[18] ## See also[edit] * Human sexuality portal * Charles Guyette * Eric Stanton * Foot fetishism * Fuck-me boots * Gene Bilbrew * Irving Klaw * John Willie * Lionel Bussey * Shoe fetishism ## References[edit] 1. ^ XBIZ. "Kinky Boots: An Enduring Symbol in Fetish Fashion". XBIZ. 2. ^ "Work Boots for Men ~ Every Occasion!". www.bootzoom.com. Retrieved 16 October 2015. 3. ^ Bradley Quinn. "The Boot". London (2010): Laurence King Publishing Ltd. ISBN 978-1-85669-663-0. Pages 68-73 4. ^ Edward Shorter: Written in the Flesh: A History of Desire. University of Toronto Press 2005, pages 222-223, ISBN 0-8020-3843-3 5. ^ see sources in the article about her 6. ^ Whitney Davis: Replications: Archaeology, Art History, Psychoanalysis. Pennsylvania Stat Press 1996, page 326, ISBN 027104411X. Accessed August 27, 2013. 7. ^ Psychoanalytic Review, Vol. 77, No. 1, 1990, pp. 11-23, American Psychological Association. Accessed August 27, 2013. 8. ^ S. Rachman: Sexual fetishism: An experimental analogue. The Psychological Record, Vol 16(3), 1966, 293-296. 9. ^ Dean Burnett: Fifty Shades of Grey matter: the psychology of sexual arousal, The Guardian, August 8, 2012. Accessed August 27, 2013. 10. ^ Quinn, p. 130 11. ^ Quinn, p. 152–169 12. ^ Quinn, p. 73 13. ^ "Bootblack Contest". International Mr. Leather. 14. ^ Hsu, Kevin J.; Bailey, J. Michael (2019). "The Poverty of Conditioning Explanations for Sexual Interests: Reply to Grey (2019)". Archives of Sexual Behavior. 49 (1): 53–55. doi:10.1007/s10508-019-01561-5. ISSN 1573-2800 – via ResearchGate. 15. ^ Quinn, p. 159–160 16. ^ Ken Tucker. All You Need Is Steed: 'Avengers' You Can Dance To, Entertainment Weekly, January 11, 1991. Accessed August 27, 2013. 17. ^ Quinn, p. 161–162 18. ^ Shoemaker, Brad (2010-10-19). "Super Meat Boy (video game )". Giant Bomb. Retrieved 2011-04-25. * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Boot fetishism	None	30,109	wikipedia	https://en.wikipedia.org/wiki/Boot_fetishism	2021-01-18T18:29:52	{"wikidata": ["Q3092561"]}
Neurodegeneration with brain iron accumulation Other namesNBIA SpecialtyNeurology Neurodegeneration with brain iron accumulation is a heterogenous group of inherited neurological disorders, still under research, in which iron accumulates in the basal ganglia, either resulting in progressive dystonia, Parkinsonism, spasticity, optic atrophy, retinal degeneration, neuropsychiatric, or diverse neurologic abnormalities.[1] Some of the NBIA disorders have also been associated with several genes in synapse and lipid metabolism related pathways.[2] NBIA is not one disease but an entire group of disorders, characterized by an accumulation of brain iron, sometimes in the presence of axonal spheroids in the central nervous system.[3] Iron accumulation can occur anywhere in the brain, with accumulation typically occurring in globus pallidus, substantia nigra, pars reticula, striatum and cerebellar dentate nuclei.[4] Symptoms can include various movement disorders, neuropsychiatric issues, seizures, visual disturbances, and cognitive decline, usually in different combinations.[4] The cause of NBIA disorders are a multitude of possible mutations in genes directly involved in iron metabolism, and/or impaired phospholipid, and/or ceramide metabolism, and/or lysosomal disorders, as well as mutations in genes with unknown functions.[4] Onset can occur at different ages, from early childhood to late adulthood.[4] ## Contents * 1 Variants * 1.1 Other variants * 2 Diagnosis * 3 Treatments * 4 References * 5 External links ## Variants[edit] Overview of NBIA subtypes[5][6][7] NBIA variant Gene Inheritance MRI diagnosis Symptoms Pantothenate kinase-associated neurodegeneration (PKAN)[8] PANK2 autosomal recessive PLA2G6-associated neurodegeneration (PLAN)[9] PLA2G6 autosomal recessive Mitochondrial membrane protein-associated neurodegeneration (MPAN)[10] C19orf12 autosomal recessive Beta-propeller protein-associated neurodegeneration (BPAN)[11] WDR45 X-linked dominant (mostly de novo mutations) Fatty acid hydroxylase-associated neurodegeneration (FAHN)[12] FA2H autosomal recessive Kufor–Rakeb syndrome ATP13A2 autosomal recessive Neuroferritinopathy FTL autosomal dominant Aceruloplasminemia CP autosomal recessive Woodhouse–Sakati syndrome DCAF17 autosomal recessive COASY protein-associated neurodegeneration (CoPAN) COASY autosomal recessive NBIA7[13] REPS1 autosomal recessive NBIA8[13] CRAT autosomal recessive ### Other variants[edit] There are a number of idiopathic NBIA variants for which details are still rare or missing. They all have in common that a disturbed iron metabolism causes havoc in the brain, especially the basal ganglia.[14] ## Diagnosis[edit] DAT-Scans, TC(D)-Sonography, PET-Scans and in some cases Magnetic resonance imaging (MRI) (type of scans depending on the symptoms)[15] are used to distinguish between the different forms of NBIA due to the accumulation of iron in different areas of the brain.[16] Patients typically fall into two different categories: (1) early onset, rapid progression or (2) late onset, slow progression.[16] The first type is considered to be the classic presentation, while the second type is thought to be a more atypical presentation. Phenotypes of the different disorders appear to be dependent on age, i.e. amount of iron accumulation and cognitive abilities.[17] ## Treatments[edit] An effective treatment has yet to be found. In many cases electrical stimulation of the globus pallidus has been shown to produce improvement of dystonia severity, however it has not been shown to delay neurodegeneration.[17][18] There is often overlap in the phenotypes of the symptoms both between different NBIA disorders and between NBIA and other disorders, leading to misdiagnoses.[18] Treatments typically treat or ameliorate the symptoms and do not address the accumulation of iron.[18] Psychopharmacology, such as with dopaminergic drugs, anticholinergics, tetrabenazine, is often used to treat the symptoms but does not improve the long term outcome of the patient.[18] ## References[edit] 1. ^ Ward, Roberta J.; Chrichton, Robert R. (2019). "Chapter 4. Ironing out the Brain". In Sigel, Astrid; Freisinger, Eva; Sigel, Roland K. O.; Carver, Peggy L. (Guest editor) (eds.). Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic. Metal Ions in Life Sciences. 19. Berlin: de Gruyter GmbH. pp. 87–122. doi:10.1515/9783110527872-010. ISBN 978-3-11-052691-2. PMID 30855105. 2. ^ Bettencourt C, Forabosco P, Wiethoff S, Heidari M, Johnstone DM, Botía JA, Collingwood JF, Hardy J, Milward EA, Ryten M, Houlden H (March 2016). "Gene co-expression networks shed light into diseases of brain iron accumulation". primary. Neurobiology of Disease. 87: 59–68. doi:10.1016/j.nbd.2015.12.004. PMC 4731015. PMID 26707700. 3. ^ Gregory A, Polster BJ, Hayflick SJ (February 2009). "Clinical and genetic delineation of neurodegeneration with brain iron accumulation". review. Journal of Medical Genetics. 46 (2): 73–80. doi:10.1136/jmg.2008.061929. PMC 2675558. PMID 18981035. 4. ^ a b c d Dusek P, Schneider SA (August 2012). "Neurodegeneration with brain iron accumulation". review. Current Opinion in Neurology. 25 (4): 499–506. doi:10.1097/wco.0b013e3283550cac. PMID 22691760. 5. ^ "Einführung und Klinische Symptomatik". NBIA-Krankheitsbilder (in German). Friedrich Baur Institute, University Hospital Munich, Germany. Retrieved 2018-05-13. 6. ^ Gregory A, Hayflick S (28 February 2013). Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). Neurodegeneration with Brain Iron Accumulation Disorders Overview. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle. PMID 23447832. 7. ^ Hogarth P (January 2015). "Neurodegeneration with brain iron accumulation: diagnosis and management". Journal of Movement Disorders. 8 (1): 1–13. doi:10.14802/jmd.14034. PMC 4298713. PMID 25614780. 8. ^ Gregory A, Hayflick SJ (2003). Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). "Pantothenate Kinase-Associated Neurodegeneration". GeneReviews [Internet]. PMID 20301663. 9. ^ Gregory A, Kurian MA, Maher ER, Hogarth P, Hayflick SJ (2008). Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). "PLA2G6-Associated Neurodegeneration". GeneReviews [Internet]. PMID 20301718. 10. ^ Gregory A, Hartig M, Prokisch H, Kmiec T, Hogarth P, Hayflick SJ (2014). Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). "Mitochondrial Membrane Protein-Associated Neurodegeneration". GeneReviews [Internet]. PMID 24575447. 11. ^ Gregory A, Kurian MA, Haack T, Hayflick SJ, Hogarth P (16 Feb 2017). Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). "Beta-Propeller Protein-Associated Neurodegeneration". GeneReviews [Internet]. PMID 28211668. 12. ^ Kruer MC, Gregory A, Hayflick SJ (28 Jun 2011). Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (eds.). "Fatty Acid Hydroxylase-Associated Neurodegeneration". GeneReviews [Internet]. PMID 21735565. 13. ^ a b Drecourt A, Babdor J, Dussiot M, Petit F, Goudin N, Garfa-Traoré M, et al. (February 2018). "Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation". primary. American Journal of Human Genetics. 102 (2): 266–277. doi:10.1016/j.ajhg.2018.01.003. PMC 5985451. PMID 29395073. 14. ^ Hogarth P. et al.: New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. In: Neurology. 2013 Jan 15;80(3):268-75. doi: 10.1212/WNL.0b013e31827e07be. Epub 2012 Dec 26. 15. ^ Brüggemann N. et al.: Recessively inherited parkinsonism: effect of ATP13A2 mutations on the clinical and neuroimaging phenotype. Arch Neurol. 2010 Nov;67(11):1357-63. doi: 10.1001/archneurol.2010.281. 16. ^ a b Hayflick SJ, Hartman M, Coryell J, Gitschier J, Rowley H (2006-06-01). "Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations". primary. AJNR. American Journal of Neuroradiology. 27 (6): 1230–3. PMC 2099458. PMID 16775270. 17. ^ a b Schneider SA, Bhatia KP (June 2012). "Syndromes of neurodegeneration with brain iron accumulation". review. Seminars in Pediatric Neurology. 19 (2): 57–66. doi:10.1016/j.spen.2012.03.005. PMID 22704258. 18. ^ a b c d Schneider SA, Dusek P, Hardy J, Westenberger A, Jankovic J, Bhatia KP (January 2013). "Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)". primary. Current Neuropharmacology. 11 (1): 59–79. doi:10.2174/157015913804999469. PMC 3580793. PMID 23814539. ## External links[edit] Classification D * ICD-10: G23.0 * MeSH: C538421 C538421, C538421 * DiseasesDB: 35160 External resources * GeneReviews: NBK121988 * Orphanet: 385 * "Neurodegeneration with Brain Iron Accumulation Information Page". National Institute of Neurological Disorders and Stroke. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Neurodegeneration with brain iron accumulation	c2931845	30,110	wikipedia	https://en.wikipedia.org/wiki/Neurodegeneration_with_brain_iron_accumulation	2021-01-18T18:46:45	{"gard": ["11899"], "mesh": ["C538421"], "umls": ["C2931845"], "orphanet": ["385"], "wikidata": ["Q16892735"]}
A number sign (#) is used with this entry because of evidence that this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A13; MDDGA13) is caused by homozygous mutation in the B3GNT1 gene (605517), which encodes a type II transmembrane protein involved in glycosylation of target proteins, on chromosome 11q13. Description Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is a autosomal recessive disorder associated with severe neurologic defects and resulting in early infantile death. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Buysse et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670). Clinical Features Buysse et al. (2013) reported a family of East Indian descent in which 4 sibs had a clinical diagnosis of Walker-Warburg syndrome. Three pregnancies were terminated and 1 affected son died at 2 years of age. The living patient showed severe hypotonia with increased serum creatine kinase and developed intractable seizures. All patients had retinal dysplasia and severe brain malformations, including hydrocephalus, brainstem and cerebellar hypoplasia, nodular heterotopia, and cobblestone lissencephaly. Other more variable abnormalities included thin corpus callosum, absent septum pellucidum, cortical cysts, and Dandy-Walker malformation. One fetus had dysplastic kidneys and testicular hypoplasia. Muscle biopsies showed decreased glycosylation of DAG. Shaheen et al. (2013) reported 7 children from a highly consanguineous Saudi Arabian family with MDDGA13. The proband was born with occipital encephalocele, anencephaly, cloudy cornea, proptotic eyes, spasticity, micropenis, and multicystic dysplastic kidneys. Serum creatine kinase was highly elevated; he died on the sixth day of life. The other affected individuals had similar features and died either in utero or shortly after birth, although 1 patient survived to 8 months of age. The longest surviving infant had severe motor and cognitive impairment, seizures, undescended testes, micropenis, severe bilateral hydronephrosis, blindness, and agenesis of the optic nerves. Inheritance The transmission pattern of MDDGA13 in the family reported by Buysse et al. (2013) was consistent with autosomal recessive inheritance. Mapping By homozygosity mapping of a family with MDDGA, Buysse et al. (2013) found linkage to a region on chromosome 11q13. Affected individuals shared a 5.24-Mb haplotype. Molecular Genetics In 4 sibs of East Indian descent with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, Buysse et al. (2013) identified homozygosity for 2 missense mutations in the B3GNT1 gene (605517.0001). The mutations, which were found by homozygosity mapping and candidate gene analysis, segregated with the disorder and were not found in 5,379 control samples or 672 in-house control exomes. Both mutations were located in the conserved glycosyltransferase domain of the protein and were shown to result in reduced glycosylation compared to wildtype when expressed in cells, consistent with a loss of function. Morpholino knockdown of b3gnt1 in zebrafish resulted in little or no glycosylated alpha-dystroglycan, and morphant embryos showed signs of muscular dystrophy. Mutations in B3GNT1 were not found in 57 additional families with dystroglycanopathy, suggesting that it is a rare cause of these disorders. In an infant, born in a large consanguineous Saudi Arabian family, with MDDGA13, Shaheen et al. (2013) identified a homozygous frameshift mutation in the B3GNT1 gene (605517.0002). The mutation, which was found by exome sequencing, was not found in the dbSNP database or in an in-house database of 250 Saudi exomes. There were 6 similarly affected family members, but DNA was not available for analysis. Functional studies and studies of patient cells were not performed. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinal dysplasia \- Optic nerve dysplasia \- Cloudy corneas \- Blindness GENITOURINARY External Genitalia (Male) \- Testicular hypoplasia \- Micropenis Kidneys \- Dysplastic kidneys \- Renal cysts \- Hydronephrosis MUSCLE, SOFT TISSUES \- Hypotonia, severe \- Decreased glycosylation of alpha-dystroglycan seen on muscle biopsy \- Muscular dystrophy NEUROLOGIC Central Nervous System \- Lack of psychomotor development \- Hydrocephalus \- Anencephaly \- Occipital encephalocele \- Enlarged ventricles \- Seizures \- Spasticity \- Agenesis of the corpus callosum \- Brainstem hypoplasia \- Cerebellar hypoplasia \- Cortical dysplasia \- Cobblestone lissencephaly \- Nodular heterotopia \- Dandy-Walker malformation LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Two unrelated families have been reported (last curated February 2017) \- Onset in utero \- Early death MOLECULAR BASIS \- Caused by mutation in the beta-1,3-N-acetylglucosaminyltransferase gene (B3GNT1, 605581.0001 ) ▲ 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-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 13	c0265221	30,111	omim	https://www.omim.org/entry/615287	2019-09-22T15:52:39	{"doid": ["0111238"], "mesh": ["D058494"], "omim": ["615287"], "orphanet": ["899"], "synonyms": ["Alternative titles", "WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, B3GNT1-RELATED"]}
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(January 2012) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Epilepsy-intellectual disability in females Other namesEIEE9, EFMR, GEF+ syndrome, epilepsy-intellectual disability in females,[1] Juberg-Hellman syndrome[2][3] epilepsy limited to females with intellectual disability (EFID)[1] Epilepsy-intellectual disability in females also known as PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9), is a rare type of epilepsy that affects predominately females and is characterized by clusters of brief seizures, which start in infancy or early childhood, and is occasionally accompanied by varying degrees of cognitive impairment.[4][5][6][7] The striking pattern of onset seizures at a young age, genetic testing and laboratory results, potential developmental delays or developmental regression and associated disorders, eases diagnosis. The National Institutes of Health Office and Rare Disease Research characterizes PCDH19 gene-related epilepsy as a rare disorder.[8] Although formal epidemiologic data is not available, results from diagnostic screenings indicate that approximately 1 out of 10 girls who have seizure onset before five years of age may have PCDH19 mutations.[9][10][11] ## Contents * 1 Signs and symptoms * 1.1 Seizures * 1.2 Developmental problems * 2 Causes * 2.1 Genetics * 2.2 Classification * 3 Diagnosis * 3.1 Diagnostic test * 4 Treatment * 4.1 Medication * 4.2 Urgent care * 5 Epidemiology * 6 History * 7 Society and culture * 8 Research * 8.1 Registry * 8.2 Basic research * 8.3 Gene therapy * 8.4 Therapeutics * 9 Notes * 10 References * 11 External links ## Signs and symptoms[edit] PCDH19 gene-related epilepsy is a highly variable and rare epileptic syndrome, characterized by the early-onset of seizure clusters, with a range of 4 – 60 months, and an average onset at 12.9 months.[4][5][6][7] Other aspects, such as varying degrees of cognitive impairment and behavioral and psychiatric problems, are also common, but are not essential for diagnosis of PCDH19 gene-related epilepsy.[4][5][6][7][12][13][14][15][16][excessive citations] PCDH19 gene-related epilepsy shares several clinical features with other early-onset epileptic encephalopathies, such as Dravet Syndrome, Generalized epilepsy with febrile seizures plus (GEFS+), FIRES (febrile infection–related epilepsy syndrome) Lennox-Gastaut syndrome or epilepsy of unknown origin.[11] However, the disorder has a distinct evolution of symptoms, and is associated with specific genetic mutations of the PCDH19 gene.[11] ### Seizures [edit] The hallmark characteristic of PCDH19 gene-related epilepsy is early-onset cluster seizures that often cause cyanotic spells, which start in infancy or early childhood.[4][5][6][7] The onset of the first cluster of seizures usually coincides with a fever (febrile seizures), however subsequent seizures may be febrile or afebrile.[4][5][17] The seizure clusters are generally brief seizures, lasting 1–5 minutes, often accompanied by fearful screaming observed in 63% of girls.[4][5][11][15][17][18][excessive citations] These cluster seizures can occur more than 10 times a day over several days, with varying amounts of time between seizure clusters.[4][11] Over time, children with PCDH19 gene-related epilepsy tend to exhibit multiple seizure types, including focal, generalized tonic-clonic, tonic, atonic, myclonus, and absence seizures.[15][16] In a small study of 35 female patients with PCDH19 gene-related epilepsy, rare episodes of status epilepticus occurred in about 30% of patients in the early course of the disorder.[18] In PCDH19 gene-related epilepsy, the seizures are often refractory to treatment, especially in infancy and childhood.[11][12][18] Additionally, seizures are usually characterized by persistence of cluster seizures, with variable frequency.[11][18] In a study of 35 female patients with PCDH19 gene-related epilepsy, approximately 30% had become seizure free in the girl's childhood (mean age of 12 years), yet some continued into adulthood.[18] In the same study, a few patients still had recurrent cluster seizures that evolved into status epilepticus in childhood or early adolescence.[18] ### Developmental problems[edit] Beyond early-onset and treatment-resistant cluster seizures, PCDH19 gene-related epilepsy is usually, but not always, associated with cognitive and sensory impairment of varying degrees, and psychiatric and behavioral problems.[4][5][6][7][11][12][13][14][15][excessive citations] It is estimated that up to 60 to 75% of the females have cognitive deficits, ranging from mild to severe intellectual disability, which do not appear to be related to frequency or severity of seizures.[6][7][11][12][13][14] Development over the course of a female patients’ childhood can follow one of three courses: delays from birth that persist into adulthood, normal development and then regression, or normal intellectual development.[6][11] It is not yet clear why some people experience delayed intellectual growth and others regress with epilepsy.[14][19] From the University of Melbourne study, two-thirds of PCDH19 gene-related epilepsy patients have borderline intellectual functioning or intellectual disability, while one third have normal intelligence.[14] A connection to depression, autism, obsessive and aggressive behaviors and other disorders has been observed in PCDH19 gene-related epilepsy.[4][5][6][7][11][12][13][14][excessive citations] Approximately 40-60% of girls diagnosed with a PCDH19 mutation are on the autism spectrum.[6][13][14][17] Many of those with PCDH19 gene mutations also exhibit behavioral and psychological problems – including ADHD, aggression, obsessive-compulsive disorder, and anxiety.[6][13][14][17] Other neurological abnormalities may present, including sleep disturbances, ictal apnea, motor deficits, hypotonia, language delay, sensory integration problems and dysautonomia.[6] ## Causes[edit] A 2008 study, found a relationship between the PCDH19 gene and early onset female seizures, with subsequent studies confirming the relationship.[14][15][19][20] PCDH19 gene-related epilepsy can arise as a single case in a family, due to a de novo error in cell replication, or it can be inherited.[11][12][13] In a large series of cases in which inheritance was determined, half of the PCDH19 mutations occurred de novo, and half were inherited from fathers in good health, and who had no evidence of seizures or cognitive disorders.[11][12][13] Men and women can transmit the PCDH19 mutation, although females, but not males, usually, but not always, exhibit symptoms, which can be very mild. Females with a mutation have a 50% chance of having children who are carriers. Men have a 100% chance of transmitting the mutation to a daughter and 0% chance to a son.[11][12][13][14] Although males do not generally exhibit PCDH19 gene-related history such as cluster seizures, in a study involving four families with PCDH19 gene mutations, 5 of the fathers had obsessive and controlling tendencies.[14] The linkage of chromosome Xq22.1 to PCDH19 gene-related epilepsy in females was confirmed in all of the families.[14] The inheritance pattern is very unusual, in that men that carry the PCDH19 gene mutation on their only X-chromosome are typically unaffected, except in rare instances of somatic mosaicism.[11][11] Alternatively, approximately 90% of women, who have the mutation on one of their two X-chromosomes, exhibit symptoms.[11][12][13] It has been suggested that the greater occurrence of PCDH19-epilepsy in females may relate to X-chromosome inactivation, through a hypothesized mechanism termed ‘‘cellular interference’’.[5][11] A 2011 study found instances where patients had PCDH19 mutation, but their parents did not. They found that "gonadal mosaicism” of a PCDH19 mutation in a parent is an important molecular mechanism associated with the inheritance of a mutated PCDH19 gene.[5][11][21] ### Genetics[edit] The PCDH19 gene is located on the long (q) arm of the X chromosome at position 22.1.[4][9][12][15] The gene encodes for protocadherin 19, a transmembrane protein of calcium-dependent cell-cell adhesion molecules that is strongly expressed in neural tissue, such as the hippocampus, cerebral cortex, thalamus, and amygdala.[11][12][15] Protocadherin 19 appears to be related to synaptic transmission and formation of synaptic connections during brain development.[12][15] A mutation in the PCDH19 gene can cause the protocadherin 19 protein to be malformed, reduced in function or not produced at all.[12] This abnormal expression of protocadherin 19 causes deficits in GABAergic signaling, causing the occurrence of seizures beginning in the early years of life.[12] The expression of the PCDH19 mutation is highly variable, with some individuals appearing unaffected, and others showing severe disease.[5] Even monozygotic twins with the mutation may have variations in seizure frequency and degree of cognitive impairment.[5] Currently, the PCDH19 gene is the second most clinically relevant gene in the epilepsy field; the second largest number of epilepsy related mutations characterized thus far occur in the PCDH19 gene.[4][5][15][17] The SCN1A gene, associated with Dravet Syndrome, is the most clinically relevant.[22][23] ### Classification[edit] Due to its recent discovery, PCDH19 gene-related epilepsy does not have a specific classification according to the International League Against Epilepsy. PCDH19 gene-related epilepsy is thought to develop based upon a deficiency of the calcium-dependent cell-adhesion PCDH19 (protocadherin 19) gene.[24][nb 1] Its cause and pathophysiology (cause and mechanisms by which damage occurs) are different from other epilepsies, although the symptoms are very similar to other epileptic syndromes, such as Generalized epilepsy with febrile seizures plus (GEFS+), Dravet syndrome with SCN1A negative, FIRES (febrile infection–related epilepsy syndrome) Lennox-Gastaut syndrome or epilepsy of unknown origin.[25] ## Diagnosis[edit] PCDH19 gene-related epilepsy is clinically based on patient and family seizure history, cognitive and behavioral neuropsychological evaluation, neurological examination, electroencephalogram (EEG) studies, and long term observation. Diagnosis is confirmed using molecular testing for PCDH19 mutations.[17][22] ### Diagnostic test[edit] The test is particularly indicated in children who have had cluster seizures in series. It is also recommended for patients who are diagnosed GEFS+ and when the seizures are associated with fever, infection, experienced regression, delayed cognitive growth or behavioral problems. The test is typically ordered by neurologists. The diagnostic test can be done by drawing blood or saliva of the patient and their immediate family. It is analyzed in laboratories that specialize in genetic testing. Genetic testing can aid in a firmer diagnosis and understanding of the disorder, may aid in identifying the optimal treatment plan and if positive, testing of the parents can determine if they are carriers.[citation needed] ## Treatment[edit] ### Medication[edit] Antiepileptic drugs (AEDs) are used in most cases to control seizures, however, PCDH19 gene-related epilepsy is generally associated with early-onset development of drug resistant seizures.[9][11][16] Existing data supports the use of “rational polypharmacy,” which consists of a step-wise addition of AEDs until a patient responds favorably or experiences intolerable adverse events.[9] In general, as in other types of uncontrolled epilepsy, the use of drugs with different mechanisms of action appears to be more effective than combining drugs with similar mechanisms of action.[9] No currently marketed AEDs have been extensively studied in PCDH19 gene-related epilepsy and there is no established treatment strategy for girls diagnosed with PCDH19 gene-related epilepsy.[16][22] Patients may respond well to treatment with levetiracetam and in cases of drug resistance, stiripentol, which is not approved in the U.S. but is available through the FDA Expanded Access IND process.[5][22] Seizures might be easier to control with age, especially after the second decade of life. However, some publications have shown that medication withdrawal is highly associated with seizure recurrence.[26] ### Urgent care[edit] At the hospital, physicians follow standard protocol for managing seizures. Cluster seizures are generally controlled by benzodiazepines such as diazepam, midazolam, lorazepam or clonazepam. The use of oxygen is recommended in the United States, but in Europe it is only recommended in cases of prolonged epileptic status.[27] ## Epidemiology[edit] The National Institute of Health Office and Rare Disease Research characterizes PCDH19 gene-related epilepsy as a rare disorder.[8] Rare diseases, by definition, are diseases that affect fewer than 200,000 people in the United States. Since the mutation associated with PCDH19 gene-related epilepsy was only recently identified in 2008, the true incidence of the disease is generally unknown.[12] Although formal epidemiologic data is not available, results from diagnostic screening indicates that approximately 1 out of 10 girls who have seizure onset before five years of age may have PCDH19 gene mutations.[9][10][11] Additionally, PCDH19 screening of several large cohorts of females with early onset febrile-related epilepsy has resulted in a rate of approximately 10% of mutation-positive individuals.[11][17][22] ## History[edit] Juberg and Hellman originally described the disorder in 1971 in the Journal of Pediatrics, where they reported a family in which 15 female relatives, who were related either as sisters or first cousins through their fathers, had early onset seizures with cognitive impairments.[4][8][16] In subsequent peer-reviewed literature, the disorder was referred to as “epilepsy and mental retardation limited to female” (EFMR), and later called EIEE9 or Juberg-Hellman Syndrome.[4][8][12] The syndrome in this family was characterized by the occurrence of childhood seizures. Some of the girls showed developmental regression with intellectual disabilities that ranged from mild to profound. The disorder has an unusual inheritance pattern. It is considered X-linked dominant with male carriers. Women and men with the affected gene can transmit the disease. The men expressed a normal phenotype. The disorder was shown to be linked to mutations via Xq22 microsatellite markers.[nb 4] [4] Due to the apparent female-limited expression of the condition, it eluded genetic mapping until 1997, which is when Ryan et al. mapped the responsible gene to the X-chromosome.[28] Eleven years after the success of Ryan et al., in 2008, systematic sequencing of X-chromosome exons in seven large families diagnosed with EFMR revealed PCDH19 gene mutations as the cause. This led to a shift in describing EMFR as PCDH19 gene-related epilepsy.[9][13][14][17][28] The discovery of the PCDH19 gene mutation led to the development of a genetic test for PCDH19 gene-related epilepsy.[citation needed] In 2009, Depienne et al. identified a male with a somatic mosaicism for PCDH19 gene deletion and a Dravet-like seizure disorder.[9][11][28][29][30] The findings resulted in Depienne et al. to identify PCDH19 mutations in patients with SCN1A negative Dravet syndrome.[9][11][28] This led to additional reports of PCDH19 positive patients, which broadened the clinical spectrum of the disorder.[28][29][30] ## Society and culture[edit] Caregivers of individuals living with PCDH19 gene-related epilepsy may seek support and information from a variety of resources, including the PCDH19 Alliance, The Cute Syndrome Foundation, and Insieme per la Ricerca PCDH19 - ONLUS (Italy).[citation needed] The PCDH19 World Conference, which is organized by Insieme per la Ricerca PCDH19 - ONLUS, occurs every other year, in odd years, in Rome, Italy. In alternating years, the PCDH19 Epilepsy Professional and Family Symposium is hosted in San Francisco, California.[citation needed] In 2014, the PCDH19 Registry was established, which is organized and funded by the PCHD19 Alliance, Boston Children's Hospital and the University of California, San Francisco.[6] International PCDH19 Awareness Day is held annually on November 9.[citation needed] ## Research[edit] ### Registry[edit] A PCDH19 Registry was established by the PCDH19 Alliance, Boston Children's Hospital and the University of California, San Francisco, to provide a meaningful resource of patients with PCDH19 gene-related epilepsy and to better understand the epilepsy and behavioral aspects associated with the mutation.[6][31] Parallel associations European families are sponsoring basic and applied research in an Australian team and researching in other projects with the aim of finding a drug target for epilepsy PCDH19.[28] ### Basic research[edit] Ann Poduri and Alex Rotenberg at Boston Children's Hospital are currently conducting PCDH19-related epilepsy in zebrafish.[31][32] The research, which is funded by grants from The Cute Syndrome Foundation and The Richard A. and Susan F. Smith President's Innovation Fund of Boston Children's Hospital, hopes to establish an animal model of PCDH19 gene-related epilepsy, which can then be used to screen potential therapeutics and treatments.[31][32] Dr. Jack Parent and his research team at the University of Michigan are currently conducting research to understand how PCHD19 gene mutations leads to disruptions in brain development.[33][34] The research, funded by a grant from The Cute Syndrome Foundation, is seeking to reprogram fibroblasts from subjects with the PCHD19 mutation into induced pluripotent stem cells (iPSC), which will then be used to make patient-specific neurons in a cell culture environment.[33][34] The researchers are looking to see if these patient-specific neurons produce epileptic-like activity, as well as to discover the mechanism underlying the seizures and cognitive dysfunction associated with PCDH19 mutations.[33][34] The Cute Syndrome Foundation and Insieme per la Ricerca PCDH19 - ONLUS recently awarded a two-year research grant to Drs. Maria Passafaro and Elena Battaglioli, from the CNR Neuroscience Institute and University of Milano, respectively.[34][35] The researchers plan to unravel the molecular mechanism of PCDH19 gene mutations.[34][35] The proposal also includes using AON exon skipping, which would be the first use of this method in epilepsy.[34][35] Parallel associations European families are sponsoring basic and applied research in an Australian team and researching in other projects with the aim of finding a drug target for epilepsy PCDH19.[36][clarification needed] ### Gene therapy[edit] It was assumed that all encephalopathies or cognitive impairments were irreversible, but an experiment with mice showed that is not always the case.[37] In that experiment, MECP2 protein was blocked; males died, and females developed Rett syndrome (seizures, cognitive and psychomotor problems, respiratory problems, etc.) When the researchers reversed the situation and let the MECP2 protein work properly, the mice recovered.[clarification needed] This research revolutionized understanding regarding genetic syndromes that present with neurological impairment or intellectual disabilities. ### Therapeutics[edit] In February 2015, Marinus Pharmaceuticals commenced a Phase 2 proof-of-concept clinical trial to evaluate the safety and efficacy of ganaxolone, a synthetic analog of the neurosteroid allopregnanolone, for the treatment of uncontrolled seizure in pediatric females with PCDH19 gene-related epilepsy.[38][39] The study will enroll up to 10 female pediatric patients, between the ages of 2 and 10 years old, with a confirmed PCDH19 genetic mutation.[33][34][39] The primary endpoint of the study is percent change in seizure frequency per 28 days relative to baseline.[38][39] The Epilepsies Research Centre and Department of Medicine, University of Melbourne, are working on a compound to treat this disease. On May 26, 2011 it patented a method of diagnosis and PCDH19 gene-related epilepsy treatment.[40] ## Notes[edit] 1. ^ Cell adhesion is mediated by cell surface proteins. ## References[edit] 1. ^ a b Stevenson RE, Holden KR, Rogers RC, Schwartz CE (May 2012). "Seizures and X-linked intellectual disability". Eur J Med Genet. 55 (5): 307–12. doi:10.1016/j.ejmg.2012.01.017. PMC 3531238. PMID 22377486. 2. ^ Carol Perez-Iratxeta; Peer Bork; Miguel A. Andrade. "Genes2Diseases database". Archived from the original on 2013-12-02. Retrieved 2013-11-22. 3. ^ "Online Mendelian Inheritance in Man® An Online Catalog of Human Genes and Genetic Disorders". 4. ^ a b c d e f g h i j k l m Depienne, C; LeGeurn, E (2012). "PCDH19-related infantile epileptic encephalopathy: an unusual X-linked inheritance disorder". Hum Mutat. 33 (4): 627–634. doi:10.1002/humu.22029. PMID 22267240. 5. ^ a b c d e f g h i j k l m n Higurashi, N.; Nakamura, M.; Sugai, M.; Ohfu, M.; Sakauchi, M.; Sugawara, Y.; Nakamura, K.; Kato, M.; Usui, D.; Mogami, Y.; Fujiwara, Y.; Ito, T.; Ikeda, H.; Imai, K.; Takahashi, Y.; Nukui, M.; Inoue, T.; Okazaki, S.; Kirino, T.; Tomonoh, Y.; Inoue, T.; Takano, K.; Shimakawa, S.; Hirose, S. (2013). "PCDH19-related female-limited epilepsy: Further details regarding early clinical features and therapeutic efficacy". Epilepsy Research. 106 (1–2): 191–199. doi:10.1016/j.eplepsyres.2013.04.005. PMID 23712037. 6. ^ a b c d e f g h i j k l m "PCDH19 Alliance". Retrieved August 22, 2016. 7. ^ a b c d e f g Specchio, N; Marini, C; Terracciano, A (2011). "Spectrum of phenotypes in female patients with epilepsy due to protocadherin 19 mutations". Epilepsia. 52 (7): 1251–1257. doi:10.1111/j.1528-1167.2011.03063.x. PMID 21480887. 8. ^ a b c d "PCDH19-related female-limited epilepsy \| Genetic and Rare Diseases Information Center(GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2016-08-22. 9. ^ a b c d e f g h i Depienne, Christel; Bouteiller, Delphine; Keren, Boris; Cheuret, Emmanuel; Poirier, Karine; Trouillard, Oriane; Benyahia, Baya; Quelin, Chloé; Carpentier, Wassila (2009-02-13). "Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects Females". PLOS Genet. 5 (2): e1000381. doi:10.1371/journal.pgen.1000381. ISSN 1553-7404. PMC 2633044. PMID 19214208. 10. ^ a b Depienne C, Trouillard O, Bouteiller D, Gourfinkel-An I, Poirier K, Rivier F, et al. (January 2011). "Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females". Hum. Mutat. 32 (1): E1959–75. doi:10.1002/humu.21373. PMC 3033517. PMID 21053371. 11. ^ a b c d e f g h i j k l m n o p q r s t u v w x Johnston, Michael (2016). Neurobiology of Disease. Oxford University Press. pp. 307–309. ISBN 978-0199937844. 12. ^ a b c d e f g h i j k l m n o p Dibbens, LM; Tarpey, PS (June 2008). "X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment". Nat Genet. 40 (6): 776–781. doi:10.1038/ng.149. PMC 2756413. PMID 18469813. 13. ^ a b c d e f g h i j k Depienne, Christel; Gourfinkel-An, Isabelle; Baulac, Stéphanie; LeGuern, Eric (2012-01-01). Noebels, Jeffrey L.; Avoli, Massimo; Rogawski, Michael A.; Olsen, Richard W.; Delgado-Escueta, Antonio V. (eds.). Genes in infantile epileptic encephalopathies (4th ed.). Bethesda (MD): National Center for Biotechnology Information (US). PMID 22787626. 14. ^ a b c d e f g h i j k l m Scheffer, Ingrid; et al. (2008). "Epilepsy and mental retardation limited to females: an under-recognized disorder". Brain. 131 (4): 918–927. doi:10.1093/brain/awm338. PMID 18234694. 15. ^ a b c d e f g h i Cappelletti, Simona; Specchio, Nicola; Moavero, Romina; Terracciano, Alessandra; Trivisano, Marina; Pontrelli, Giuseppe; Gentile, Simonetta; Vigevano, Federico; Cusmai, Raffaella (2015). "Cognitive development in females with PCDH19 gene-related epilepsy". Epilepsy & Behavior. 42: 36–40. doi:10.1016/j.yebeh.2014.10.019. PMID 25499160. 16. ^ a b c d e Nordli Jr., Douglas (2016). Pellock's Pediatric Epilepsy: Diagnosis and Therapy. Springer Publishing Company. p. 386. ISBN 978-1617052439. 17. ^ a b c d e f g h Marini C, Mei D, Parmeggiani L, Norci V, Calado E, Ferrari A, Moreira A, Pisano T, Specchio N, Vigevano F, Battaglia D, Guerrini R (August 2010). "Protocadherin 19 mutations in girls with infantile-onset epilepsy". Neurology. 75 (7): 646–53. doi:10.1212/WNL.0b013e3181ed9e67. PMID 20713952. 18. ^ a b c d e f Marini C, Darra F, Specchio N, Mei D, Terracciano A, Parmeggiani L, et al. (December 2012). "Focal seizures with affective symptoms are a major feature of PCDH19 gene-related epilepsy". Epilepsia. 53 (12): 2111–9. doi:10.1111/j.1528-1167.2012.03649.x. ISSN 1528-1167. PMID 22946748. 19. ^ a b Marini C.; et al. (June 29, 2010). Infantile onset focal epilepsy and epilepetic encephalopathies associated with PCDH19 gene mutations: New de novo and familial mutations. 9th European Congress on Epileptology. 51. pp. 1–189. doi:10.1111/j.1528-1167.2010.02658.x. hdl:11446/404. PMID 20590792. 20. ^ Specchio, N (2011-08-01). "Stormy Onset Epilepsy in Girls with De Novo Protocadherin 19 Mutations". Epilepsia. 52: 4–22. doi:10.1111/j.1528-1167.2011.03206.x. ISSN 1528-1167. 21. ^ Dibbens, L. M.; Kneen, R.; Bayly, M. A.; Heron, S. E.; Arsov, T.; Damiano, J. A.; Desai, T.; Gibbs, J.; McKenzie, F. (2011-04-26). "Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations". Neurology. 76 (17): 1514–1519. doi:10.1212/WNL.0b013e318217e7b6. ISSN 0028-3878. PMID 21519002. 22. ^ a b c d e Miller, Ian O.; Sotero de Menezes, Marcio A. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). SCN1A-Related Seizure Disorders. Seattle (WA): University of Washington, Seattle. PMID 20301494. 23. ^ Sugawara, Takashi; Tsurubuchi, Yuji; Agarwala, Kishan Lal; Ito, Masatoshi; Fukuma, Goryu; Mazaki-Miyazaki, Emi; Nagafuji, Hiroshi; Noda, Masaharu; Imoto, Keiji (2001-05-22). "A missense mutation of the Na+ channel αII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction". Proceedings of the National Academy of Sciences. 98 (11): 6384–6389. Bibcode:2001PNAS...98.6384S. doi:10.1073/pnas.111065098. ISSN 0027-8424. PMC 33477. PMID 11371648. 24. ^ "PCDH19 Gene". Genetic Home Reference. Retrieved December 30, 2011. 25. ^ Nicola Specchio; Lucia Fusco; Federico Vigevano (November 2011). "Acute-onset epilepsy triggered by fever mimicking FIRES febrile infection–related epilepsy syndrome: The role of protocadherin 19 (PCDH19) gene mutation". Epilepsia. 52 (11): e172–e175. doi:10.1111/j.1528-1167.2011.03193.x. PMID 21777234. 26. ^ Aledo-Serrano, Ángel; Ser, Teodoro del; Gil-Nagel, Antonio (2020-06-05). "Antiseizure medication withdrawal in seizure-free patients with PCDH19-related epilepsy: a multinational cohort survey". Seizure - European Journal of Epilepsy. 0 (0). doi:10.1016/j.seizure.2020.06.007. ISSN 1059-1311. 27. ^ "The Epilepsies and Seizures: Hope Through Research". www.ninds.nih.gov. Retrieved 2016-08-22. 28. ^ a b c d e Tan, Chuan; Shard, Chloe; Ranieri, Enzo; Hynes, Kim; Pham, Duyen H.; Leach, Damian; Buchanan, Grant; Corbett, Mark; Shoubridge, Cheryl (2015-09-15). "Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency". Human Molecular Genetics. 24 (18): 5250–5259. doi:10.1093/hmg/ddv245. ISSN 0964-6906. PMID 26123493. 29. ^ a b Terracciano, Alessandra; Trivisano, Marina; Cusmai, Raffaella; De Palma, Luca; Fusco, Lucia; Compagnucci, Claudia; Bertini, Enrico; Vigevano, Federico; Specchio, Nicola (2016-03-01). "PCDH19-related epilepsy in two mosaic male patients". Epilepsia. 57 (3): e51–e55. doi:10.1111/epi.13295. ISSN 1528-1167. PMID 26765483. 30. ^ a b Thiffault, Isabelle; Farrow, Emily; Smith, Laurie; Lowry, Jennifer; Zellmer, Lee; Black, Benjamin; Abdelmoity, Ahmed; Miller, Neil; Soden, Sarah (2016-06-01). "PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant". American Journal of Medical Genetics Part A. 170 (6): 1585–1589. doi:10.1002/ajmg.a.37617. ISSN 1552-4833. PMID 27016041. 31. ^ a b c 2013, Boston Childrens Hospital. "Epilepsy Genetics Program \| Research and Innovation \| Boston Children's Hospital". www.childrenshospital.org. Retrieved 2016-08-22.CS1 maint: numeric names: authors list (link) 32. ^ a b "PCDH19 and SCN8A Research Funded By The Cute Syndrome". The Cute Syndrome Foundation: Funding PCDH19 Epilepsy & SCN8A Epilepsy Research. Retrieved 2016-08-22. 33. ^ a b c d "RESEARCH - PCDH19 Alliance". PCDH19 Alliance. Retrieved 2016-08-22. 34. ^ a b c d e f g "News about PCDH19 Epilepsy and SCN8A Epilepsy and The Cute Syndrome Foundation". The Cute Syndrome Foundation: Funding PCDH19 Epilepsy & SCN8A Epilepsy Research. Retrieved 2016-08-22. 35. ^ a b c "Insieme per la Ricerca PCDH19 – ONLUS". www.pcdh19research.org. Archived from the original on 2016-07-26. Retrieved 2016-08-22. 36. ^ PCDH19 Association "Insieme per la Ricerca PCDH19" 37. ^ Guy, Jacky; Gan, Jian; Selfridge, Jim; Cobb, Stuart; Bird, Adrian (2007-02-23). "Reversal of Neurological Defects in a Mouse Model of Rett Syndrome". Science. 315 (5815): 1143–1147. Bibcode:2007Sci...315.1143G. doi:10.1126/science.1138389. ISSN 0036-8075. PMID 17289941. 38. ^ a b "Marinus Pharmaceuticals Initiates Clinical Trial With Ganaxolone in PCDH19 Female Pediatric Epilepsy (NASDAQ:MRNS)". ir.marinuspharma.com. Retrieved 2016-08-22. 39. ^ a b c "A Multicenter, Open-Label Proof-of-Concept Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-08-22. 40. ^ 2011/0126302 A1 US pending US 2011/0126302 A1, Dibbens, L.M.; Scheffer, I.; Berkovic, S.F.; Mulley, J.C.; Geez, J, "Diagnostic and Therapeutic Methods for EFMR (Epilepsy and Mental Retardation", published May 26, 2011 ## External links[edit] Classification D * OMIM: 300088 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Epilepsy-intellectual disability in females	c1848137	30,112	wikipedia	https://en.wikipedia.org/wiki/Epilepsy-intellectual_disability_in_females	2021-01-18T18:28:36	{"gard": ["10806"], "mesh": ["C564715"], "orphanet": ["101039"], "wikidata": ["Q3813663"]}
## Description Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002). For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750. Mapping To identify risk variants contributing to celiac disease susceptibility other than those in the HLA-DQ region (see CELIAC1, 212750), Hunt et al. (2008) genotyped 1,020 of the most strongly associated non-HLA markers identified by van Heel et al. (2007) in an additional 1,643 cases of celiac disease and 3,406 controls. Hunt et al. (2008) identified 2 correlated SNPs, rs653178 (P overall = 8 x 10(-8)) and rs3184504 that mapped in the vicinity of the SH2B3 gene (605093). Modest LD was seen over a broader region of approximately 1 Mb containing multiple other genes. Strong association with type 1 diabetes was reported in this region with rs3184504 entirely accounting for the association signal (Todd et al., 2007). SH2B3 is strongly expressed in monocytes and dendritic cells, as well as to a lesser extent in resting B, T, and natural killer cells. Hunt et al. (2008) found SH2B3 to be strongly expressed in small intestine; higher expression in inflamed celiac biopsies may reflect leukocyte recruitment and activation. The nonsynonymous SNP rs3184504 is located in exon 3 of SH2B3, leading to an R262W amino acid change in the pleckstrin homology domain. This domain may be important in plasma membrane targeting. SH2B3 regulates T-cell receptor, growth factor, and cytokine receptor-mediated signaling implicated in leukocyte and myeloid cell homeostasis. Hunt et al. (2008) also noted strong correlation between rs3184504 and another SNP, rs653178 (r(2) = 0.99). Smyth et al. (2008) evaluated the association between type 1 diabetes (222100) and 8 loci related to the risk of celiac disease in 8,064 patients with type 1 diabetes, 2,828 families providing 3,064 parent-child trios, and 9,339 controls. The authors confirmed association between IDDM20 (612520) and rs3184504 in the SH2B3 gene, which is associated with CELIAC13. In an Italian cohort involving 538 patients with celiac disease and 593 healthy controls, Romanos et al. (2009) confirmed association at rs3184504 (p = 0.0050). Population Genetics Zhernakova et al. (2010) assessed signatures of natural selection for 10 confirmed celiac disease loci in several genomewide data sets comprising 8,154 controls from 4 European populations and 195 individuals from a North African population and found consistent signs of positive selection for disease-associated alleles at 3 loci, including rs3184504 at SH2B3 in the European populations. Functional investigation of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide showed that carriers of the SH2B3 rs3184504 'A' risk allele showed stronger activation of the NOD2 recognition pathway than did carriers of the nonrisk 'G' allele, suggesting that SH2B3 plays a role in protection against bacterial infection and providing a possible explanation for the selective sweep, which occurred sometime between 1,200 and 1,700 years ago. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	CELIAC DISEASE, SUSCEPTIBILITY TO, 13	c2677601	30,113	omim	https://www.omim.org/entry/612011	2019-09-22T16:02:33	{"omim": ["612011"], "synonyms": ["Alternative titles", "GLUTEN-SENSITIVE ENTEROPATHY, SUSCEPTIBILITY TO, 13"]}
A number sign (#) is used with this entry because of evidence that susceptibility to schizophrenia-16 is associated with duplication of a 362-kb region on chromosome 7q36.3 that includes the VIPR2 gene (601970) (chr7:158.4-158.8 Mb, NCBI36). For a phenotypic description and discussion of genetic heterogeneity of schizophrenia, see 181500. Molecular Genetics Vacic et al. (2011) performed a large 2-stage genomewide scan of rare copy number variants (CNVs) and reported the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kb region (158,448,321-158,810,016) and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kb upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic AMP signaling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. Vacic et al. (2011) concluded that their findings implicated altered vasoactive intestinal peptide signaling in the pathogenesis of schizophrenia and indicated the VPAC2 receptor as a potential target for the development of antipsychotic drugs. Inheritance of the duplication at 7q36.3 could be evaluated in 3 families. In 1 family, the duplication was confirmed in the proband, but not detected in either of the unaffected parents, and thus is apparently de novo. In a second family, the duplication was detected in the proband and in the mother with a diagnosis of depression. In the third family, the duplication was detected in the proband and in the unaffected mother. The proband's mother also had a son with a diagnosis of schizophrenia from a second marriage, but DNA from this individual was not available. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	SCHIZOPHRENIA 16	c3151408	30,114	omim	https://www.omim.org/entry/613959	2019-09-22T15:56:57	{"omim": ["613959"], "synonyms": ["Alternative titles", "SCHIZOPHRENIA SUSCEPTIBILITY LOCUS, CHROMOSOME 7q36.3-RELATED", "CHROMOSOME 7q36.3 DUPLICATION SYNDROME, 362-KB"]}
6q terminal deletion syndrome is marked by a characteristic facial dysmorphism, short neck and psychomotor retardation, generally associated with a range of non-specific malformations. ## Epidemiology Isolated terminal 6q deletion syndrome is very rare with less than 20 cases being reported in the literature. ## Clinical description The most frequent craniofacial anomalies include microcephaly, broad nose with prominent nasal root and bulbous nasal tip, large ears that may be malformed and low-set, and a characteristic downturned mouth. The most commonly described neurological features are psychomotor retardation, hypotonia and seizures. Retinal anomalies are also common among individuals carrying the 6q terminal deletion, highlighting the importance of ophthalmologic examinations for all patients. ## Etiology The breakpoints for the 6q terminal deletion are located between chromosome regions 6q25.3 and 6q26, within the fragile site FRA6E. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	6q terminal deletion syndrome	c4304514	30,115	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75857	2021-01-23T19:06:39	{"icd-10": ["Q93.5"]}
A number sign (#) is used with this entry because early-onset ataxia with oculomotor apraxia and hypoalbuminemia (EAOH) is caused by homozygous or compound heterozygous mutation in the gene encoding aprataxin (APTX; 606350) on chromosome 9p21. Adult-onset ataxia with oculomotor apraxia is also caused by mutation in the APTX gene. Description Ataxia-oculomotor apraxia syndrome is an early-onset autosomal recessive cerebellar ataxia with peripheral axonal neuropathy, oculomotor apraxia (defined as the limitation of ocular movements on command), and hypoalbuminemia (Moreira et al., 2001). ### Genetic Heterogeneity of Ataxia-Oculomotor Apraxia See also AOA2 (606002), caused by mutation in the SETX gene (608465) on chromosome 9q34; AOA3 (615217), caused by mutation in the PIK3R5 gene (611317) on chromosome 17p; and AOA4 (616267), caused by mutation in the PNKP gene (605610) on chromosome 19q13. Clinical Features Aicardi et al. (1988) described an autosomal recessive syndrome that closely resembled ataxia-telangiectasia (AT; 208900) but differed in important respects. They reported 14 patients in 10 families with a neurologic syndrome of oculomotor apraxia, ataxia, and choreoathetosis who had none of the extraneurologic features of AT. Although the neurologic signs were indistinguishable from those of AT, the onset tended to be later and none of the patients had a tendency to frequent infections; further, immunoglobulins, alpha-fetoprotein, T- and B-lymphocyte markers, and chromosomes 7 and 14 were normal in all patients tested. Barbot et al. (2001) reported 22 Portuguese patients with autosomal recessive cerebellar ataxia, ocular apraxia, and peripheral neuropathy with a mean age of onset of 4.7 years. There was no associated mental retardation, telangiectasia, or immunodeficiency. Barbot et al. (2001) concluded that ataxia with oculomotor apraxia may be more frequent than previously believed. Koeppen (2002) suggested that the patients reported by Barbot et al. (2001) may have exhibited supranuclear pseudoophthalmoplegia, which may be due to lesions in the nucleus pontis centralis caudalis of the paramedian pontine reticular formation. Shimazaki et al. (2002) reported 5 Japanese patients with autosomal recessive EAOH from 3 families and 1 sporadic case. Clinical features included age of onset from 3 to 12 years, cerebellar ataxia, peripheral neuropathy, oculomotor apraxia and external ophthalmoplegia, choreiform movements of the limbs, facial grimacing, mental deterioration, cerebellar atrophy, hypoalbuminemia, and hypercholesterolemia. Amouri et al. (2004) reported 3 unrelated Tunisian families with AOA, confirmed by mutation in the APTX gene (606350.0007; 606350.0008). The mean age at onset was 5 years with gait ataxia as the presenting symptom. Cerebellar ataxia affecting all 4 limbs and the trunk developed soon thereafter. Other features included dysarthria, ocular apraxia, distal sensory axonal neuropathy, and marked cerebellar atrophy by brain imaging. Hypoalbuminemia and hypercholesterolemia were also present. Affected members of 1 of the families had a somewhat atypical phenotype with absence of oculomotor apraxia, except in 1 patient, and preservation of knee reflexes. None of the patients had mental impairment. Criscuolo et al. (2004) reported 3 unrelated Italian patients with AOA confirmed by genetic analysis. Two of the patients had adult onset at ages 28 and 29, respectively. Criscuolo et al. (2005) reported a patient with adult-onset AOA confirmed by genetic analysis (606350.0009). The patient had onset of gait ataxia and dysarthria at age 40 years. Physical examination showed normal ocular movements, tongue and limb fasciculations, areflexia, and decreased vibration sense at the external malleoli. MRI showed cerebellar atrophy. Serum albumin was normal. Criscuolo et al. (2005) emphasized that milder phenotypes of AOA may occur in adults. Castellotti et al. (2011) identified APTX mutations in 13 (6.4%) of 204 Italian patients with progressive cerebellar ataxia. The patients had onset between ages 3 and 7 years, but most were examined as adults. The phenotype was homogeneous, characterized mainly by gait and limb ataxia, dysarthria, nystagmus, lower limb areflexia, sensory neuropathy, cognitive decline, dysarthria, and oculomotor deficits. Some had choreic movements of the upper limbs and face, and many had distal muscle weakness and atrophy affecting both upper and lower limbs. Six patients were wheelchair-bound in young adulthood. Six patients had mental retardation since early childhood, whereas 5 showed cognitive decline later in life. Hypoalbuminemia was found in 58%, and hypercholesterolemia in 69%. Three patients had increased alpha-fetoprotein (AFP; 104150). Analyses of coenzyme Q10 in muscle, fibroblasts, and plasma demonstrated normal levels of coenzyme in 5 of 6 patients. There were no genotype/phenotype correlations. Biochemical Features Hannan et al. (1994) studied cultured fibroblasts from 3 patients with ataxia-oculomotor apraxia and their asymptomatic relatives in comparison with fibroblasts from a classic AT homozygote, an AT heterozygote, and 4 healthy subjects. Cell survival after acute and chronic irradiation was investigated. While a moderately increased cellular sensitivity (compared to normal) was observed in 2 AOA patients and most of their relatives, the degree of their radiosensitivity was quite different from that of the AT homozygote after both acute and chronic irradiation. A comparison of peripheral blood lymphocytes from spontaneous and acute radiation-induced chromosomal breaks also failed to show similarity between AOA and AT. The data were interpreted as indicating either that AOA and AT are distinct disease entities controlled by separate genes or that AOA is due to compound heterozygosity involving different AT genes that promote the manifestation of AOA characteristics. Pathogenesis Aprataxin has been shown to interact with poly(ADP-ribose) polymerase-1 (PARP1; 173870), a key player in the detection of DNA single-strand breaks. Harris et al. (2009) reported reduced expression of PARP1, apurinic endonuclease-1 (APEX1; 107748) and OGG1 (601982) in AOA1 cells and demonstrated a requirement for PARP1 in the recruitment of aprataxin to sites of DNA single-strand breaks. Mouse embryonic fibroblasts (MEFs) derived from Parp1-knockout mice showed reduced levels of aprataxin and reduced DNA-adenylate hydrolysis; however, inhibition of PARP1 activity did not affect aprataxin activity in vitro. Rather, aprataxin failed to relocalize to sites of DNA single-strand breaks in Parp1-null MEFs compared to wildtype cells, and inhibition of PARP1 activity resulted in delayed recruitment of aprataxin to DNA breaks. There were elevated levels of oxidative DNA damage in AOA1 cells coupled with reduced base excision and gap filling repair efficiencies indicative of a synergy between aprataxin, PARP1, APE1 and OGG1 in the DNA damage response. Harris et al. (2009) proposed both direct and indirect modulating functions for aprataxin on base excision repair. Garcia-Diaz et al. (2015) found that most, but not all, cell lines derived from AOA1 patient fibroblasts showed coenzyme Q10 (CoQ10) deficiency due to reduced mRNA and protein expression of PDSS1 (607429), the first committed enzyme of CoQ10 biosynthesis. Low PDSS1 was caused by reduced activity of a transcriptional regulatory pathway that included APE1, NRF1 (600879), and NRF2 (see 600609). Knockdown of APTX or APE1 in HeLa cells recapitulated CoQ10 deficiency and other mitochondrial abnormalities, and these abnormalities were reversed by upregulation of NRF2. Garcia-Diaz et al. (2015) concluded that mitochondrial dysfunction in APTX-depleted cells is not due to involvement of APTX in mtDNA repair, but rather to a role for APTX in transcriptional regulation of mitochondrial function. Mapping ### 9p Locus (APTX gene) Date et al. (2001) identified a group of Japanese patients whose clinical presentation was characterized by autosomal recessive inheritance, early age at onset, Friedreich ataxia (FRDA; 229300)-like clinical presentations, and hypoalbuminemia. Linkage to the FRDA locus was excluded. They confirmed that the disorder in these patients was linked to the same locus, 9p13, as the ataxia-oculomotor apraxia syndrome. Moreira et al. (2001) studied 13 Portuguese families with AOA and found that the 2 largest families showed linkage to 9p, with lod scores of 4.13 and 3.82, respectively, at a recombination fraction of 0.0. These and 3 smaller families, all from northern Portugal, showed homozygosity and haplotype sharing over a 2-cM region on 9p13.3, demonstrating founder effect and linkage to this locus, designated AOA1, in the 5 families. Three other families were excluded from this locus, demonstrating nonallelic heterogeneity in AOA. They also analyzed 2 unrelated Japanese families with early-onset cerebellar ataxia with hypoalbuminemia (EOCA-HA). This disorder, described only in Japan (Uekawa et al., 1992; Fukuhara et al., 1995; Sekijima et al., 1998; Tachi et al., 2000), is characterized by marked cerebellar atrophy, peripheral neuropathy, mental retardation, and occasionally oculomotor apraxia. Both families appeared to show linkage to the AOA1 locus. Subsequently, the authors found hypoalbuminemia in all 5 Portuguese families with AOA1 with a long disease duration, suggesting that AOA1 and EOCA-HA correspond to the same entity that accounts for a significant proportion of all recessive ataxias. ### 9q Locus Nemeth et al. (2000) identified a family with ataxia and oculomotor apraxia in which the disorder showed linkage to 9q34; see 606002. Bomont et al. (2000) performed linkage studies in the Japanese family reported by Watanabe et al. (1998) in which 4 affected sibs had spinocerebellar ataxia associated with elevated levels of serum creatine kinase, gamma-globulin, and alpha-fetoprotein. Homozygosity over a 20-cM region allowed demonstration of linkage at 9q33.3-q34.3 with a lod score of 3.0. Koenig (2001) concluded that there are 2 recessive ataxia loci on chromosome 9: one on 9p, the site of the APTX gene, and one on 9q. The disorder that maps to 9p13 appears always to be associated with oculomotor apraxia (Barbot et al., 2001), early onset (usually between 2 and 6 years of age), and hypoalbuminemia after a long disease duration. The disorder on 9q34 is of later onset (between 11 and 22 years) and is occasionally associated with oculomotor apraxia or elevated gamma-globulin, alpha-fetoprotein, and creatine kinase. Tentatively, early-onset ataxia with oculomotor apraxia and hypoalbuminemia, which appears to map to 9p13.3 and to be caused by mutation in the aprataxin gene, will be referred to as ataxia-oculomotor apraxia-1, whereas ataxia of later onset with inconsistent association of oculomotor apraxia will be designated ataxia-oculomotor apraxia-2. Koenig (2001) suggested that the designation AOA is inappropriate for the form of ataxia mapped to 9q. Population Genetics By 2001, the ongoing survey initiated in 1993 of hereditary ataxias and spastic paraplegias in Portugal, a country of 9.8 million persons, had identified 107 patients with autosomal recessive ataxia (Barbot et al., 2001). Friedreich ataxia (FRDA; 229300) accounted for 38% of the cases. The next most common recessive ataxia in the survey, accounting for 21% of the cases, was ataxia with oculomotor apraxia. Anheim et al. (2010) found that AOA1 was the fourth most common form of autosomal recessive cerebellar ataxia in a cohort of 102 patients from Alsace, France. Of 57 patients for whom a molecular diagnosis could be determined, 3 were affected with AOA1. FRDA was the most common diagnosis, found in 36 of 57 patients, AOA2 (606002) was the second most common diagnosis, found in 7 patients, and ataxia-telangiectasia (AT; 208900) was the third most common diagnosis, found in 4 patients. Marinesco-Sjogren syndrome (MSS; 248800) was also found in 3 patients. Molecular Genetics Date et al. (2001) characterized 7 families from various regions of Japan with clinical manifestations like those of the ataxia-oculomotor apraxia syndrome and again showed mapping to 9p13 as in Europeans and people of European descent. They narrowed the candidate region and identified a novel gene encoding a member of the histidine triad (HIT, e.g., 601153, 601314) superfamily as the causative gene. They called its product aprataxin and assigned the gene symbol APTX (606350); this was the first member of the HIT superfamily to be linked to a distinct phenotype. Moreira et al. (2001) and Date et al. (2001) demonstrated mutations in the APTX gene as the cause of AOA in their Portuguese and Japanese populations (606350.0001-606350.0004). Castellotti et al. (2011) identified recessive APTX mutations in 13 (6.4%) of 204 Italian probands with progressive cerebellar ataxia. The most common mutation was W279X (606350.0006), which was found in homozygous state in 7 patients and in compound heterozygosity with another pathogenic APTX mutation in 1 patient. Three additional novel mutations were identified. Western blot analysis of patient lymphocytes showed severely decreased levels of APTX protein, consistent with loss of function as a disease mechanism. There were no genotype/phenotype correlations. Genotype/Phenotype Correlations Quinzii et al. (2005) found that 3 sibs originally reported by Musumeci et al. (2001) as having familial cerebellar ataxia with muscle coenzyme Q10 (CoQ10) deficiency (see, e.g., COQ10D1, 607426) actually had AOA1 due to a homozygous mutation in the APTX gene (W279X; 606350.0006). All 3 patients responded well to CoQ10 supplementation. Thirteen additional patients with coenzyme Q deficiency did not have APTX mutations. Quinzii et al. (2005) noted that CoQ10 deficiency has been associated with 3 major clinical phenotypes and remarked that the finding of mutation in the APTX gene in these sibs supports the hypothesis that the ataxic form of CoQ10 deficiency is a genetically heterogeneous entity in which deficiency of CoQ10 can be secondary. Le Ber et al. (2007) found decreased muscle CoQ10 in 5 of 6 patients with AOA1. Three patients who were homozygous for the W279X mutation had the lowest values. The CoQ10 deficiency did not correlate with disease duration, severity, or other blood parameters, and mitochondrial morphology and respiratory function were normal. Nomenclature Date et al. (2001) suggested that the best name for this disorder is 'early-onset ataxia with oculomotor apraxia and hypoalbuminemia' (EAOH). According to Dawson (2001), the syndrome of ataxia with oculomotor apraxia is sometimes referred to as Aicardi syndrome; this runs the risk of confusion with the other Aicardi syndrome, agenesis of the corpus callosum with chorioretinal abnormalities (304050). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Oculomotor apraxia (in 86% of patients) \- Hypometric saccades \- Gaze-evoked nystagmus \- Progressive external ophthalmoplegia SKELETAL Spine \- Scoliosis Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Distal muscular atrophy due to peripheral neuropathy \- Muscle weakness \- Muscle coenzyme Q deficiency NEUROLOGIC Central Nervous System \- Cerebellar ataxia, severe \- Gait ataxia \- Limb ataxia \- Trunk ataxia \- Mosy patients become wheelchair-bound after 10 years \- Oculomotor apraxia \- Choreoathetosis (in 79%, more frequent at disease onset) \- Tremor \- Dystonia \- Dysarthria \- Mental deterioration (in a subset of patients) \- Dementia (in a subset of patients) \- Cerebellar atrophy Peripheral Nervous System \- Axonal sensory and motor peripheral neuropathy, severe \- Distal sensory loss \- Hyporeflexia \- Areflexia \- Nerve biopsy shows axonal degeneration and axonal sprouting \- Depletion of large myelinated fibers LABORATORY ABNORMALITIES \- Hypoalbuminemia (in 83%) \- Hypercholesterolemia (in 75%) MISCELLANEOUS \- Onset is usually in childhood or adolescence (2 to 18 years) \- Adult onset has been reported \- Oculomotor apraxia is not always present MOLECULAR BASIS \- Caused by mutation in the aprataxin gene (APTX, 606350.0001 ) ▲ 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, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA	c1859598	30,116	omim	https://www.omim.org/entry/208920	2019-09-22T16:30:38	{"doid": ["0050754"], "mesh": ["C538013"], "omim": ["208920"], "orphanet": ["1168"], "synonyms": ["Alternative titles", "ATAXIA-OCULOMOTOR APRAXIA SYNDROME", "ATAXIA-OCULOMOTOR APRAXIA 1", "ATAXIA-TELANGIECTASIA-LIKE SYNDROME", "CEREBELLAR ATAXIA, EARLY-ONSET, WITH HYPOALBUMINEMIA"], "genereviews": ["NBK1456"]}
The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (September 2018) (Learn how and when to remove this template message) Emotional and behavioral disorders with onset usually occurring in childhood and adolescence SpecialtyPsychiatry, psychology Emotional and behavioral disorders (EBD; also known as behavioral and emotional disorders (ICD-10))[1][2] refer to a disability classification used in educational settings that allows educational institutions to provide special education and related services to students who have displayed poor social and/or academic progress.[3] The classification is often given to students after conducting a Functional Behavior Analysis. These students need individualized behavior supports such as a Behavior Intervention Plan, to receive a free and appropriate public education. Students with EBD may be eligible for an Individualized Education Plan (IEP) and/or accommodations in the classroom through a 504 Plan.[4] ## Contents * 1 History * 1.1 Early history * 1.2 Use and development of the term * 2 Criteria * 2.1 Criticisms * 3 Student characteristics * 4 Internalizing and externalizing behavior * 5 Effect on cognition * 6 Types of services * 6.1 Texas * 6.2 New York * 6.3 California * 6.4 Michigan * 6.5 Florida * 7 References * 8 External links ## History[edit] ### Early history[edit] Before any studies were done on the subject, mental illnesses were often thought to be a form of demonic possession or witchcraft. Since much was unknown, there was little to no distinction between the different types of mental illness and developmental disorders that we refer to today. Most often, they were dealt with by performing an exorcism on the person exhibiting signs of any mental illness.[5] In the early to mid 1800s, asylums were introduced to America and Europe. There, patients were treated cruelly and often referred to as lunatics by the doctors in the professional fields.[6] The main focus of asylums were to shun people with mental illnesses from the public. In 1963, the Community Mental Health Centers Construction Act (Public Law 88-164), was passed by Congress and signed by John F. Kennedy, which provided federal funding to community mental health centers. This legislation changed the way that mental health services were handled and also led to the closure of many large asylums.[5] Many laws soon followed assisting more and more people with EBDs. 1978 came with the passing of Public Law 94- 142 which required free and public education to all handicapped children including those with EBDs. An extension of PL 94-142, PL 99-457, was put into act which would provide services to all handicapped children from the ages of 3-5 by the 1990-91 school year.[7] PL 94-142 has since been renamed to the Individuals with Disabilities Education Act (IDEA). ### Use and development of the term[edit] Various terms have been used to describe irregular emotional and behavioral disorders. Many of the terms such as mental illness and psychopathology were used to describe adults with such conditions.[8] Mental illness was a label for most people with any type of disorder and it was common for people with emotional and behavioral disorders to be labeled with a mental illness.[9] However, those terms were avoided when describing children as it seemed too stigmatizing. In the late 1900s the term "behaviorally disordered" appeared. Some professionals in the field of special education accepted the term while others felt it ignored emotional issues.[8] In order to make a more uniformed terminology, the National Mental Health and Special Education Coalition, which consists of over thirty professional and advocacy groups, coined the term "emotional and behavioral disorders" in 1988. ## Criteria[edit] According to the Individuals with Disabilities Education Act an EBD classification is required if one or more of the following characteristics is excessively observed in a student over a significant amount of time:[10] * Learning challenges that cannot be explained by intellectual, sensory, or health factors. * Trouble keeping up or building satisfactory relationships with peers and teachers. * Inappropriate behavior (against self or others) or emotions (shares the need to harm others or self, low self-worth) in normal conditions. * A overall attitude of unhappiness or depression. * A tendency to develop physical symptoms or fears related with individual or school issues. The term "EBD" includes students diagnosed with schizophrenia. However, it does not have any significant bearing on students who are socially maladjusted unless they also meet the above criteria. ### Criticisms[edit] Providing or failing to provide an EBD classification to a student may be controversial, as the IDEA does not clarify which children would be considered "socially maladjusted". Students with a psychiatric diagnosis of conduct disorder are not guaranteed to receive additional educational services under an EBD classification.[11] Students with an EBD classification who meet the diagnostic criteria for various disruptive behavior disorders, including attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), or conduct disorder (CD) do not have an automatic eligibility to receive an IEP or 504 Plan.[11] Students considered "socially maladjusted", but ineligible for an EBD classification (i.e., students diagnosed with conduct disorder), often receive better educational services in special education classrooms or alternative schools with high structure, clear rules, and consistent consequences.[12] ## Student characteristics[edit] Students with EBD are a diverse population with a wide range of intellectual and academic abilities. Males, African-Americans, and economically disadvantaged students are over-represented in the EBD population, and students with EBD are more likely to live in single-parent homes, foster homes, or other non-traditional living situations.[13] These students also tend to have low rates of positive social interactions with peers in educational contexts.[14] Students with EBD are often categorized as "internalizers" (e.g., have poor self-esteem, or are diagnosed with an anxiety disorder or mood disorder) or "externalizers" (e.g., disrupt classroom instruction, or are diagnosed with disruptive behavior disorders such as oppositional defiant disorder and conduct disorder). Male students may be over-represented in the EBD population because they appear to be more likely to exhibit disruptive externalizing behavior that interferes with classroom instruction. Females may be more likely to exhibit internalizing behavior that does not interfere with classroom instruction, though to what extent this perception is due to social expectations of differences in male and female behavior is unclear. In any case, it is important to note that both internalizing and externalizing behaviour can and do occur in either sex;[15] Students with EBD are also at an increased risk for learning disabilities, school dropout, substance abuse, and juvenile delinquency.[15] ## Internalizing and externalizing behavior[edit] A person with EBD with "internalizing" behavior may have poor self-esteem, suffer from depression, experience loss of interest in social, academic, and other life activities, and may exhibit non-suicidal self-injury or substance abuse. Students with internalizing behavior may also have a diagnosis of separation anxiety or another anxiety disorder, post-traumatic stress disorder (PTSD), specific or social phobia, obsessive–compulsive disorder (OCD), panic disorder, and/or an eating disorder. Teachers are more likely to write referrals for students that are overly disruptive. Screening tools used to detect students with high levels of "internalizing" behavior are not sensitive and are rarely used in practice.[16] Students with EBD with "externalizing" behavior may be aggressive, non-compliant, extroverted, or disruptive. Students with EBD that show externalizing behavior are often diagnosed with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder, and/or bipolar disorder; however, this population can also include typically developing children that have learned to exhibit externalizing behavior for various reasons (e.g., escape from academic demands or access to attention). These students often have difficulty inhibiting emotional responses resulting from anger, frustration, and disappointment. Students who "externalize" exhibit behaviors such as insulting, provoking, threatening, bullying, cursing, and fighting, along with other forms of aggression. Male students with EBD exhibit externalizing behavior more often than their female counterparts.[16] Children and adolescents with ADD or ADHD may display different types of externalizing behavior and should be either medicated or going through behavioral treatment for their diagnosis.[17] Adolescents with severe ADHD would likely benefit most from both medication and behavioral treatment. Younger children should go through behavioral treatment before being treated with medication. Another recommended form of treatment for children and adolescents diagnosed with ADHD would be counseling from a mental health professional. Treatment options will improve performance of children and adolescents on emotion recognition tasks, specifically response time as there is no difficulty recognizing human emotions.[18] The degree of required treatments vary depending on the degree of ADD or ADHD the individual has. Treatment for these types of behaviors should include the parents as it is evident that their parenting skills impact on how their child deals with their symptoms, especially when at a younger age. Parents going through a parenting skills training program were reported a decrease in internalizing and externalizing behavior in their children post-training program.[19] The program included learning how to give positive attention, increase good behavior with small frequent rewards and specific praise as well as learning how to decrease attention when the child behaved poorly. ## Effect on cognition[edit] In recent years, many researchers have been interested in exploring the relationship between emotional disorders and cognition. Evidence has revealed that there is a relationship between the two. Strauman (1989) investigated how emotional disorders shape a person's cognitive structure, that is, the mental processes people utilize to make sense of the world around them.[20] He recruited three groups of individuals: those with social phobias, those with depression, and controls with no emotional disorder diagnosis. He wanted to determine whether these groups had a cognitive structure showing an actual/ideal (AI) discrepancy (referring to an individual not believing that they have achieved their personal desires) or actual/own/other (AOO) discrepancy (referring to an individual's actions not living up to what their significant other believes that they need to be). He found that depressed individuals had the highest AI discrepancy and social phobics had the greatest AOO discrepancy, while the controls were lower or in between the two for both discrepancies.[21] Specific cognitive processes (e.g., attention) may be different in those with emotional disorders. MacLeod, Mathews, and Tata (1986) tested the reaction times of 32 participants, some of whom were diagnosed with Generalized Anxiety disorder, when presented with threatening words. They found that when threatening words were presented, people with greater anxiety tended to have increased selective attention, meaning that they reacted quicker to a stimulus in an area where a threatening word was just presented (32-59ms faster). When in the control group, subjects reacted slower when there was a threatening word proceeding the stimulus (16-32ms slower).[22] Emotional disorders can also alter the way people regulate their emotions. Joormann and Gotlib (2010) conducted a study with depressed, or previously depressed, individuals to test this. They found that, when compared to individuals who have never had a depressive episode, previously and currently depressed individuals tended to use maladaptive emotion regulation strategies (such as rumination or brooding) more. They also found that when depressed individuals displayed cognitive inhibition (slowing of response to a variable that had been previously ignored) when asked to describe a negative word (ignored variable was a positive word), they were less likely to ruminate or brood. When they displayed cognitive inhibition when asked to describe a positive word (ignored variable was a negative word), they were more likely to reflect.[23] ## Types of services[edit] There are many types of services available to EBD students, referenced below. One service is one-on-one support (or an aide) who assists in everyday activities and academics. Another service is foundations offer behavior services as well as counseling support. Some services include classrooms that are dedicated to educational foundations and work on building the student up possessively. States also offer dedicated schools with multiple resources that help students with EBD excel and transition (back) into local schools. ### Texas[edit] The state of Texas has the Texas Behavior Support Initiative (TBSI) authorized by Senate Bill 1196 and Texas Administrative Code §89.1053. With its design to provide knowledge for the use of constructive behavior interventions and to aid students, including students with disabilities. TBSI meets the legislative requirements for the use of restraint and time-out, along with providing the baseline work for behavior strategies and prevention throughout each environment.[24] ### New York[edit] The state of New York has the Foundations Behavioral Health that has been approved out of state educations and residential provider with the New York State Education Dept. Foundations offer Academic and Behavioral Health Services to students between the ages of 14-21. This program allows students educational experience to have strategic interventions to aid their social and behavioral functioning. Some of the program's highlights include Functional Behavioral Assessment (FBA), Behavioral Intervention Plan (BIP) & Community Based Instruction (CBI).[25] ### California[edit] The state of California has Spectrum Center classrooms in Los Angeles and the San Francisco area which are providing Emotional Disabilities and Behavioral Services. They provide academic classrooms for students who are actively working to improve grade-level standards and working toward getting their high school diploma. The main practice is the use of Positive Behavior Interventions and Supports (PBIS). PBIS instructional practices help students determine their skill level and progress, restore their skills through direct instruction, knowing the standards on their grade level and small group counseling.[26] ### Michigan[edit] The state of Michigan has a Behavioral Education Center (BEC) in Bangor. Its purpose is to aid local schools directs with students between the ages of 5–26 years old with EBD's.[27] Along with having students use appropriate behaviors and skills to successfully return to their local school setting. Classroom programs, consultation, coaching, and professional development services are available within the school districts.[28] ### Florida[edit] The state of Florida has Students with Emotional/Behavioral Disabilities Network (SEDNET). SEDNET projects across the state aid the local school districts to work with those at-risk of EBD's. “Dealing with adverse behavior in the educational environment,” it serves students who poorly function at home, school, or community due to drugs and substance abuse or mental health issues. SEDNET 2A Services: Family Services Planning Team (FSPT)- agencies, school officials and SEDNET meet with parents to assist and aid the child's poor performance at school and home. Positive Behavior Support providing technical assistance to promote positive behavior. Classroom Observation/Teacher Consultation- working with EBD children using successful strategies and tips in a classroom environment.[29] ## References[edit] 1. ^ World Health Organization (2016). "International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10): Behavioural and emotional disorders with onset usually occurring in childhood and adolescence (F90–F98)". Retrieved 2 November 2018. 2. ^ World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders. Clinical descriptions and diagnostic guidelines (PDF). Geneva. p. 40. 3. ^ "EMOTIONAL AND BEHAVIORAL DISORDER (EBD)" (PDF). Cherokee County School District. 4. ^ "Are Students with EBD Given an IEP Plan? \| Synonym". classroom.synonym.com. Retrieved 2019-05-06. 5. ^ a b "Mental Health Treatment: Then and Now \| Introduction to Psychology". courses.lumenlearning.com. Retrieved 2019-05-07. 6. ^ "The History of Asylums in the 1800s - Video & Lesson Transcript". Study.com. Retrieved 2019-05-07. 7. ^ Fong, Yvonne. "The History of Emotional and Behavioral Disorders". Cite journal requires `\|journal=` (help) 8. ^ a b "Overview of Emotional and Behavioral Disorders" (PDF). Pro Ed Inc. 9. ^ "History of Emotional Behavioral Disorders". Emotional Behavioral Disorders. Retrieved 2019-05-07. 10. ^ "Emotional Disturbance \| Center for Parent Information and Resources". www.parentcenterhub.org. Retrieved 2019-05-06. 11. ^ a b "Students with Emotional Disturbance: Eligibility and Characteristics". cecp.air.org. Archived from the original on 18 October 2015. Retrieved 22 October 2015. 12. ^ "Social Maladjustment". behavior-consultant.com. Retrieved 22 October 2015. 13. ^ Danielson, Melissa L.; Bitsko, Rebecca H.; Ghandour, Reem M.; Holbrook, Joseph R.; Kogan, Michael D.; Blumberg, Stephen J. (2018). "Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016". Journal of Clinical Child & Adolescent Psychology. 47 (2): 199–212. doi:10.1080/15374416.2017.1417860. PMC 5834391. PMID 29363986. 14. ^ Wehby, Joseph; Symons, F.; Shores, R. E. (1995). "A descriptive analysis of aggressive behavior in classrooms for children with emotional and behavioral disorders". Behavioral Disorders. 20 (2): 87–105. doi:10.1177/019874299502000207. 15. ^ a b Danielson, Melissa L.; Bitsko, Rebecca H.; Ghandour, Reem M.; Holbrook, Joseph R.; Kogan, Michael D.; Blumberg, Stephen J. (2018-03-04). "Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016". Journal of Clinical Child & Adolescent Psychology. 47 (2): 199–212. doi:10.1080/15374416.2017.1417860. ISSN 1537-4416. PMC 5834391. PMID 29363986. 16. ^ a b Wells, Erica L.; Day, Taylor N.; Harmon, Sherelle L.; Groves, Nicole B.; Kofler, Michael J. (2018-11-26). "Are emotion recognition abilities intact in pediatric ADHD?". Emotion. 19: 1192–1205. doi:10.1037/emo0000520. ISSN 1931-1516. PMC 6535378. PMID 30475028. 17. ^ Danielson, Melissa L.; Bitsko, Rebecca H.; Ghandour, Reem M.; Holbrook, Joseph R.; Kogan, Michael D.; Blumberg, Stephen J. (2018). "Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016". Journal of Clinical Child & Adolescent Psychology. 47 (2): 199–212. doi:10.1080/15374416.2017.1417860. PMC 5834391. PMID 29363986. 18. ^ Wells, Erica L.; Day, Taylor N.; Harmon, Sherelle L.; Groves, Nicole B.; Kofler, Michael J. (2018). "Are emotion recognition abilities intact in pediatric ADHD?". Emotion. 19: 1192–1205. doi:10.1037/emo0000520. PMC 6535378. PMID 30475028. 19. ^ Cartwright-Hatton, Sam; McNally, Deborah; White, Caroline; Verduyn, Chrissie (2005). "Parenting Skills Training: An Effective Intervention for Internalizing Symptoms in Younger Children?". Journal of Child and Adolescent Psychiatric Nursing. 18 (2): 45–52. doi:10.1111/j.1744-6171.2005.00014.x. 20. ^ Garner, B. K. (2007). Getting to “got it!”. Alexandria, VA: Association for Supervision and Curriculum Development. 21. ^ Strauman T. J. (1989). "Self-discrepancies in clinical depression and social phobia: Cognitive structures that underlie emotional disorders?". Journal of Abnormal Psychology. 98 (1): 14–22. doi:10.1037/0021-843x.98.1.14. PMID 2708634. 22. ^ MacLeod, Colin; Mathews, Andrew; Tata, Philip (1986). "Attentional bias in emotional disorders". Journal of Abnormal Psychology. 95: 15–20. doi:10.1037/0021-843x.95.1.15. PMID 3700842. 23. ^ Joormann, Jutta; Gotlib, Ian H. (2010). "Emotion regulation in depression: Relation to cognitive inhibition". Cognition & Emotion. 24 (2): 281–298. doi:10.1080/02699930903407948. PMC 2839199. PMID 20300538. 24. ^ "Texas Support Initiative". www.txbehaviorsupport.org. Retrieved 2019-05-08. 25. ^ "Out of State Education and Residential Provider \| New York State". Foundations Behavioral Health (in Russian). Retrieved 2019-05-08. 26. ^ "Emotional Disabilities and Behavioral Services \| Spectrum Center". Spectrum Center Schools and Programs. Retrieved 2019-05-08. 27. ^ "Behavioral Education Center / Behavioral Education Center". www.vbisd.org. Retrieved 2019-05-08. 28. ^ "Classrooms for Students With Severe Emotional Impairment / Description". www.vbisd.org. Retrieved 2019-05-08. 29. ^ "Students with Emotional/Behavioral Disabilities Network (SEDNET) - Panhandle Area Educational Consortium". my.paec.org. Retrieved 2019-05-08. ## External links[edit] * What is an emotional or behavioral disorder? * Behaviour Management (EBD) Review Group: Published reviews Classification D * ICD-10: F90–F98 * ICD-9-CM: 312 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy * v * t * e Emotional and behavioral disorders Emotional/behavioral * ADHD * Conduct disorder * Oppositional defiant disorder * Emotional/behavioral disorder (EBD) * Separation anxiety * Social functioning * Selective mutism * RAD * DAD * Tic disorders * Tourette syndrome * Speech disorders * Stuttering * Cluttering * Stereotypic movement disorder * Elimination disorders * Enuresis * Encopresis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Emotional and behavioral disorders	None	30,117	wikipedia	https://en.wikipedia.org/wiki/Emotional_and_behavioral_disorders	2021-01-18T18:53:26	{"icd-9": ["314", "312"], "icd-10": ["F90", "F91", "F95", "F93", "F98", "F92", "F94"], "wikidata": ["Q3063847"]}
A form of limb-girdle muscular dystrophy characterized by an onset in childhood or adolescence of rapidly progressive proximal limb muscle weakness (particularly affecting the neck, hip girdle, and shoulder abductors), hypertrophy in the calves and quadriceps, ankle contractures, and myopia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	POMGNT1-related limb-girdle muscular dystrophy R15	c3150417	30,118	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=206564	2021-01-23T17:53:23	{"gard": ["12540"], "omim": ["613157"], "icd-10": ["G71.0"], "synonyms": ["Autosomal recessive limb-girdle muscular dystrophy type 2O", "LGMD type 2O", "LGMD2O", "Limb-girdle muscular dystrophy type 2O", "POMGNT1-related LGMD R15"]}
Cormier-Daire et al. (2001) reported a female fetus with an apparently novel lethal skeletal dysplasia that clinically resembled achondrogenesis (see 200600), but with distinctive radiologic and chondroosseous morphologic features. These included bifid distal ends of the long bones of the limbs; absent vertebral body ossification; a unique 'baby rattle' pelvic configuration with tall and broad ilia; absent endochondral ossification; regions of mesenchymal cells within the resting cartilage; and abnormal mesenchymal ossification. Both parents were Caucasian. A diagnosis of achondrogenesis was made at 32 weeks, and the pregnancy was terminated by Pitocin-induced vaginal delivery. At birth the infant was noted to have micromelia, large fontanels, pronounced midface hypoplasia, a short neck, and a protuberant abdomen. Other than the skeletal abnormalities, a postmortem examination showed only pulmonary hypoplasia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	BABY RATTLE PELVIS DYSPLASIA	c1853911	30,119	omim	https://www.omim.org/entry/605838	2019-09-22T16:10:52	{"mesh": ["C565282"], "omim": ["605838"]}
A number sign (#) is used with this entry because of evidence that one form of cerebral cavernous malformations (CCM1) is caused by heterozygous mutation in the KRIT1 gene (604214) on chromosome 7q21. Description Cerebral cavernous angiomas are relatively rare vascular malformations that may involve any part of the central nervous system. Cerebral cavernous angiomas are to be distinguished from cerebral arteriovenous malformations (106070, 108010). CCMs are venous and not demonstrable by arteriography; hence they are referred to as angiographically silent. Capillary hemangiomas (602089) are classified as distinct from vascular malformations in that hemangiomas are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. Hemangiomas develop shortly after birth. In contrast, vascular malformations are present from birth, tend to grow with the individual, do not regress, and show normal rates of endothelial cell turnover (Mulliken and Young, 1988). ### Genetic Heterogeneity of CCM CCM2 (603284) is caused by mutation in the CCM2/malcavernin gene (607929), and CCM3 (603285) is caused by mutation in the PDCD10 gene (609118). Evidence suggests that a 2-hit mechanism involving biallelic germline and somatic mutations is responsible for CCM1 pathogenesis; see PATHOGENESIS and MOLECULAR GENETICS sections. Clinical Features Some CCMs are clinically silent, whereas others cause seizures, hemorrhage, or focal neurologic deficit. Identification of these lesions is important because surgical removal of many is relatively easy. Magnetic resonance imaging (MRI) is replacing computerized axial tomography as the diagnostic modality of choice. Bicknell et al. (1978) found 3 reports of familial incidence of CCM and added 2 from their own experience. In 1 family a woman, 2 of her sons, and 1 of her son's sons were affected; in the second family a woman and her daughter were affected. Successive generations were affected in families reported by Michael and Levin (1936), Kidd and Cumings (1947), and Clark (1970). Michael and Levin (1936) described a Swedish family in which a mother, her 2 brothers, and 3 daughters had multiple 'telangiectases' of the brain, which were likely cavernous angiomata. Convulsions and migraine attacks were observed. Autopsy in one case demonstrated calcification in the vascular lesions of the brain. Clark (1970) described cavernous angioma of the brain in a man who died in 1945 at age 27 and in his daughter who died in 1969 at age 28. Hayman et al. (1982) examined 43 relatives in 1 kindred by cranial computed tomography (CCT) and found 15 affected with cerebral vascular angiomas. Angiography failed to detect lesions in 5 patients who had positive CCT. Expression was variable and in 2 individuals, each the parent of an affected offspring, the CCT was normal. Familial cavernous angioma should be included in the differential diagnosis of any young person with cerebrovascular impairment, seizures, intracranial calcifications, or hemorrhage. Gorlin (1985) reported an extensively affected 3-generation family. Michels et al. (1985) stated that 19 families with 77 persons with cavernous angiomas of the central nervous system and retina have been described. They described a 3-generation family ascertained through an 8-year-old boy with seizures and 2 unexplained lesions on CT and MRI. His mother presented a year later with a seizure and similar brain lesions. Angiography and eye examination were normal. The asymptomatic grandfather had 5 intracranial lesions on MRI scan. Mason et al. (1988) described cavernous angiomas in 10 of 22 members of a large Hispanic family. The authors commented that 2 families previously reported by them (Bicknell et al., 1978), the family reported by Hayman et al. (1982), and 5 of the 6 families reported in abstract by Rigamonti et al. (1987) were Hispanic as well. Dobyns et al. (1987) described a family in which 4 persons from 3 generations had multiple cavernous malformations ('angiomas') of the CNS and/or retina. They found reports of 16 other families containing a total of 50 cases. Excluding the probands, 68% of the patients were symptomatic. Cutaneous vascular lesions were an inconsistent manifestation. They recommended that any patient with a vascular malformation, especially a cavernous one of the brain, spinal cord, or retina, be evaluated for the possibility of this syndrome, which they referred to as 'familial cavernous malformations of CNS and retina' (FCMCR). The authors also suggested that all first-degree relatives should undergo a full evaluation if multiple vascular malformations are detected in the index patient or if the family history is suggestive because of seizures, cutaneous vascular lesions, recognized intracranial hemorrhage, or sudden unexplained death. Presymptomatic diagnosis in affected relatives would permit genetic counseling and close monitoring to allow prompt treatment if symptoms occur. Dobyns et al. (1987) concluded that there is a second group of patients with multiple cutaneous lesions and inconsistent CNS lesions referred to as hereditary neurocutaneous angioma (106070). The vascular lesions in this group were always arteriovenous malformations and were often located in the spinal cord. Rigamonti et al. (1988) reviewed familial occurrence, presenting signs and symptoms, and radiographic features of the disorder in 24 patients with histologically verified cerebral cavernous malformations. Eleven patients had no evidence of a heritable trait and had negative family histories. The other 13 patients were members of 6 unrelated Mexican-American families. Among 64 first-degree and second-degree relatives, 11% had seizures. MRI was performed in 16 relatives (5 of whom were asymptomatic); 14 studies showed cavernous malformations and 11 studies identified multiple lesions. MRI was far more accurate in detecting these lesions than computerized tomography or angiography. Rigamonti et al. (1988) concluded that a familial form of this disorder is particularly frequent among Mexican-Americans. Bicknell (1989) described cavernous angioma of the brainstem in a 23-year-old Hispanic woman whose mother had died of brain hemorrhage. After moving to Baltimore from the southwestern part of the United States, Rigamonti (1993) concluded that there is not an unusual frequency of the disorder among Mexican-Americans. He emphasized that cavernous angiomas are not arteriovenous malformations; they represent a honeycomb of veins. They are not demonstrated by arteriography and therefore have been referred to as angiographically silent. Epilepsy is the most frequent symptom; bleeds occur in some cases. Steichen-Gersdorf et al. (1992) reported a family in which cavernous angiomas of the brain were documented in 6 individuals in 5 sibships of 4 generations of a family. Two brothers in the third generation were asymptomatic but showed changes on MRI. Filling-Katz et al. (1989, 1992) described a family with cavernous angiomatosis in which 2 members had terminal transverse defects at the midforearm. Multiple family members had had episodic bleeding from cavernous angiomas of the central nervous system. Two had had retinal cavernous angiomas, 1 hepatic angioma, and 2 cavernous angiomas of soft tissue; skin angiomas were frequent. Studies of the forearm in 1 of the affected individuals showed abrupt termination distal to the normal radius and ulnar heads and apparently normal blood vessels. Filling-Katz et al. (1989, 1992) suggested that acute vascular disruption is the cause and that this is related to the fundamental defect in familial cavernous angiomatosis. Corboy and Galetta (1989) described a family in which the proband had suffered for 9 years from recurrent 'acute chiasmal syndrome,' diagnosed at first as retrobulbar neuritis. Dellemijn and Vanneste (1993) investigated 20 relatives of a 23-year-old woman with cavernous angiomatosis of the central nervous system. Studies revealed 4 additional patients with symptomatic cavernous angioma and 1 with asymptomatic cavernous angioma. The basis of the neurologic symptoms had not previously been identified in the symptomatic patients. The pedigree pattern was consistent with autosomal dominant inheritance. Computed tomography and MRI led to reassessment of the incidence of cavernous angioma of the brain including its familial occurrence. Drigo et al. (1994) described an Italian family with multiple cavernous angiomas of the brain, sometimes in association with liver angiomas, in 10 members of 4 generations. No neurologic symptoms were detected in subjects from the first 2 generations but symptoms were found in adult age in members of the third generation; 2 fourth-generation members came under medical observation at 2.5 years of age. Symptoms included partial epileptic fits which sometimes became generalized later and were generally controlled adequately by therapy. None of the patients was mentally retarded or restricted in daily life. Because of symptomatic hepatomegaly and postmortem finding of multiple liver and brain angiomas in a member of the first generation, liver ultrasonography was performed in all members of the family with detection of liver angiomas in members of the second and third generation. Retinal angioma was detected in 1 patient. Labauge et al. (1998) established the clinical and genetic features of hereditary cavernous angiomas in a series of 57 French families. Neuroimaging investigations confirmed the high frequency of multiple lesions in hereditary cavernous angiomas. It also showed a correlation between the number of lesions and the age of the patient, suggesting a dynamic nature for the lesions. Among 202 KRIT1 mutation carriers from 64 families, Denier et al. (2004) found that 126 had CCM and 76 were symptom-free. Mean age at clinical onset was 29.7 years, with 55% of patients presenting with generalized and/or partial seizures, and 32% with cerebral hemorrhages. The number of lesions averaged 4.9 on T2-weighted MRI and 19.8 on gradient echo MRI. Only 5 asymptomatic mutation carriers had no detectable lesions on T2-weighted MRI and gradient echo MRI. Denier et al. (2004) found that nearly half of mutation carriers aged 50 years or more were symptom-free, demonstrating clinical and radiologic incomplete penetrance of the disease. Waters et al. (2005) reported a patient with familial CCM1 and a history of multiple CCMs, including an acutely hemorrhagic left cerebellar CCM that was resected. He also had an angiomatous skin lesion. The patient presented with acute onset of bilateral lower extremity weakness and numbness, and inability to urinate for 36 hours. Spinal MRI showed an intramedullary mass at levels T11 to T12, consistent with a cavernous angioma and hematoma. Surgical resection was successful. Waters et al. (2005) emphasized that patients with multiple CCMs tend to have predominantly intracerebral lesions, but that malformations may occur throughout the neuroaxis, including the spinal cord. In a comparison of clinical features between mutation carriers from 86 families with CCM1 and 25 families with CCM2, Denier et al. (2006) observed that the number of gradient-echo sequence cerebral lesions increased more rapidly with age in patients with CCM1 than in those with CCM2. Battistini et al. (2007) reported 5 unrelated Italian families with CCM1. The mean age at symptom onset was 15.9 years (range 4 to 36). The most common presenting symptoms included seizures (67%), recurrent headache (20%), and cerebral hemorrhage (13%). Genetic analysis identified 5 different heterozygous KRIT1 mutations (see, e.g., 604214.0009). The families included 33 mutation carriers, 57.6% of whom had no symptoms. Brain MRI revealed lesions in 82.3% of symptom-free mutation carriers. ### Cutaneous Involvement Norwood and Everett (1964) reported the case of a 21-year-old black female who during pregnancy developed large hemangiomas at many sites, such as earlobe and axilla, and heart failure as a result. After delivery, the hemangiomas rapidly subsided. The patient's mother and 6-year-old son had macular hemangiomas of the face and trunk and her brother had classic Klippel-Trenaunay-Weber syndrome (149000) of the right lower extremity. Beers and Clark (1942) described a family with cutaneous hemangiomas ranging in size from a millimeter to many centimeters in diameter, in 12 persons in 3 generations. Metatarsus atavicus (second toe longer than the first toe, see 189200) was an independent dominant trait in this family. Keret et al. (1990) described an 18-year-old male with left scrotal cavernous hemangioma. Cutaneous hemangiomata were found in 34 relatives (21 males and 13 females). Only the proband had a genital lesion. The differentiation of scrotal hemangioma from varicocele was discussed. Hyperkeratotic cutaneous capillary-venous malformations (HCCVMs) are crimson-colored, irregularly shaped lesions, the size of which may extend to several centimeters. By light microscopy, the lesions extend into both dermis and hypodermis and are composed of dilated capillaries and blood-filled venous-like channels. The overlying epidermis is hyperkeratotic. HCCVMs have been reported to be associated with cerebral capillary malformations (CCMs) (Labauge et al., 1999; Ostlere et al., 1996). Cerebral capillary malformations resemble HCCVMs in that both are composed of abnormal capillaries and venous-like vessels. In families in which these lesions coexist, all members who have HCCVMs also have CCMs (Eerola et al., 2000). Diagnosis Lehnhardt et al. (2005) found that MRI with T2-weighted gradient-echo sequences was more sensitive than routine MRI with T1-weighted and T2-weighted spin-echo sequences in determining lesion number and disease extent in affected members of a 3-generation family with CCM. One patient with a single lesion on routine MRI showed an additional lesion on gradient-echo sequences only, and 2 patients showed greater extent of disease only on gradient-echo sequences. Pathogenesis For each of the 3 CCM genes, Pagenstecher et al. (2009) showed complete localized loss of either KRIT1 (604214), CCM2/malcavernin, or PDCD10 (609118) protein expression depending on the respective inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein, but stained positively for the 2 other proteins. Immunohistochemical studies demonstrated endothelial cell mosaicism as neoangiogenic vessels within caverns from a CCM1 patient and normal brain endothelium from a CCM2 patient stained positively for KRIT1 and CCM2/malcavernin, respectively. Pagenstecher et al. (2009) suggested that complete lack of CCM protein in affected endothelial cells from CCM germline mutation carriers supports a 2-hit mechanism for CCM formation. Maddaluno et al. (2013) demonstrated that endothelial-specific disruption of the KRIT1 gene in mice induces endothelial-to-mesenchymal transition, which contributes to the development of vascular malformations. Endothelial-to-mesenchymal transition in KRIT1-ablated endothelial cells is mediated by the upregulation of endogenous bone morphogenetic protein-6 (BMP6; 112266) that, in turn, activates the transforming growth factor-beta (TGF-beta; 190180) and BMP signaling pathway. Inhibitors of the TGF-beta and BMP pathway prevented endothelial-to-mesenchymal transition both in vitro and in vivo and reduced the number and size of vascular lesions in KRIT1-deficient mice. Thus, increased TGF-beta and BMP signaling, and the consequent endothelial-to-mesenchymal transition of KRIT1-null endothelial cells, are crucial events in the onset and progression of cerebral cavernous malformation disease. Using a neonatal mouse model of CCM disease, Zhou et al. (2016) showed that expression of the MEKK3 (602539) target genes Klf2 (602016) and Klf4 (602253), as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. By contrast, Zhou et al. (2016) found no evidence of endothelial-mesenchymal transition or increased SMAD (e.g., 601595) or Wnt (see 164820) signaling during early CCM formation. Endothelial-specific loss of Map3k3 (Mekk3), Klf2, or Klf4 markedly prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, Zhou et al. (2016) showed that endothelial expression of KLF2 and KLF4 is increased in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation is normally expressed in HEK293 cells, binds KRIT1 and PDCD10 comparably to wildtype, but abrogates the MEKK3 interaction without affecting CCM complex formation. The authors concluded that their studies identified gain of MEKK3 signaling and KLF2/4 function as causal mechanisms for CCM pathogenesis. Tang et al. (2017) identified TLR4 (603030) and the gut microbiome as critical stimulants of CCM formation. Activation of TLR4 by gram-negative bacteria or lipopolysaccharide accelerated CCM formation, and genetic or pharmacologic blockade of TLR4 signaling prevented CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its coreceptor CD14 (158120) were associated with higher CCM lesion burdens in humans. Germ-free mice were protected from CCM formation, and a single course of antibiotics permanently altered CCM susceptibility in mice. Tang et al. (2017) concluded that their studies identified unexpected roles for the microbiome and innate immune signaling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment. Mapping Using linkage analysis and a set of short tandem repeat polymorphisms, Dubovsky et al. (1995) mapped a gene responsible for cerebral cavernous malformations in a large Hispanic kindred to 7q11-q22. The maximum pairwise lod score of 4.2 was obtained at zero recombination with a marker at locus D7S804. Lod scores in excess of 3.0 were obtained with 4 additional markers closely linked to D7S804. A chromosome 7q haplotype of 33 cM on the sex-averaged map was shared by all affected individuals, indicating that the gene lies between D7S502 and D7S479. Using a linkage approach in 2 extended cavernous malformation kindreds, Gunel et al. (1995) also linked cavernous malformations to 7q, specifically 7q11.2-q21. Multipoint linkage analysis yielded a maximum lod score of 6.88 with zero recombination with D7S669 and localized the gene to a 7-cM region in the interval between ELN (130160) and D7S802. This gene is symbolized CCM1 for 'cerebral cavernous malformations-1.' Marchuk et al. (1995) likewise mapped the CCM1 gene to proximal 7q by linkage methods. In 2 families, 1 of Italian-American origin and 1 of Mexican-American origin, they found a combined maximum lod score of 3.92 at theta = 0.0 for marker D7S479. Haplotype analysis placed the locus between D7S502 proximally and D7S515 distally, an interval of approximately 41 cM. The chromosomal location distinguishes this disorder from the autosomal dominant vascular malformation syndrome (VMCM; 600195) in which lesions are primarily cutaneous; VMCM is due to mutation in a gene that maps to 9p21. Johnson et al. (1995) refined the CCM1 locus assignment to a 4-cM interval bracketed by D7S2410 and D7S689. Gunel et al. (1996) found that 47 affected members of 14 Hispanic American kindreds shared identical alleles for up to 15 markers linked to the CCM1 gene in a short segment of proximal 7q. Ten patients with sporadic cases also shared these same alleles, indicating that they too had inherited the same mutation. Thirty-three asymptomatic carriers of the disease gene were identified, demonstrating the variability and age dependence of the development of symptoms and explaining the appearance of apparently sporadic cases. Gunel et al. (1996) concluded that virtually all cases of familial and sporadic cavernous malformation among Hispanic Americans of Mexican descent are due to the inheritance of the same mutation from a common ancestor. ### Genetic Heterogeneity Craig et al. (1998) reported analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. Analyses showed linkage to 2 loci other than CCM1: CCM2 (603284) at 7p15-p13, and CCM3 (603285) at 3q25.2-q27. Multilocus analysis yielded a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2, and 40% linked to CCM3, with highly significant evidence for linkage to 3 loci. Linkage to these 3 loci could account for inheritance of CCM in all kindreds studied. The penetrance of symptomatic disease among apparent gene carriers for kindreds linked to CCM1, CCM2, and CCM3 was 88%, 100%, and 63%, respectively. These differences were not explained by differences in age or gender of gene carriers among families, and none of the asymptomatic gene carriers in this analysis was under age 20. Laberge et al. (1999) conducted a genetic linkage analysis on 36 French CCM1 families using 8 microsatellite markers mapping within the CCM1 interval. Admixture analysis showed that 65% of these families were linked to the CCM1 locus. Haplotype analysis of CCM1-linked families did not show any evidence for a strong founder effect. Molecular Genetics In 12 of 20 pedigrees with cerebral cavernous malformations, Laberge-Le Couteulx et al. (1999) identified mutations in the CCM1 gene (see, e.g., 604214.0001) that segregated with the affected phenotype. They suggested that the mutations in the CCM1 gene might result in a dominant-negative effect or a loss of function; they favored the second hypothesis. Sporadic forms of cavernous angiomas manifest as unique lesions and familial forms as multiple lesions, which evokes a Knudson double-hit mechanism and would be consistent with the need for a complete loss of CCM1 function for the appearance of cavernous angiomas. All the mutations they reported predicted truncated CCM1 proteins completely or partially devoid of the putative RAP1A-interacting region. In 1 family in which 2 of 4 members with CCMs also had hyperkeratotic cutaneous capillary-venous malformations, Eerola et al. (2000) found a 1-basepair deletion in the KRIT1 gene (604214.0005). Another novel mutation in this gene (604214.0006) was found in a family with CCM only. In a family in which 5 individuals had both retinal and cerebral cavernous angiomas, Laberge-Le Couteulx et al. (2002) identified a heterozygous mutation in the KRIT1/CCM1 gene (604214.0010). In 29 families and 5 sporadic cases with CCM, Davenport et al. (2001) identified 10 novel mutations and 1 previously described mutation in the KRIT1 gene (see, e.g., 604214.0008). The high frequency of loss-of-function mutations suggested loss of a tumor suppressor mechanism. In a follow-up study, Verlaan et al. (2002) reported 7 additional novel mutations and 1 previously described mutation in the KRIT1 gene in families with CCM. In combination with the previous study, Verlaan et al. (2002) found that approximately 47% of CCM families carry KRIT1 mutations. The authors noted that the majority of mutations in the KRIT1 gene lead to a substantial alteration of the gene product, supporting a loss-of-function mechanism consistent with a tumor suppressor gene. Cave-Riant et al. (2002) screened the KRIT1 gene in 121 unrelated CCM probands having at least 1 affected relative and/or showing multiple lesions on cerebral MRI. Fifty-two individuals (43%) were shown to have a KRIT1 mutation, and 42 distinct mutations were identified, all of which were predicted to result in premature stop codons. Cave-Riant et al. (2002) concluded that the underlying mechanism of CCM may be KRIT1 mRNA decay due to the presence of premature stop codons and KRIT1 haploinsufficiency. Verlaan et al. (2004) identified a pathogenic mutation in the KRIT1 gene in 4 (29%) of 14 unrelated patients with sporadic CCM and multiple malformations. None of 21 unrelated patients with a single malformation had a KRIT1 mutation. Verlaan et al. (2004) concluded that genetic analysis is warranted in sporadic cases of CCM with multiple malformations. In 2 additional patients of the 14 sporadic CCM patients reported by Verlaan et al. (2004), Felbor et al. (2007) used multiplex ligation-dependent probe amplification to detect a large duplication and a large deletion, respectively, within the KRIT1 gene. Thus, 6 (42%) of the 14 sporadic patients had a KRIT1 mutation. Revencu and Vikkula (2006) reviewed the 3 genetic forms of familial cerebral cavernous malformation identified to that time and evidence on disturbed function. They pointed to work indicating that the 3 CCM genes are expressed in neurons rather than in blood vessels. The interaction between CCM1 and CCM2, which was expected on the basis of their structure, had been proven, suggesting a common functional pathway. Among 24 Italian families with CCM, Liquori et al. (2008) identified 5 with deletions in the CCM1 gene, including 1 complete deletion of the gene. Through repeated cycles of amplification, subcloning, and sequencing of multiple clones per amplicon, Akers et al. (2009) identified somatic mutations that were otherwise invisible by direct sequencing of the bulk amplicon. Biallelic germline and somatic mutations were identified in CCM lesions from all 3 forms of inherited CCMs. The somatic mutations were found only in a subset of the endothelial cells lining the cavernous vessels and not in interstitial lesion cells. Although widely expressed in the different cell types of the brain, the authors also suggested a unique role for the CCM proteins in endothelial cell biology. Akers et al. (2009) suggested that CCM lesion genesis may require complete loss of function for 1 of the CCM genes. Cau et al. (2009) identified 2 different mutations in the KRIT1 gene (see, e.g., C329X; 604214.0011) in 5 (71%) of 7 Sardinian families with CCM. Haplotype analysis of patients from 4 of the affected families indicated a founder effect for the C329X mutation. ### Modifying Polymorphisms Tang et al. (2017) found that TLR4 and CD14 expression parallels human CCM burden. They studied 830 genetic variants of 56 inflammatory and immune-related genes in 188 patients who carried a KRIT1 Q455X (604214.0004) variant and measured CCM lesion burden using MRI. Following statistical analysis, SNPs in only 2 genes, TLR4 (rs10759930) and CD14 (rs778587), were found to be significantly associated with increased CCM lesion number. Further analysis of genes in TLR4-MEKK3-KLF2/4 signaling pathways identified additional SNPs for TLR4 (rs10759931) and CD14 (rs778588) in linkage disequilibrium with those previously identified, but none in other pathway genes that associated with altered lesion burden. Tang et al. (2017) found that the SNPs in TLR4 and CD14 that are associated with increased CCM lesion number are in the 5-prime genomic region of each gene and constitute cis expression quantitative trait loci (QTLs) that positively regulate whole blood cell expression of TLR4 and CD14 in a dose-dependent manner corresponding with risk allele number. These results were corroborated using the GTEx Consortium data. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Retinal vascular malformations ABDOMEN Liver \- Hepatic vascular malformations SKIN, NAILS, & HAIR Skin \- Hyperkeratotic cutaneous vascular lesions MUSCLE, SOFT TISSUES \- Soft tissue vascular malformations NEUROLOGIC Central Nervous System \- Intracranial thin-walled sinusoidal vessel (cavernous) malformations \- Seizures \- Headache \- Intracranial hemorrhage \- Focal neurologic deficits \- Intracranial calcifications \- Angiographically 'silent' \- MRI is best imaging modality to detect lesions MISCELLANEOUS \- Most common age of clinical onset ranges from 16 to 33 years \- Incomplete penetrance \- Multiple lesions in familial cases \- Single lesions in sporadic cases \- Genetic heterogeneity (CCM2 603284 , CCM3 603285 ) MOLECULAR BASIS \- Caused by mutation in the Krev interaction trapped 1 gene (KRIT1 604214.0001 ). ▲ 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	CEREBRAL CAVERNOUS MALFORMATIONS	c2931263	30,120	omim	https://www.omim.org/entry/116860	2019-09-22T16:43:33	{"doid": ["0080491"], "mesh": ["C536610"], "omim": ["116860"], "orphanet": ["221061"], "synonyms": ["Alternative titles", "CAVERNOUS ANGIOMA, FAMILIAL", "CAVERNOUS ANGIOMATOUS MALFORMATIONS", "CEREBRAL CAPILLARY MALFORMATIONS"], "genereviews": ["NBK1293"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Pancytopenia" – news · newspapers · books · scholar · JSTOR (July 2020) Pancytopenia SpecialtyHematology Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets. If only two parameters from the complete blood count are low, the term bicytopenia can be used. The diagnostic approach is the same as for pancytopenia. ## Contents * 1 Causes * 2 Mechanism * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Causes[edit] Iatrogenic causes of pancytopenia include chemotherapy for malignancies if the drug or drugs used cause bone marrow suppression. Rarely, drugs (antibiotics, blood pressure medication, heart medication) can cause pancytopenia. For example, the antibiotic chloramphenicol can cause pancytopenia in some individuals.[1] Rarely, pancytopenia may have other causes, such as mononucleosis or other viral diseases. Increasingly, HIV is itself a cause of pancytopenia. * Familial hemophagocytic syndrome * Aplastic anemia * Gaucher's disease * Metastatic carcinoma of bone * Multiple Myeloma * Overwhelming infections * Lymphoma * Myelofibrosis * Dyskeratosis congenita * Myelodysplastic syndrome * Leukemia * Leishmaniasis * Severe folate or vitamin B12 deficiency * Systemic lupus erythematosus * Paroxysmal nocturnal hemoglobinuria (blood test) * Viral infections (such as HIV, EBV; an undetermined virus is most common) * Alimentary toxic aleukia * Copper deficiency * Pernicious anemia * Medication * Hypersplenism * Osteopetrosis * Organic acidurias (Propionic Acidemia, Methylmalonic Aciduria, Isovaleric Aciduria) * Low dose arsenic poisoning * Sako disease (Myelodysplastic-cytosis) * Chronic radiation sickness[2] * LIG4 syndrome ## Mechanism[edit] The mechanisms for pancytopenia differ according to the etiology. For example, in hemophagocytic lymphohistiocytosis (HLH) there is marked inappropriate and ineffective T cell activation that leads to an increased hemophagocytic activity. The T cell activated macrophages engulf erythrocytes, leukocytes, platelets, as well as their progenitor cells. Along with pancytopenia, HLH is characterized by fever, splenomegaly, and hemophagocytosis in bone marrow, liver, or lymph nodes.[citation needed] ## Diagnosis[edit] Pancytopenia usually requires a bone marrow biopsy in order to distinguish among different causes. * anemia: hemoglobin < 13.5 g/dL (male) or 12 g/dL (female). * leukopenia: total white cell count < 4.0 x 109/L. Decrease in all types of white blood cells (revealed by doing a differential count). * thrombocytopenia: platelet count < 150×109/L. ## Treatment[edit] Treatment is done to address the underlying cause. Blood transfusion with packed red blood cells (PRBC) may be indicated according to need. ## References[edit] 1. ^ Abdollahi, M.; Mostafalou, S. (2014), "Chloramphenicol", Encyclopedia of Toxicology, Elsevier, pp. 837–840, doi:10.1016/b978-0-12-386454-3.00709-0, ISBN 978-0-12-386455-0, retrieved 2020-12-11 2. ^ Kossenko MM, Akleyev AA, Degteva MO, Kozheurov VP, Degtyaryova RC (August 1994). "Analysis of Chronic Radiation Sickness Cases in the Population of the Southern Urals (AD-A286 238)". DTIC. p. 5. Retrieved 1 August 2013. "Complete blood counts, when taken, revealed pancytopenia." ## External links[edit] * EID Journal (Volume 6, Number 6), CDC, December 2000. Classification D * ICD-10: D61.9 * ICD-9-CM: 284.1 * MeSH: D010198 * DiseasesDB: 24135 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Pancytopenia	c0030312	30,121	wikipedia	https://en.wikipedia.org/wiki/Pancytopenia	2021-01-18T18:52:27	{"mesh": ["D010198"], "umls": ["C0030312"], "wikidata": ["Q1757427"]}
Not to be confused with Pervasive developmental disorder. Developmental disorder SpecialtyPsychiatry Developmental disorders comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas. There are several ways of using this term.[1] The most narrow concept is used in the category "Specific Disorders of Psychological Development" in the ICD-10.[1] These disorders comprise developmental language disorder, learning disorders, motor disorders, and autism spectrum disorders.[2] In broader definitions ADHD is included, and the term used is neurodevelopmental disorders.[1] Yet others include antisocial behavior and schizophrenia that begins in childhood and continues through life.[1] However, these two latter conditions are not as stable as the other developmental disorders, and there is not the same evidence of a shared genetic liability.[1] Developmental disorders are present from early life. Most improve as the child grows older, but some entail impairments that continue throughout life. There is a strong genetic component; more males are afflicted than females.[1] ## Contents * 1 Emergence * 1.1 Causes * 2 Types * 2.1 Autism spectrum disorder (ASD) * 2.1.1 Diagnosis * 2.1.2 Abnormalities in the brain * 2.1.3 Symptoms * 2.1.3.1 Persistent issues in social interactions and communications * 2.1.3.2 Repetitive behavioral patterns * 2.1.4 Treatment * 2.2 Attention deficit hyperactivity disorder (ADHD) * 2.2.1 Symptoms * 2.2.2 Treatment options * 2.2.2.1 Behavioral therapy * 2.2.2.2 Drug therapy * 2.3 Other disorders * 3 See also * 4 References * 5 External links ## Emergence[edit] Learning disabilities are diagnosed when the children are young and just beginning school. Most learning disabilities are found under the age of 9.[3] Young children with communication disorders may not speak at all, or may have a limited vocabulary for their age.[4] Some children with communication disorders have difficulty understanding simple directions or are unable to name objects.[4] Most children with communication disorders are able to speak by the time they enter school, however, they continue to have problems with communication.[4] School-aged children often have problems understanding and formulating words.[4] Teens may have more difficulty with understanding or expressing abstract ideas.[4] ### Causes[edit] The scientific study of the causes of developmental disorders involves many different theories. Some of the major differences between these theories involves whether or not environment disrupts normal development, or if abnormalities are pre-determined.[5] Normal development occurs with a combination of contributions from both the environment and genetics. The theories vary in the part each factor has to play in normal development, thus affecting how the abnormalities are caused.[5] One theory that supports environmental causes of developmental disorders involves stress in early childhood. Researcher and child psychiatrist Bruce D. Perry, M.D., Ph.D, theorizes that developmental disorders can be caused by early childhood traumatization.[6] In his works he compares developmental disorders in traumatized children to adults with post-traumatic stress disorder, linking extreme environmental stress to the cause of developmental difficulties.[6] Other stress theories suggest that even small stresses can accumulate to result in emotional, behavioral, or social disorders in children.[7] A 2017 study[8][9] tested all 20,000 genes in about 4,300 families with children with rare developmental difficulties in the UK and Ireland in order to identify if these difficulties had a genetic cause. They found 14 new developmental disorders caused by spontaneous genetic mutations not found in either parent (such as a fault in the CDK13 gene). They estimated that about one in 300 children are born with spontaneous genetic mutations associated with rare developmental disorders.[10] ## Types[edit] ### Autism spectrum disorder (ASD)[edit] #### Diagnosis[edit] The first diagnosed case of ASD was published in 1943 by American psychiatrist Leo Kanner. There is a wide range of cases and severity to ASD so it is very hard to detect the first signs of ASD. A diagnosis of ASD can be made accurately before the child is 3 years old, but the diagnosis of ASD is not commonly confirmed until the child is somewhat older. The age of diagnosis can range from 9 months to 14 years, and the mean age is 4 years old in the USA.[11] On average each case of ASD is tested at three different diagnostic centers before confirmed. Early diagnosis of the disorder can diminish familial stress, speed up referral to special educational programs and influence family planning.[12] The occurrence of ASD in one child can increase the risk of the next child having ASD by 50 to 100 times. #### Abnormalities in the brain[edit] The cause of ASD is still uncertain. What is known is that a child with ASD has a pervasive problem with how the brain is wired. Genes related to neurotransmitter receptors (serotonin and gamma-aminobutyric acid [GABA]) and CNS structural control (HOX genes) are found to be potential target genes that get affected in ASD.[13] Autism spectrum disorder is a disorder of the many parts of the brain. Structural changes are observed in the cortex, which controls higher functions, sensation, muscle movements, and memory. Structural defects are seen in the cerebellum too, which affect the motor and communication skills.[14] Sometimes the left lobe of the brain is affected and this causes neuropsychological symptoms. The distribution of white matter, the nerve fibers that link diverse parts of the brain, is abnormal. The corpus callosum, the band of nerve fibers, that connects the left and right hemispheres of the brain also gets affected in ASD. A study also found that 33% of people who suffered from AgCC (agenesis of the corpus callosum), a condition in which the corpus callosum is partially or completely absent, had scores higher than the autism screening cut-off.[15] An ASD child’s brain grows at a very rapid rate and is almost fully grown by the age of 10.[12] Recent fMRI studies have also found altered connectivity within the social brain areas due to ASD and may be related to the social impairments encountered in ASD.[16][17] #### Symptoms[edit] The symptoms have a wide range of severity. The symptoms of ASD can be broadly categorised[13] as the following: ##### Persistent issues in social interactions and communications[edit] These are predominantly seen by unresponsiveness in conversations, lesser emotional sharing, inability to initiate conversations, inability to interpret body language, avoidance of eye-contact and difficulty maintaining relationships. ##### Repetitive behavioral patterns[edit] These patterns can be seen in the form of repeated movements of the hand or the phrases used while talking. A rigid adherence to schedules and inflexibility to adapt even if a minor change is made to their routine is also one of the behavioral symptoms of ASD. They could also display sensory patterns such as extreme aversion to certain odors or indifference to pain or temperature. There are also different symptoms at different ages based on developmental milestones. Children between 0 and 36 months with ASD show a lack of eye contact, seem to be deaf, lack a social smile, do not like being touched or held, have unusual sensory behavior and show a lack of imitation. Children between 12 and 24 months with ASD show a lack of gestures, prefer to be alone, do not point to objects to indicate interest, are easily frustrated with challenges, and lack of functional play. And finally children between the ages 24 to 36 months with ASD show a lack of symbolic play and an unusual interest in certain objects, or moving objects.[12] #### Treatment[edit] There is no specific treatment for autism spectrum disorders, but there are several types of therapy effective in easing the symptoms of autism, such as Applied Behavior Analysis (ABA), Speech-language therapy, Occupational therapy or Sensory integration therapy. Applied behavioral analysis (ABA) is considered the most effective therapy for Autism spectrum disorders by the American Academy of Pediatrics.[18] ABA focuses on teaching adaptive behaviors like social skills, play skills, or communication skills[19][20] and diminishing problematic behaviors like self-injury.[21] This is done by creating a specialized plan that uses behavioral therapy techniques, such as positive or negative reinforcement, to encourage or discourage certain behaviors over-time.[22] Occupational therapy helps autistic children and adults learn everyday skills that help them with daily tasks, such as personal hygiene and movement. These skills are then integrated into their home, school, and work environments. Therapists will oftentimes help patients learn to adapt their environment to their skill level.[23] This type of therapy could help autistic people become more engaged in their environment.[24] An occupational therapist will create a plan based on the patient's’ needs and desires and work with them to achieve their set goals. Speech-language therapy can help those with autism who need to develop or improve communication skills. According to the organization Autism Speaks, “speech-language therapy is designed to coordinate the mechanics of speech with the meaning and social use of speech”.[24] People with low-functioning autism may not be able to communicate with spoken words. Speech-language Pathologists (SLP) may teach someone how to communicate more effectively with others or work on starting to develop speech patterns.[25] The SLP will create a plan that focuses on what the child needs. Sensory integration therapy helps people with autism adapt to different kinds of sensory stimuli. Many children with autism can be oversensitive to certain stimuli, such as lights or sounds, causing them to overreact. Others may not react to certain stimuli, such as someone speaking to them.[26] Many types of therapy activities involve a form of play, such as using swings, toys and trampolines to help engage the patients with sensory stimuli.[24] Therapists will create a plan that focuses on the type of stimulation the person needs integration with. ### Attention deficit hyperactivity disorder (ADHD)[edit] Attention deficit hyperactivity disorder is a neurodevelopmental disorder that occurs in early childhood. ADHD affects 8 to 11% of children in the school going age but because the criteria for diagnosing ADHD is unclear, this number is believed to be an overestimate by many researchers. ADHD is characterised by significant levels of hyperactivity, inattentiveness, and impulsiveness. There are three subtypes of ADHD: predominantly inattentive, predominantly hyperactive, and combined (which presents as both hyperactive and inattentive subtypes).[27] ADHD is twice as common in boys than girls but it is seen that the hyperactive/impulsive type is more common in boys while the inattentive type affects both sexes equally.[28] #### Symptoms[edit] Symptoms of ADHD include inattentiveness, impulsiveness, and hyperactivity. Many of the behaviors that are associated with ADHD include poor control over actions resulting in disruptive behavior and academic problems. Another area that is affected by these disorders is the social arena for the person with the disorder. Many children that have this disorder exhibit poor interpersonal relationships and struggle to fit in socially with their peers.[27] Behavioral study of these children can show a history of other symptoms such as temper tantrums, mood swings, sleep disturbances and aggressiveness.[28] #### Treatment options[edit] Treatment of ADHD often includes a combination of psychological, behavioural, pharmaceutical and educational advice and interventions. ##### Behavioral therapy[edit] Sessions of counselling, cognitive behavioral therapy (CBT), making environmental changes in noise and visual stimulation are some behavioral management techniques followed. But it has been observed that behavioral therapy alone is less effective than therapy with stimulant drugs alone. ##### Drug therapy[edit] Medications commonly used in the treatment of ADHD are primarily stimulants such as methylphenidate and lisdexamphetamine and non-stimulants such as atomoxetine. They could cause side effects such as headache, stomach pain, depression and sleep disturbances. SSRI antidepressants may be unhelpful, and could worsen symptoms of ADHD.[29] However ADHD is often misdiagnosed as depression, particularly when no hyperactivity is present. ### Other disorders[edit] * Learning disabilities * Communication disorders * Developmental coordination disorder * Genetic disorders, such as Down syndrome or Williams syndrome * Tic disorders such as Tourette syndrome. ## See also[edit] * Auditory processing disorder * Dysgraphia * Intellectual disability ## References[edit] 1. ^ a b c d e f Michael Rutter; Dorothy V. M. Bishop; Daniel S. Pine; et al., eds. (2008). Rutter's Child and Adolescent Psychiatry. Dorothy Bishop and Michael Rutter (5th ed.). Blackwell Publishing. pp. 32–33. ISBN 978-1-4051-4549-7. 2. ^ "ICD 10". priory.com. 3. ^ National, Disabilities Learning (1982). "Learning disabilities: Issues on definition". Asha. 24 (11): 945–947. 4. ^ a b c d e Communication Disorders. (n.d.). Children's Hospital of Wisconsin in Milwaukee, WI, Retrieved December 6, 2011, from http://www.chw.org/display/PPF/DocID/ 5. ^ a b Karmiloff Annette (October 1998). "Development itself is key to understanding developmental disorders". Trends in Cognitive Sciences. 2 (10): 389–398. doi:10.1016/S1364-6613(98)01230-3. PMID 21227254. S2CID 38117177. 6. ^ a b Perry, Bruce D. and Szalavitz, Maia. "The Boy Who Was Raised As A Dog", Basic Books, 2006, p.2. ISBN 978-0-465-05653-8 7. ^ Payne, Kim John. “Simplicity Parenting: Using the Extraordinary Power of Less to Raise Calmer, Happier, and More Secure Kids”, Ballantine Books, 2010, p. 9. ISBN 9780345507983 8. ^ "Deciphering Developmental Disorders (DDD) project". www.ddduk.org. Wellcome Trust Sanger Institute. Retrieved 2017-01-27. 9. ^ McRae, Jeremy F.; Clayton, Stephen; Fitzgerald, Tomas W.; Kaplanis, Joanna; Prigmore, Elena; Rajan, Diana; Sifrim, Alejandro; Aitken, Stuart; Akawi, Nadia (2017). "Prevalence and architecture of de novo mutations in developmental disorders" (PDF). Nature. 542 (7642): 433–438. Bibcode:2017Natur.542..433M. doi:10.1038/nature21062. PMC 6016744. PMID 28135719. 10. ^ Walsh, Fergus (2017-01-25). "Child gene study identifies new developmental disorders". BBC News. Retrieved 2017-01-27. 11. ^ "Hunting for Autism's Earliest Clues". Autism Speaks. 18 September 2013. 12. ^ a b c Dereu, Mieke. (2010). Screening for Autism Spectrum Disorders in Flemish Day-Care Centers with the Checklist for Early Signs of Developmental Disorders. Springer Science+Business Media. 1247-1258. 13. ^ a b "Autism Spectrum Disorders - Pediatrics". MSD Manual Professional Edition. Retrieved 2019-10-30. 14. ^ "Autism: Facts, causes, risk-factors, symptoms, & management". FactDr. 2018-06-25. Retrieved 2019-10-30. 15. ^ Lau, Yolanda C.; Hinkley, Leighton B. N.; Bukshpun, Polina; Strominger, Zoe A.; Wakahiro, Mari L. J.; Baron-Cohen, Simon; Allison, Carrie; Auyeung, Bonnie; Jeremy, Rita J.; Nagarajan, Srikantan S.; Sherr, Elliott H. (May 2013). "Autism traits in individuals with agenesis of the corpus callosum". Journal of Autism and Developmental Disorders. 43 (5): 1106–1118. doi:10.1007/s10803-012-1653-2. ISSN 0162-3257. PMC 3625480. PMID 23054201. 16. ^ Gotts S. J.; Simmons W. K.; Milbury L. A.; Wallace G. L.; Cox R. W.; Martin A. (2012). "Fractionation of social brain circuits in autism spectrum disorders". Brain. 135 (9): 2711–2725. doi:10.1093/brain/aws160. PMC 3437021. PMID 22791801. 17. ^ Subbaraju V, Sundaram S, Narasimhan S (2017). "Identification of lateralized compensatory neural activities within the social brain due to autism spectrum disorder in adolescent males". European Journal of Neuroscience. 47 (6): 631–642. doi:10.1111/ejn.13634. PMID 28661076. S2CID 4306986. 18. ^ Myers, Scott M.; Johnson, Chris Plauché (1 November 2007). "Management of Children With Autism Spectrum Disorders". Pediatrics. 120 (5): 1162–1182. doi:10.1542/peds.2007-2362. ISSN 0031-4005. PMID 17967921. 19. ^ "Applied Behavioral Analysis (ABA): What is ABA?". Autism partnership. 20. ^ Matson, Johnny; Hattier, Megan; Belva, Brian (January–March 2012). "Treating adaptive living skills of persons with autism using applied behavior analysis: A review". Research in Autism Spectrum Disorders. 6 (1): 271–276. doi:10.1016/j.rasd.2011.05.008. 21. ^ Summers, Jane; Sharami, Ali; Cali, Stefanie; D'Mello, Chantelle; Kako, Milena; Palikucin-Reljin, Andjelka; Savage, Melissa; Shaw, Olivia; Lunsky, Yona (November 2017). "Self-Injury in Autism Spectrum Disorder and Intellectual Disability: Exploring the Role of Reactivity to Pain and Sensory Input". Brain Sci. 7 (11): 140. doi:10.3390/brainsci7110140. PMC 5704147. PMID 29072583. 22. ^ "Applied Behavioral Strategies - Getting to Know ABA". Archived from the original on 2015-10-06. Retrieved 2015-12-16. 23. ^ fact sheet.ashx "Occupational Therapy's Role with Autism" Check `\|url=` value (help). American Occupational Therapy Association. 24. ^ a b c "What Treatments are Available for Speech, Language and Motor Issues?". Autism Speaks. Archived from the original on 2015-12-22. Retrieved 2015-12-16. 25. ^ for you/parents-and-cares/pc speech and language therapy.aspx "Speech and Language Therapy" Check `\|url=` value (help). Autism Education Trust. 26. ^ Smith, M; Segal, J; Hutman, T. "Autism Spectrum Disorders". Cite journal requires `\|journal=` (help) 27. ^ a b Tresco, Katy E. (2004). Attention Deficit Disorders: School-Based Interventions. Pennsylvania: Bethlehem. 28. ^ a b "Attention-Deficit/Hyperactivity Disorder (ADD, ADHD) - Pediatrics". MSD Manual Professional Edition. Retrieved 2019-10-30. 29. ^ C. W. Popper (1997). "Antidepressants in the treatment of attention-deficit/hyperactivity disorder". The Journal of Clinical Psychiatry. 58 Suppl 14: 14–29. PMID 9418743. ## External links[edit] Classification D * ICD-10: F80-F84 * ICD-9-CM: 299, 315 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy * v * t * e Dyslexia and related specific developmental disorders Conditions Speech, language, and communication * Expressive language disorder * Infantile speech * Landau–Kleffner syndrome * Language disorder * Lisp * Mixed receptive-expressive language disorder * Specific language impairment * Speech and language impairment * Speech disorder * Speech error * Speech sound disorder * Stuttering * Tip of the tongue Learning disability * Dyslexia * Dyscalculia * Dysgraphia * Disorder of written expression Motor * Developmental coordination disorder * Developmental verbal dyspraxia Sensory * Auditory processing disorder * Sensory processing disorder Related topics * Dyslexia research * Irlen filters * Learning Ally * Learning problems in childhood cancer * Literacy * Management of dyslexia * Multisensory integration * Neuropsychology * Reading acquisition * Spelling * Writing system Lists * Dyslexia in fiction * Languages by Writing System * People with dyslexia * v * t * e Pervasive developmental disorders and autism spectrum Main * Causes * Comorbid conditions * Epidemiology * Heritability * Societal and cultural aspects * Medical model * Therapies Diagnoses * Autism spectrum (High-functioning autism * Classic autism * Asperger syndrome * Pervasive developmental disorder not otherwise specified * Childhood disintegrative disorder * Rett syndrome) Related conditions * Alexithymia * Attention deficit hyperactivity disorder * Anxiety disorder (obsessive–compulsive disorder) * Late talker * Epilepsy * Fragile X syndrome * Hyperlexia * Savant syndrome * Sensory processing disorder * Intellectual disability * Developmental coordination disorder * Multiple complex developmental disorder Controversies * Autism rights movement * Autistic enterocolitis * Facilitated communication * MMR vaccine * Rapid prompting method * Thiomersal (Chelation) Diagnostic scales * Gilliam Asperger's disorder scale * Autism Diagnostic Observation Schedule * Autism Diagnostic Interview * Autism-spectrum quotient * Childhood Autism Rating Scale Lists * Autism-related topics * Fictional characters * Schools Authority control * NDL: 00982124 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Developmental disorder	c0008073	30,122	wikipedia	https://en.wikipedia.org/wiki/Developmental_disorder	2021-01-18T18:29:24	{"mesh": ["D002658"], "icd-9": ["315", "299"], "icd-10": ["F89", "F80", "F88"], "wikidata": ["Q3087172"]}
Apraxia is a neurological disorder characterized by the inability to perform tasks or movements, despite having the desire and physical ability to perform them. It is caused by damage to the brain, especially the parietal lobe, and can arise from many diseases, tumors, a stroke, or traumatic brain injury. In some cases it is present from birth. There are several types of apraxia, which may occur alone or together. These include: * Buccofacial or orofacial apraxia is the inability to carry out facial movements on demand. This may include licking the lips, sticking out the tongue, whistling, coughing, or winking. * Ideational apraxia is the inability to carryout learned, complex tasks with multiple, sequential movements. This may include dressing, eating, and bathing. * Ideomotor apraxia is the inability to perform a learned task (such as using a tool) or communicate using gestures (like waving good-bye). * Limb-kinetic apraxia is the inability to make fine, precise movements with an arm or leg. This may include buttoning a shirt or tying a shoe. * Verbal apraxia is difficulty coordinating mouth and speech movements. Verbal apraxia may be acquired or present from birth. * Constructional apraxia is the inability to copy, draw, or construct simple figures. * Oculomotor apraxia is difficulty moving the eyes on command. Treatment of apraxia may include physical, speech, or occupational therapy. If apraxia occurs as a symptom of another disorder, treatment should be directed to the underlying condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	Apraxia	c0003635	30,123	gard	https://rarediseases.info.nih.gov/diseases/5838/apraxia	2021-01-18T18:02:03	{"mesh": ["D001072"], "synonyms": ["Dyspraxia"]}
X-linked spinocerebellar ataxia type 3 is a form of spinocerebellar degeneration characterized by onset in infancy of hypotonia, ataxia, sensorineural deafness, developmental delay, esotropia, and optic atrophy, and by a progressive course leading to death in childhood. It has been described one family with at least six affected males from five different sibships (connected through carrier females). It is transmitted as an X-linked recessive trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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 spinocerebellar ataxia type 3	c1844936	30,124	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85297	2021-01-23T17:25:02	{"gard": ["9981"], "mesh": ["C537315"], "omim": ["301790"], "umls": ["C1844936"], "icd-10": ["G11.1"], "synonyms": ["SCAX3", "X-linked ataxia-deafness syndrome", "X-linked ataxia-hearing loss syndrome"]}
For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300. Mapping In a systematic survey of the human genome in patients with AD, Zubenko et al. (1998) identified D10S1423, located at 10p13, as a candidate susceptibility locus. The allelic associations in this survey were observed in independent samples of autopsied AD cases and controls from geographically disparate sites (Boston and Pittsburgh). Majores et al. (2000) replicated these findings by identifying an association of the D10S1423 234-bp allele with AD in an ethnically homogeneous group of 397 German AD cases and controls. Zubenko et al. (2001) described a prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 234-bp allele, the APOE E4 allele (107741), or both, after 11.5 years of systematic follow-up. They found that with the best-fitting model, only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1. After controlling for these genotypes, female gender was also significantly associated with increased risk of developing AD. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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 7	c0276496	30,125	omim	https://www.omim.org/entry/606187	2019-09-22T16:10:35	{"doid": ["0110039"], "mesh": ["D000544"], "omim": ["606187"], "orphanet": ["1020"], "synonyms": ["Alternative titles", "ALZHEIMER DISEASE, FAMILIAL, 7", "AD7"]}
Testicular cancer Other namesTestis tumor[1] 7.4 × 5.5-cm seminoma in a radical orchiectomy specimen. SpecialtyOncology SymptomsLump in the testicle, swelling or pain in the scrotum[2] Usual onset20 to 34 years old males[3] TypesGerm cell tumors (seminomas and nonseminomas), sex-cord stromal tumors, lymphomas[4][5] Risk factorsUndescended testis, family history of the disease, previous history of testicular cancer[5] Diagnostic methodPhysical exam, ultrasound, blood tests, surgical removal of the testicle[2] Differential diagnosisSpermatocele, epididymitis, inguinal hernia, appendix testis[1] TreatmentSurgery, radiation therapy, chemotherapy, stem cell transplantation[2] PrognosisFive-year survival rate rates ~ 95% (US)[3] Frequency686,000 (2015)[6] Deaths9,400 (2015)[7] Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.[2] Symptoms may include a lump in the testicle, or swelling or pain in the scrotum.[2] Treatment may result in infertility.[2] Risk factors include an undescended testis, family history of the disease, and previous history of testicular cancer.[5] The most common type is germ cell tumors which are divided into seminomas and nonseminomas.[5] Other types include sex-cord stromal tumors and lymphomas.[4] Diagnosis is typically based on a physical exam, ultrasound, and blood tests.[2] Surgical removal of the testicle with examination under a microscope is then done to determine the type.[2] Testicular cancer is highly treatable and usually curable.[5] Treatment options may include surgery, radiation therapy, chemotherapy, or stem cell transplantation.[2] Even in cases in which cancer has spread widely, chemotherapy offers a cure rate greater than 80%.[4] Globally testicular cancer affected about 686,000 people in 2015.[6] That year it resulted in 9,400 deaths up from 7,000 deaths in 1990.[7][8] Rates are lower in the developing than the developed world.[9] Onset most commonly occurs in males 20 to 34 years old, rarely before 15 years old.[3][10] The five-year survival rate in the United States is about 95%.[3] Outcomes are better when the disease remains localized.[3] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanisms * 4 Diagnosis * 4.1 Screening * 4.2 Staging * 4.3 Classification * 5 Treatment * 5.1 Testicle removal * 5.2 Retroperitoneal lymph node dissection * 5.3 Adjuvant treatment * 5.4 Radiation therapy * 5.5 Chemotherapy * 5.5.1 Non-seminoma * 5.5.2 Seminoma * 6 Prognosis * 6.1 Surveillance * 6.2 Fertility * 7 Epidemiology * 7.1 United States * 7.2 United Kingdom * 8 Other animals * 9 References * 10 External links ## Signs and symptoms[edit] Image showing the first sign of testicular cancer One of the first signs of testicular cancer is often a lump or swelling in the testes. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for testicular cancer in asymptomatic adolescent and adults including routine testicular self-exams.[11] However, the American Cancer Society suggests that some men should examine their testicles monthly, especially if they have a family history of cancer, and the American Urological Association recommends monthly testicular self-examinations for all young men.[12][13] Symptoms may also include one or more of the following: * a lump in one testis which may or may not be painful[14][15] * sharp pain or a dull ache in the lower abdomen or scrotum[15] * a feeling often described as "heaviness" in the scrotum[15] * firmness of the testicle[15] * breast enlargement (gynecomastia) from hormonal effects of β-hCG[14][15] * low back pain (lumbago) due to the cancer spreading to the lymph nodes along the back[14][15] It is not very common for testicular cancer to spread to other organs, apart from the lungs. If it has, however, the following symptoms may be present: * shortness of breath (dyspnea), cough or coughing up blood (hemoptysis) from metastatic spread to the lungs[14][15] * a lump in the neck due to metastases to the lymph nodes[14][15] Testicular cancer, cryptorchidism, hypospadias, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome. ## Causes[edit] A major risk factor for the development of testis cancer is cryptorchidism (undescended testicles). It is generally believed that the presence of a tumor contributes to cryptorchidism; when cryptorchidism occurs in conjunction with a tumor then the tumor tends to be large. Other risk factors include inguinal hernias, Klinefelter syndrome, and[16] mumps orchitis.[17] Physical activity is associated with decreased risk and sedentary lifestyle is associated with increased risk. Early onset of male characteristics is associated with increased risk. These may reflect endogenous or environmental hormones. Higher rates of testicular cancer in Western nations have been linked to the use of cannabis .[18][19][20][21] ## Mechanisms[edit] Most testicular germ cell tumors have too many chromosomes, and most often they are triploid to tetraploid. An isochromosome 12p (the short arm of chromosome 12 on both sides of the same centromere) is present in about 80% of the testicular cancers, and also the other cancers usually have extra material from this chromosome arm through other mechanisms of genomic amplification.[22] ## Diagnosis[edit] This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2014) (Learn how and when to remove this template message) Micrograph (high magnification) of a seminoma. H&E stain. The main way testicular cancer is diagnosed is via a lump or mass inside a testis. More generally, if a young adult or adolescent has a single enlarged testicle, which may or may not be painful, this should give doctors reason to suspect testicular cancer. Mixed germ cell tumor containing embryonal carcinoma, seminoma, and yolk sac tumor. The embryonal carcinoma component (upper left, upper right, and lower left) shows pseudoglandular growth with high-grade features of large, epithelioid, anaplastic cells with prominent nucleoli, indistinct cell borders with nuclear overlapping, pleomorphism, and frequent mitoses. The seminoma component (upper center) shows large, round-polyhedral cells with distinct cell membranes, abundant clear/watery cytoplasm, large central nuclei and prominent nucleoli. The yolk sac component (lower right, hugging the embryonal component) exhibits microcystic/reticular growth pattern. Other conditions may also have symptoms similar to testicular cancer: * Epididymitis or epididymoorchitis * Hematocele * Varicocele * Orchitis * Prostate infections or inflammations (prostatitis), bladder infections or inflammations (cystitis), or kidney (renal) infections (nephritis) or inflammations which have spread to and caused swelling in the vessels of the testicles or scrotum * Testicular torsion or a hernia * Infection, inflammation, retro-peritonitis, or other conditions of the lymph nodes or vessels near the scrotum, testicles, pubis, anorectal area, and groin * Benign tumors or lesions of the testicles * Metastasis to the testicles from another, primary tumor site(s) The nature of any palpated lump in the scrotum is often evaluated by scrotal ultrasound, which can determine exact location, size, and some characteristics of the lump, such as cystic vs solid, uniform vs heterogeneous, sharply circumscribed or poorly defined. The extent of the disease is evaluated by CT scans, which are used to locate metastases. The differential diagnosis of testicular cancer requires examining the histology of tissue obtained from an inguinal orchiectomy \- that is, surgical excision of the entire testis along with attached structures (epididymis and spermatic cord). A biopsy should not be performed, as it raises the risk of spreading cancer cells into the scrotum.[23] Inguinal orchiectomy is the preferred method because it lowers the risk of cancer cells escaping. This is because the lymphatic system of the scrotum, through which white blood cells (and, potentially, cancer cells) flow in and out, links to the lower extremities, while that of the testicle links to the back of the abdominal cavity (the retroperitoneum). A transscrotal biopsy or orchiectomy will potentially leave cancer cells in the scrotum and create two routes for cancer cells to spread, while in an inguinal orchiectomy only the retroperitoneal route exists. Blood tests are also used to identify and measure tumor markers (usually proteins present in the bloodstream) that are specific to testicular cancer. Alpha-fetoprotein, human chorionic gonadotropin (the "pregnancy hormone"), and LDH-1 are the typical tumor markers used to spot testicular germ cell tumors. A pregnancy test may be used to detect high levels of chorionic gonadotropin; however, the first sign of testicular cancer is usually a painless lump.[24] Note that only about 25% of seminomas have elevated chorionic gonadotropin, so a pregnancy test is not very sensitive for making out testicular cancer.[25] ### Screening[edit] The American Academy of Family Physicians recommends against screening males without symptoms for testicular cancer.[26] ### Staging[edit] After removal, the testicle is fixed with Bouin's solution[27][28] because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging.[29] In broad terms, testicular cancer is staged as follows: * Stage I: the cancer remains localized to the testis. * Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm). * Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.[30] Further information on the detailed staging system is available on the website of the American Cancer Society.[31] ### Classification[edit] This article's factual accuracy may be compromised due to out-of-date information. The reason given is: New WHO classification (2016). Please update this article to reflect recent events or newly available information. (May 2017) Although testicular cancer can be derived from any cell type found in the testicles, more than 95% of testicular cancers are germ cell tumors (GCTs). Most of the remaining 5% are sex cord–gonadal stromal tumours derived from Leydig cells or Sertoli cells. Correct diagnosis is necessary to ensure the most effective and appropriate treatment. To some extent, this can be done via blood tests for tumor markers, but definitive diagnosis requires examination of the histology of a specimen by a pathologist. Most pathologists use the World Health Organization classification system for testicular tumors:[32][33] * Germ cell tumors * Precursor lesions * Intratubular germ cell neoplasia * Unclassified type (carcinoma in situ) * Specified types * Tumors of one histologic type (pure forms) * Seminoma * Variant - Seminoma with syncytiotrophoblastic cells * Spermatocytic tumor * Variant - spermatocytic tumor with sarcoma * Embryonal carcinoma * Yolk sac tumor * Trophoblastic tumors * Choriocarcinoma * Variant - monophasic choriocarcinoma * Placental site trophoblastic tumour * Cystic trophoblastic tumor * Teratoma * Variant - Dermoid cyst * Variant - Epidermoid cyst * Variant - Monodermal teratoma (Carcinoid), Primitive neuroectodermal tumor (PNET), Nephroblastoma-like tumor, others. * Variant - Teratomic with somatic-type malignancy * Tumours of more than one histologic type (mixed forms) * Embryonal carcinoma and teratoma * Teratoma and seminoma * Choriocarcinoma and teratoma.embryonal carcinoma * Others * Sex cord/Gonadal stromal tumors * Leydig cell tumor * Sertoli cell tumor * Lipid rich variant * Scleriosing variant * Large cell calcifying variant * Intratubular sertoli cell neoplasia in Peutz–Jeghers syndrome * Granulosa cell tumor * Adult type * Juvenile type * Thecoma fibroma group * Thecoma * Fibroma * Sex cord/gonadal stromal tumor - incompletely differentiated * Sex cord/gonadal stromal tumor - mixed types * Mixed germ cell and sex cord/gonadal stromal tumors * Gonadoblastoma * Germ cell-sex cord/gonadal stromal tumor, unclassified * Miscellaneous tumours of the testis * Lymphomas * Primary testicular diffuse large B-cell lymphoma * Mantle cell lymphoma of the testes * extranodal marginal zone B cell lymphoma of the testes * Extranodal NK/T-cell lymphoma, nasal type of the testes * Peripheral T-cell lymphoma of the testes * activin receptor-like kinase-1–negative anaplastic large cell lymphoma of the testes * pediatric-type follicular lymphoma of the testes * Carcinoid * Tumors of ovarian epithelial types * Serous tumor of borderline malignancy * Serous carcinoma * Well differentiated endometrioid tumor * Mucinous cystadenoma * Mucinous cystadenocarcinoma * Brenner tumor * Nephroblastoma * Paraganglioma * Haematopoietic tumors * Tumours of collecting ducts and rete * Adenoma * Carcinoma * Tumors of the paratesticular structures * Adenomatoid tumor * Malignant and benign mesothelioma * Adenocarcinoma of the epididymis * Papillary cystadenoma of the epididymis * Melanotic neuroectodermal tumor * Desmoplastic small round cell tumor * Mesenchymal tumors of the spermatic cord and testicular adnexae * Lipoma * Liposarcoma * Rhabdomyosarcoma * Aggressive angiomyxoma * Angiomyofibroblastoma-like tumor (see Myxoma) * Fibromatosis * Fibroma * Solitary fibrous tumor * Others * Secondary tumors of the testis ## Treatment[edit] The three basic types of treatment are surgery, radiation therapy, and chemotherapy.[34] Surgery is performed by urologists; radiation therapy is administered by radiation oncologists; and chemotherapy is the work of medical oncologists. In most patients with testicular cancer, the disease is cured readily with minimal long-term morbidity. While treatment success depends on the stage, the average survival rate after five years is around 95%, and stage 1 cancer cases, if monitored properly, have essentially a 100% survival rate.[35] ### Testicle removal[edit] The initial treatment for testicular cancer is surgery to remove the affected testicle (orchiectomy). While it may be possible, in some cases, to remove testicular cancer tumors from a testis while leaving the testis functional, this is almost never done, as the affected testicle usually contains pre-cancerous cells spread throughout the entire testicle. Thus removing the tumor alone without additional treatment greatly increases the risk that another cancer will form in that testicle. Since only one testis is typically required to maintain fertility, hormone production, and other male functions, the afflicted testis is almost always removed completely in a procedure called inguinal orchiectomy. (The testicle is almost never removed through the scrotum; an incision is made beneath the belt line in the inguinal area.) In the UK, the procedure is known as a radical orchidectomy. ### Retroperitoneal lymph node dissection[edit] In the case of nonseminomas that appear to be stage I, surgery may be done on the retroperitoneal/paraaortic lymph nodes (in a separate operation) to accurately determine whether the cancer is in stage I or stage II and to reduce the risk that malignant testicular cancer cells that may have metastasized to lymph nodes in the lower abdomen. This surgery is called retroperitoneal lymph node dissection (RPLND). However, this approach, while standard in many places, especially the United States, is out of favor due to costs and the high level of expertise required to perform successful surgery. Sperm banking is frequently carried out prior to the procedure (as with chemotherapy), as there is a risk that RPLND may damage the nerves involved in ejaculation, causing ejaculation to occur internally into the bladder rather than externally. Many patients are instead choosing surveillance, where no further surgery is performed unless tests indicate that the cancer has returned. This approach maintains a high cure rate because of the growing accuracy of surveillance techniques. ### Adjuvant treatment[edit] Since testicular cancers can spread, patients are usually offered adjuvant treatment \- in the form of chemotherapy or radiotherapy \- to kill any cancerous cells that may exist outside of the affected testicle. The type of adjuvant therapy depends largely on the histology of the tumor (i.e. the size and shape of its cells under the microscope) and the stage of progression at the time of surgery (i.e. how far cells have 'escaped' from the testicle, invaded the surrounding tissue, or spread to the rest of the body). If the cancer is not particularly advanced, patients may be offered careful surveillance by periodic CT scans and blood tests, in place of adjuvant treatment. Before 1970, survival rates from testicular cancer were low. Since the introduction of adjuvant chemotherapy, chiefly platinum-based drugs like cisplatin and carboplatin, the outlook has improved substantially. Although 7000 to 8000 new cases of testicular cancer occur in the United States yearly, only 400 men are expected to die of the disease. In the UK, a similar trend has emerged: since improvements in treatment, survival rates have risen rapidly to cure rates of over 95%.[36] ### Radiation therapy[edit] Radiation may be used to treat stage II seminoma cancers, or as adjuvant (preventative) therapy in the case of stage I seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is ineffective against and is therefore never used as a primary therapy for nonseminoma. ### Chemotherapy[edit] #### Non-seminoma[edit] Chemotherapy is the standard treatment for non-seminoma when the cancer has spread to other parts of the body (that is, stage 2B or 3). The standard chemotherapy protocol is three, or sometimes four, rounds of Bleomycin-Etoposide-Cisplatin (BEP). BEP as a first-line treatment was first reported by Professor Michael Peckham in 1983.[37] The landmark trial published in 1987 which established BEP as the optimum treatment was conducted by Dr. Lawrence Einhorn at Indiana University.[38] An alternative, equally effective treatment involves the use of four cycles of Etoposide-Cisplatin (EP). Lymph node surgery may also be performed after chemotherapy to remove masses left behind (stage 2B or more advanced), particularly in the cases of large nonseminomas. #### Seminoma[edit] As an adjuvant treatment, use of chemotherapy as an alternative to radiation therapy in the treatment of seminoma is increasing, because radiation therapy appears to have more significant long-term side effects (for example, internal scarring, increased risks of secondary malignancies, etc.). Two doses, or occasionally a single dose of carboplatin, typically delivered three weeks apart, is proving to be a successful adjuvant treatment, with recurrence rates in the same ranges as those of radiotherapy. The concept of carboplatin as a single-dose therapy was developed by Tim Oliver, Professor of Medical Oncology at Barts and The London School of Medicine and Dentistry.[39] However, very long-term data on the efficacy of adjuvant carboplatin in this setting do not exist. Since seminoma can recur decades after the primary tumor is removed, patients receiving adjuvant chemotherapy should remain vigilant and not assume they are cured 5 years after treatment. ## Prognosis[edit] Treatment of testicular cancer is one of the success stories of modern medicine, with sustained response to treatment in more than 90% of cases, regardless of stage.[40] In 2011 overall cure rates of more than 95% were reported, and 80% for metastatic disease—the best response by any solid tumor, with improved survival being attributed primarily to effective chemotherapy.[4] By 2013 more than 96 per cent of the 2,300 men diagnosed each year in the U.K. were deemed cured, a rise by almost a third since the 1970s, the improvement attributed substantially to the chemotherapy drug cisplatin.[41] In the United States, when the disease is treated while it is still localized, more than 99% of people survive 5 years.[42] ### Surveillance[edit] For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate and patients will undergo surveillance instead.[43] The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients that need it. The number of patients ultimately cured is the same using surveillance as post-operative “adjuvant” treatments, but the patients have to be prepared to follow a prolonged series of visits and tests. For both non-seminomas and seminomas, surveillance tests generally include physical examination, blood tests for tumor markers, chest x-rays and CT scanning. However, the requirements of a surveillance program differ according to the type of disease since, for seminoma patients, relapses can occur later and blood tests are not as good at indicating relapse. CT scans are performed on the abdomen (and sometimes the pelvis) and also the chest in some hospitals. Chest x-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT. The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimizing the radiation exposure. For patients treated for stage I non-seminoma, a randomised trial (Medical Research Council TE08)[44] showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage. For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomized trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST.[45][46] This is assessing how often scans should take place and whether magnetic resonance imaging (MRI) can be used instead of CT scans. MRI is being investigated because it does not expose the patient to radiation and so, if it is shown to be as good at detecting relapses, it may be preferable to CT. For more advanced stages of testicular cancer, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) after treatment will vary on the basis of the circumstances, but normally should be done for five years in uncomplicated cases and for longer in those with higher risks of relapse. ### Fertility[edit] A man with one remaining testis may maintain fertile. However, sperm banking may be appropriate for men who still plan to have children, since fertility may be adversely affected by chemotherapy and/or radiotherapy. A man who loses both testicles will be infertile after the procedure, though he may elect to bank viable, cancer-free sperm prior to the procedure. ## Epidemiology[edit] Globally testicular cancer resulted in 8,300 deaths in 2013 up from 7,000 deaths in 1990.[8] Testicular cancer has the highest prevalence in the U.S. and Europe, and is uncommon in Asia and Africa.[47] Worldwide incidence has doubled since the 1960s, with the highest rates of prevalence in Scandinavia, Germany, and New Zealand.[citation needed] Although testicular cancer is most common among men aged 15–40 years, it has three peaks: infancy through the age of four as teratomas and yolk sac tumors, ages 25–40 years as post-pubertal seminomas and nonseminomas, and from age 60 as spermatocytic tumors.[48] Germ cell tumors of the testis are the most common cancer in young men between the ages of 15 and 35 years.[49] ### United States[edit] In the United States, about 8,900 cases are diagnosed a year.[3] The risk of testicular cancer in white men is approximately 4-5 times the risk in black men, and more than three times that of Asian American men.[47] The risk of testicular cancer in Latinos and American Indians is between that of white and Asian men.[47] The cause of these differences is unknown.[47] ### United Kingdom[edit] In the UK, approximately 2,000 people are diagnosed a year.[50] Over a lifetime, the risk is roughly 1 in 200 (0.5%).[51] It is the 16th most common cancer in men. It accounts for less than 1% of cancer deaths in men (around 60 men died in 2012).[52] ## Other animals[edit] Testicular tumors occur also in animals. In horses, these include interstitial cell tumors and teratomas. Typically, the former are found in older stallions (affected stallions may become extremely vicious, suggesting excessive production of androgen), and the latter are found in young horses and are large.[53] ## References[edit] 1. ^ a b Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 1253. ISBN 9780323529570. 2. ^ a b c d e f g h i "Testicular Cancer Treatment". National Cancer Institute. 7 July 2016. 3. ^ a b c d e f "Cancer of the Testis - Cancer Stat Facts". SEER. Retrieved 19 December 2017. 4. ^ a b c d Feldman DR; Bosl GJ; Sheinfeld J; Motzer RJ (13 February 2008). "Medical treatment of advanced testicular cancer". JAMA. 299 (6): 672–684. doi:10.1001/jama.299.6.672. 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PMID 18555499. 50. ^ CancerStats, 2007 UK incidence data Archived 4 May 2011 at the Wayback Machine, Cancer Research UK. 51. ^ "Testicular cancer incidence statistics". Cancer Research UK. 25 August 2011. Retrieved 10 October 2013. 52. ^ "Testicular cancer statistics". Cancer Research UK. 14 May 2015. 53. ^ Jones TC, Hunt RD, King NW (1997). Veterinary pathology (6th ed.). Wiley-Blackwell. p. 1210. ISBN 9780683044812. ## External links[edit] Wikimedia Commons has media related to Testicular cancer. * Ball Checker, self-exam app from the Testicular Cancer Society * Testicular Cancer – detailed guide from the American Cancer Society * Testicular Cancer – National Health Service information and resource page (UK) * Testicular cancer statistics from Cancer Research UK Classification D * ICD-10: C62 * ICD-9-CM: 186.9 * OMIM: 273300 * MeSH: D013736 * DiseasesDB: 12966 External resources * MedlinePlus: 001288 * eMedicine: med/2250 med/3232 med/863 * v * t * e * Tumors of the male urogenital system Testicles Sex cord– gonadal stromal * Sertoli–Leydig cell tumour * Sertoli cell tumour * Leydig cell tumour Germ cell G * Seminoma * Spermatocytic tumor * Germ cell neoplasia in situ NG * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma * Choriocarcinoma * Embryoma Prostate * Adenocarcinoma * High-grade prostatic intraepithelial neoplasia * HGPIN * Small-cell carcinoma * Transitional cell carcinoma Penis * Carcinoma * Extramammary Paget's disease * Bowen's disease * Bowenoid papulosis * Erythroplasia of Queyrat * Hirsuties coronae glandis Authority control * GND: 4160317-5 * LCCN: sh2010010377 * NDL: 00575998 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Testicular cancer	c0153594	30,126	wikipedia	https://en.wikipedia.org/wiki/Testicular_cancer	2021-01-18T19:06:55	{"gard": ["7746"], "mesh": ["D013736"], "umls": ["C1333010", "C0153594", "C0039590"], "wikidata": ["Q324464"]}
For a general phenotypic description and a discussion of genetic heterogeneity of neuroblastoma, see NBLST1 (256700). Mapping To identify genetic risk factors for neuroblastoma, Wang et al. (2011) performed a genomewide association study on 2,251 patients and 6,097 control subjects of European ancestry from 4 case series. Wang et al. (2011) reported a significant association with LMO1 (186921) at 11p15.4 (rs110419, combined p = 5.2 x 10(-16), odds ratio (OR) risk allele = 1.34, 95% CI 1.25-1.44). The signal was enriched in the subset of patients with the most aggressive form of the disease. LMO1 encodes a cysteine-rich transcriptional regulator, and its paralogs LMO2 (180385), LMO3 (180386), and LMO4 (603129) have each been implicated in cancer. In parallel, Wang et al. (2011) analyzed genomewide DNA copy number alterations in 701 primary tumors and found that the LMO1 locus was aberrant in 12.4% through a duplication event, and that this event was associated with more advanced disease (p less than 0.0001) and survival (p = 0.041). The germline SNP risk alleles and somatic copy number gains were associated with increased LMO1 expression in neuroblastoma cell lines and primary tumors, consistent with a gain-of-function role in tumorigenesis. Short hairpin RNA-mediated depletion of LMO1 inhibited growth of neuroblastoma cells with high LMO1 expression, whereas forced expression of LMO1 in neuroblastoma cells with low LMO1 expression enhanced proliferation. Wang et al. (2011) concluded that their studies showed that common polymorphisms at the LMO1 locus are strongly associated with susceptibility to developing neuroblastoma, but also may influence the likelihood of further somatic alterations at this locus, leading to malignant progression. Molecular Genetics Oldridge et al. (2015) investigated the causal DNA variant at the LMO1 locus and the mechanism by which it leads to neuroblastoma tumorigenesis. The authors first imputed all possible genotypes across the LMO1 locus and then mapped highly associated SNPs to areas of chromatin accessibility, evolutionary conservation, and transcription factor-binding sites. The authors showed that SNP rs2168101G-T (186921.0001) is the most highly associated variant (combined p = 7.47 x 10(-29), OR 0.65, 95% CI 0.60-0.70), and resides in a superenhancer defined by extensive acetylation of histone H3 lysine-27 (H3K27) within the first intron of LMO1. The ancestral G allele that is associated with tumor formation resides in a conserved GATA transcription factor-binding motif. Oldridge et al. (2015) showed that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (p = 0.028) in neuroblastoma primary tumors, and ablates GATA3 binding (p less than 0.0001). Oldridge et al. (2015) demonstrated allelic imbalance favoring the G-containing strand in tumors heterozygous for this SNP, as demonstrated both by RNA sequencing and reporter assays. The authors concluded that their findings indicated that a recently evolved polymorphism within a superenhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumor cells. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	NEUROBLASTOMA, SUSCEPTIBILITY TO, 7	c0027819	30,127	omim	https://www.omim.org/entry/616792	2019-09-22T15:47:56	{"mesh": ["D009447"], "omim": ["616792"], "orphanet": ["635"]}
Biemond syndrome type 2 (BS2) is a rare genetic neurological and developmental disorder reported in a very small number of patients with a poorly defined phenotype which includes iris coloboma, short stature, obesity, hypogonadism, postaxial polydactyly, and intellectual disability. Hydrocephalus and facial dysostosis were also reported. BS2 shares features with Bardet-Biedl syndrome. There have been no further descriptions in the literature since 1997. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Biemond syndrome type 2	c1859487	30,128	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141333	2021-01-23T18:53:42	{"gard": ["882"], "mesh": ["C565902"], "omim": ["210350"], "umls": ["C1859487", "C2930903"], "synonyms": ["Hypogonadism-short stature-coloboma-preaxial polydactyly syndrome"]}
A number sign (#) is used with this entry because Li-Fraumeni syndrome-2 is caused by heterozygous mutation in the CHEK2 gene (604373) on chromosome 22q12. For a general phenotypic description and a discussion of genetic heterogeneity of Li-Fraumeni syndrome (LFS), see LFS1 (151623). Clinical Features In affected members of 3 unrelated families, 1 family with classic LFS and 2 with LFS-variant, without mutations in the TP53 gene (191170), Bell et al. (1999) identified heterozygous germline mutations in the CHK2 gene (see, e.g., 604373.0001 and 604373.0002). They defined LFS-variant as the occurrence in an individual of 3 separate primary cancers, with the first cancer diagnosed under age 45 years, or the combination of a proband with childhood cancer or LFS component tumor diagnosed under age 45 years, a first- or second-degree relative with LFS component tumor diagnosed at any age, and a first- or second-degree relative with any cancer diagnosed under age 60 years. CHK2 is a homolog of Saccharomyces cerevisiae RAD53 and Schizosaccharomyces pombe cds1+, protein kinases required for DNA damage and replication checkpoints. Vahteristo et al. (2001) reported 2 Finnish families with LFS and a mutation in the CHK gene. The phenotype in both families was considered atypical because of the lack of sarcomas or childhood cancers. Molecular Genetics Vahteristo et al. (2001) analyzed the CHK1 (603078), CHK2, and p53 genes for mutations in 44 Finnish families with Li-Fraumeni syndrome, Li-Fraumeni-like syndrome, or a phenotype suggestive of Li-Fraumeni syndrome. Five different disease-causing mutations were observed in 7 families: 4 in the p53 gene and 1 in the CHK2 gene. The CHK2 mutation occurred in 2 families and was the same as the mutation reported by Bell et al. (1999) in a family with classic LFS: 1100delC (604373.0001). The families originated from different parts of Finland, were not known to be related, and segregated different chromosome 22 haplotypes. Thus, 1100delC is clearly a disease-causing mutation and represents a mutation hotspot in the CHK2 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	LI-FRAUMENI SYNDROME 2	c0085390	30,129	omim	https://www.omim.org/entry/609265	2019-09-22T16:06:20	{"doid": ["3012"], "mesh": ["D016864"], "omim": ["609265"], "orphanet": ["524"]}
Familial nonmedullary thyroid carcinoma (fNMTC) is a rare non-syndromic form of thyroid cancer characterized by occurrence of thyroid carcinoma (TC) as the primary feature in a familial setting. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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 nonmedullary thyroid carcinoma	None	30,130	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319494	2021-01-23T18:45:52	{"icd-10": ["C73"]}
A rare non-syndromic cerebral malformation characterized by congenital partial or complete absence of the corpus callosum. Patients are often asymptomatic but may also present with intellectual disability, visual impairment, delayed speech development, seizures, feeding difficulties, impaired hand-eye coordination, and behavioral abnormalities. Patients may have a normal intelligence quotient while exhibiting specific cognitive deficits, such as reduced interhemispheric transfer of sensorimotor information, reduced cognitive processing speed, and deficits in complex reasoning and novel problem-solving. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Isolated corpus callosum agenesis	None	30,131	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=200	2021-01-23T17:24:20	{"icd-10": ["Q04.0"]}
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: "Fear of mice and rats" – news · newspapers · books · scholar · JSTOR (March 2016) (Learn how and when to remove this template message) Fear of mice and rats is one of the most common specific phobias. It is sometimes referred to as musophobia (from Greek μῦς "mouse") or murophobia (a coinage from the taxonomic adjective "murine" for the family Muridae that encompasses mice and rats), or as suriphobia, from French souris, "mouse". The phobia, as an unreasonable and disproportionate fear, is distinct from reasonable concern about rats and mice contaminating food supplies, which may potentially be universal to all times, places, and cultures where stored grain attracts rodents, which then consume or contaminate the food supply. ## Contents * 1 Cause * 2 Treatment * 2.1 Elephants and mice * 2.2 Patron saint * 3 In popular culture * 4 See also * 5 References ## Cause[edit] In many cases a phobic fear of mice is a socially induced conditioned response, combined with (and originated in) the startle response (a response to an unexpected stimulus) common in many animals, including humans, rather than a real disorder. At the same time, as is common with specific phobias, an occasional fright may give rise to abnormal anxiety that requires treatment. ## Treatment[edit] Fear of mice may be treated by any standard treatment for specific phobias. The standard treatment of animal phobia is systematic desensitization, and this can be done in the consulting room (in vivo), or in hypnosis (in vitro). Some clinicians use a combination of both in vivo and in vitro desensitization during treatment. It is also helpful to encourage patients to experience some positive associations with mice: thus, the feared stimulus is paired with the positive rather than being continuously reinforced by the negative.[1] ### Elephants and mice[edit] There is a common folk belief that elephants are afraid of mice. The earliest reference to this claim is probably by Pliny the Elder in his Naturalis Historia, book VIII. As translated by Philemon Holland (1601), "Of all other living creatures, they [elephants] cannot abide a mouse or a rat." Numerous zoos and zoologists have shown that elephants can be conditioned not to react. MythBusters performed an experiment in which, indeed, multiple elephants did attempt to avoid a mouse, showing there may be some basis for this belief. Regardless, elephantine murophobia remains the basis of various jokes and metaphors. The classical board game Dou Shou Qi has the Rat kill an Elephant, and multiple editions of the rule book mentions that the Rat would crawl into the Elephant's ears to gnaw into its brain. This is considered to be a folk tale.[2] ### Patron saint[edit] Gertrude of Nivelles is the patron saint of murophobia, and is also invoked against rats and mice in general.[3] ## In popular culture[edit] Woman displaying musophobia An exaggerated, phobic fear of mice and rats has traditionally been depicted as a stereotypical trait of women, with numerous books, cartoons, television shows, and films portraying women screaming and jumping onto chairs or tables at the sight of a mouse. Despite this portrayal, murophobia has always been experienced by individuals of both sexes. However, women are twice as likely as men to suffer from specific phobias, such as musophobia.[4] * In George Orwell's novel Nineteen Eighty-Four the protagonist Winston Smith has a phobic fear of rats. Strapping a cage of hungry rats to his face is a technique used to get him to implicate his lover in thoughtcrimes. * In Indiana Jones and the Last Crusade, Henry Jones, Sr. is described as being "scared to death" of rats. * The titular character in the Doraemon series is scared of mice, due to having had his robotic ears bitten off by mice due to a mistaken order by Sewashi, as decipted in 1995 short film 2112: The Birth of Doraemon. * The incarnation of Princess Zelda from The Legend of Zelda: Spirit Tracks will freeze in fear if she is met by rats. * Madame Medusa, the main antagonist of Disney's The Rescuers (1977), an adaptation of Margery Sharp's children's novels, suffers from extreme musophobia, becoming hysterical upon encountering the film's protagonists, a pair of friendly mice, while aiming to protect herself by jumping onto a chair and firing her shotgun. Ironically, her far more threatening pet crocodiles hardly make her uneasy. * Tin Top from Roary the Racing Car exhibited musophobia in the episode "Tin Top Gets Scared". * Injun Joe is afraid of mice and rats in the 1995 anime movie, Huck and Tom's Mississippi Adventure. * In the video game Donkey Kong Country 3: Dixie Kong's Double Trouble! the rideable elephant Ellie is afraid of rats and must throw a barrel at them. ## See also[edit] * List of phobias ## References[edit] 1. ^ Kraft D & Kraft T (2010). Use of in vivo and in vitro desensitization in the treatment of mouse phobia: review and case study. Contemporary Hypnosis, 27 (3): 184-194. 2. ^ Bell, R.C. (1983), The Boardgame Book, p. 119. Exeter Books. 3. ^ Gertrude of Nivelles 4. ^ Cameron, Alasdair (2004). Crash Course Psychiatry. Elsevier Ltd. ISBN 0-7234-3340-2. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Fear of mice and rats	None	30,132	wikipedia	https://en.wikipedia.org/wiki/Fear_of_mice_and_rats	2021-01-18T18:30:09	{"wikidata": ["Q3440772"]}
A number sign (#) is used with this entry because of evidence that multiple types of congenital heart defects (CHTD4) are caused by heterozygous mutation in the NR2F2 gene (107773) on chromosome 15q26. For a discussion of genetic heterogeneity of multiple types of congenital heart defects, see 306955. Molecular Genetics Al Turki et al. (2014) performed exome sequencing in 13 parent-offspring trios and 112 unrelated individuals with nonsyndromic atrioventricular septal defects (AVSDs, see 606215) and identified 5 rare missense mutations in the highly conserved NR2F2 gene (see, e.g., 107773.0001 and 107773.0002), representing significant enrichment compared to 5,194 controls (p = 7.7 x 10(-7)). In other patient cohorts with non-AVSD congenital heart disease (CHD), they identified 3 additional CHD-affected families with other variants in NR2F2. These included a 3-bp duplication (107773.0003) that segregated with CHD in a multiplex family in which 2 affected brothers had AVSD and aortic stenosis with ventricular septal defect (VSD, see 614429), respectively, and their father had tetralogy of Fallot (see 187500); a de novo substitution disrupting a splice donor site (107773.0004) in a patient with hypoplastic left heart syndrome (see 241550); and a de novo balanced chromosomal translocation 46,XY,t(14;15)(q23;q26.3) in a patient with coarctation of the aorta and other developmental anomalies who was previously studied by Baptista et al. (2008). The translocation was fine-mapped to the first intron of NR2F2, with the breakpoint predicted to truncate all annotated transcripts and generate a null allele. All 6 coding sequence variants significantly altered the activity of NR2F2 on target promoters. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrioventricular septal defect \- Ventricular septal defect \- Aortic stenosis \- Tetralogy of Fallot \- Hypoplastic left heart Vascular \- Coarctation of aorta MOLECULAR BASIS \- Caused by mutation in the nuclear receptor subfamily 2, group F, member 2 gene (NR2F2, 107773.0001 ) ▲ 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	CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 4	c1389018	30,133	omim	https://www.omim.org/entry/615779	2019-09-22T15:50:59	{"mesh": ["C562831"], "omim": ["615779"], "orphanet": ["98722"]}
Doyne honeycomb retinal dystrophy (DHRD) is a condition that affects the eyes and causes vision loss. It is characterized by small, round, white spots known as drusen that accumulate beneath the retinal pigment epithelium (the pigmented layer of the retina). Over time, drusen may grow and come together, creating a honeycomb pattern. It usually begins in early to mid adulthood, but the age of onset varies. The degree of vision loss also varies. DHRD is usually caused by mutations in the EFEMP1 gene and is inherited in an autosomal dominant manner. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Doyne honeycomb retinal dystrophy	c1832174	30,134	gard	https://rarediseases.info.nih.gov/diseases/1912/doyne-honeycomb-retinal-dystrophy	2021-01-18T18:00:49	{"mesh": ["C535602"], "omim": ["126600"], "synonyms": ["DHRD", "Doyne honeycomb degeneration of retina", "DHD"]}
Toriello Carey syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysmorphic features, cerebral anomalies, swallowing difficulties, cardiac defects and hypotonia. ## Epidemiology At least 50 cases have been reported since the first description in 1988. ## Clinical description Main clinical signs include telecanthus, short palpebral fissures, small nose with anteverted nares, Pierre Robin sequence (micrognathia, glossoptosis and cleft palate), abnormally shaped ears, redundant neck skin and features of midline structural abnormalities with agenesis of corpus callosum, laryngeal anomalies and congenital heart defects. Short hands and hypotonia may also be observed. Patients have a moderate to severe intellectual disability. ## Etiology The etiology of Toriello-Carey syndrome is not fully understood, but there is evidence that this is a heterogeneous condition, with chromosome anomalies identified in approximately 20%, and at least two candidate genes identified: MN1 (22q12.1) which has been reported in a microdeletion and SATB2 (2q33.1), interrupted by a de novo balanced translocation in another patient. ## Diagnostic methods Imaging studies of the brain to determine if the corpus callosum is abnormal and physical examination paying particular attention to ocular spacing and palatal structure. A chromosomal microarray is indicated in any child with a Toriello-Carey phenotype. ## Differential diagnosis There are few conditions which include the combination of abnormalities of the corpus callosum and Pierre-Robin sequence. Two such conditions are Aicardi syndrome (in which Robin anomaly is a rare occurrence) and TARP syndrome (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava) (see these terms). ## Antenatal diagnosis The combination of corpus callosum anomalies and micrognathia should suggest the diagnosis. ## Genetic counseling If a chromosomal microdeletion/duplication has been ruled out, inheritance is autosomal recessive and the recurrence risk is likely 25%. ## Management and treatment Management is supportive. ## Prognosis The syndrome is associated with decreased life span. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Toriello-Carey syndrome	c0796184	30,135	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3338	2021-01-23T17:32:05	{"gard": ["5225"], "mesh": ["C563127"], "omim": ["217980"], "umls": ["C0796184"], "icd-10": ["Q87.8"], "synonyms": ["Corpus callosum agenesis-blepharophimosis-Robin sequence syndrome"]}
Tuberculous meningitis Other namesTB meningitis, Tubercular meningitis CT scan showing tuberculous meningitis SpecialtyNeurology SymptomsFever[1] CausesHIV/AIDS, Alcoholism[2] Diagnostic methodBlood culture, CT scan[2] TreatmentAntibiotic therapy and corticosteroids[3] Tuberculous meningitis is also known as TB meningitis or tubercular meningitis. Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelop the central nervous system.[2][4] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 4.1 Nucleic acid amplification tests (NAAT) * 5 Treatment * 6 References * 7 External links ## Signs and symptoms[edit] Fever and headache are the cardinal features; confusion is a late feature and coma bears a poor prognosis. Meningism is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits.[1][5] ## Causes[edit] Mycobacterium tuberculosis of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the brain.[6] When the inflammation is in the brain stem subarachnoid area, cranial nerve roots may be affected. The symptoms will mimic those of space-occupying lesions.[7] Blood-borne spread certainly occurs, presumably by crossing the blood–brain barrier; but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain;[8] an even smaller proportion get it from rupture of a bony focus in the spine.[9] ## Pathophysiology[edit] The pathophysiology of tuberculous meningitis has bacilli root itself to the brain parenchyma, which causes the formation of small subpial focus. Then there is an increase in size of Rich focus until rupture. Tubercles rupture in subarachnoid area causes meningitis.[3] ## Diagnosis[edit] Tuberculous-meningitis-autopsy, showing associated brain oedema and congestion Diagnosis of TB meningitis is made by analysing cerebrospinal fluid collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml).[10] The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, M. tuberculosis is grown in culture.[11] A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding. ELISPOT testing is not useful for the diagnosis of acute TB meningitis and is often false negative,[12] but may paradoxically become positive after treatment has started, which helps to confirm the diagnosis. ### Nucleic acid amplification tests (NAAT)[edit] This is a group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid.[13] These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor.[14] In 2007, review concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%)", they found the pooled prevalence of TB meningitis to be 29%.[15] ## Treatment[edit] See also: Tuberculosis treatment The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months.[16] Steroids help reduce the risk of death in those without HIV.[17] Steroids can be used in the first six weeks of treatment,[18] A few people may require immunomodulatory agents such as thalidomide.[19] Hydrocephalus occurs as a complication in about a third of people with TB meningitis. The addition of aspirin may reduce or delay mortality, possibly by reducing complications such as infarcts.[20][21] ## References[edit] 1. ^ a b Harman, Robin J.; Mason, Pamela (2002-01-01). Handbook of Pharmacy Healthcare: Diseases and Patient Advice. Pharmaceutical Press. p. 93. ISBN 9780853695073. 2. ^ a b c "Meningitis - tuberculous: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-06-02. 3. ^ a b "Tuberculous Meningitis: Background, Pathophysiology, Etiology". 2018-05-23. Cite journal requires `\|journal=` (help) 4. ^ "Tuberculous Meningitis -- Medical Definition". www.medilexicon.com. Retrieved 2015-06-02. 5. ^ Leach, Richard M. (2010-06-11). Acute and Critical Care Medicine at a Glance. John Wiley & Sons. p. 101. ISBN 9781444327229. 6. ^ Christodoulides, Myron (2013). Meningitis: Cellular and Molecular Basis. CABI. p. 154. ISBN 9781780641621. 7. ^ p1301 Robbins and Cotran, Pathologic Basis of Disease, 8th edition 8. ^ Nicoll, J. A. R.; Bone, Ian; Graham, David (2006-11-24). Adams & Graham's Introduction to Neuropathology 3Ed. CRC Press. p. 127. ISBN 9780340811979. 9. ^ Behera, D. (2010). Textbook of Pulmonary Medicine. Jaypee Brothers Publishers. p. 505. ISBN 9788184487497. 10. ^ "Cerebral spinal fluid (CSF) collection: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-06-02. 11. ^ Irani, David N. (2008). Cerebrospinal Fluid in Clinical Practice. Elsevier Health Sciences. p. 196. ISBN 978-1416029083. 12. ^ Gram-Positive Bacterial Infections: Advances in Research and Treatment: 2011 Edition. ScholarlyEditions. 2012-01-09. p. 77. ISBN 9781464929717. 13. ^ Takahashi, Teruyuki; Tamura, Masato; Takasu, Toshiaki (2012). "The PCR-Based Diagnosis of Central Nervous System Tuberculosis: Up to Date". Tuberculosis Research and Treatment. 2012: 1–17. doi:10.1155/2012/831292. PMC 3359676. PMID 22666577. 14. ^ "CDC \|TB \| ...the Uses of Nucleic Acid Amplification Tests for the Diagnosis of TB: Background". www.cdc.gov. Retrieved 2015-06-02. 15. ^ Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A (2007). "A systematic review of rapid diagnostic tests for the detection of tuberculosis infection". Health Technol Assess. 11 (3): 1–196. doi:10.3310/hta11030. PMID 17266837. 16. ^ Barnett, Anthony H. (2006). Diabetes: Best Practice & Research Compendium. Elsevier Health Sciences. p. 146. ISBN 978-0323044011. 17. ^ Prasad, Kameshwar; Singh, Mamta B; Ryan, Hannah (28 April 2016). "Corticosteroids for managing tuberculous meningitis". Cochrane Database of Systematic Reviews. 4: CD002244. doi:10.1002/14651858.cd002244.pub4. PMC 4916936. PMID 27121755. 18. ^ Harrison, James; Kulkarni, Kunal; Baguneid, Mohamed; Prendergast, Bernard (2009). Oxford Handbook of Key Clinical Evidence. OUP Oxford. p. 336. ISBN 9780199234073. 19. ^ Central Nervous System Bacterial Infections—Advances in Research and Treatment: 2012 Edition: ScholarlyBrief. ScholarlyEditions. 2012-12-26. p. 28. ISBN 9781481616232. 20. ^ Rajshekhar, Vedantam (2009). "Management of hydrocephalus in patients with tuberculous meningitis Rajshekhar V Neurol India". Neurology India. 57 (4): 368–74. doi:10.4103/0028-3886.55572. PMID 19770534. 21. ^ Meningitis: New Insights for the Healthcare Professional: 2011 Edition: ScholarlyBrief. ScholarlyEditions. 2012-01-09. p. 2. ISBN 9781464905292. ## External links[edit] Classification D * ICD-10: A17.0, G01 * ICD-9-CM: 013.0, 322.9 * MeSH: D014390 External resources * MedlinePlus: 000650 * eMedicine: neuro/385 Scholia has a topic profile for Tuberculous meningitis. * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis * v * t * e Meningitis and other diseases of meninges Meningitis * Arachnoiditis * Bacterial * Tuberculous * Haemophilus * Pneumococcal * Viral * Herpesviral * Fungal * Cryptococcal * Aseptic * Drug-induced Other * Meningoencephalitis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Tuberculous meningitis	c0041318	30,136	wikipedia	https://en.wikipedia.org/wiki/Tuberculous_meningitis	2021-01-18T19:06:13	{"gard": ["7828"], "mesh": ["D014390"], "umls": ["C0041318"], "icd-9": ["013.0", "013.00"], "icd-10": ["A17.0", "G01"], "wikidata": ["Q3854687"]}
Hemihyperplasia–multiple lipomatosis syndrome SpecialtyDermatology Hemihyperplasia–multiple lipomatosis syndrome is a cutaneous condition characterized by multiple lipomas in association with asymmetric (but non-progressive and non-distorting) overgrowth, cutaneous capillary malformations, and thickened plantar skin with prominent creases.[1] ## See also[edit] * Involutional lipoatrophy * 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. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	Hemihyperplasia–multiple lipomatosis syndrome	None	30,137	wikipedia	https://en.wikipedia.org/wiki/Hemihyperplasia%E2%80%93multiple_lipomatosis_syndrome	2021-01-18T19:09:30	{"orphanet": ["276280"], "synonyms": ["HHML"], "wikidata": ["Q5711647"]}
A number sign (#) is used with this entry because of evidence that Meier-Gorlin syndrome-4 (MGORS4) is caused by homozygous or compound heterozygous mutation in the CDT1 gene (605525) on chromosome 16q24. For a general phenotypic description and a discussion of genetic heterogeneity of Meier-Gorlin syndrome, see 224690. Clinical Features Feingold (2002) reported 4 patients with Meier-Gorlin syndrome from 2 families. All 4 patients had microcephaly but none had mental retardation, and some were of high intellect. On radiography, all 4 patients had absent or hypoplastic patella, abnormal glenoid fossa, hook-shaped clavicles, and long slender bones. Bicknell et al. (2011) noted that 2 affected sisters from 1 of the families described by Feingold (2002) also displayed mammary gland hypoplasia. Guernsey et al. (2011) restudied 1 of the patients with Meier-Gorlin syndrome, originally reported by Bongers et al. (2001) ('patient 8'), a 15-year-old girl born of consanguineous parents of Louisiana Cajun ancestry. Feeding was difficult in infancy, and she required a gastrostomy tube until 3 years of age. She had patent ductus arteriosus that required closure with interventional coiling. She had short stature and microtia; her patellae were nonpalpable in childhood but in adolescence were noted to be present but markedly hypoplastic, and she also had genu recurvatum. She developed thoracic scoliosis in the second decade of life that required fusion of the T3 to T12 vertebrae. In childhood she was noted to have hypoplastic labia majora, and at 15 years of age, she had no breast development. Molecular Genetics Bicknell et al. (2011) analyzed the candidate gene CDT1 in patients with an established diagnosis of Meier-Gorlin syndrome and identified compound heterozygous mutations (see, e.g., 605525.0001-605525.0004) in 7 patients from 5 families, including 3 sibs from 1 of the families previously described by Feingold (2002). In a 15-year-old girl with Meier-Gorlin syndrome, previously reported by Bongers et al. (2001), Guernsey et al. (2011) sequenced candidate genes encoding ORC complex or pathway-associated proteins and identified homozygosity for a missense mutation in the CDT1 gene (605525.0005). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature \- Birth length less than 3rd percentile Weight \- Birth weight less than 3rd percentile Other \- Intrauterine growth retardation (IUGR) \- Failure to thrive HEAD & NECK Head \- Microcephaly Ears \- Microtia \- Low-set ears \- Abnormally formed ears Mouth \- Small mouth \- Full lips \- Maxillary hypoplasia \- Mandibular hypoplasia RESPIRATORY \- Respiratory problems Lung \- Emphysema, congenital CHEST Ribs Sternum Clavicles & Scapulae \- Hook-shaped clavicles \- Abnormal glenoid fossa Breasts \- Breast hypoplasia ABDOMEN Gastrointestinal \- Feeding difficulties in early infancy GENITOURINARY External Genitalia (Male) \- Cryptorchidism SKELETAL \- Delayed bone age Limbs \- Slender long bones \- Absent patellae \- Genu recurvatum NEUROLOGIC Central Nervous System \- No mental retardation \- Intellect high (in some patients) MOLECULAR BASIS \- Caused by mutation in the chromatin licensing and DNA replication factor 1 gene (CDT1, 605525.0001 ) ▲ 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	MEIER-GORLIN SYNDROME 4	c1868684	30,138	omim	https://www.omim.org/entry/613804	2019-09-22T15:57:28	{"doid": ["0080515"], "mesh": ["C538012"], "omim": ["613804"], "orphanet": ["2554"]}
Camel spongiform encephalopathy Other namesCSE SpecialtyNeurology Camel spongiform encephalopathy (CSE), commonly known as mad camel disease, is similar to mad cow disease. It was discovered by the Algerian veterinarian Baaissa Babelhadj, Lecturer-researcher Semir Bechir Suheil GAOUAR (university of Tlemcen) and a colleague in Ouargla, in collaboration with Italian researchers.[1] This infection is a form of prion disease (transmissible spongiform encephalopathy, TSE) that affects camels.[2][3] ## References[edit] 1. ^ "maghrebemergent.info Deux chercheurs algériens découvrent la maladie du " dromadaire fou " à Ouargla". Archived from the original on 2018-05-24. Retrieved 2018-05-27. 2. ^ "huffpostmaghreb.com Deux chercheurs algériens découvrent la maladie du "chameau fou" à Ouargla". Archived from the original on 2018-05-24. Retrieved 2018-05-27. 3. ^ Babelhadj, B; Di Bari, MA; Pirisinu, L; Chiappini, B; Gaouar, SBS; Riccardi, G; Marcon, S; Agrimi, U; Nonno, R; Vaccari, G (June 2018). "Prion Disease in Dromedary Camels, Algeria". Emerging Infectious Diseases. 24 (6): 1029–1036. doi:10.3201/eid2406.172007. PMC 6004840. PMID 29652245. * v * t * e Prion diseases and transmissible spongiform encephalopathy Prion diseases in humans inherited/PRNP: * fCJD * Gerstmann–Sträussler–Scheinker syndrome * Fatal familial insomnia sporadic: * sCJD * Sporadic fatal insomnia * Variably protease-sensitive prionopathy acquired/ transmissible: * iCJD * vCJD * Kuru Prion diseases in other animals * Bovine spongiform encephalopathy * Camel spongiform encephalopathy * Scrapie * Chronic wasting disease * Transmissible mink encephalopathy * Feline spongiform encephalopathy * Exotic ungulate encephalopathy This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Camel spongiform encephalopathy	None	30,139	wikipedia	https://en.wikipedia.org/wiki/Camel_spongiform_encephalopathy	2021-01-18T19:09:27	{"wikidata": ["Q54304132"]}
## Clinical Features Nivelon et al. (1992) described 2 sibs with an apparently 'new' chondrodysplasia-pseudohermaphroditism syndrome. Both had severe dwarfism, antenatal in origin, with general chondrodysplasia, severe microcephaly with cerebellar vermis hypoplasia, hypoplastic iris, and coloboma of the optic disc. The first affected sib had shown intrauterine growth retardation on ultrasonography at the age of 5 months, at which time the limbs were considered to be short. The karyotype at that time was 46,XY; however, a phenotypic female was delivered at 38 weeks of gestation. The external genitalia and the internal genitalia, examined by sonography and laparotomy at the age of 14 months, were considered normal. The SRY gene, studied in 2 laboratories, was found to be normal with no deletion. The child was 3 years old at last description. The second affected pregnancy began when the first child was 2.5 years old. The karyotype was normal 46,XX. At 17 weeks of gestation, ultrasound examination showed abnormalities in the vertebral column and thereafter there were other skeletal changes prompting termination of the pregnancy. Both sibs showed narrow, bell-shaped thorax, micromelia, trapezoidal shape of vertebral bodies, abnormal clavicles, and short metacarpals and phalanges. The parents were young and nonconsanguineous. INHERITANCE \- Autosomal recessive GROWTH Height \- Dwarfism, severe antenatal HEAD & NECK Head \- Microcephaly Eyes \- Iris hypoplasia \- Optic disc coloboma CHEST External Features \- Narrow thorax Ribs Sternum Clavicles & Scapulae \- Abnormal clavicles GENITOURINARY External Genitalia (Female) \- Normal female genitalia Internal Genitalia (Female) \- Normal female genitalia SKELETAL \- Chondrodysplasia Spine \- Trapezoid-shaped vertebral bodies Limbs \- Micromelia Hands \- Short metacarpals \- Short phalanges NEUROLOGIC Central Nervous System \- Cerebellar vermis hypoplasia LABORATORY ABNORMALITIES \- 46,XY karyotype (1 of 2 patients) ▲ 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	CHONDRODYSPLASIA-PSEUDOHERMAPHRODITISM SYNDROME	c1838654	30,140	omim	https://www.omim.org/entry/600092	2019-09-22T16:16:43	{"doid": ["0060644"], "mesh": ["C536123"], "omim": ["600092"], "orphanet": ["1422"]}
A number sign (#) is used with this entry because of evidence that intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities (IDDSFTA) is caused by heterozygous mutation in the BCL11B gene (606558) on chromosome 14q32. Heterozygous mutation in the BCL11B gene can also cause immunodeficiency-49 (IMD49; 617237), which shows overlapping features, including intellectual disability. Clinical Features Lessel et al. (2018) reported 11 unrelated patients between 1.5 and 29 years of age with a similar neurodevelopmental disorder. All patients had delayed psychomotor development with intellectual disability and speech delay. Additional features included autistic features, attention deficit-hyperactivity disorder, anxiety, and other behavioral abnormalities. Several patients were able to attend special schools. Most had mildly delayed walking by a few months or years, although 1 patient was unable to sit, walk, or speak at 6 years of age. Spasticity and abnormal movements were observed in a few patients. The patients also had overlapping dysmorphic features, including myopathic facies, thin eyebrows, small palpebral fissures, hypertelorism, epicanthal folds, prominent nose, long philtrum, thin upper lip, and small mouth. Brain imaging was normal except in 2 patients, one with moderate ectopia of the amygdala and the other with hypoplasia of the globus pallidus. One patient had infantile seizures associated with hypsarrhythmia on EEG and secondary microcephaly (-3.6 SD); this patient had a family history of microcephaly. Less common features observed in only a few patients included hypotonia, feeding difficulties, hyperopia, myopia, and dental anomalies, such as hypodontia or enamel defects. Although none of the patients presented with or were ascertained due to an immunodeficiency, 4 patients were noted to have frequent infections and 6 had allergies or asthma. Detailed immunologic workup showed increased eosinophils in 3 patients, low T cells in 2 patients, and subtle alterations in the T-cell compartment in 7 patients compared to controls. Patients also had decreased numbers of type 2 innate lymphoid cells (ILC2s). Molecular Genetics In 9 unrelated patients with IDDSFTA, Lessel et al. (2018) identified heterozygous frameshift or nonsense mutations in the BCL11B gene (see, e.g., 606558.0003-606558.0006), all of which were predicted to result in a loss of function and haploinsufficiency. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were not present in the dbSNP, ExAC, or gnomAD databases. All mutations occurred de novo, except for 1 that was transmitted from a similarly affected mother. Most of the mutations occurred in the last exon (exon 4) and were predicted to escape nonsense-mediated mRNA decay. Expression of the most C-terminal frameshift mutation (606558.0003) into hippocampal slice cultures derived from Bcl11b mice failed to produce a detectable protein and failed to rescue the progenitor cell proliferative defect, suggesting that it is a null allele. Functional studies of the other mutations were not performed. Two additional unrelated patients with a similar disorder carried de novo balanced translocations that interrupted a regulatory domain of the BCL11B gene. These patient cells showed about a 50% decrease in BCL11B mRNA, consistent with haploinsufficiency. The overall findings implicated BCL11B haploinsufficiency as a pathogenetic mechanism underlying the disorder. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Myopathic facies \- Long philtrum Eyes \- Hypertelorism \- Short palpebral fissures \- Hyperopia \- Myopia \- Thin eyebrows \- Epicanthal folds Nose \- Prominent nose Mouth \- Thin upper lip \- Small mouth Teeth \- Small teeth \- Oligodontia \- Hypodontia \- Enamel defects RESPIRATORY \- Asthma (in some patients) ABDOMEN Gastrointestinal \- Poor feeding MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Delayed walking \- Unsteady gait \- Intellectual disability, moderate to severe \- Speech delay \- Spasticity \- Abnormal movements Behavioral Psychiatric Manifestations \- Autistic features \- ADHD \- Anxiety IMMUNOLOGY \- Recurrent infections (in some patients) \- Allergies (in some patients) \- Asthma (in some patients) \- Eosinophilia (in some patients) \- Abnormal T cell compartment \- Decreased numbers of type 2 innate lymphoid cells (ILC2s) MISCELLANEOUS \- Onset in first months of life \- De novo mutation (in most patients) \- Variable phenotype MOLECULAR BASIS \- Caused by mutation in the BAF chromatin remodeling complex subunit BCL11B gene (BCL11B, 606558.0002 ) ▲ 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	INTELLECTUAL DEVELOPMENTAL DISORDER WITH SPEECH DELAY, DYSMORPHIC FACIES, AND T-CELL ABNORMALITIES	None	30,141	omim	https://www.omim.org/entry/618092	2019-09-22T15:43:39	{"omim": ["618092"]}
Keratosis palmaris et plantaris-clinodactyly syndrome is characterised by the association of palmoplantar keratosis with clinodactyly of the fifth finger. Less than 20 cases have been described in the literature so far, and the majority of reported patients were of Mexican origin. Transmission is autosomal dominant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	Keratosis palmaris et plantaris-clinodactyly syndrome	c1835663	30,142	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86919	2021-01-23T18:34:24	{"mesh": ["C563646"], "omim": ["148520"], "umls": ["C1835663"], "icd-10": ["Q82.8"], "synonyms": ["Palmoplantar keratoderma-clinodactyly syndrome"]}
A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-2 (EV2) is conferred by homozygous mutation in the TMC8 gene (605829) gene on chromosome 17q25. Description Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400). Clinical Features Ramoz et al. (2002) described 5 families, including 3 (A1, A2, and C1) that were previously reported (Ramoz et al., 1999), with epidermodysplasia verruciformis. Patients had early onset of the disease, a disseminated infection by EV-specific HPV genotypes, including at least one of the potentially oncogenic genotypes (HPV types 5, 8, 14, 17, or 20), and lesions of the skin showing the cytopathic effect pathognomonic of EV. Significant variations were observed, however, in the HPV genotypes detected, the extension of the lesions and the development of skin carcinomas. HPV5, the genotype most frequently associated with EV cancers, was detected only in families A1, A2, and C1, whereas the less oncogenic HPV20, an HPV5-related genotype, was found in all 5 families. Imahorn et al. (2017) reported 3 Turkish sibs, aged 12, 17, and 18 years, who developed plane (flat) warts during early childhood. Histopathologic analysis showed the presence of blue cells, confirming the diagnosis of EV. Infections with beta-HPV5 and beta-HPV9 were detected in all 3 patients' warts. Family history revealed that 2 aunts and 1 uncle were also affected. Mapping In Algerian and Colombian consanguineous families segregating EV, Ramoz et al. (2000) mapped the disorder to a 1-cM interval on chromosome 17q25. Molecular Genetics In affected members of consanguineous Colombian and Algerian families with EV mapped to chromosome 17q25, Ramoz et al. (2002) identified 2 homozygous nonsense mutations in the EVER1 gene (TMC6; 605828.0001-605828.0002) and 2 homozygous mutations in the EVER2 gene (TMC8; 605829.0001-605829.0002). In a Turkish family with EV, Imahorn et al. (2017) analyzed the TMC6 and TMC8 genes, and identified homozygosity for a splice site mutation in the TMC8 gene (605829.0003) that segregated fully with disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	EPIDERMODYSPLASIA VERRUCIFORMIS, SUSCEPTIBILITY TO, 2	c0014522	30,143	omim	https://www.omim.org/entry/618231	2019-09-22T15:43:00	{"mesh": ["D004819"], "omim": ["618231"], "orphanet": ["302"]}
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative genetic disorder characterized by adult-onset proximal and distal muscle weakness (clinically resembling limb-girdle muscular dystrophy; see this term); early-onset Paget disease of bone (see this term), manifesting with bone pain, deformity and enlargement of the long-bones; and premature frontotemporal dementia (see this term), manifesting first with dysnomia, dyscalculia and comprehension deficits followed by progressive aphasia, alexia, and agraphia. As the disease progresses, muscle weakness begins to affect the other limbs and respiratory muscles, ultimately resulting in respiratory or cardiac failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	c1833662	30,144	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=52430	2021-01-23T18:25:39	{"gard": ["10899"], "mesh": ["C563476"], "omim": ["167320", "615422", "615424"], "umls": ["C1833662"], "icd-10": ["G71.8"], "synonyms": ["IBMPFD", "Limb-girdle muscular dystrophy with Paget disease of bone", "Pagetoid amyotrophic lateral sclerosis", "Pagetoid neuroskeletal syndrome"]}
Isolated pauciimmune pulmonary capillaritis is a small vessel vasculitis restricted to the lungs that may induce diffuse alveolar hemorrhage with dyspnea, anemia, chest pain, hemoptysis, bilateral and diffuse alveolar infiltrates at chest X-rays, without any underlying systemic disease. ANCA are frequently positive but could be negative. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Isolated pulmonary capillaritis	c3854530	30,145	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=264691	2021-01-23T17:19:10	{"umls": ["C3854530"]}
## Summary ### Clinical characteristics. Holt-Oram syndrome (HOS) is characterized by upper-limb defects, congenital heart malformation, and cardiac conduction disease. Upper-limb malformations may be unilateral, bilateral/symmetric, or bilateral/asymmetric and can range from triphalangeal or absent thumb(s) to phocomelia. Other upper-limb malformations can include unequal arm length caused by aplasia or hypoplasia of the radius, fusion or anomalous development of the carpal and thenar bones, abnormal forearm pronation and supination, abnormal opposition of the thumb, sloping shoulders, and restriction of shoulder joint movement. An abnormal carpal bone is present in all affected individuals and may be the only evidence of disease. A congenital heart malformation is present in 75% of individuals with HOS and most commonly involves the septum. Atrial septal defect and ventricular septal defect can vary in number, size, and location. Complex congenital heart malformations can also occur in individuals with HOS. Individuals with HOS with or without a congenital heart malformation are at risk for cardiac conduction disease. While individuals may present at birth with sinus bradycardia and first-degree atrioventricular (AV) block, AV block can progress unpredictably to a higher grade including complete heart block with and without atrial fibrillation. ### Diagnosis/testing. The diagnosis of HOS is established in a proband with a preaxial radial ray anomaly and a personal or family history of cardiac septation and/or conduction defects. More than 70% of individuals who meet strict clinical diagnostic criteria have an identifiable heterozygous pathogenic variant in TBX5. ### Management. Treatment of manifestations: Management involves a multidisciplinary team of specialists in medical genetics, cardiology, orthopedics, and hand surgery. Treatment for arrhythmias may require medication, surgery, and/or pacemaker implantation. Pharmacologic treatment for individuals with pulmonary hypertension. Cardiac surgery for congenital heart defects is standard; affected individuals and families are also likely to benefit from programs providing social support to those with limb anomalies. Prevention of secondary complications: A cardiologist can assist in determining the need for anticoagulants and antibiotic prophylaxis for bacterial endocarditis. Surveillance: Annual ECG for all affected individuals, annual Holter monitor for individuals with known conduction disease, and echocardiogram every one to five years for those with septal defects or as directed by a cardiologist. Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in relatives at risk to identify those who would benefit from appropriate cardiac management. Pregnancy management: Affected women who have not undergone cardiac evaluation should do so prior to pregnancy or as soon as the pregnancy is recognized; those with a known history of a structural cardiac defect or cardiac conduction abnormality should be followed by a cardiologist during pregnancy. ### Genetic counseling. HOS is inherited in an autosomal dominant manner. Approximately 85% of affected individuals have HOS as the result of a de novo pathogenic variant. Offspring of an affected individual are at a 50% risk of being affected. In pregnancies at 50% risk, detailed high-resolution prenatal ultrasound examination may detect upper-limb malformations and/or congenital heart malformations. Prenatal molecular genetic testing may be used to confirm a diagnosis if the TBX5 pathogenic variant has been identified in an affected relative. ## Diagnosis Clinical diagnostic criteria for Holt-Oram syndrome have been established and validated through molecular genetic testing [McDermott et al 2005]. ### Suggestive Findings Holt-Oram syndrome (HOS) should be suspected in individuals with the following limb anomalies, cardiac findings, and family history: * Upper-limb malformation involving the carpal bone(s) and, variably, the radial and/or thenar bones * Upper-limb malformations may be unilateral, bilateral/symmetric, or bilateral/asymmetric. * An abnormal carpal bone, present in all affected individuals and identified by performing a posterior-anterior hand x-ray [Poznanski et al 1970, Basson et al 1994], may be the only evidence of disease. * Congenital heart malformation, most commonly ostium secundum atrial septal defect (ASD) and ventricular septal defect (VSD), especially those occurring in the muscular trabeculated septum * Cardiac conduction disease * Family history of a first-degree relative with a congenital heart defect or cardiac conduction disease Note: Congenital malformations involving the following structures or organ systems are not typically within the spectrum of HOS and should prompt the clinician to consider alternate diagnoses: ulnar ray only, kidney, vertebra, craniofacies, auditory system (ear malformations ± hearing loss), lower limb, anus, and eye. ### Establishing the Diagnosis The diagnosis of Holt-Oram syndrome is established in a proband with either a preaxial radial ray anomaly and a personal or family history of cardiac septation and/or conduction defects or, if clinical findings are insufficient, a heterozygous pathogenic variant in TBX5 identified by molecular genetic testing (see Table 1). Molecular testing approaches can include single-gene testing and – if the phenotype includes features that are atypical for Holt-Oram syndrome – a multigene panel. Though rare, chromosome rearrangements involving 12q24 have been reported in individuals with Holt-Oram syndrome [Li et al 1997, Basson et al 1999]. * Single-gene testing. Sequence analysis of TBX5 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. * A multigene panel that includes TBX5 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in Holt-Oram Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method TBX5Sequence analysis 3>70%4 Gene-targeted deletion/duplication analysis 5<1% 6 Unknown 7NA 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\. Individuals meeting the strict diagnostic criteria of upper-limb defect and personal and/or family history of structural or conductive heart disease have a heterozygous TBX5 pathogenic variant predicted to cause disease [McDermott et al 2005, Debeer et al 2007]. Lower pathogenic variant detection rates (30%-40%) reported in some studies likely result from the inclusion of individuals who would not meet the strict diagnostic criteria outlined above [Cross et al 2000, Brassington et al 2003]. 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\. Deletion of one or more exons or the entire gene was detected in about 2% of individuals with HOS who did not have a pathogenic variant identified by sequence analysis/variant scanning [Borozdin et al 2006]. 7\. That current molecular analysis fails to identify a heterozygous pathogenic variant in TBX5 in up to 30% of individuals with HOS suggests the presence of pathogenic variants in noncoding regions or regulatory regions around TBX5 [McDermott et al 2005, Debeer et al 2007]. ## Clinical Characteristics ### Clinical Description Holt-Oram syndrome is characterized by upper-limb defects, congenital heart malformation, and cardiac conduction disease [Holt & Oram 1960]. Upper-limb malformations may be unilateral, bilateral/symmetric, or bilateral/asymmetric and can range from triphalangeal or absent thumb(s) to phocomelia, a malformation in which the hands are attached close to the body; intermediate presentations resulting from abnormal development of the bones involved may also be observed. Other upper-limb malformations can include unequal arm length caused by aplasia or hypoplasia of the radius, fusion or anomalous development of the carpal and thenar bones, abnormal forearm pronation and supination, abnormal opposition of the thumb, and sloping shoulders and restriction of shoulder joint movement. While all individuals have an upper-limb defect, the broad range of severity of these findings is such that some individuals with the mildest upper-limb malformations and mild or no congenital heart malformation may escape diagnosis. These individuals may only be diagnosed when a more severely affected relative is born or when symptoms develop in middle age as a result of cardiac abnormalities such as pulmonary hypertension, high-grade atrioventricular block, and/or atrial fibrillation. Cardiac conduction disease can be progressive. A congenital heart malformation is present in 75% of individuals with HOS and most commonly involves the septum. Atrial septal defect (ASD) and ventricular septal defect (VSD) can vary in number, size, and location. ASDs can present as a common atrium and are often associated with cardiac chamber isomerism; that is, the defining features of the cardiac chambers, based on their anatomic location, are altered (e.g., what may be considered right atrium based on its anatomic location may not have the atrial appendage morphology typical of the right atrium). Some individuals with severe congenital heart malformation may require surgery early in life to repair significant septal defects [Sletten & Pierpont 1996]. Other individuals may have complex congenital heart malformations [Faria et al 2008, Baban et al 2014, Barisic et al 2014]; conotruncal malformations, though observed in HOS, are not common and may be caused by other genetic defects. Cardiac conduction disease. Individuals with HOS with or without a congenital heart malformation are at risk for cardiac conduction disease. While individuals may present at birth with sinus bradycardia and first-degree atrioventricular (AV) block, AV block can progress unpredictably to a higher grade including complete heart block with and without atrial fibrillation. The natural history of HOS varies by individual and largely depends on the severity of the congenital heart malformation. Potential complications (which can be life threatening if not recognized and appropriately managed) include congestive heart failure, pulmonary hypertension, arrhythmias, heart block, atrial fibrillation, and infective endocarditis. ### Genotype-Phenotype Correlations It has been reported that pathogenic missense variants at the 5' end of the T-box (which binds the major groove of the target DNA sequence) are associated with more serious cardiac defects. Pathogenic missense variants at the 3' end of the T-box (which binds the minor groove of the target DNA) result in more pronounced limb defects. Caution is warranted, however, in applying these population-based associations to individuals in whom pathogenic variants may not predict specific phenotypes [Basson et al 1999, Brassington et al 2003]. In addition, genotypes do not appear to predict the progressive hemodynamic course associated with any particular cardiac septal defect. ### Penetrance The upper-limb malformations in HOS are fully penetrant. Congenital heart malformations occur in approximately 75% of affected individuals [Basson et al 1999]. Conduction defects may occur in the presence or absence of structural heart defects. ### Nomenclature HOS has been referred to as heart-hand syndrome, a nonspecific designation that could apply to any number of conditions with involvement of these structures. ### Prevalence HOS is the most common of the heart-hand syndromes. The estimated prevalence of HOS is between 0.7 and 1 per 100,000 births [Elek et al 1991, Barisic et al 2014]. HOS has been reported from a number of countries worldwide and in individuals of different racial and ethnic backgrounds [Boehme & Shotar 1989, Yang et al 2000, Barisic et al 2014, Kimura et al 2015]. ## Differential Diagnosis Diagnoses summarized in Table 2 can be considered when anomalies involving the ulna, lower limbs, kidneys, genitourinary system, vertebrae, craniofaces, and auditory or ocular systems are present [Newbury-Ecob et al 1996, Allanson & Newbury-Ecob 2003, Bressan et al 2003]. ### Table 2. Disorders to Consider in the Differential Diagnosis of Holt-Oram Syndrome (HOS) View in own window Disorder/ConditionGene(s) / Genetic MechanismMOIClinical DescriptionComments Duane-radial ray syndromeSALL4AD * Uni- or bilateral Duane anomaly * Radial ray malformation (e.g, thenar hypoplasia, thumb hypoplasia, aplasia, duplication or triphalangeal thumb, radius hypoplasia or aplasia, shortening & radial deviation of forearms) * SALL4 pathogenic variants may rarely cause what appears to be clinically typical HOS (i.e., radial ray malformations & cardiac malformations). * Further clinical investigations frequently demonstrate features considered exclusionary of HOS (e.g., renal anomalies, Duane anomaly, sensorineural hearing loss). Acro-renal-ocular syndromeAD * Radial ray malformations * Renal abnormalities * Ocular coloboma * Duane anomaly Ulnar-mammary syndrome (OMIM 181450)TBX3AD * Primarily involves ulnar ray (e.g., postaxial polydactyly) * Breast & nipple hypoplasia & delayed puberty * Congenital heart malformations (not commonly observed) Townes-Brocks syndromeSALL1AD * Triad of: imperforate anus; dysplastic ears (overfolded superior helices & preauricular tags) frequently associated w/sensorineural &/or conductive hearing impairment; & thumb malformations (duplication, hypoplasia, or triphalangeal thumbs) * Renal impairment incl ESRD w/or w/out structural abnormalities * Congenital heart disease * Foot malformations (flat feet, overlapping toes) * Genitourinary malformations * ID in ~10% of affected individuals Heart-hand syndrome II (Tabatznik syndrome) 1Not identifiedAD * Type D brachydactyly (shortening of distal phalanx of the thumb ± shortening of 4th & 5th metacarpals) * Sloping shoulders * Short upper limbs, bowing of distal radii, absence of styloid process of the ulna * Cardiac arrhythmias (e.g., supraventricular tachycardia) * Mild dysmorphic facial features * Mild ID Heart-hand syndrome III (Spanish type) (OMIM 140450)Not identifiedAD * Type C brachydactyly (shortening of the middle phalanges) w/accessory wedge-shaped ossicle on proximal phalanx of index fingers * Feet typically more mildly affected * Intraventricular conduction defects (e.g., sick sinus syndrome) Long thumb brachydactyly syndrome (OMIM 112430)Not identifiedAD * Symmetric elongation of thumb distal to proximal interphalangeal joint * Index finger brachydactyly * Clinodactyly * Narrow shoulders * Secondary short clavicles * Pectus excavatum * Cardiac abnormality is often a conduction defect. Heart-hand syndrome, Slovenian type (OMIM 610140)LMNAAD * Familial progressive sinoatrial & atrioventricular conduction disease of adult onset w/sudden death * Dilated cardiomyopathy * Brachydactyly * Feet also involved Fanconi anemia>20 genes 2AR AD XL * Short stature * Abnormal skin pigmentation * Malformations of thumbs, forearms, eyes, ears, oral cavity, genitourinary system, heart, gastrointestinal system, central nervous system * DD * Progressive bone marrow failure w/pancytopenia typically presenting in 1st decade, often initially w/thrombocytopenia or leukopenia * Increased risk for malignancy Thrombocytopenia-absent radius syndrome (TAR)RBM8A 3AR * Bilateral absence of radii w/presence of both thumbs * Thrombocytopenia (<50 platelets/nL), generally transient Other findings in TAR, (esp hematologic & neurologic) & frequent involvement of lower limbs differentiate TAR from HOS. 22q11.2 deletion syndrome (del22q11.2)Deletion of 22q11.2 DGCRAD * Congenital heart disease * ~6% of individuals exhibit upper-extremity anomalies including pre- & postaxial polydactyly, which may result in misdiagnosis of HOS. Other features in del22q11.2 incl palatal abnormalities (69%), learning difficulties (70%-90), & immune deficiency (77%), distinguish del22q11.2 from HOS. AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; DGCR = DiGeorge chromosome region; ESRD = end-stage renal disease; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked 1\. Silengo et al [1990] 2\. Genes known to be associated with Fanconi anemia: BRCA2, BRIP1, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, XRCC2 3\. The diagnosis of TAR syndrome is established in a proband with bilateral absent radii, present thumbs, and thrombocytopenia. Identification of a heterozygous null allele (most often a minimally deleted 200-kb region at chromosome band 1q21.1) in trans with a heterozygous RBM8A hypomorphic allele on molecular genetic testing confirms the diagnosis. ### Other Diagnoses to Consider in the Differential Diagnosis of HOS Disorders of unknown cause * VACTERL (vertebral defects, anal atresia, cardiac malformation, tracheo-esophageal fistula with esophageal atresia, renal anomalies, and limb anomalies) Teratogen exposure * Thalidomide. Exposure to thalidomide in pregnancy places the fetus at risk for severe upper- and lower-limb defects (e.g., phocomelia, amelia), cardiac defects, and malformations in other systems not observed in HOS (renal, ocular, auditory, gastrointestinal, and craniofacial) [Matthews & McCoy 2003, McDermott et al 2005, Vianna et al 2013]. * Valproate. Exposure to valproate, particularly in the first trimester, places the fetus at risk for major congenital defects including congenital heart defects that can overlap those seen in HOS; however, the other malformations seen (e.g., polydactyly, spina bifida) are not features of HOS [McDermott et al 2005, Wyszynski et al 2005]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Holt-Oram syndrome (HOS), 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 Holt-Oram Syndrome View in own window System/ConcernEvaluationComment MusculoskeletalPhysical examination for limb involvementHand & upper-limb radiographs may be recommended by orthopedist to aid in management of radial ray malformations. CardiacChest radiographyTo identify enlarged pulmonary arteries caused by pulmonary hypertension or cardiomegaly &/or evidence of congestive heart failure EchocardiographyTo identify septal defects or other structural cardiac anomalies ECGTo identify cardiac conduction disease OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations The management of individuals with HOS optimally involves a multidisciplinary team approach with specialists in medical genetics, cardiology, and orthopedics, including a specialist in hand surgery. A cardiologist can assist in determining the need for antiarrhythmic medications and surgery. Individuals with severe heart block may require pacemaker implantation. Pharmacologic treatment for affected individuals with pulmonary hypertension may be appropriate. Individuals with pulmonary hypertension and/or structural heart malformation may require tertiary care center cardiology follow up. Cardiac surgery, if required for congenital heart defect, is standard. The orthopedic team may be able to guide individuals in decisions regarding surgery for improved upper-limb and hand function as well as physical and occupational therapy options. Those individuals born with severe upper-limb malformations may be candidates for surgery to improve function, such as pollicization (creation of a thumb-like digit by moving another digit into the thenar position) in individuals with thumb aplasia/hypoplasia [Vaienti et al 2009]. Children with severe limb shortening may benefit from prostheses as well as from physical and occupational therapy. Individuals and families are also likely to benefit from programs providing social support to those with limb anomalies. ### Prevention of Secondary Complications A cardiologist can assist in determining the need for anticoagulants and antibiotic prophylaxis for bacterial endocarditis (SBE). ### Surveillance ### Table 4. Recommended Surveillance for Individuals with Holt-Oram Syndrome View in own window System/ConcernEvaluationFrequency CardiacECGAnnually in individuals at risk of developing a conduction defect ECG combined w/Holter monitorAnnually in individuals w/known conduction disease to assess progression EchocardiogramEvery 1-5 yrs – may be recommended by the managing cardiologist depending on nature & significance of potential septal defects. ### Agents/Circumstances to Avoid Certain medications may be contraindicated in individuals with arrhythmias, cardiomyopathy, and/or pulmonary hypertension. People with such disorders require individual assessment by a cardiologist. ### Evaluation of Relatives at Risk It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from appropriate cardiac management. Evaluations can include: * Molecular genetic testing if the TBX5 pathogenic variant in the family is known; * Echocardiography, ECG, and hand x-rays (anterior/posterior view) if the pathogenic variant in the family is not known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Pregnant women with HOS who have a known history of a structural cardiac defect or cardiac conduction abnormality should be followed by a multidisciplinary team (including a cardiologist) during pregnancy. Affected women who have not undergone cardiac evaluation should do so prior to pregnancy if possible, or as soon as the pregnancy is recognized. See MotherToBaby for further information on medication use during pregnancy. ### 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	Holt-Oram Syndrome	c0265264	30,146	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1111/	2021-01-18T21:19:33	{"mesh": ["C535326"], "synonyms": ["Heart and Hand Syndrome"]}
Junctional epidermolysis bullosa, localized non-Herlitz-type is a form of non-Herlitz junctional epidermolysis bullosa (JEB-nH, see this term) characterized by localized blistering, and dystrophic or absent nails. ## Epidemiology Prevalence is unknown. Fewer than 20 cases have been described. ## Clinical description Onset is at birth or soon thereafter. Skin blistering is mainly confined to hands, feet, lower legs and face. Additional findings comprise mild nail dystrophy, dental enamel hypoplasia, and an increased incidence of caries. Primary hair is normal, while axillary and pubic hair can be sparse. ## Etiology Localized non-Herlitz junctional epidermolysis bullosa is caused by mutations in the type XVII collagen gene : COL17A1 (10q24.3). ## Genetic counseling The condition follows an autosomal recessive pattern of inheritance. ## Prognosis Prognosis is generally good. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Localized junctional epidermolysis bullosa, non-Herlitz type	c0079301	30,147	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251393	2021-01-23T18:29:26	{"gard": ["12923"], "mesh": ["D016109"], "omim": ["226650"], "icd-10": ["Q81.8"], "synonyms": ["JEB-nH loc"]}
Poisoning by lead in the body, especially affects the brain Lead poisoning Other namesPlumbism, colica pictorum, saturnism, Devon colic, painter's colic An X ray demonstrating the characteristic finding of lead poisoning in humans—dense metaphyseal lines. SpecialtyToxicology SymptomsIntellectual disability, abdominal pain, constipation, headaches, irritability, memory problems, inability to have children, tingling in the hands and feet[1][2] ComplicationsAnemia, seizures, coma[1][2] CausesExposure to lead via contaminated air, water, dust, food, consumer products[2] Risk factorsBeing a child[2] Diagnostic methodBlood lead level[2] Differential diagnosisIron deficiency anemia, malabsorption, anxiety disorder, polyneuropathy[3] PreventionRemoving lead from the home, improved monitoring and education in the workplace, laws that ban lead in products[2][4][5][6] TreatmentChelation therapy[4] MedicationDimercaprol, edetate calcium disodium, succimer[7] Deaths540,000 (2016)[2] Lead poisoning is a type of metal poisoning caused by lead in the body.[2] The brain is the most sensitive.[2] Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, infertility, and tingling in the hands and feet.[1] It causes almost 10% of intellectual disability of otherwise unknown cause and can result in behavioral problems.[2] Some of the effects are permanent.[2] In severe cases anemia, seizures, coma, or death may occur.[1][2] Exposure to lead can occur by contaminated air, water, dust, food, or consumer products.[2] Children are at greater risk as they are more likely to put objects in their mouth such as those that contain lead paint and absorb a greater proportion of the lead that they eat.[2] Exposure at work is a common cause of lead poisoning in adults with certain occupations at particular risk.[7] Diagnosis is typically by measurement of the blood lead level.[2] The Centers for Disease Control (US) has set the upper limit for blood lead for adults at 10 µg/dl (10 µg/100 g) and for children at 5 µg/dl.[8][9] Elevated lead may also be detected by changes in red blood cells or dense lines in the bones of children as seen on X-ray.[4] Lead poisoning is preventable.[2] This includes individual efforts such as removing lead-containing items from the home,[5] workplace efforts such as improved ventilation and monitoring,[6] state laws that ban the use of and national policies such as laws that ban lead in products such as paint, gasoline, ammunition, wheel weights, and fishing weights reduce allowable levels in water or soil, and provide for cleanup of contaminated soil.[2][4] Workers’ education could be helpful as well.[10] The major treatments are removal of the source of lead and the use of medications that bind lead so it can be eliminated from the body, known as chelation therapy.[4] Chelation therapy in children is recommended when blood levels are greater than 40–45 µg/dl.[4][11] Medications used include dimercaprol, edetate calcium disodium, and succimer.[7] In 2016, lead is believed to have resulted in 540,000 deaths worldwide.[2] It occurs most commonly in the developing world.[2] Those who are poor are at greater risk.[2] Lead is believed to result in 0.6% of the world's disease burden.[5] People have been mining and using lead for thousands of years.[4] Descriptions of lead poisoning date to at least 2000 BC,[4] while efforts to limit lead's use date back to at least the 16th century.[5] Concerns for low levels of exposure begin in the 1970s with there being no safe threshold for lead exposure.[2][4][12] Poisoning by lead in the body, especially affects the brain ## Contents * 1 Classification * 2 Signs and symptoms * 2.1 Acute poisoning * 2.2 Chronic poisoning * 2.3 Effects on children * 2.4 By organ system * 2.4.1 Kidneys * 2.4.2 Cardiovascular system * 2.4.3 Reproductive system * 2.4.4 Nervous system * 3 Exposure routes * 3.1 Occupational exposure * 3.2 Food * 3.3 Paint * 3.4 Soil * 3.5 Water * 3.6 Lead-containing products * 3.7 Bullets * 3.8 Opium * 4 Pathophysiology * 4.1 Enzymes * 4.2 Neurons * 5 Diagnosis * 5.1 Reference levels * 6 Prevention * 6.1 Screening * 6.2 Education * 7 Treatment * 8 Epidemiology * 8.1 Notable cases * 9 Prognosis * 9.1 Reversibility * 9.2 Encephalopathy * 9.3 Long-term * 10 Violence * 11 History * 12 Other species * 12.1 Wildlife * 13 Notes * 14 Further reading * 15 External links ## Classification[edit] Classically, "lead poisoning" or "lead intoxication" has been defined as exposure to high levels of lead typically associated with severe health effects.[13] Poisoning is a pattern of symptoms that occur with toxic effects from mid to high levels of exposure; toxicity is a wider spectrum of effects, including subclinical ones (those that do not cause symptoms).[14] However, professionals often use "lead poisoning" and "lead toxicity" interchangeably, and official sources do not always restrict the use of "lead poisoning" to refer only to symptomatic effects of lead.[14] The amount of lead in the blood and tissues, as well as the time course of exposure, determine toxicity.[15] Lead poisoning may be acute (from intense exposure of short duration) or chronic (from repeat low-level exposure over a prolonged period), but the latter is much more common.[16] Diagnosis and treatment of lead exposure are based on blood lead level (the amount of lead in the blood), measured in micrograms of lead per deciliter of blood (μg/dL). Urine lead levels may be used as well, though less commonly. In cases of chronic exposure, lead often sequesters in the highest concentrations first in the bones, then in the kidneys. If a provider is performing a provocative excretion test, or "chelation challenge", a measurement obtained from urine rather than blood is likely to provide a more accurate representation of total lead burden to a skilled interpreter.[17] The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 μg/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level.[18][19] Authorities such as the American Academy of Pediatrics define lead poisoning as blood lead levels higher than 10 μg/dL.[20] Lead forms a variety of compounds and exists in the environment in various forms.[21] Features of poisoning differ depending on whether the agent is an organic compound (one that contains carbon), or an inorganic one.[22] Organic lead poisoning is now very rare, because countries across the world have phased out the use of organic lead compounds as gasoline additives, but such compounds are still used in industrial settings.[22] Organic lead compounds, which cross the skin and respiratory tract easily, affect the central nervous system predominantly.[22] ## Signs and symptoms[edit] Symptoms of lead poisoning. Lead poisoning can cause a variety of symptoms and signs which vary depending on the individual and the duration of lead exposure.[23][24] Symptoms are nonspecific and may be subtle, and someone with elevated lead levels may have no symptoms.[25] Symptoms usually develop over weeks to months as lead builds up in the body during a chronic exposure, but acute symptoms from brief, intense exposures also occur.[26] Symptoms from exposure to organic lead, which is probably more toxic than inorganic lead due to its lipid solubility, occur rapidly.[27] Poisoning by organic lead compounds has symptoms predominantly in the central nervous system, such as insomnia, delirium, cognitive deficits, tremor, hallucinations, and convulsions.[22] Symptoms may be different in adults and children; the main symptoms in adults are headache, abdominal pain, memory loss, kidney failure, male reproductive problems, and weakness, pain, or tingling in the extremities.[28] Early symptoms of lead poisoning in adults are commonly nonspecific and include depression, loss of appetite, intermittent abdominal pain, nausea, diarrhea, constipation, and muscle pain.[29] Other early signs in adults include malaise, fatigue, decreased libido, and problems with sleep.[23] An unusual taste in the mouth and personality changes are also early signs.[30][31] In adults, symptoms can occur at levels above 40 μg/dL, but are more likely to occur only above 50–60 μg/dL.[23] Symptoms begin to appear in children generally at around 60 μg/dL.[5] However, the lead levels at which symptoms appear vary widely depending on unknown characteristics of each individual.[32] At blood lead levels between 25 and 60 μg/dL, neuropsychiatric effects such as delayed reaction times, irritability, and difficulty concentrating, as well as slowed motor nerve conduction and headache can occur.[33] Anemia may appear at blood lead levels higher than 50 μg/dL.[29] In adults, abdominal colic, involving paroxysms of pain, may appear at blood lead levels greater than 80 μg/dL.[24] Signs that occur in adults at blood lead levels exceeding 100 μg/dL include wrist drop and foot drop, and signs of encephalopathy (a condition characterized by brain swelling), such as those that accompany increased pressure within the skull, delirium, coma, seizures, and headache.[34] In children, signs of encephalopathy such as bizarre behavior, discoordination, and apathy occur at lead levels exceeding 70 μg/dL.[34] For both adults and children, it is rare to be asymptomatic if blood lead levels exceed 100 μg/dL.[24] ### Acute poisoning[edit] In acute poisoning, typical neurological signs are pain, muscle weakness, numbness and tingling, and, rarely, symptoms associated with inflammation of the brain.[28] Abdominal pain, nausea, vomiting, diarrhea, and constipation are other acute symptoms.[35] Lead's effects on the mouth include astringency and a metallic taste.[35] Gastrointestinal problems, such as constipation, diarrhea, poor appetite, or weight loss, are common in acute poisoning. Absorption of large amounts of lead over a short time can cause shock (insufficient fluid in the circulatory system) due to loss of water from the gastrointestinal tract.[35] Hemolysis (the rupture of red blood cells) due to acute poisoning can cause anemia and hemoglobin in the urine.[35] Damage to kidneys can cause changes in urination such as decreased urine output.[35] People who survive acute poisoning often go on to display symptoms of chronic poisoning.[35] ### Chronic poisoning[edit] Chronic poisoning usually presents with symptoms affecting multiple systems,[22] but is associated with three main types of symptoms: gastrointestinal, neuromuscular, and neurological.[28] Central nervous system and neuromuscular symptoms usually result from intense exposure, while gastrointestinal symptoms usually result from exposure over longer periods.[35] Signs of chronic exposure include loss of short-term memory or concentration, depression, nausea, abdominal pain, loss of coordination, and numbness and tingling in the extremities.[30][unreliable medical source?] Fatigue, problems with sleep, headaches, stupor, slurred speech, and anemia are also found in chronic lead poisoning.[28] A "lead hue" of the skin with pallor and/or lividity is another feature.[36][37] A blue line along the gum with bluish black edging to the teeth, known as a Burton line, is another indication of chronic lead poisoning.[38] Children with chronic poisoning may refuse to play or may have hyperkinetic or aggressive behavior disorders.[28] Visual disturbance may present with gradually progressing blurred vision as a result of central scotoma, caused by toxic optic neuritis.[39] ### Effects on children[edit] As lead safety standards become more stringent, fewer children in the US are found to have elevated lead levels. A pregnant woman who has elevated blood lead levels is at greater risk of a premature birth or with a low birth weight.[40] Children are more at risk for lead poisoning because their smaller bodies are in a continuous state of growth and development.[41] Young children are much more vulnerable to lead poisoning, as they absorb 4 to 5 times more lead than an adult from a given source.[42] Furthermore, children, especially as they are learning to crawl and walk, are constantly on the floor and therefore more prone to ingesting and inhaling dust that is contaminated with lead.[43] The classic signs and symptoms in children are loss of appetite, abdominal pain, vomiting, weight loss, constipation, anemia, kidney failure, irritability, lethargy, learning disabilities, and behavioral problems.[44] Slow development of normal childhood behaviors, such as talking and use of words, and permanent intellectual disability are both commonly seen. Although less common, it is possible for fingernails to develop leukonychia striata if exposed to abnormally high lead concentrations.[45] On July 30, 2020, a report by UNICEF and Pure Earth revealed that lead poisoning is affecting children on a “massive and previously unknown scale.” According to the report, one in three children, up to 800 million globally, have blood lead levels at, or above, 5 micrograms per decilitre (µg/dL), the amount at which action is required.[46] [47] ### By organ system[edit] Lead affects every one of the body's organ systems, especially the nervous system, but also the bones and teeth, the kidneys, and the cardiovascular, immune, and reproductive systems.[48] Hearing loss and tooth decay have been linked to lead exposure,[49] as have cataracts.[50] Intrauterine and neonatal lead exposure promote tooth decay.[51][52][53][54][55][56][57] Aside from the developmental effects unique to young children, the health effects experienced by adults are similar to those in children, although the thresholds are generally higher.[58] #### Kidneys[edit] Kidney damage occurs with exposure to high levels of lead, and evidence suggests that lower levels can damage kidneys as well.[59] The toxic effect of lead causes nephropathy and may cause Fanconi syndrome, in which the proximal tubular function of the kidney is impaired.[60] Long-term exposure at levels lower than those that cause lead nephropathy have also been reported as nephrotoxic in patients from developed countries that had chronic kidney disease or were at risk because of hypertension or diabetes mellitus.[61] Lead poisoning inhibits excretion of the waste product urate and causes a predisposition for gout, in which urate builds up.[62][63][64] This condition is known as saturnine gout. #### Cardiovascular system[edit] Evidence suggests lead exposure is associated with high blood pressure, and studies have also found connections between lead exposure and coronary heart disease, heart rate variability, and death from stroke, but this evidence is more limited.[65] People who have been exposed to higher concentrations of lead may be at a higher risk for cardiac autonomic dysfunction on days when ozone and fine particles are higher.[66] #### Reproductive system[edit] Lead affects both the male and female reproductive systems. In men, when blood lead levels exceed 40 μg/dL, sperm count is reduced and changes occur in volume of sperm, their motility, and their morphology.[67] A pregnant woman's elevated blood lead level can lead to miscarriage, prematurity, low birth weight, and problems with development during childhood.[68] Lead is able to pass through the placenta and into breast milk, and blood lead levels in mothers and infants are usually similar.[26] A fetus may be poisoned in utero if lead from the mother's bones is subsequently mobilized by the changes in metabolism due to pregnancy; increased calcium intake in pregnancy may help mitigate this phenomenon.[69] #### Nervous system[edit] The brains of adults who were exposed to lead as children show decreased volume, especially in the prefrontal cortex, on MRI. Areas of volume loss are shown in color over a template of a normal brain.[70] See also: Lead–crime hypothesis Lead affects the peripheral nervous system (especially motor nerves) and the central nervous system.[26] Peripheral nervous system effects are more prominent in adults and central nervous system effects are more prominent in children.[32] Lead causes the axons of nerve cells to degenerate and lose their myelin coats.[26] Lead exposure in young children has been linked to learning disabilities,[71] and children with blood lead concentrations greater than 10 μg/dL are in danger of developmental disabilities.[35] Increased blood lead level in children has been correlated with decreases in intelligence, nonverbal reasoning, short-term memory, attention, reading and arithmetic ability, fine motor skills, emotional regulation, and social engagement.[68] The effect of lead on children's cognitive abilities takes place at very low levels.[49][68][72] There is apparently no lower threshold to the dose-response relationship (unlike other heavy metals such as mercury).[73] Reduced academic performance has been associated with lead exposure even at blood lead levels lower than 5 μg/dL.[74][75] Blood lead levels below 10 μg/dL have been reported to be associated with lower IQ and behavior problems such as aggression, in proportion with blood lead levels.[14] Between the blood lead levels of 5 and 35 μg/dL, an IQ decrease of 2–4 points for each μg/dL increase is reported in children.[35] However, studies that show associations between low-level lead exposure and health effects in children may be affected by confounding and overestimate the effects of low-level lead exposure.[76] High blood lead levels in adults are also associated with decreases in cognitive performance and with psychiatric symptoms such as depression and anxiety.[77] It was found in a large group of current and former inorganic lead workers in Korea that blood lead levels in the range of 20–50 μg/dL were correlated with neuro-cognitive defects.[78] Increases in blood lead levels from about 50 to about 100 μg/dL in adults have been found to be associated with persistent, and possibly permanent, impairment of central nervous system function.[59] Lead exposure in children is also correlated with neuropsychiatric disorders such as attention deficit hyperactivity disorder and anti-social behaviour.[72] Elevated lead levels in children are correlated with higher scores on aggression and delinquency measures.[5] A correlation has also been found between prenatal and early childhood lead exposure and violent crime in adulthood.[68] Countries with the highest air lead levels have also been found to have the highest murder rates, after adjusting for confounding factors.[5] A May 2000 study by economic consultant Rick Nevin theorizes that lead exposure explains 65% to 90% of the variation in violent crime rates in the US.[79][80] A 2007 paper by the same author claims to show a strong association between preschool blood lead and subsequent crime rate trends over several decades across nine countries.[81][82] Lead exposure in childhood appears to increase school suspensions and juvenile detention among boys.[83] It is believed that the U.S. ban on lead paint in buildings in the late 1970s, as well as the phaseout of leaded gasoline in the 1970s and 1980s, partially helped contribute to the decline of violent crime in the United States since the early 1990s.[82] ## Exposure routes[edit] Lead is a common environmental pollutant.[20] Causes of environmental contamination include industrial use of lead, such as found in facilities that process lead-acid batteries or produce lead wire or pipes, and metal recycling and foundries.[84] Storage batteries and ammunition are made with the largest amounts of lead consumed in the economy each year, in the US as of 2013.[85] Children living near facilities that process lead, such as lead smelters, have been found to have unusually high blood lead levels.[86] In August 2009, parents rioted in China after lead poisoning was found in nearly 2000 children living near zinc and manganese smelters.[87] Lead exposure can occur from contact with lead in air, household dust, soil, water, and commercial products.[18] Leaded gasoline has also been linked to increases in lead pollution.[88][89] Some research has suggested a link between leaded gasoline and crime rates.[90][91] Man made lead pollution has been elevated in the air for the past 2000 years.[92][93][94] Lead pollution in the air is entirely due to human activity (mining and smelting). ### Occupational exposure[edit] Battery recycling workers are at risk for lead exposure.[95] This worker ladles molten lead into billets in a lead-acid battery recovery facility. In adults, occupational exposure is the main cause of lead poisoning.[5] People can be exposed when working in facilities that produce a variety of lead-containing products; these include radiation shields, ammunition, certain surgical equipment, developing dental x-ray films prior to digital x-rays (each film packet had a lead liner to prevent the radiation from going through), fetal monitors, plumbing, circuit boards, jet engines, and ceramic glazes.[30][unreliable medical source?] In addition, lead miners and smelters, plumbers and fitters, auto mechanics, glass manufacturers, construction workers, battery manufacturers and recyclers, firing range workers, and plastic manufacturers are at risk for lead exposure.[86] Other occupations that present lead exposure risks include welding, manufacture of rubber, printing, zinc and copper smelting, processing of ore, combustion of solid waste, and production of paints and pigments.[96] Lead exposure can also occur with intense use of gun ranges, regardless of whether these ranges are indoor or out.[97] Parents who are exposed to lead in the workplace can bring lead dust home on clothes or skin and expose their children.[96] Occupational exposure to lead increases the risk of cardiovascular disease, in particular: stroke, and high blood pressure.[98] ### Food[edit] Lead may be found in food when food is grown in soil that is high in lead, airborne lead contaminates the crops, animals eat lead in their diet, or lead enters the food either from what it was stored or cooked in.[99] In Bangladesh, lead compounds have been added to turmeric to make it more yellow.[100] This is believed to have started in the 1980s and continues as of 2019.[100] It is believed to be one of the main sources of high lead levels in the country.[101] In Hong Kong the maximum allowed lead parts per million is 6 in solid foods and 1 in liquid foods.[102] ### Paint[edit] Some lead compounds are colorful and are used widely in paints,[103] and lead paint is a major route of lead exposure in children.[104] A study conducted in 1998–2000 found that 38 million housing units in the US had lead-based paint, down from a 1990 estimate of 64 million.[105] Deteriorating lead paint can produce dangerous lead levels in household dust and soil.[106] Deteriorating lead paint and lead-containing household dust are the main causes of chronic lead poisoning.[28] The lead breaks down into the dust and since children are more prone to crawling on the floor, it is easily ingested.[105] Many young children display pica, eating things that are not food. Even a small amount of a lead-containing product such as a paint chip or a sip of glaze can contain tens or hundreds of milligrams of lead.[107] Eating chips of lead paint presents a particular hazard to children, generally producing more severe poisoning than occurs from dust.[108] Because removing lead paint from dwellings, e.g. by sanding or torching, creates lead-containing dust and fumes, it is generally safer to seal the lead paint under new paint (excepting moveable windows and doors, which create paint dust when operated).[109] Alternatively, special precautions must be taken if the lead paint is to be removed.[109] In oil painting it was once common for colours such as yellow or white to be made with lead carbonate. Lead white oil colour was the main white of oil painters until superseded by compounds containing zinc or titanium in the mid-20th century. It is speculated that the painter Caravaggio and possibly Francisco Goya and Vincent Van Gogh had lead poisoning due to overexposure or carelessness when handling this colour.[110] ### Soil[edit] A lead warning on a fuel pump. Tetraethyllead, which used to be added to automotive gasoline (and still is added to some aviation gasolines), contributed to soil contamination. Residual lead in soil contributes to lead exposure in urban areas.[14] It has been thought that the more polluted an area is with various contaminants, the more likely it is to contain lead. However, this is not always the case, as there are several other reasons for lead contamination in soil.[111] Lead content in soil may be caused by broken-down lead paint, residues from lead-containing gasoline, used engine oil, tire weights, or pesticides used in the past, contaminated landfills, or from nearby industries such as foundries or smelters.[112] Although leaded soil is less of a problem in countries that no longer have leaded gasoline, it remains prevalent, raising concerns about the safety of urban agriculture;[113] eating food grown in contaminated soil can present a lead hazard.[114] Lead wheel weight eroding on road ### Water[edit] Lead from the atmosphere or soil can end up in groundwater and surface water.[115] It is also potentially in drinking water, e.g. from plumbing and fixtures that are either made of lead or have lead solder.[108][116] Since acidic water breaks down lead in plumbing more readily, chemicals can be added to municipal water to increase the pH and thus reduce the corrosivity of the public water supply.[108] Chloramines, which were adopted as a substitute for chlorine disinfectants due to fewer health concerns, increase corrositivity.[117] In the US, 14–20% of total lead exposure is attributed to drinking water.[117] In 2004, a team of seven reporters from The Washington Post discovered high levels of lead in the drinking water in Washington DC and won an award for investigative reporting for a series of articles about this contamination.[118][119] In the Flint water crisis (Flint, Michigan), a switch to a more corrosive municipal water source caused elevated lead levels in domestic tap water.[120][121] Like Flint MI and Washington DC, a similar situation affects the State of Wisconsin, where estimates call for replacement of up to 176,000 underground pipes made of lead known as lead service lines. The city of Madison, Wisconsin addressed the issue and replaced all of their lead service lines, but there are still others that have yet to follow suit. While there are chemical methods that could help reduce the amount of lead in the water distributed, a permanent fix would be to replace the pipes completely. While the state may replace the pipes below ground, it will be up to the homeowners to replace the pipes on their property, at an average cost of $3,000.[122] Experts say that if the city were to replace their pipes and the citizens were to keep the old pipes located within their homes, there would be a potential for more lead to dissolve into their drinking water.[122] Collected rainwater from roof runoff used as potable water may contain lead, if there are lead contaminants on the roof or in the storage tank.[18] The Australian Drinking Water Guidelines allow a maximum of 0.01 mg/L (10 ppb) lead in water.[18] Lead wheel weights have been found to accumulate on roads and interstates and erode in traffic entering the water runoff through drains. Leaded fishing weights accumulate in rivers, streams, ponds, and lakes. ### Lead-containing products[edit] Lead can be found in products such as kohl, an ancient cosmetic from the Middle East, South Asia, and parts of Africa that has many other names; and from some toys.[14] In 2007, millions of toys made in China were recalled from multiple countries owing to safety hazards including lead paint.[123] Vinyl mini-blinds, found especially in older housing, may contain lead.[20] Lead is commonly incorporated into herbal remedies such as Indian Ayurvedic preparations and remedies of Chinese origin.[18][23] There are also risks of elevated blood lead levels caused by folk remedies like azarcon and greta, which each contain about 95% lead.[23] Ingestion of metallic lead, such as small lead fishing lures, increases blood lead levels and can be fatal.[124][125][126][127] Ingestion of lead-contaminated food is also a threat. Ceramic glaze often contains lead, and dishes that have been improperly fired can leach the metal into food, potentially causing severe poisoning.[128] In some places, the solder in cans used for food contains lead.[30] When manufacturing medical instruments and hardware, solder containing lead may be present.[129] People who eat animals hunted with lead bullets may be at risk for lead exposure.[130] Bullets lodged in the body rarely cause significant levels of lead,[131][132] but bullets lodged in the joints are the exception, as they deteriorate and release lead into the body over time.[133] In May 2015, Indian food safety regulators in the state of Uttar Pradesh found that samples of Maggi 2 Minute Noodles contained lead up to 17 times beyond permissible limits.[134][135][136][137] On 3 June 2015, New Delhi Government banned the sale of Maggi noodles in New Delhi stores for 15 days because it was found to contain lead beyond the permissible limit.[138] The Gujarat FDA on June 4, 2015 banned the noodles for 30 days after 27 out of 39 samples were detected with objectionable levels of metallic lead, among other things.[139] Some of India's biggest retailers like Future Group, Big Bazaar, Easyday and Nilgiris have imposed a nationwide ban on Maggi noodles.[140] Many other states too have banned Maggi noodles. ### Bullets[edit] Contact with ammunition is a source of lead exposure. As of 2013, lead-based ammunition production is the second largest annual use of lead in the US, accounting for over 84,800 metric tons consumed in 2013,[85] second only to the manufacture of storage batteries.[85][141] The Environmental Protection Agency (EPA) cannot regulate cartridges and shells, as a matter of law.[142] Lead birdshot is banned in some areas, but this is primarily for the benefit of the birds and their predators, rather than humans.[143] Contamination from heavily used gun ranges are of concern to those who live near by.[144] Non-lead alternatives include steel, tungsten-nickel-iron, bismuth-tin, and tungsten-polymer. Because game animals can be shot using lead bullets, the potential for lead ingestion from game meat consumption has been studied clinically and epidemiologically. In a recent study conducted by the CDC,[145] a cohort from North Dakota was enrolled and asked to self-report historical consumption of game meat, and participation in other activities that could cause lead exposure. The study found that participants' age, sex, housing age, current hobbies with potential for lead exposure, and game consumption were all associated with blood lead level (PbB). According to a study published in 2008, 1.1% of the 736 persons consuming wild game meat tested had PbB ≥5 μg/dl[146] In November 2015 The US HHS/CDC/NIOSH designated 5 µg/dL (five micrograms per deciliter) of whole blood, in a venous blood sample, as the reference blood lead level for adults. An elevated BLL is defined as a BLL ≥5 µg/dL. This case definition is used by the ABLES program, the Council of State and Territorial Epidemiologists (CSTE), and CDC's National Notifiable Diseases Surveillance System (NNDSS). Previously (i.e. from 2009 until November 2015), the case definition for an elevated BLL was a BLL ≥10 µg/dL.[147] Copper-jacketed, lead-based bullets are more economical to produce and use than lead or any other material. Alternative materials are available such as steel, copper, and tungsten, but alternatives are universally less effective and/or more expensive. However, the biggest impediment to using the vast majority of alternatives relates to current laws in the United States pertaining to armor-piercing rounds. Laws and regulations relating to armor-piercing ammunition expressly prohibit the use of brass, bronze, steel, tungsten, and nearly every metallic alternative in any bullet that can be shot by a handgun, which at this time is nearly every caliber smaller than 50BMG (including the popular .223 Remington, .308 Winchester and .30-06 to name just a few). Some lead-based bullets are resistant to fragmentation, offering hunters the ability to clean game animals with negligible risk of including lead fragments in prepared meat. Other bullets are prone to fragmentation and exacerbate the risk of lead ingestion from prepared meat. In practice, use of a non-fragmenting bullet and proper cleaning of the game animal's wound can eliminate the risk of lead ingestion from eating game;[130] however, isolating such practice to experimentally determine its association with blood lead levels in study is difficult. Bismuth is an element used as a lead-replacement for shotgun pellets used in waterfowl hunting although shotshells made from bismuth are nearly ten times the cost of lead. ### Opium[edit] Lead contaminated opium has been the source of poisoning in Iran and other Middle Eastern countries. This has also appeared in the illicit narcotic supply in North America, resulting in confirmed lead poisoning.[148] ## Pathophysiology[edit] Tetraethyllead, still used as an additive in some fuels, can be absorbed through the skin.[30][unreliable medical source?] Exposure occurs through inhalation, ingestion or occasionally skin contact. Lead may be taken in through direct contact with mouth, nose, and eyes (mucous membranes), and through breaks in the skin. Tetraethyllead, which was a gasoline additive and is still used in avgas, passes through the skin; however inorganic lead found in paint, food, and most lead-containing consumer products is only minimally absorbed through the skin.[30][unreliable medical source?] The main sources of absorption of inorganic lead are from ingestion and inhalation.[29] In adults, about 35–40% of inhaled lead dust is deposited in the lungs, and about 95% of that goes into the bloodstream.[29] Of ingested inorganic lead, about 15% is absorbed, but this percentage is higher in children, pregnant women, and people with deficiencies of calcium, zinc, or iron.[23] Infants may absorb about 50% of ingested lead, but little is known about absorption rates in children.[149] The main body tissues that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone.[23] Lead in the bones, teeth, hair, and nails is bound tightly and not available to other tissues, and is generally thought not to be harmful.[150] In adults, 94% of absorbed lead is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health effects on children.[19] The estimated half-life of lead in bone is 20 to 30 years, and bone can introduce lead into the bloodstream long after the initial exposure is gone.[30][unreliable medical source?] The half-life of lead in the blood in men is about 40 days, but it may be longer in children and pregnant women, whose bones are undergoing remodeling, which allows the lead to be continuously re-introduced into the bloodstream.[19] Also, if lead exposure takes place over years, clearance is much slower, partly due to the re-release of lead from bone.[151] Many other tissues store lead, but those with the highest concentrations (other than blood, bone, and teeth) are the brain, spleen, kidneys, liver, and lungs.[26] Lead is removed from the body very slowly, mainly through urine.[15] Smaller amounts of lead are also eliminated through the feces, and very small amounts in hair, nails, and sweat.[152] Lead has no known physiologically relevant role in the body,[48][84] and its harmful effects are myriad. Lead and other heavy metals create reactive radicals which damage cell structures including DNA and cell membranes.[153] Lead also interferes with DNA transcription, enzymes that help in the synthesis of vitamin D, and enzymes that maintain the integrity of the cell membrane.[26] Anemia may result when the cell membranes of red blood cells become more fragile as the result of damage to their membranes.[154] Lead interferes with metabolism of bones and teeth[155] and alters the permeability of blood vessels and collagen synthesis.[5] Lead may also be harmful to the developing immune system, causing production of excessive inflammatory proteins; this mechanism may mean that lead exposure is a risk factor for asthma in children.[155] Lead exposure has also been associated with a decrease in activity of immune cells such as polymorphonuclear leukocytes.[155] Lead also interferes with the normal metabolism of calcium in cells and causes it to build up within them.[108] ### Enzymes[edit] ALAD enzyme with lead bound (PDB: 1QNV) The primary cause of lead's toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes.[15] Part of lead's toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act.[26] Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme's ability to catalyze its normal reaction or reactions. Among the essential metals with which lead interacts are calcium, iron, and zinc.[152] The lead ion has a lone pair in its electronic structure, which can result in a distortion in the coordination of ligands, and in 2007 was hypothesized to be important in lead poisoning's effects on enzymes (see Lone pair § Unusual lone pairs).[156] One of the main causes for the pathology of lead is that it interferes with the activity of an essential enzyme called delta-aminolevulinic acid dehydratase, or ALAD (see image of the enzyme structure), which is important in the biosynthesis of heme, the cofactor found in hemoglobin.[157][158][159] Lead also inhibits the enzyme ferrochelatase, another enzyme involved in the formation of heme.[19][160] Ferrochelatase catalyzes the joining of protoporphyrin and Fe2+ to form heme.[19][26][30][unreliable medical source?] Lead's interference with heme synthesis results in production of zinc protoporphyrin and the development of anemia.[161] Another effect of lead's interference with heme synthesis is the buildup of heme precursors, such as aminolevulinic acid, which may be directly or indirectly harmful to neurons.[162] Elevation of aminolevulinic acid results in lead poisoning having symptoms similar to porphyria.[163][164][165][166][167] ### Neurons[edit] Lead exposure damages cells in the hippocampus, a part of the brain involved in memory. Hippocampi of lead-exposed rats (bottom) show structural damage such as irregular nuclei (IN) and denaturation of myelin (DMS) compared to controls (top).[168] The brain is the organ most sensitive to lead exposure.[70] Lead is able to pass through the endothelial cells at the blood brain barrier because it can substitute for calcium ions and be uptaken by calcium-ATPase pumps.[169] Lead poisoning interferes with the normal development of a child's brain and nervous system; therefore children are at greater risk of lead neurotoxicity than adults are.[170] In a child's developing brain, lead interferes with synapse formation in the cerebral cortex, neurochemical development (including that of neurotransmitters), and organization of ion channels.[161] It causes loss of neurons' myelin sheaths, reduces numbers of neurons, interferes with neurotransmission, and decreases neuronal growth.[15] Lead-ions (Pb2+), like magnesium-ions (Mg2+), block NMDA receptors. Therefore, an increase in Pb2+ concentration will effectively inhibit ongoing long-term potentiation (LTP), and lead to an abnormal increase in long-term depression (LTD) on neurons in the affected parts of the nervous system. These abnormalities lead to the indirect downregulation of NMDA-receptors, effectively initiating a positive feedback-loop for LTD.[171] The targeting of NMDA receptors is thought to be one of the main causes for lead's toxicity to neurons.[168] ## Diagnosis[edit] Diagnosis includes determining the clinical signs and the medical history, with inquiry into possible routes of exposure.[172] Clinical toxicologists, medical specialists in the area of poisoning, may be involved in diagnosis and treatment. The main tool in diagnosing and assessing the severity of lead poisoning is laboratory analysis of the blood lead level (BLL).[25] Basophilic stippling (arrows) of red blood cells in a 53-year-old who had elevated blood lead levels due to drinking repeatedly from glasses decorated with lead paint.[173] Blood film examination may reveal basophilic stippling of red blood cells (dots in red blood cells visible through a microscope), as well as the changes normally associated with iron-deficiency anemia (microcytosis and hypochromasia).[60] This may be known as sideroblastic anemia.[174] However, basophilic stippling is also seen in unrelated conditions, such as megaloblastic anemia caused by vitamin B12 (colbalamin) and folate deficiencies.[175] Contrary to other sideroblastic anemia, there are no ring sideroblasts in a bone marrow smear.[176] Exposure to lead also can be evaluated by measuring erythrocyte protoporphyrin (EP) in blood samples.[30][unreliable medical source?] EP is a part of red blood cells known to increase when the amount of lead in the blood is high, with a delay of a few weeks.[24] Thus EP levels in conjunction with blood lead levels can suggest the time period of exposure; if blood lead levels are high but EP is still normal, this finding suggests exposure was recent.[24][33] However, the EP level alone is not sensitive enough to identify elevated blood lead levels below about 35 μg/dL.[30][unreliable medical source?] Due to this higher threshold for detection and the fact that EP levels also increase in iron deficiency, use of this method for detecting lead exposure has decreased.[177] Blood lead levels are an indicator mainly of recent or current lead exposure, not of total body burden.[178] Lead in bones can be measured noninvasively by X-ray fluorescence; this may be the best measure of cumulative exposure and total body burden.[33] However this method is not widely available and is mainly used for research rather than routine diagnosis.[95] Another radiographic sign of elevated lead levels is the presence of radiodense lines called lead lines at the metaphysis in the long bones of growing children, especially around the knees.[179] These lead lines, caused by increased calcification due to disrupted metabolism in the growing bones, become wider as the duration of lead exposure increases.[179] X-rays may also reveal lead-containing foreign materials such as paint chips in the gastrointestinal tract.[22][179] Fecal lead content that is measured over the course of a few days may also be an accurate way to estimate the overall amount of childhood lead intake. This form of measurement may serve as a useful way to see the extent of oral lead exposure from all the diet and environmental sources of lead.[180] Lead poisoning shares symptoms with other conditions and may be easily missed.[35] Conditions that present similarly and must be ruled out in diagnosing lead poisoning include carpal tunnel syndrome, Guillain–Barré syndrome, renal colic, appendicitis, encephalitis in adults, and viral gastroenteritis in children.[172] Other differential diagnoses in children include constipation, abdominal colic, iron deficiency, subdural hematoma, neoplasms of the central nervous system, emotional and behavior disorders, and intellectual disability.[25] ### Reference levels[edit] The current reference range for acceptable blood lead concentrations in healthy persons without excessive exposure to environmental sources of lead is less than 5 µg/dL for children.[8] It was less than 25 µg/dL for adults.[181] Previous to 2012 the value for children was 10 (µg/dl).[182] Lead-exposed workers in the U.S. are required to be removed from work when their level is greater than 50 µg/dL if they do construction and otherwise greater than 60 µg/dL.[183] In 2015, US HHS/CDC/NIOSH designated 5 µg/dL (five micrograms per deciliter) of whole blood, in a venous blood sample, as the reference blood lead level for adults. An elevated BLL is defined as a BLL ≥5 µg/dL. This case definition is used by the ABLES program, the Council of State and Territorial Epidemiologists (CSTE), and CDC's National Notifiable Diseases Surveillance System (NNDSS). Previously (i.e. from 2009 until November 2015), the case definition for an elevated BLL was a BLL ≥10 µg/dL.[147] The U.S. national BLL geometric mean among adults was 1.2 μg/dL in 2009–2010.[184] Blood lead concentrations in poisoning victims have ranged from 30->80 µg/dL in children exposed to lead paint in older houses, 77–104 µg/dL in persons working with pottery glazes, 90–137 µg/dL in individuals consuming contaminated herbal medicines, 109–139 µg/dL in indoor shooting range instructors and as high as 330 µg/dL in those drinking fruit juices from glazed earthenware containers.[185] ## Prevention[edit] Testing kits are commercially available for detecting lead. These swabs, when wiped on a surface, turn red in the presence of lead. See also: Lead abatement in the United States In most cases, lead poisoning is preventable[86] by avoiding exposure to lead.[18] Prevention strategies can be divided into individual (measures taken by a family), preventive medicine (identifying and intervening with high-risk individuals), and public health (reducing risk on a population level).[14] Recommended steps by individuals to reduce the blood lead levels of children include increasing their frequency of hand washing and their intake of calcium and iron, discouraging them from putting their hands to their mouths, vacuuming frequently, and eliminating the presence of lead-containing objects such as blinds and jewellery in the house.[186] In houses with lead pipes or plumbing solder, these can be replaced.[186] Less permanent but cheaper methods include running water in the morning to flush out the most contaminated water, or adjusting the water's chemistry to prevent corrosion of pipes.[186] Lead testing kits are commercially available for detecting the presence of lead in the household.[128] As hot water is more likely than cold water to contain higher amounts of lead, use only cold water from the tap for drinking, cooking, and making baby formula. Since most of the lead in household water usually comes from plumbing in the house and not from the local water supply, using cold water can avoid lead exposure.[187] Measures such as dust control and household education do not appear to be effective in changing children's blood levels.[188] Prevention measures also exist on national and municipal levels. Recommendations by health professionals for lowering childhood exposures include banning the use of lead where it is not essential and strengthening regulations that limit the amount of lead in soil, water, air, household dust, and products.[49] Regulations exist to limit the amount of lead in paint; for example, a 1978 law in the US restricted the lead in paint for residences, furniture, and toys to 0.06% or less.[103] In October 2008, the US Environmental Protection Agency reduced the allowable lead level by a factor of ten to 0.15 micrograms per cubic meter of air, giving states five years to comply with the standards.[189] The European Union's Restriction of Hazardous Substances Directive limits amounts of lead and other toxic substances in electronics and electrical equipment. In some places, remediation programs exist to reduce the presence of lead when it is found to be high, for example in drinking water.[186] As a more radical solution, entire towns located near former lead mines have been "closed" by the government, and the population resettled elsewhere, as was the case with Picher, Oklahoma in 2009.[190][191] Removing lead from airplane fuel would also be useful.[192] ### Screening[edit] Screening may be an important method of prevention for those at high risk,[14] such as those who live near lead-related industries.[25] The USPSTF has stated that general screening of those without symptoms include children and pregnant women is of unclear benefit as of 2019.[193] The ACOG and APP, however, recommends asking about risk factors and testing those who have them.[194] ### Education[edit] The education of workers on lead, its danger and how its workplace exposure can be decreased, especially when initial blood lead level and urine lead level are high, could help reduce the risk of lead poisoning in the workplace.[10] ## Treatment[edit] CDC management guidelines for children with elevated blood levels[195] Blood lead level (μg/dL) Treatment 10–14 Education, repeat screening 15–19 Repeat screening, case management to abate sources 20–44 Medical evaluation, case management 45–69 Medical evaluation, chelation, case management >69 Hospitalization, immediate chelation, case management The mainstays of treatment are removal from the source of lead and, for people who have significantly high blood lead levels or who have symptoms of poisoning, chelation therapy.[196] Treatment of iron, calcium, and zinc deficiencies, which are associated with increased lead absorption, is another part of treatment for lead poisoning.[197] When lead-containing materials are present in the gastrointestinal tract (as evidenced by abdominal X-rays), whole bowel irrigation, cathartics, endoscopy, or even surgical removal may be used to eliminate it from the gut and prevent further exposure.[198] Lead-containing bullets and shrapnel may also present a threat of further exposure and may need to be surgically removed if they are in or near fluid-filled or synovial spaces.[107] If lead encephalopathy is present, anticonvulsants may be given to control seizures, and treatments to control swelling of the brain include corticosteroids and mannitol.[22][199] Treatment of organic lead poisoning involves removing the lead compound from the skin, preventing further exposure, treating seizures, and possibly chelation therapy for people with high blood lead concentrations.[200] EDTA, a chelating agent, binds a heavy metal, sequestering it. A chelating agent is a molecule with at least two negatively charged groups that allow it to form complexes with metal ions with multiple positive charges, such as lead.[201] The chelate that is thus formed is nontoxic[202] and can be excreted in the urine, initially at up to 50 times the normal rate.[162] The chelating agents used for treatment of lead poisoning are edetate disodium calcium (CaNa2EDTA), dimercaprol (BAL), which are injected, and succimer and d-penicillamine, which are administered orally.[203] Chelation therapy is used in cases of acute lead poisoning,[30][unreliable medical source?] severe poisoning, and encephalopathy,[198] and is considered for people with blood lead levels above 25 µg/dL.[35] While the use of chelation for people with symptoms of lead poisoning is widely supported, use in asymptomatic people with high blood lead levels is more controversial.[22] Chelation therapy is of limited value for cases of chronic exposure to low levels of lead.[204] Chelation therapy is usually stopped when symptoms resolve or when blood lead levels return to premorbid levels.[22] When lead exposure has taken place over a long period, blood lead levels may rise after chelation is stopped because lead is leached into blood from stores in the bone;[22] thus repeated treatments are often necessary.[5] People receiving dimercaprol need to be assessed for peanut allergies since the commercial formulation contains peanut oil. Calcium EDTA is also effective if administered four hours after the administration of dimercaprol. Administering dimercaprol, DMSA (Succimer), or DMPS prior to calcium EDTA is necessary to prevent the redistribution of lead into the central nervous system.[205] Dimercaprol used alone may also redistribute lead to the brain and testes.[205] An adverse side effect of calcium EDTA is renal toxicity. Succimer (DMSA) is the preferred agent in mild to moderate lead poisoning cases. This may be the case in instances where children have a blood lead level >25μg/dL. The most reported adverse side effect for succimer is gastrointestinal disturbances.[206] It is also important to note that chelation therapy only lowers blood lead levels and may not prevent the lead-induced cognitive problems associated with lower lead levels in tissue. This may be because of the inability of these agents to remove sufficient amounts of lead from tissue or inability to reverse preexisting damage.[206] Chelating agents can have adverse effects;[95] for example, chelation therapy can lower the body's levels of necessary nutrients like zinc.[202][207] Chelating agents taken orally can increase the body's absorption of lead through the intestine.[208] Chelation challenge, also known as provocation testing, is used to indicate an elevated and mobilizable body burden of heavy metals including lead.[95] This testing involves collecting urine before and after administering a one-off dose of chelating agent to mobilize heavy metals into the urine.[95] Then urine is analyzed by a laboratory for levels of heavy metals; from this analysis overall body burden is inferred.[209] Chelation challenge mainly measures the burden of lead in soft tissues, though whether it accurately reflects long-term exposure or the amount of lead stored in bone remains controversial.[17][22] Although the technique has been used to determine whether chelation therapy is indicated and to diagnose heavy metal exposure, some evidence does not support these uses as blood levels after chelation are not comparable to the reference range typically used to diagnose heavy metal poisoning.[95] The single chelation dose could also redistribute the heavy metals to more sensitive areas such as central nervous system tissue.[95] ## Epidemiology[edit] Since lead has been used widely for centuries, the effects of exposure are worldwide.[186] Environmental lead is ubiquitous, and everyone has some measurable blood lead level.[23][151] Atmospheric lead pollution increased dramatically beginning in the 1950s as a result of the widespread use of leaded gasoline.[210] Lead is one of the largest environmental medicine problems in terms of numbers of people exposed and the public health toll it takes.[50] Lead exposure accounts for about 0.2% of all deaths and 0.6% of disability adjusted life years globally.[211] Although regulation reducing lead in products has greatly reduced exposure in the developed world since the 1970s, lead is still allowed in products in many developing countries.[50] In all countries that have banned leaded gasoline, average blood lead levels have fallen sharply.[204] However, some developing countries still allow leaded gasoline,[186] which is the primary source of lead exposure in most developing countries.[71] Beyond exposure from gasoline, the frequent use of pesticides in developing countries adds a risk of lead exposure and subsequent poisoning.[212] Poor children in developing countries are at especially high risk for lead poisoning.[71] Of North American children, 7% have blood lead levels above 10 μg/dL, whereas among Central and South American children, the percentage is 33 to 34%.[186] About one fifth of the world's disease burden from lead poisoning occurs in the Western Pacific, and another fifth is in Southeast Asia.[186] In developed countries, people with low levels of education living in poorer areas are most at risk for elevated lead.[50] In the US, the groups most at risk for lead exposure are the impoverished, city-dwellers, and immigrants.[68] African-American children and those living in old housing have also been found to be at elevated risk for high blood lead levels in the US.[213] Low-income people often live in old housing with lead paint, which may begin to peel, exposing residents to high levels of lead-containing dust. Risk factors for elevated lead exposure include alcohol consumption and smoking (possibly because of contamination of tobacco leaves with lead-containing pesticides).[151] Adults with certain risk factors might be more susceptible to toxicity; these include calcium and iron deficiencies, old age, disease of organs targeted by lead (e.g. the brain, the kidneys), and possibly genetic susceptibility.[78] Differences in vulnerability to lead-induced neurological damage between males and females have also been found, but some studies have found males to be at greater risk, while others have found females to be.[32] In adults, blood lead levels steadily increase with increasing age.[18] In adults of all ages, men have higher blood lead levels than women do.[18] Children are more sensitive to elevated blood lead levels than adults are.[214] Children may also have a higher intake of lead than adults; they breathe faster and may be more likely to have contact with and ingest soil.[106] Children of ages one to three tend to have the highest blood lead levels, possibly because at that age they begin to walk and explore their environment, and they use their mouths in their exploration.[32] Blood levels usually peak at about 18–24 months old.[15] In many countries including the US, household paint and dust are the major route of exposure in children.[106] ### Notable cases[edit] Main article: Lead poisoning epidemics Cases of mass lead poisoning can occur. 15,000 people are being relocated from Jiyuan in central Henan province to other locations after 1000 children living around China's largest smelter plant (owned and operated by Yuguang Gold and Lead) were found to have excess lead in their blood. The total cost of this project is estimated to around 1 billion yuan ($150 million). 70% of the cost will be paid by local government and the smelter company, while the rest will be paid by the residents themselves. The government has suspended production at 32 of 35 lead plants.[215] The affected area includes people from 10 different villages.[216] The Zamfara State lead poisoning epidemic occurred in Nigeria in 2010. As of October 5, 2010 at least 400 children have died from the effects of lead poisoning.[217] ## Prognosis[edit] ### Reversibility[edit] Outcome is related to the extent and duration of lead exposure.[218] Effects of lead on the physiology of the kidneys and blood are generally reversible; its effects on the central nervous system are not.[60] While peripheral effects in adults often go away when lead exposure ceases, evidence suggests that most of lead's effects on a child's central nervous system are irreversible.[32] Children with lead poisoning may thus have adverse health, cognitive, and behavioral effects that follow them into adulthood.[112] ### Encephalopathy[edit] Lead encephalopathy is a medical emergency and causes permanent brain damage in 70–80% of children affected by it, even those that receive the best treatment.[25] The mortality rate for people who develop cerebral involvement is about 25%, and of those who survive who had lead encephalopathy symptoms by the time chelation therapy was begun, about 40% have permanent neurological problems such as cerebral palsy.[35] ### Long-term[edit] Exposure to lead may also decrease lifespan and have health effects in the long term.[5] Death rates from a variety of causes have been found to be higher in people with elevated blood lead levels; these include cancer, stroke, and heart disease, and general death rates from all causes.[18] Lead is considered a possible human carcinogen based on evidence from animal studies.[219] Evidence also suggests that age-related mental decline and psychiatric symptoms are correlated with lead exposure.[151] Cumulative exposure over a prolonged period may have a more important effect on some aspects of health than recent exposure.[151] Some health effects, such as high blood pressure, are only significant risks when lead exposure is prolonged (over about one year).[78] Furthermore, the neurological effects of lead exposure have been shown to be exacerbated and long lasting in low income children in comparison to those of higher economic standing.[220] ## Violence[edit] Leading poisoning in children has been linked to changes brain function that can result in low IQ, and increased impulsivity and aggression.[221] These traits of childhood lead exposure are associated criminality that lead the crimes of passion, such as aggravated assault in young adults.[222] Therefore, an increase in lead exposure in children has been linked to an increase aggravated assault rates 22 year later.[223] For instance, the peak in leaded gasoline use in the late 1970's corresponds to a peak in aggravated assault rates in the late 1990's in urban areas across the United States.[223] ## History[edit] Dioscorides noted lead's effect on the mind in the first century A.D. Roman lead water pipes with taps Lead poisoning was among the first known and most widely studied work regarding environmental hazards.[153] One of the first metals to be smelted and used,[103] lead is thought to have been discovered and first mined in Anatolia around 6500 BC.[104] Its density, workability, and corrosion resistance were among the metal's attractions.[153] In the 2nd century BC the Greek botanist Nicander described the colic and paralysis seen in lead-poisoned people.[28][5] Dioscorides, a Greek physician who lived in the 1st century AD, wrote that lead makes the mind "give way".[103][224] Lead was used extensively in Roman aqueducts from about 500 BC to 300 AD[104] Julius Caesar's engineer, Vitruvius, reported, "water is much more wholesome from earthenware pipes than from lead pipes. For it seems to be made injurious by lead, because white lead is produced by it, and this is said to be harmful to the human body."[225] Gout, prevalent in affluent Rome, is thought to be the result of lead, or leaded eating and drinking vessels. Sugar of lead (lead(II) acetate) was used to sweeten wine, and the gout that resulted from this was known as "saturnine" gout.[226] It is even hypothesized that lead poisoning may have contributed to the decline of the Roman Empire,[5][103] a hypothesis thoroughly disputed: > The great disadvantage of lead has always been that it is poisonous. This was fully recognised by the ancients, and Vitruvius specifically warns against its use. Because it was nevertheless used in profusion for carrying drinking water, the conclusion has often been drawn that the Romans must therefore have suffered from lead poisoning; sometimes conclusions are carried even further and it is inferred that this caused infertility and other unwelcome conditions, and that lead plumbing was largely responsible for the decline and fall of Rome. Two things make this otherwise attractive hypothesis impossible. First, the calcium carbonate deposit that formed so thickly inside the aqueduct channels also formed inside the pipes, effectively insulating the water from the lead, so that the two never touched. Second, because the Romans had so few taps and the water was constantly running, it was never inside the pipes for more than a few minutes, and certainly not long enough to become contaminated.[227] However, recent research supports the idea that the lead found in the water came from the supply pipes, rather than another source of contamination. It was not unknown for locals to punch holes in the pipes to draw water off, increasing the number of people exposed to the lead. > Thirty years ago, Jerome Nriagu argued in a milestone paper that Roman civilization collapsed as a result of lead poisoning. Clair Patterson, the scientist who convinced governments to ban lead from gasoline, enthusiastically endorsed this idea, which nevertheless triggered a volley of publications aimed at refuting it. Although today lead is no longer seen as the prime culprit of Rome’s demise, its status in the system of water distribution by lead pipes (fistulæ) still stands as a major public health issue. By measuring Pb isotope compositions of sediments from the Tiber River and the Trajanic Harbor, the present work shows that “tap water” from ancient Rome had 100 times more lead than local spring waters.[228][229][230] Romans also consumed lead through the consumption of defrutum, carenum, and sapa, musts made by boiling down fruit in lead cookware. Defrutum and its relatives were used in ancient Roman cuisine and cosmetics, including as a food preservative.[231] The use of leaden cookware, though popular, was not the general standard and copper cookware was used far more generally. There is also no indication how often sapa was added or in what quantity. The consumption of sapa as having a role in the fall of the Roman Empire was used in a theory proposed by geochemist Jerome Nriagu[232] to state that "lead poisoning contributed to the decline of the Roman Empire". In 1984, John Scarborough, a pharmacologist and classicist, criticized the conclusions drawn by Nriagu's book as "so full of false evidence, miscitations, typographical errors, and a blatant flippancy regarding primary sources that the reader cannot trust the basic arguments."[233] After antiquity, mention of lead poisoning was absent from medical literature until the end of the Middle Ages.[234] In 1656 the German physician Samuel Stockhausen recognized dust and fumes containing lead compounds as the cause of disease, called since ancient Roman times morbi metallici, that were known to afflict miners, smelter workers, potters, and others whose work exposed them to the metal.[235][236] The painter Caravaggio might have died of lead poisoning. Bones with high lead levels were recently found in a grave thought likely to be his.[237] Paints used at the time contained high amounts of lead salts. Caravaggio is known to have exhibited violent behavior, a symptom commonly associated with lead poisoning. In 17th-century Germany, the physician Eberhard Gockel discovered lead-contaminated wine to be the cause of an epidemic of colic.[235] He had noticed that monks who did not drink wine were healthy, while wine drinkers developed colic,[28] and traced the cause to sugar of lead, made by simmering litharge with vinegar.[235] As a result, Eberhard Ludwig, Duke of Württemberg issued an edict in 1696 banning the adulteration of wines with litharge.[235] In the 18th century lead poisoning was fairly frequent on account of the widespread drinking of rum, which was made in stills with a lead component (the "worm"). It was a significant cause of mortality amongst slaves and sailors in the colonial West Indies.[238][239] Lead poisoning from rum was also noted in Boston.[240] Benjamin Franklin suspected lead to be a risk in 1786.[241] Also in the 18th century, "Devonshire colic" was the name given to the symptoms suffered by people of Devon who drank cider made in presses that were lined with lead.[28] Lead was added to cheap wine illegally in the 18th and early 19th centuries as a sweetener.[242] The composer Beethoven, a heavy wine drinker, suffered elevated lead levels (as later detected in his hair) possibly due to this; the cause of his death is controversial, but lead poisoning is a contender as a factor.[242][243] With the Industrial Revolution in the 19th century, lead poisoning became common in the work setting.[103] The introduction of lead paint for residential use in the 19th century increased childhood exposure to lead; for millennia before this, most lead exposure had been occupational.[32] An important step in the understanding of childhood lead poisoning occurred when toxicity in children from lead paint was recognized in Australia in 1897.[103] France, Belgium, and Austria banned white lead interior paints in 1909; the League of Nations followed suit in 1922.[104] However, in the United States, laws banning lead house paint were not passed until 1971, and it was phased out and not fully banned until 1978.[104] The 20th century saw an increase in worldwide lead exposure levels due to the increased widespread use of the metal.[244] Beginning in the 1920s, lead was added to gasoline to improve its combustion; lead from this exhaust persists today in soil and dust in buildings.[18] Blood lead levels worldwide have been declining sharply since the 1980s, when leaded gasoline began to be phased out.[18] In those countries that have banned lead in solder for food and drink cans and have banned leaded gasoline additives, blood lead levels have fallen sharply since the mid-1980s.[245] The levels found today in most people are orders of magnitude greater than those of pre-industrial society.[74] Due to reductions of lead in products and the workplace, acute lead poisoning is rare in most countries today, but low level lead exposure is still common.[246] It was not until the second half of the 20th century that subclinical lead exposure became understood to be a problem.[234] During the end of the 20th century, the blood lead levels deemed acceptable steadily declined.[247] Blood lead levels once considered safe are now considered hazardous, with no known safe threshold.[86][248] In the late 1950s through the 1970s Herbert Needleman and Clair Cameron Patterson did research trying to prove lead's toxicity to humans.[249] In the 1980s Needleman was falsely accused of scientific misconduct by the lead industry associates.[250][251] In 2002 Tommy Thompson, secretary of Health and Human Services appointed at least two persons with conflicts of interest to the CDC's Lead Advisory Committee.[252][253] In 2014 a case by the state of California against a number of companies decided against Sherwin-Williams, NL Industries and ConAgra and ordered them to pay $1.15 billion.[254] The disposition of The People v. ConAgra Grocery Products Company et al. in the California 6th Appellate District Court on November 14, 2017 is that > ... the judgment is reversed, and the matter is remanded to the trial court with directions to (1) recalculate the amount of the abatement fund to limit it to the amount necessary to cover the cost of remediating pre-1951 homes, and (2) hold an evidentiary hearing regarding the appointment of a suitable receiver. The Plaintiff shall recover its costs on appeal.[255] On December 6, 2017, the petitions for rehearing from NL Industries, Inc., ConAgra Grocery Products Company and The Sherwin-Williams Company were denied.[255] Studies have found a weak link between lead from leaded gasoline and crime rates.[256] ## Other species[edit] Main article: Animal lead poisoning Humans are not alone in suffering from lead's effects; plants and animals are also affected by lead toxicity to varying degrees depending on species.[114] Animals experience many of the same effects of lead exposure as humans do, such as abdominal pain, peripheral neuropathy, and behavioral changes such as increased aggression.[50] Much of what is known about human lead toxicity and its effects is derived from animal studies.[32] Animals are used to test the effects of treatments, such as chelating agents,[257] and to provide information on the pathophysiology of lead, such as how it is absorbed and distributed in the body.[258] Farm animals such as cows and horses[259] as well as pet animals are also susceptible to the effects of lead toxicity.[202] Sources of lead exposure in pets can be the same as those that present health threats to humans sharing the environment, such as paint and blinds, and there is sometimes lead in toys made for pets.[202] Lead poisoning in a pet dog may indicate that children in the same household are at increased risk for elevated lead levels.[50] ### Wildlife[edit] Turkey vultures, Cathartes aura (shown), and California condors can be poisoned when they eat carcasses of animals shot with lead pellets. Lead, one of the leading causes of toxicity in waterfowl, has been known to cause die-offs of wild bird populations.[202] When hunters use lead shot, waterfowl such as ducks can ingest the spent pellets later and be poisoned; predators that eat these birds are also at risk.[260] Lead shot-related waterfowl poisonings were first documented in the US in the 1880s.[50] By 1919, the spent lead pellets from waterfowl hunting was positively identified as the source of waterfowl deaths.[261] Lead shot has been banned for hunting waterfowl in several countries,[50] including the US in 1991 and Canada in 1997.[262] Other threats to wildlife include lead paint, sediment from lead mines and smelters, and lead weights from fishing lines.[262] Lead in some fishing gear has been banned in several countries.[50] The critically endangered California condor has also been affected by lead poisoning. As scavengers, condors eat carcasses of game that have been shot but not retrieved, and with them the fragments from lead bullets; this increases their lead levels.[263] Among condors around the Grand Canyon, lead poisoning due to eating lead shot is the most frequently diagnosed cause of death.[263] In an effort to protect this species, in areas designated as the California condor's range the use of projectiles containing lead has been banned to hunt deer, feral pigs, elk, pronghorn antelope, coyotes, ground squirrels, and other non-game wildlife.[264] Also, conservation programs exist which routinely capture condors, check their blood lead levels, and treat cases of poisoning.[263] ## Notes[edit] 1. ^ a b c d "Lead Information for Workers". CDC. 30 September 2013. Archived from the original on 18 October 2016. Retrieved 14 October 2016. 2. ^ a b c d e f g h i j k l m n o p q r s t u "Lead poisoning and health". WHO. September 2016. Archived from the original on 18 October 2016. Retrieved 14 October 2016. 3. ^ Ferri FF (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 L. ISBN 978-0323076999. 4. ^ a b c d e f g h i Dapul H, Laraque D (August 2014). "Lead poisoning in children". Advances in Pediatrics. 61 (1): 313–33. doi:10.1016/j.yapd.2014.04.004. PMID 25037135. 5. ^ a b c d e f g h i j k l m Needleman H (2004). "Lead poisoning". Annual Review of Medicine. 55: 209–22. doi:10.1146/annurev.med.55.091902.103653. PMID 14746518. 6. ^ a b "Lead Information for Employers". CDC. 30 September 2013. Archived from the original on 18 October 2016. Retrieved 14 October 2016. 7. ^ a b c Gracia RC, Snodgrass WR (January 2007). "Lead toxicity and chelation therapy". American Journal of Health-System Pharmacy. 64 (1): 45–53. doi:10.2146/ajhp060175. PMID 17189579. 8. ^ a b "Advisory Committee On Childhood Lead Poisoning Prevention (ACCLPP)". 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Environmental Toxicology: Biological and Health Effects of Pollutants. CRC Press. ISBN 978-1-56670-670-4. ## Further reading[edit] * Binns HJ, Ricks OB. "Helping Parents Prevent Lead Poisoning". ERIC Digest. * Karalus DE (2010). "Review: The Great Lead Water Pipe Disaster". Electronic Green Journal. 1 (29). doi:10.5070/G312910819. * Küpper H (2017). "Chapter 15. Lead Toxicity in Plants". In Astrid S, Helmut S, Sigel RK (eds.). Lead: Its Effects on Environment and Health. Metal Ions in Life Sciences. 17. de Gruyter. pp. 491–500. doi:10.1515/9783110434330-015. ISBN 9783110434330. PMID 28731308. ## External links[edit] * Agency for Toxic Substances and Disease Registry (August 20, 2007). "Lead Toxicity". Environmental Health and Medicine Education. U.S. Department of Health and Human Services. Course: WB 1105. * Health and Safety Executive UK. "Lead". Working safely with lead. HSE. * Katz NL (June 26, 2007). "City payout to Brooklyn family largest ever in lead poisoning". NY Daily News. * National Institute for Occupational Safety and Health (2018-06-20). "Lead". NIOSH Workplace Safety & Health Topics. Centers for Disease Control and Prevention. * National Pollutant Inventory. "Lead and compounds: Health effects". Fact Sheets. Canberra, Australia: Department of Sustainability, Environment, Water, Population and Communities. Archived from the original on 2012-03-20. * National Safety Council (2008). "Lead Poisoning" (PDF). Fact Sheets. Itasca, Illinois, U.S.: National Safety Council. Archived from the original (PDF) on 2017-12-22. Retrieved 2016-06-11. Classification D * ICD-10: T56.0 * ICD-9-CM: 984.9 * MeSH: D007855 * DiseasesDB: 7307 External resources * MedlinePlus: 002473 * eMedicine: article/815399 * Patient UK: Lead poisoning * Orphanet: 330015 * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D 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syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric 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## Summary ### Clinical characteristics. Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present. ### Diagnosis/testing. The diagnosis of PFBC relies on: visualization of bilateral calcification of the basal ganglia on neuroimaging; presence of progressive neurologic dysfunction; and absence of metabolic, infectious, toxic, or traumatic cause. A family history consistent with autosomal dominant inheritance is often found as well. Thus, the diagnosis of PFBC should be left for those cases where other neurologic or systemic disorders potentially associated with ectopic calcium deposits have not been identified after appropriate examinations. A heterozygous pathogenic variant in PDGFB, PDGFRB, SLC20A2, or XPR1 has been identified in a little more than half of those individuals with a clinical diagnosis of PFBC. ### Management. Treatment of manifestations: Pharmacologic treatment to improve anxiety, depression, obsessive-compulsive behaviors, as well as for movement disorders (e.g., tremors) or dystonia; anticholinergics for urinary incontinence; antiepileptic drugs for seizures. Surveillance: Annual neurologic and neuropsychiatric assessments. Agents/circumstances to avoid: Cautious use of neuroleptic medications as they may exacerbate extrapyramidal symptoms. ### Genetic counseling. PFBC is inherited in an autosomal dominant manner. Most individuals diagnosed with PFBC have an affected parent identified either clinically or by brain CT scan. However, the transmitting parent may be clinically asymptomatic throughout life or may develop disease manifestations that are later in onset or less severe than those in the proband. If a parent of the proband is affected and/or is known to be heterozygous for a PFBC-related pathogenic variant, sibs of a proband are at a 50% risk of inheriting the pathogenic variant; however, the risk to sibs of being clinically affected may be slightly lower due to reduced penetrance. Offspring of an affected individual have a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in an affected family member. ## Diagnosis ### Suggestive Findings Primary familial brain calcification (PFBC) should be suspected in individuals who meet the following criteria (modified from Moskowitz et al [1971], Ellie et al [1989], and Manyam [2005]): * Progressive neurologic dysfunction, generally including a movement disorder and/or neuropsychiatric manifestations. Age of onset is typically in the fourth or fifth decade, although this dysfunction may present in childhood or later in life. * Bilateral calcification of the basal ganglia visualized on neuroimaging. Other brain regions may also be affected, including the cerebellum, the brain stem, the centrum semiovale, and the subcortical white matter. Of note, the presence of brain calcifications in asymptomatic individuals is possible. * Absence of biochemical abnormalities and somatic features suggestive of a mitochondrial or metabolic disease or other systemic disorder * Absence of an infectious, toxic, or traumatic cause * Family history consistent with autosomal dominant inheritance Imaging studies. The calcifications in PFBC are generally not distinguishable from those due to hypoparathyroidism or to other causes. However, some clues, such as the appearance and localization of the calcium deposits, may point to specific, mostly non-idiopathic causes [Livingston et al 2013]. * Brain CT scan, which easily detects calcium, is the preferred method of localizing and assessing the extent of cerebral calcifications. Most frequently affected is the lenticular nucleus, especially the internal globus pallidus. Calcifications in the putamen, thalami, caudate, and dentate nuclei are common. Occasionally, calcium deposits begin or predominate in regions outside the basal ganglia. Calcification appears to be progressive, since these deposits are generally more extensive in older individuals and an increase in calcification can sometimes be documented on follow up of affected individuals. Cerebellum, the brain stem, centrum semiovale, and subcortical white matter may also be affected [Manyam et al 1992]. Diffuse atrophic changes with dilatation of the subarachnoid space and/or ventricular system may coexist with calcifications. * Magnetic resonance imaging (MRI). Calcified areas in the basal ganglia give a low-intensity signal on T2-weighted images and a low- or high-intensity signal on T1-weighted planes. In the cerebellum and cerebral white matter, the lesions may be more heterogeneous, sometimes seen as high signal on both T1 and T2, perhaps as a result of reactive gliosis or degenerating tissue within the calcified areas [Avrahami et al 1994]. MRI provides better anatomic detail than CT but is less sensitive in detecting calcification. Calcified lesions on MRI produce various levels of signal intensities that may be misinterpreted as not representing brain calcification. Kozic et al [2009] reported three individuals with brain calcification easily identified on CT scan for which MRI was interpreted as either completely normal, inconclusive, or wrongly compatible with toxic/metabolic demyelination. * Plain skull radiograph. The calcifications appear as clusters of punctate densities symmetrically distributed above the sella turcica and lateral to the midline. Subcortical and cerebellar calcifications may appear wavy. Although the sensitivity of CT scan largely surpasses that of plain skull radiographs, the latter are still useful to evaluate abnormalities of bone structures suggestive of other diagnoses. ### Testing Normal findings. In order to evaluate for other genetic and acquired causes of brain calcifications, a diagnostic approach has been revised for adults [Bonazza et al 2011]. In individuals with PFBC the following evaluations are typically normal: * Serum concentration of calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin, and parathyroid hormone (PTH) * Routine hematologic and biochemical investigations * Workup for metabolic, inflammatory, and infectious conditions * Blood and urine heavy metal concentrations * Ellsworth Howard test (i.e., a 10- to 20-fold increase of urinary cAMP excretion following stimulation with 200 U of PTH) * Cerebrospinal fluid evaluation for bacteria, viruses, and parasites. However, a slight increase in protein has been described [Boller et al 1977]. Neuropathology * Gross pathologic examination shows accumulation of a granular material and solid nodules in the striatum, internal capsule, white matter, and cerebellum. Circumscribed calcium deposits may also be seen in the thalamus and cerebral cortex. Mild lobar atrophy is common [Wider et al 2009]. * Histologic examination of affected areas shows concentric calcium deposits within the walls of small and medium-sized arteries and, less frequently, veins [Norman & Urich 1960, Cervos-Navarro & Urich 1995]. Droplet calcifications can be observed along capillaries. These deposits may eventually obliterate the lumina of vessels. Multifocal parenchymal mineral deposits may also be present. The pallidal deposits stain positive for iron [Cervos-Navarro & Urich 1995]. Diffuse gliosis may surround the large deposits, but significant loss of nerve cells is rare. Ischemic changes may be present in the basal ganglia, as well as in cortical and subcortical regions [Wider et al 2009]. * On electron microscopy, the mineral deposits appear as amorphous or crystalline material surrounded by a basal membrane. Calcium granules are seen within the cytoplasm of neuronal and glial cells. ### Establishing the Diagnosis The diagnosis of PFBC is established in a proband with: bilateral calcification mainly in the basal ganglia; presence of progressive neurologic dysfunction; and absence of metabolic, infectious, toxic, or traumatic causes. Identification of a heterozygous pathogenic variant in PDGFB, PDGFRB, SLC20A2, or XPR1 (see Table 1) by molecular genetic testing confirms the clinical diagnosis of PFBC. Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Serial single-gene testing should be performed sequentially based on the relative frequency of pathogenic variants of each PFBC-associated gene (see Table 1). Conventionally, sequence analysis of SLC20A2 is performed first, and if no causal variants are identified, sequence analysis of PDGFB, PDGFRB, and then XPR1 is performed, followed by gene-targeted deletion/duplication analysis if no pathogenic variants are found in any of these genes. * A multigene panel that includes PDGFB, PDGFRB, SLC20A2, XPR1, and other genes of interest (see Differential Diagnosis) may be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene varies by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Primary Familial Brain Calcification View in own window Gene 1, 2Proportion of PFBC Attributed to Pathogenic Variants 3 in GeneProportion of Pathogenic Variants 3 Detected by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 PDGFB~11%21/221/22 6 PDGFRB~2%6/6None reported 7 SLC20A2~40%67/747/74 8 XPR1~2%5/5Unknown 9 Unknown 10~46%NA 1\. Genes are listed alphabetically. 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. Variants in these genes have been curated: see PDGFB; PDGFRB; SLC20A2; XPR1. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 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\. Nicolas et al [2014b] identified a PDGFB heterozygous deletion spanning exons 2 to 7 in an affected individual. No data on detection rate of gene-targeted deletion/duplication analysis are available. 7\. No del/dup variants were found in a total of 52 cases screened for CNVs in PDGFRB [Nicolas et al 2014b, David et al 2016, Pasanen et al 2017]. 8\. Pasanen et al [2017] identified one individual with a large SCL20A2 deletion that removes the 5' UTR region, the non-coding exon 1, and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. David et al [2016] identified intragenic deletions of SLC20A2 in four unrelated patients. Baker et al [2014] identified a family with PFBC with a large genomic deletion affecting multiple genes including SLC20A2 and the known dystonia-related gene THAP1. Grütz et al [2016] identified a heterozygous multiexon SLC20A2 deletion in several affected members of a family with PFBC. 9\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 10\. Author, personal laboratory data ## Clinical Characteristics ### Clinical Description Since the first description of primary familial brain calcification (PFBC) [Foley 1951], more than 100 affected kindreds (which further highlight the heterogeneous clinical presentation) have been reported [Manyam et al 2001a, Volpato et al 2009, Ashtari & Fatehi 2010, Batla et al 2017]. The clinical manifestations of PFBC are limited to the nervous system. Most individuals with PFBC are in good health during childhood and young adulthood. Age of onset. Typically, the age of onset is between 30 and 60 years with gradual progression of the movement disorder and neuropsychiatric symptoms. Variability. Age at onset, clinical presentation, and severity of PFBC are variable both between and within families. No correlation has been identified between age of onset, extent of calcium deposits, and neurologic deficits. In some instances, calcifications precede the clinical manifestations by several years [Manyam et al 1992] while there are other reports of young symptomatic individuals with no changes observed on CT scan who only later develop radiologically visible calcifications [Geschwind et al 1999]. The movement disorder often first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping [Manyam et al 1992, Manyam et al 2001b]. Neurologic evaluation generally reveals features similar to those seen in Parkinson disease, with variable combinations of bradykinesia, rigidity, festinating gait, hypophonia, mask-like facies, diminished blinking, dystonia, tremor, choreoathetosis, or dyskinesia. Palmomental and other frontal release signs may be elicited. Pyramidal or cerebellar signs may also be present; in some cases the cerebellar picture predominates. Dystonia is prominent in a few families [Larsen et al 1985]. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild concentration and memory deficits to changes in personality or behavior to psychosis and dementia [Geschwind et al 1999, Benke et al 2004, Shakibai et al 2005, Nicolas et al 2013a]. It has been suggested that those who become symptomatic early in adulthood are more likely to have psychosis. The pattern of dementia includes frequent frontal-executive dysfunction and resembles that occurring in other disorders affecting subcortical structures, including Wilson disease and Huntington disease [Geschwind et al 1999, Benke et al 2004, Modrego et al 2005, Weisman et al 2007]. Although premorbid psychomotor development is generally normal, low IQ and mild delay in motor or intellectual milestones during school age are described. Other * Seizures of various types occur frequently. * Some individuals experience chronic headache and vertigo [Geschwind et al 1999]. * Urinary urgency or incontinence and impotence may be present [Manyam et al 1992]. * Severe hypertension has been reported in two sisters with basal ganglia calcification with no other neurologic or systemic abnormalities [Puvanendran & Wong 1980]. Whether this represents an unusual association, a rare manifestation of PFBC, or a distinct genetic disorder with basal ganglia calcification is unknown. * General medical examination, growth, and facial appearance are normal. Strength and sensation are generally intact. Specifically, no abnormalities are detected in the skull, hands, teeth, nails, or skin, and there is no evidence of a parathyroid disorder. * Neurophysiologic studies are generally normal. ### Genotype-Phenotype Correlations Batla et al [2017] reviewed 137 cases of PFBC published in the literature with a positive genetic test result and characteristic CT scan findings. In these, parkinsonism was more commonly observed in those with SLC20A2 pathogenic variants and headache was more common in those with PDGFB pathogenic variants. Thalamus and dentate nucleus were reported as more frequently involved in association with SLC20A2 pathogenic variants, while only those with PDGFB pathogenic variants were noted to have cysts in the white matter. In addition, the limited number of affected individuals with PDGFRB pathogenic variants showed clinical and radiologic manifestations that are indistinguishable from families with pathogenic variants in SCL20A2 and from affected individuals with no detected pathogenic variants [Nicolas et al 2013b]. ### Penetrance Incomplete and age-related penetrance is reported in PFBC, but the factors that influence clinical manifestations are unknown. The degree of penetrance may depend on whether diagnosis is considered at an anatomic level (presence of calcifications in the brain) or at a clinical level (presence of clinical symptoms). With respect to calcium deposits, analysis of reported pedigrees indicates about 95% penetrance by age 50 years or older. If clinical manifestations are considered, the penetrance is incomplete and may vary between and within families. The precise clinical penetrance has not been fully established for the different PFBC-related genes and pathogenic variants, but it may be around 70% or even lower [Westenberger & Klein 2014]. This figure can be difficult to establish for late-onset slowly progressive neurologic disorders whose symptoms overlap with common traits such as migraine headache, vertigo, and mild psychiatric manifestations including anxiety or depression. No reliable correlations exist between age of onset, extent of calcium deposits, and neurologic deficit. Although most individuals with calcifications eventually develop neurologic dysfunction, the type or severity of clinical symptoms cannot be predicted from the pattern of calcification. ### Anticipation Anticipation has occasionally been observed in kindreds with PFBC [Geschwind et al 1999, Shirahama et al 2010, Maeda et al 2012]. ### Nomenclature Traditionally described as "Fahr's disease," this disorder has been referred to in the literature by about 35 different names [Manyam 2005], with familial idiopathic basal ganglia calcification (FIBGC) being until recently the preferred term. With the identification of the first associated genes, following an autosomal dominant trait, the term "idiopathic" (i.e., calcifications of unknown cause) ceased to be appropriate and was replaced by "primary" (as opposed to calcifications secondary to infectious, inflammatory, toxic, or other causes). Therefore, and because calcium deposits are not limited to the basal ganglia but can also be seen in other brain areas (as described in Suggestive Findings), the designation "primary familial brain calcification" (PFBC) has been proposed. Although the term Fahr's disease is still often used to designate either familial or sporadic basal ganglia calcification, it is unknown whether the nonfamilial cases represent the same disease. The term Fahr's disease is ambiguous and therefore should be avoided. ### Prevalence The prevalence of PFBC is unknown; more than 100 kindreds and sporadic cases have been reported. However, the disorder is probably under-recognized because of insufficient investigation of other family members of individuals presenting with brain calcification. ## Differential Diagnosis ### Parathyroid Disorders Hypoparathyroidism (HP), idiopathic or postsurgical, is the most common cause of symmetric calcification of the basal ganglia [Illum & Dupont 1985]. HP usually begins in childhood or adolescence (i.e., earlier than what is observed in PFBC). In individuals with HP, decreased serum concentration of parathyroid hormone (PTH) results in hypocalcemia and hyperphosphatemia and their clinical manifestations (i.e., tetany, muscle weakness, paresthesia, seizures, cardiac arrhythmias, and cognitive impairment). Additional features include cataracts, renal dysfunction, and increased bone density [Abate & Clarke 2017]. Genetic forms have been described, both syndromic (e.g., 21q and 22q chromosome abnormalities) and nonsyndromic (e.g., pathogenic variants in PTH, GCM2, SOX3, CASR, GNA11). Because treatment of HP may lead to marked clinical improvement, it is important to evaluate individuals with calcification of the basal ganglia for HP. Pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) are the phenotypic spectrum caused by germline inactivating (loss-of-function) GNAS variants (GNAS encodes the alpha subunit of a G-protein involved in signal transduction). PHP and PPHP can occur in the same family. Occasionally, variants of PHP or PPHP may have few or no somatic abnormalities, making diagnosis on clinical grounds difficult. Inheritance is autosomal dominant. See Disorders of GNAS Inactivation. PHP results from end-organ unresponsiveness to PTH. The biochemical hallmarks are hypocalcemia and hyperphosphatemia with an elevated serum concentration of PTH. The average age of onset of PHP is age eight to ten years. Most clinical manifestations are related to hypocalcemia, and thus similar to those in hypoparathyroidism, with intellectual disability being somewhat more common in PHP. Affected individuals may have other manifestations of Albright hereditary osteodystrophy, including short stature, round facies, obesity, soft tissue calcification, short metacarpals or metatarsals, and other hormone resistance, resulting in hypothyroidism and/or hypogonadism. PPHP is characterized by the physical findings of Albright hereditary osteodystrophy with normal serum concentration of calcium and phosphorus and normal response to PTH stimulation. Kenny-Caffey syndrome type 1 (OMIM 244460) is characterized by growth delay, cortical thickening of the long bones, hypocalcemia, hypoparathyroidism, and calcification of the basal ganglia. It is caused by pathogenic variants in TBCE, which encodes a chaperone protein required for proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers [Parvari et al 2002]. Inheritance is autosomal recessive. ### Infectious Diseases Intrauterine or perinatal infection with toxoplasmosis, rubella, cytomegalovirus, or herpes simplex virus may result in calcification of the basal ganglia and dentate nucleus, as well as irregular masses of calcium distributed throughout the brain. Central nervous system (CNS) infection should be considered when clinical onset occurs soon after birth, especially in the presence of chorioretinitis, microcephaly, or neurologic abnormalities. Noncongenital, active viral encephalitis should also be considered in individuals with brain calcifications and no family history [Morita et al 1998]. In HIV/AIDS, either opportunistic infections or inflammatory changes may cause symmetric calcified lesions in the basal ganglia, mostly in children. Bacterial or parasitic infections such as brucellosis, toxoplasmosis, or cysticercosis should be considered, although the appearance and distribution of calcium deposits are generally quite different from PFBC. * Brucellosis. Although cerebral calcification is rare, the detection of basal ganglia calcification in individuals residing in endemic areas should raise the possibility of a CNS brucellar infection. * Toxoplasmosis. The basal ganglia are affected in up to 75% of cases. * Parenchymatous cysticercosis. Calcifications are a manifestation of larval death and are generally rounded, less symmetric, and scattered within the grey matter or grey-white matter junction, sometimes in the basal ganglia or in the deep matter. This diagnostic possibility should be considered in regions where cysticercal infection is common. MRI is more sensitive than CT scan in identifying the parasitic cysts. ### Mitochondrial Disorders Mineral deposits in the basal ganglia and other brain structures are observed in mitochondrial diseases (see Mitochondrial Disorders Overview). Some mitochondrial disorders only affect a single organ (such as the eye in Leber hereditary optic neuropathy), but many involve multiple organ systems and often present with prominent neurologic and myopathic features. Many individuals with mitochondrial abnormalities have a discrete clinical syndrome such as Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, clinical variability is considerable and many do not fit perfectly into a recognized syndrome. ### Inherited Congenital or Early-Onset Syndromes Calcifications in the basal ganglia and other brain structures are observed in several congenital or early-onset syndromes with normal calcium-phosphorus metabolism and are frequently associated with intellectual disability. Cockayne syndrome is an autosomal recessive disorder caused by impaired DNA repair resulting from pathogenic variants in ERCC6 and ERCC8; it is characterized by developmental delay, photosensitivity, retinal degeneration, and deafness. Intracranial calcifications, including of the basal ganglia, are observed in some individuals [Rapin et al 2006]. Aicardi-Goutières syndrome is typically an early-onset encephalopathy characterized by severe intellectual and neuromuscular problems associated with calcification of the basal ganglia (particularly the putamen, globus pallidus, and thalamus), leukodystrophy, cerebral atrophy, and chronic CSF leukocytosis. Seven associated genes have been identified: ADAR, RNASEH2A, IFIH1, RNASEH2B, RNASEH2C, SAMHD1, and TREX1. Inheritance is most frequently autosomal recessive. Immunodeficiency 38 with basal ganglia calcification (OMIM 616126) is an autosomal recessive immune system disorder caused by a deficiency in the interferon-induced protein ISG15 and associated with basal ganglia calcifications [Zhang et al 2015]. Tuberous sclerosis complex involves abnormalities of the skin (hypomelanotic macules, facial angiofibromas, shagreen patches, fibrous facial plaques, ungual fibromas), brain (cortical tubers, subependymal nodules, seizures, intellectual disability/developmental delay), kidney (angiomyolipomas, cysts), and heart (rhabdomyomas, arrhythmias). The cerebral hamartomas may be calcified, however, they are mainly periventricular or subcortical. Two associated genes, TSC1 and TSC2, have been identified. Inheritance is autosomal dominant. Cerebroretinal microangiopathy with calcifications and cysts (OMIM 612199). This autosomal recessive condition, also referred to as Coats plus syndrome, is caused by pathogenic variants in CTC1 [Anderson et al 2012]. The spectrum of neurologic manifestations is complex and includes cognitive deterioration, seizures, spastic tetraparesis, and cerebellar signs. Neuroimaging features are highly characteristic of an encephalopathy with diffuse intracranial calcifications and formation of parenchymal cysts. Affected individuals also have growth retardation, retinal exudates, and skeletal malformations [Linnankivi et al 2006, Briggs et al 2008]. Pantothenate kinase-associated neurodegeneration (PKAN) is a form of neurodegeneration with brain iron accumulation (NBIA). PKAN is characterized by progressive dystonia and basal ganglia iron deposition, with onset that usually occurs before age ten. Commonly associated features include dysarthria, rigidity, and pigmentary retinopathy. About 25% of affected individuals have an "atypical" presentation with later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease. Approximately 50% of individuals with a clinical diagnosis of NBIA have pathogenic variants in PANK2. To date, all individuals with NBIA and "eye-of-the-tiger" sign on T2-weighted MRI have at least one pathogenic variant in PANK2. Inheritance is autosomal recessive. Down syndrome. Reports of basal ganglia calcifications in Down syndrome are abundant [Takashima & Becker 1985]. Other. Additional rare conditions associated with brain calcification include lipoid proteinosis, dyskeratosis congenita, carbonic anhydrase deficiency (OMIM 259730), biotinidase deficiency, tetrahydrobiopterin-deficient hyperphenylalaninemia (OMIM 261630), and hereditary folate malabsorption. ### Adult-Onset Neurodegenerative Conditions Neuroferritinopathy, another form of NBIA, typically presents with progressive adult-onset chorea or dystonia and subtle cognitive deficits. The movement disorder involves additional limbs within five to ten years and becomes more generalized within 20 years. Cognitive deficits, behavioral issues, and dysphagia are major problems with time. The diagnosis of neuroferritinopathy is based on clinical findings, including adult-onset chorea or dystonia, and MRI or CT showing excess iron storage or cystic degeneration in the putamina. FTL is the only gene currently known to be associated with neuroferritinopathy. Inheritance is autosomal dominant. DRPLA (dentatorubral-pallidoluysian atrophy). Bilateral calcification of the globus pallidus has also been reported in a large African American family from North Carolina with DRPLA (referred to as the Haw River syndrome [Burke et al 1994a, Burke et al 1994b]). Affected individuals showed a varied combination of gait ataxia, dysarthria, involuntary movements, seizures, psychosis, and dementia, overlapping with the clinical picture of families with PFBC. The diagnosis of DRPLA was based on positive family history, characteristic clinical findings, and the detection of a CAG repeat expansion in ATN1. Spinocerebellar ataxia type 20 (SCA20) is associated with pronounced cerebellar calcifications affecting the dentate nucleus, typically without involvement of the basal ganglia. Inheritance is autosomal dominant and the disease locus has been mapped to chromosome 11 in a single large family. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL, Nasu-Hakola disease) is characterized by fractures (resulting from polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. Bilateral calcifications of the basal ganglia, most often in the putamina, are commonly observed in CT scans, and may occur before CNS symptoms appear [Paloneva et al 2001]. Variants in TYROBP and TREM2 are known to cause PLOSL. Inheritance is autosomal recessive. Diffuse neurofibrillary tangles with calcification (DNTC, or Kosaka-Shibayama disease [Ukai & Kosaka 2016]) is a rare entity, largely observed in individuals of Japanese descent, characterized by dementia, cortical (temporal or frontotemporal) atrophy, neurofibrillary tangles, and symmetric brain calcifications. Dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is a movement disorder resulting from manganese accumulation in the basal ganglia. This condition results from biallelic loss-of-function variants in SLC30A10. Neuroimaging findings in individuals with this condition may mimic those seen in individuals with PFBC [Quadri et al 2012, Tuschl et al 2012]. ### Other Calcifications of the basal ganglia may result from the following: * Necrosis of neural tissue caused by traumatic, toxic, or physical insults. These include but are not limited to perinatal anoxia, Rh incompatibility, vitamin D and carbon monoxide intoxication, mercury and lead poisoning, exposure to ionizing radiation, and methotrexate therapy. * Systemic lupus erythematosus (SLE). A subset of patients with cerebral lupus can present brain calcifications, which can be extensive [Raymond et al 1996]. * Celiac disease. Although intracranial calcifications have been described, the calcium deposits are mainly occipital. Other neurologic manifestations can include cerebellar ataxia, epilepsy, and peripheral neuropathy. * Normal aging. Calcification of the basal ganglia is an incidental finding in about 0.3%-1.5% of brain CT scans, especially in elderly individuals. Microscopic calcifications can be observed in the globus pallidus and dentate nucleus in up to 70% of autopsy series. These calcifications are generally confined to the globus pallidus and do not have associated clinical findings [Förstl et al 1992]. Basal ganglia calcifications in the elderly have been associated with psychotic symptoms [Ostling et al 2003]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with primary familial brain calcification (PFBC), the following evaluations are recommended: * Thorough neurologic and neuropsychiatric assessment * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations The following are appropriate: * Pharmacologic treatment to improve anxiety, depression, and obsessive-compulsive behaviors * To alleviate dystonia and other associated involuntary movements, pharmacologic therapies as typically used in neurologic practice for the treatment of movement disorders * For urinary urgency or incontinence, oxybutynin or other anticholinergic medications * Antiepileptic treatment for seizures * Symptomatic treatment for headaches ### Surveillance Thorough neurologic and neuropsychiatric assessment is indicated annually. ### Agents/Circumstances to Avoid Neuroleptic medications should be used cautiously, since they may exacerbate extrapyramidal symptoms [Cummings et al 1983]. A poor response to neuroleptics was noted in a family with PFBC and mainly psychotic manifestations [Callender 1995]. Extrapyramidal symptoms may also be elicited or worsened by other drugs (e.g., some antiepileptics, medications to treat vertigo or dizziness). ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. ### Other The response of parkinsonian features to levodopa therapy is generally poor. Manyam et al [2001a] attributed a positive response to levodopa in an affected member of a family with PFBC to the coexistence of PFBC and idiopathic Parkinson disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Primary Familial Brain Calcification	c4324314	30,149	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1421/	2021-01-18T21:02:31	{"synonyms": []}
For a general phenotypic description and a discussion of genetic heterogeneity of preeclampsia, see PEE1 (189800). Mapping Hypothesizing that the genetic background of preeclampsia might show reduced heterogeneity in a founder population such as that of the Kainuu province in central eastern Finland, Laivuori et al. (2003) performed a genomewide scan in 15 multiplex families in that area. They found 2 loci that exceeded the threshold for significant linkage: 2p25, at 21.70 cM (PEE2; 609402), and 9p13 (PEE3), at 38.90 cM. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	PREECLAMPSIA/ECLAMPSIA 3	c0032914	30,150	omim	https://www.omim.org/entry/609403	2019-09-22T16:06:16	{"doid": ["10591"], "mesh": ["D011225"], "omim": ["609403"], "orphanet": ["275555"]}
For the genus of plant, see Distichia (plant). Distichia Distichiae of the upper and lower lid of a dog SpecialtyOphthalmology A distichia is an eyelash that arises from an abnormal part of the eyelid. This abnormality, attributed to a genetic mutation, is known to affect dogs and humans. Distichiae (the abnormal eyelash) usually exit from the duct of the meibomian gland at the eyelid margin. They are usually multiple, and sometimes more than one arises from a duct. They can affect either the upper or lower eyelid and are usually bilateral. The lower eyelids of dogs usually have no eyelashes.[1] Distichiae usually cause no symptoms, because the lashes are soft, but they can irritate the eye and cause tearing, squinting, inflammation, corneal ulcers and scarring.[2] Treatment options include manual removal, electrolysis, electrocautery, CO2 laser ablation,[3] cryotherapy, and surgery. ## Contents * 1 Commonly affected breeds * 2 Ectopic cilia * 3 See also * 4 References * 5 External links ## Commonly affected breeds[edit] In veterinary medicine, some canine breeds are affected by distichiasis more frequently than others: * Cocker Spaniel * Dachshund (especially the miniature longhaired Dachshund) * Bulldog * Pekingese * Yorkshire Terrier * Flat-Coated Retriever * Shetland Sheepdog * Boxer * Poodle[4] ## Ectopic cilia[edit] An ectopic cilia is a special type of distichia usually found in younger dogs. Commonly affected breeds include Poodles, Golden Retrievers, and Shih Tzus.[5] The eyelash exits through the conjunctiva of the eyelid facing toward the eye, usually at the middle of the upper eyelid. It can cause intense pain and corneal ulcers. Treatment is surgery or cryotherapy. ## See also[edit] * Trichiasis * Lymphedema distichiasis ## References[edit] 1. ^ Brooks, Dennis E. (2005). "Ophthalmic Examination Made Ridiculously Simple". Proceedings of the 30th World Congress of the World Small Animal Veterinary Association. Retrieved 2007-02-20. 2. ^ "Eyelids: Conformational Abnormalities". The Merck Veterinary Manual. 2006. Retrieved 2007-02-20. 3. ^ Winkler, Christopher (2020-01-06) [2019]. "There's something in his eye: CO2 surgical lasers for distichia". Aesculight. Retrieved 2020-01-06. 4. ^ Gelatt, Kirk N., ed. (1999). Veterinary Ophthalmology (3rd ed.). Lippincott, Williams & Wilkins. ISBN 0-683-30076-8. 5. ^ Ketring, Kerry I. (2006). "The Top Ten Ophthalmic Mistakes" (PDF). Proceedings of the North American Veterinary Conference. Archived from the original (PDF) on 2007-09-29. Retrieved 2007-02-20. ## External links[edit] Classification D * ICD-10: Q10.3 * ICD-9-CM: 743.63 * OMIM: 126300 * DiseasesDB: 33329 External resources * eMedicine: oph/603 * v * t * e Congenital malformations and deformations of eyes Adnexa Eyelid * Ptosis * Ectropion * Entropion * Distichia * Blepharophimosis * Ablepharon * Marcus Gunn phenomenon Lacrimal apparatus * Congenital lacrimal duct obstruction Globe Entire eye * Anophthalmia (Cystic eyeball, Cryptophthalmos) * Microphthalmia Lens * Ectopia lentis * Aphakia Iris * Aniridia Anterior segment * Axenfeld–Rieger syndrome Cornea * Keratoglobus * Megalocornea Other * Buphthalmos * Coloboma (Coloboma of optic nerve) * Hydrophthalmos * Norrie disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Distichia	None	30,151	wikipedia	https://en.wikipedia.org/wiki/Distichia	2021-01-18T18:32:01	{"icd-9": ["743.63"], "icd-10": ["Q10.3"], "orphanet": ["98600"], "wikidata": ["Q1229478"]}
Geographic tongue A patient with Geographic Tongue SpecialtyDermatology SymptomsBurning sensation (rare) CausesUnknown Diagnostic methodVisual examination Differential diagnosisOral lichen planus, erythematous candidiasis, leukoplakia, glossitis, and chemical burns PreventionNone TreatmentReassurance, time MedicationNone Frequency2-3% DeathsNone Geographic tongue, also known by several other terms,[note 1] a condition of the mucous membrane of the tongue, usually on the dorsal surface. It is a common condition, affecting approximately 2–3% of the general population.[2][7] It is characterized by areas of smooth, red depapillation (loss of lingual papillae) which migrate over time. The name comes from the map-like appearance of the tongue,[8] with the patches resembling the islands of an archipelago.[2] The cause is unknown, but the condition is entirely benign (importantly, it does not represent oral cancer), and there is no curative treatment. Uncommonly, geographic tongue may cause a burning sensation on the tongue, for which various treatments have been described with little formal evidence of efficacy. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 Notes * 8 References * 9 External links ## Signs and symptoms[edit] The appearance of geographic tongue is variable from one person to the next and changes over time. The bottom image shows fissured tongue combined with geographic tongue. It is common for these two conditions to coexist. In health, the dorsal surface of the tongue is covered in tuft-like projections called lingual papillae (some of which are associated with taste buds), which give the tongue an irregular surface texture and a white-pink color. Geographic tongue is characterized by areas of atrophy and depapillation (loss of papillae), leaving an erythematous (darker red) and smoother surface than the unaffected areas. The depapillated areas are usually well-demarcated,[4] and bordered by a slightly raised, white, yellow or grey, serpiginous (snaking) peripheral zone.[9] A lesion of geographic tongue may start as a white patch before the depapillation occurs.[4] In certain cases there may be only one lesion, but this is uncommon;[4] the lesions will typically occur in multiple locations on the tongue and coalesce over time to form the typical map-like appearance. The lesions usually change in shape and size, and migrate to other areas, sometimes within hours.[10] The condition may affect only part of the tongue, with a predilection for the tip and the sides of the tongue,[4] or the entire dorsal surface at any one time. The condition goes through periods of remission and relapse. Loss of the white peripheral zone is thought to signify periods of mucosal healing.[9] There are usually no symptoms other than the unusual appearance of the tongue, but in some cases persons may experience pain or burning, e.g. when eating hot, acidic, spicy or other kinds of foods (e.g. cheese, tomatoes, fruit).[1][10] Where there is a burning symptom, other causes of a burning sensation on the tongue are considered, such as oral candidiasis.[11] ## Causes[edit] The cause is unknown.[1][12][13] Geographic tongue does not usually cause any symptoms, and in those cases where there are symptoms, an oral parafunctional habit may be a contributory factor.[9] Persons with parafunctional habits related to the tongue may show scalloping on the sides of the tongue (crenated tongue). Some suggest that hormonal factors may be involved,[2] because one reported case in a female appeared to vary in severity in correlation with oral contraceptive use.[4] People with geographic tongue frequently claim that their condition worsens during periods of psychologic stress.[9] Geographic tongue is inversely associated with smoking and tobacco use.[12] Sometimes geographic tongue is said to run in families,[2] and it is reported to be associated with several different genes, though studies show family association may also be caused by similar diets. Some have reported links with various human leukocyte antigens, such as increased incidence of HLA-DR5, HLA-DRW6 and HLA-Cw6 and decreased incidence in HLA-B51.[10] Vitamin B2 deficiency (ariboflavinosis) can cause several signs in the mouth, possibly including geographic tongue,[14] although other sources state that geographic tongue is not related to nutritional deficiency.[2] Fissured tongue often occurs simultaneously with geographic tongue,[1] and some consider fissured tongue to be an end stage of geographic tongue.[9] In the past, some research suggested that geographic tongue was associated with diabetes, seborrheic dermatitis and atopy, however newer research does not corroborate these findings.[12] Others suggest allergy as a major factor, e.g. to nickel sulphate.[15] Some studies have reported a link between geographic tongue and psoriasis,[16] although 90% of children who are diagnosed with geographic tongue do not develop psoriasis.[13] Again however, modern research studies do not support any link between psoriasis and geographic tongue.[12] Lesions that are histologically indistinguishable from geographic tongue may also be diagnosed in reactive arthritis (arthritis, uveitis/conjunctivitis and urethritis).[9] ## Diagnosis[edit] The differential diagnosis includes oral lichen planus,[11] erythematous candidiasis,[11] leukoplakia,[11] lupus erythematosus,[10] glossitis,[10] and chemical burns.[2] Atrophic glossitis is usually distinguished from benign migratory glossitis on the basis of the migrating pattern of the lesions and the presence of a whitish border, features which are not present in atrophic glossitis, which instead shows lesions which enlarge rather than migrate.[17] Rarely, blood tests may be required to distinguish from glossitis associated with anemia or other nutritional deficiencies.[10] Since the appearance and the history of the condition (i.e. migrating areas of depapillation) are so striking, there is rarely any need for biopsy.[11] When biopsy is taken, the histopathologic appearance is quite similar to psoriasis: * Hyperparakeratosis. * Acanthosis. * Subepithelial T lymphocyte inflammatory infiltrate. * Migration of neutrophilic granulocytes into the epithelial layer, which may create superficial microabscesses, similar to the Munro's microabscesses described in pustular psoriasis.[9] ### Classification[edit] Geographic tongue could be considered to be a type of glossitis. It usually presents only on the dorsal 2/3 and lateral surfaces of the tongue,[1] but less commonly an identical condition can occur on other mucosal sites in the mouth, such as the ventral surface (undersurface) of the tongue, mucosa of the cheeks or lips, soft palate or floor of mouth; usually in addition to tongue involvement.[11] In such cases, terms such as stomatitis erythema migrans,[11] ectopic geographic tongue,[11] areata migrans,[7] geographic stomatitis,[9] or migratory stomatitis are used instead of geographic tongue. Beside the differences in locations of presentation inside the oral cavity and prevalence among the general population, in all other aspects of clinical significance, symptoms, treatment, and histopathologic appearance, these two forms are identical. This condition is sometimes termed (oral) erythema migrans, but this has no relation to the more common use of the term erythema migrans (erythema chronicum migrans), to describe the appearance of skin lesions in Lyme disease.[10] ## Treatment[edit] Since most cases cause no symptoms, reassuring the person affected that the condition is entirely benign is usually the only treatment.[1] When symptoms are present, topical anesthetics can be used to provide temporary relief. Other medications that have been used to manage the symptoms include antihistamines, corticosteroids or anxiolytics, but these drugs have not been formally assessed for efficacy in geographic tongue.[9] If some foods exacerbate or trigger the symptoms, then cutting these foods out of the diet may benefit.[13] One uncontrolled trial where patients increased zinc intake has shown some benefit in controlling the symptoms of geographic tongue.[4] ## Prognosis[edit] The condition may disappear over time, but it is impossible to predict if or when this may happen.[9] ## Epidemiology[edit] Geographic tongue is a common condition, affecting 2-3% of the adult general population,[1] although other sources report a prevalence of up to 14%.[12] It is one of the most common tongue disorders that occurs in children.[18] The condition often starts in childhood, sometimes at an early age, but others report that the highest incidence occurs in the over 40 age group.[18] Females are sometimes reported to be more commonly affected than males,[1] in a 2:1 ratio,[4] although others report that the gender distribution is equal.[9] ## Notes[edit] 1. ^ Also known as benign migratory glossitis,[1] erythema migrans,[1] erythema migrans lingualis,[2] glossitis areata exfoliativa,[3] glossitis areata migrans, lingua geographica, psoriasiform mucositis, stomatitis areata migrans, wandering rash of the tongue,[4] and transitory benign plaques of the tongue.[5][6] ## References[edit] 1. ^ a b c d e f g h i Kerawala C, Newlands C (editors) (2010). Oral and maxillofacial surgery. Oxford: Oxford University Press. p. 427. ISBN 9780199204830.CS1 maint: extra text: authors list (link) 2. ^ a b c d e f g Mangione, Salvatore (2012). Physical Diagnosis Secrets: With STUDENT CONSULT Online Access. Elsevier. pp. 604–605. ISBN 978-0323112116. Retrieved November 12, 2012. 3. ^ "Geographic Glossitis entry on Medical Subject Headings (MeSH)". National Library of Medicine. Retrieved 19 July 2013. 4. ^ a b c d e f g h Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 677–679. ISBN 978-0721690032. 5. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. p. 800. ISBN 978-0-7216-2921-6. 6. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 7. ^ a b Ship, Jonathan A.; Joan Phelan, and A. Ross Kerr (2003). "Chapter 112: Biology and Pathology of the Oral Mucosa". In Freedberg; et al. (eds.). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. p. 1208. ISBN 0-07-138067-1. 8. ^ Desai, A. B.; Vishwanathan, J. (1989). Textbook Of Paediatrics. India: Orient Blackswan. p. 405. ISBN 978-8125004400. Retrieved November 12, 2012. 9. ^ a b c d e f g h i j k Greenberg, MS; Glick, M; Ship, JA (2008). Burket's oral medicine (11th ed.). Hamilton, Ont.: BC Decker. pp. 103, 104. ISBN 978-1550093452. 10. ^ a b c d e f g Scully, Crispian (2008). Oral and maxillofacial medicine : the basis of diagnosis and treatment (2nd ed.). Edinburgh: Churchill Livingstone. p. 205,206. ISBN 9780443068188. 11. ^ a b c d e f g h Treister NS, Bruch JM (2010). Clinical oral medicine and pathology. New York: Humana Press. pp. 20, 21. ISBN 978-1-60327-519-4. 12. ^ a b c d e Reamy, BV; Derby, R; Bunt, CW (Mar 1, 2010). "Common tongue conditions in primary care". American Family Physician. 81 (5): 627–34. PMID 20187599. 13. ^ a b c Cameron, Peter; Jelinek, George; Everitt, Ian (2006). Tratado de Medicina de Urgencias Pediátricas. Elsevier. p. 365. ISBN 978-0443073489. Retrieved November 12, 2012. 14. ^ Tadataka Yamada; David H. Alpers; et al., eds. (2009). Textbook of gastroenterology (5th ed.). Chichester, West Sussex: Blackwell Pub. p. 2547. ISBN 978-1-4051-6911-0. 15. ^ Minciullo, PL; Paolino, G; Vacca, M; Gangemi, S; Nettis, E (1 September 2016). "Unmet diagnostic needs in contact oral mucosal allergies". Clinical and Molecular Allergy. 14 (1): 10. doi:10.1186/s12948-016-0047-y. PMC 5007719. PMID 27587983. 16. ^ Migratory Glossitis (Geographic Tongue) on Maxillofacialcenter.com Archived 2005-11-24 at the Wayback Machine. 17. ^ Adeyemo, TA; Adeyemo, WL; Adediran, A; Akinbami, AJ; Akanmu, AS (May–Jun 2011). "Orofacial manifestations of hematological disorders: anemia and hemostatic disorders". Indian Journal of Dental Research. 22 (3): 454–61. doi:10.4103/0970-9290.87070. PMID 22048588. 18. ^ a b Rioboo-Crespo Mdel, R; Planells-del Pozo, P; Rioboo-García, R (Nov–Dec 2005). "Epidemiology of the most common oral mucosal diseases in children" (PDF). Medicina Oral, Patologia Oral y Cirugia Bucal. 10 (5): 376–87. PMID 16264385. ## External links[edit] Classification D * ICD-10: K14.1 * ICD-9-CM: 529.1 * MeSH: D005929 External resources * MedlinePlus: 001049 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Geographic tongue	c0017677	30,152	wikipedia	https://en.wikipedia.org/wiki/Geographic_tongue	2021-01-18T18:41:47	{"gard": ["6493"], "mesh": ["D005929"], "umls": ["C0017677"], "wikidata": ["Q1981315"]}
FG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first family diagnosed with the disorder. FG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker. The physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs, and wide first (big) toes. Abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum) are also common. Most affected individuals have constipation, and many have abnormalities of the anus such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, underdeveloped ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures). Additional features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Other health problems have also been reported, including heart defects, seizures, undescended testes (cryptorchidism) in males, and a soft out-pouching in the lower abdomen (an inguinal hernia). ## Frequency The prevalence of FG syndrome is unknown, although several hundred cases have been reported worldwide. Researchers suspect that FG syndrome may be overdiagnosed because many of its signs and symptoms are also seen with other disorders. ## Causes Researchers have identified changes in five regions of the X chromosome that are linked to FG syndrome in affected families. Mutations in a gene called MED12, which is located in one of these regions, appear to be the most common cause of the disorder. Researchers are investigating genes in other regions of the X chromosome that may also be associated with FG syndrome. The MED12 gene provides instructions for making a protein that helps regulate gene activity. Specifically, the MED12 protein forms part of a large complex (a group of proteins that work together) that turns genes on and off. The MED12 protein is thought to play an essential role in development both before and after birth. At least two mutations in the MED12 gene have been found to cause FG syndrome. Although the mutations alter the structure of the MED12 protein, it is unclear how they lead to intellectual disability, behavioral changes, and the physical features associated with this condition. ### Learn more about the genes associated with FG syndrome * CASK * FLNA * MED12 Additional Information from NCBI Gene: * UPF3B ## Inheritance Pattern FG syndrome is inherited in an X-linked recessive pattern. The genes likely associated with this disorder, including MED12, are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually must occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of a gene on the X chromosome, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	FG syndrome	c1845902	30,153	medlineplus	https://medlineplus.gov/genetics/condition/fg-syndrome/	2021-01-27T08:25:18	{"gard": ["2317"], "mesh": ["C537923"], "omim": ["300321", "300406", "300422", "300581", "305450"], "synonyms": []}
Villonodular synovitis is a type of synovial swelling. Types include: * Pigmented villonodular synovitis * Giant cell tumor of the tendon sheath Though they have very different names, they have the same histology, and stain positive for CD68, HAM56, and vimentin.[1] They are sometimes discussed together.[2][3][4] ## References[edit] 1. ^ O'Connell JX, Fanburg JC, Rosenberg AE (July 1995). "Giant cell tumor of tendon sheath and pigmented villonodular synovitis: immunophenotype suggests a synovial cell origin". Human Pathology. 26 (7): 771–5. doi:10.1016/0046-8177(95)90226-0. PMID 7628850. 2. ^ Mackie GC (November 2003). "Pigmented villonodular synovitis and giant cell tumor of the tendon sheath: scintigraphic findings in 10 cases". Clinical Nuclear Medicine. 28 (11): 881–5. doi:10.1097/01.rlu.0000093083.77866.5c. PMID 14578700. 3. ^ Maheshwari AV, Muro-Cacho CA, Pitcher JD (October 2007). "Pigmented villonodular bursitis/diffuse giant cell tumor of the pes anserine bursa: a report of two cases and review of literature". Knee. 14 (5): 402–7. doi:10.1016/j.knee.2007.06.004. PMID 17669658. 4. ^ Murphey MD, Rhee JH, Lewis RB, Fanburg-Smith JC, Flemming DJ, Walker EA (2008). "Pigmented villonodular synovitis: radiologic-pathologic correlation". Radiographics. 28 (5): 1493–518. doi:10.1148/rg.285085134. PMID 18794322. * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte * v * t * e Soft tissue disorders Capsular joint Synoviopathy * Synovitis/Tenosynovitis * Calcific tendinitis * Stenosing tenosynovitis * Trigger finger * De Quervain syndrome * Transient synovitis * Ganglion cyst * osteochondromatosis * Synovial osteochondromatosis * Plica syndrome * villonodular synovitis * Giant-cell tumor of the tendon sheath Bursopathy * Bursitis * Olecranon * Prepatellar * Trochanteric * Subacromial * Achilles * Retrocalcaneal * Ischial * Iliopsoas * Synovial cyst * Baker's cyst * Calcific bursitis Noncapsular joint Symptoms * Ligamentous laxity * Hypermobility Enthesopathy/Enthesitis/Tendinopathy upper limb * Adhesive capsulitis of shoulder * Impingement syndrome * Rotator cuff tear * Golfer's elbow * Tennis elbow lower limb * Iliotibial band syndrome * Patellar tendinitis * Achilles tendinitis * Calcaneal spur * Metatarsalgia * Bone spur other/general: * Tendinitis/Tendinosis Nonjoint Fasciopathy * Fasciitis: Plantar * Nodular * Necrotizing * Eosinophilic Fibromatosis/contracture * Dupuytren's contracture * Plantar fibromatosis * Aggressive fibromatosis * Knuckle pads This article about a disease of musculoskeletal and connective tissue is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	Villonodular synovitis	c0158168	30,154	wikipedia	https://en.wikipedia.org/wiki/Villonodular_synovitis	2021-01-18T18:36:43	{"umls": ["C0158168"], "wikidata": ["Q19001412"]}
Bullous dystrophy, macular type is a genetic disorder characterised by formation of bullae without traumatic origin, alopecia, hyperpigmentation, acrocyanosis, short stature, microcephaly, intellectual deficit, tapering fingers and nail abnormalities. Two families (one of whom was Dutch and the other Italian) have been described up to now, in which only males were affected. Transmission is X-linked recessive. The bullous dystrophy locus has been mapped to Xq26.3 in the Italian family and to Xq27.3 in the Dutch 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	Hereditary bullous dystrophy, macular type	c0795974	30,155	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1867	2021-01-23T18:02:41	{"gard": ["1038"], "mesh": ["C563065"], "omim": ["302000"], "umls": ["C0795974"], "icd-10": ["Q81.8"]}
Reinke's edema Other namesReinke's oedema,[1] polypoid degeneration, polypoid corditis, edematous hyptertrophy Reinke's edema SpecialtyOtorhinolaryngology Reinke's edema is the swelling of the vocal cords due to fluid (edema) collected within the Reinke's space.[2] First identified by the German anatomist Friedrich B. Reinke in 1895, the Reinke's space is a gelatinous layer of the vocal cord located underneath the outer cells of the vocal cord.[3][4] When a person speaks, the Reinke's space vibrates to allow for sound to be produced (phonation). The Reinke's space is sometimes referred to as the superficial lamina propria.[5] Reinke's edema is characterized by the "sac-like" appearance of the fluid-filled vocal cords.[6] The swelling of the vocal folds causes the voice to become deep and hoarse. Therefore, the major symptom of Reinke's edema is a hoarseness similar to laryngitis. The major cause associated with Reinke's edema is smoking. In fact, 97% of patients diagnosed with Reinke's edema are habitual smokers. Other identified risk factors include overuse of the vocal cords, gastroesophageal reflux, and hypothyroidism.[7] The disease is more often cited in women than in men, because lower voice changes are more noticeable in women.[2][4][7] The first cases of Reinke's edema were recorded in 1891 by M. Hajek,[8] followed by F. Reinke in 1895. In his investigations, Reinke injected a stained glue into the superficial lamina propria (Reinke's space) to mimic edema.[9] Reinke's edema is considered to be a benign (non-cancercous) polyp (protrusion) that represents 10% of all benign laryngeal pathologies.[4] Treatment of Reinke's edema starts with the elimination of associated risk factors, such as smoking, gastric reflux, and hypothyroidism. Advanced cases may undergo phonosurgery to remove the fluid from the vocal cords.[7] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 Research * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] List of common symptoms: * "sac-like" appearance of the vocal folds[6] * Hoarseness and deepening of the voice[10] * Trouble speaking (Dysphonia)[7] * Reduced vocal range with diminished upper limits[7] * Stretching of the mucosa (Distension)[2] * Shortness of breath (Dyspnoea)[11] Reinke's edema is characterized by a "sac-like" appearance of the vocal folds.[6] The edema is a white translucent fluid that causes a bulging (distension) of the vocal cord.[2][12] The most common clinical symptom associated with Reinke's edema is an abnormally low pitched voice with hoarseness. The low pitch voice is a direct result of increased fluid in the Reinke's space, which vibrates at a lower frequency than normal (females <130 Hz; males <110 Hz).[10] Hoarseness is a common problem of many laryngeal diseases, such as laryngitis. It is described as a harsh and breathy tone of voice. Hoarseness is often seen alongside dysphonia, a condition in which the individual has difficulty speaking.[7] The swelling of the vocal cords and the lowering of the voice are warning signs that an individual has Reinke's edema. At the microscopic level, an examination of the vocal cords in patients with Reinke's edema will show lowered levels of collagen, elastin, and extracellular matrix proteins.[4] These characteristics can be used to diagnose Reinke's edema. Reinke's edema is considered a benign polyp that may become precancerous if smoking is involved.[12] An indicator of cancer is the development of leukoplakia, which manifests as white patches on the vocal folds.[7] Smoking, gastric reflux, and hypothyroidism are all risk factors for Reinke's edema. The symptoms of Reinke's edema are considered to be chronic symptoms because they develop gradually over time and depend on how long the individual is exposed to the risk factor. In the case of smoking, as long as the individual continues the habit of smoking, the Reinke's edema will continue to progress. This is true for other risk factors as well, such as untreated gastric reflux and overuse of the voice, which is common to professions such as singers and radio announcers.[2][4][7] ## Causes[edit] Smoking is the number one cause of Reinke's edema. Other factors include gastroesophageal reflux, hypothyroidism and chronic overuse of the voice. Smoking is the only risk factor that may lead to cancer.[7] Additionally, the combination of several risk factors increase the likelihood of an individual developing Reinke's edema. For example, an individual who smokes and also has gastric reflux would have an increased susceptibility for developing Reinke's edema over time.[4] Reinke's edema is commonly diagnosed in middle-aged females with a history of smoking (aged 50 years or older). Because males have lower pitched voices than females, males are less likely to observe a significant changes in the voice, and are therefore less likely to seek treatment. Females also report more physical discomfort due to Reinke's edema. The risk of Reinke's edema increases with age and also with prolonged exposure to smoking. Additionally, individuals in professions that require constant use of the voice, such as singers, teachers, and radio hosts, may be at an increased risk for developing the disease.[11] Because the disease is heavily linked to smoking, there is no established way to screen for Reinke's edema. Similarly, the only way to prevent Reinke's edema is to avoid smoking. By adopting a non-smoking lifestyle after being diagnosed with Reinke's edema, it is possible to stop the disease's progression, although it is not possible to reverse it. Therefore, it is critical to maintain a non-smoking lifestyle even after surgery, because the fluid can re-emerge. In fact, in many cases surgeons will not perform surgery without the guarantee that the individual will stop smoking.[7] ## Mechanism[edit] The movement of the vocal folds during speech The vocal cords consist of five layers of cells: * Squamous epithelium * Superficial lamina propria (Reinke's space) * Intermediate lamina propria * Deep lamina propria * Vocalis muscle In order for humans to produce sound for speech, the vocal folds must readily vibrate. The two layers of the vocal cords that vibrate are the Reinke's space and the overlying epithelium. In fact, these layers move freely over the more rigid intermediate and deep lamina proprias.[7] Accumulation of fluid within the Reinke's space alters the elasticity of the vocal cord, making it less stiff and more gelatinous. This slows the vocal cord vibration, which results in a deepened and hoarse voice. Because men normally have a lower voice than women, the change is more noticeable in women.[11] Edema usually occurs on both vocal cords. This is known as bilateral Reinke's edema.[7] The pathophysiology or mechanism of Reinke's edema is not well known, however, chemicals contained within cigarette smoke are associated with an increased vascular permeability of blood vessels, which results in fluid leaking into the Reinke's space. Normally, the vocal cords are surrounded by neatly aligned blood vessels, however, these blood vessels can become disarranged and fragile in Reinke's edema.[13] In addition, cigarette smoke can create reactive oxygen species that alter the environment of the vocal cords. Tissue analysis of Reinke's edema shows decreased amounts of the proteins fibronectin, elastin, collagens I and III, and extracellular matrix proteins. This leads to an overall decreased stiffness of the tissue layer, which vibrates more slowly and produces a deeper sounding voice.[2][4] The progression of Reinke's edema is gradual and is directly related to the duration of exposure to risk factors, such as smoking and gastric reflux.[2] Disease progression is divided into two types: "pale" and "livid". The “pale” type of Reinke's edema is defined by a glazed appearance of the vocal cords with a clear (colorless) fluid underneath. This represents the early stage of the disease. The advanced “livid” type of Reinke's edema is identified by an increased amount of fluid, accompanied by a color change from colorless to yellow-grey.[2] The swelling of the vocal folds cause ballooned-like appearance, known as a polyp. The polyps of Reinke's edema are usually benign, however, there may be a risk of cancer if the patient is a smoker. Additionally, if the edema becomes too severe, patients may experience difficulty breathing due to blockage of the airway.[2][10] ## Diagnosis[edit] Rigid laryngoscope instrument Reinke's edema is often diagnosed by an Ear, Nose & Throat (ENT) specialist or an Otolaryngologist by examination of the vocal cords. First, the doctor will review the patient's medical history and symptoms, such as hoarseness, dysphonia, and reduced vocal range. There is no familial or hereditary link to Reinke's edema. Because Reinke's edema is linked heavily to smoking, the doctor will need to know if the patient is a habitual smoker. Once the patient's history is reviewed, the vocal cords will be visualized using laryngoscopy, a technique in which a tube with a camera (endoscope) is passed through the nose and down the larynx.[10][14] Laryngoscopes can be rigid or flexible. Flexible laryngoscopes, such as fiber laryngoscopes, allow the patient to produce sound as the tube is placed, and therefore allows the doctor to visualize movement of the vocal cord.[14] The use of rigid laryngoscopes generally requires general anaesthesia due to the discomfort involved in distracting the soft tissues of the mouth and pharynx. Based on the results of the laryngoscopy, Reinke's edema can be classified using a standardized system set in place by Yonekawa. This system characterizes the disease based disease severity.[10] Yonekawa Classification:[10] * Grade I – Lesions contact the anterior third of the vocal fold * Grade II – Lesions contact the anterior two-thirds of the vocal fold * Grade III – Lesions contact the entirety of the vocal fold If further evaluation is needed, stroboscopy is used to examine mucosal waves of the vocal cords. Mucosal waves describe the waves produced by vibration of the vocal cords during speech. Stroboscopes produce flashes of light that are timed to the patient's vocal frequency. Every time the light is flashed, it will create a still frame image of the vocal cords at that particular moment in time. These are combined to produce an image of the wave. In the case of Reinke's edema, structural changes to the vocal cords will result in abnormal wave patterns.[15] ## Treatment[edit] The first step in treating Reinke's edema is to eliminate or control those risk factors that are causing the disease. This includes the cessation of smoking, the control of gastric reflux using antacids and/or Proton Pump Inhibitors (PPIs), and the discontinuation of activities that cause vocal distress.[4] Those experiencing a hoarseness of the voice may choose to undergo voice therapy to improve the voice's quality and range.[2][4] Most cases of Reinke's edema are caused by the long term usage of cigarettes. In this case, it is important to make lifestyle changes to stop smoking. While this will not resolve or improve the edema, the cessation of smoking will halt the disease's progression.[7] If the elimination of risk factors is not sufficient to improve the patient's symptoms, surgery may be required. The most common type of surgery performed today for Reinke's edema is called surgical microlaryngoscopy. Most procedures follow the microflap technique set in place by Hirano.[7][10] During surgery, an incision is made into the vocal cord using either microscissors or a CO2 laser. A flap of mucosa is lifted and the affected tissue is removed using suction or a microdebrider. The flap is then re-draped and trimmed to the appropriate size.[7] Most cases of Reinke's Edema are bilateral - effecting both vocal cords - rather than unilateral. In the case of bilateral edema, the surgeon must choose whether to operate each side of the vocal cord in two separate surgeries or to operate both sides in a single surgery.[7] The complication associated with removing tissue from both sides in a single surgery is that the raw, cut ends of the vocal cords may form an anterior glottis web, in which the two sides grow together in a continuous sheet.[4][7] Other complications of surgery include tissue scarring due to damage to the vocal ligament during the incision and vocal cord stiffening due to over-suctioning of the superficial lamina propria (Reinke's space).[10] While surgical microlarynscopy has its associated risks, if left untreated, Reinke's edema can lead to a variety of long-term complications. Besides dysphonia (impaired speech), the most serious of these complications is airway obstruction due to severe inflammation of the vocal cords. The risk of complications has decreased drastically with the creation of new tools, such as the CO2 laser for surgical microlaryngoscopy. Before the Hirano microflap method was developed in 1895,[dubious – discuss] vocal stripping was the most common procedure used to correct Reinke's Edema. Vocal stripping was often performed without magnification and with a monocular laryngoscope, instead of a binocular scope. This led to major complications such as vocal ligament scarring. Women are more likely than men to undergo surgery due to a greater change in vocal pitch and quality. Surgery is capable of restoring the voice, with the condition that smoking is not resumed after surgery. Post-operative voice therapy is also advised to restore the voice's strength. Reinke's edema is not a fatal pathology unless the tissue becomes precancerous.[10] ## Research[edit] Recent studies have examined the role of specific cell types in Reinke's edema, including the role of vocal cord fibroblasts. In normal tissue, these spindle-shaped CD34+ fibroblasts produce extracellular matrix proteins such as collagen and elastin. Recent findings have shown a morphological change in fibroblasts extracted from the tissue of Reinke's edema to a more dendritic-like shape with several protrusions. Large populations of these altered CD34+ fibroblasts have been found surrounding the areas of edema. They lack normal expression of several Cluster Differentiation (CD) proteins and express additional proteins that are not expressed in normal vocal cord fibroblasts.[16] Furthermore, cigarette smoke was discovered to increase COX-2 and PGE2 expression in fibroblasts, which could indicate the role of cigarette smoke in Reinke's edema.[17] While smoking is a clear risk factor to Reinke's edema, other risk factors are being identified to explain Reinke's edema in nonsmokers. Research has suggested the role of bacterial colonies in non-neoplastic lesions such as Reinke's edema. Using pyrosequencing, strains of S. pseudopneumoniae were found as the dominant bacterial strain across most non-neoplastic lesions. Of all the sequences analyzed, streptococcus represented 72.9% of bacteria found within these lesions. While smoking, gastric reflux, and vocal abuse have been more widely agreed upon in literature as risk factors for Reinke's edema, the altered bacterial cultures could be developed as a diagnostic tool in the future.[18] The majority of the research within the last ten years focuses on improving surgery for Reinke's edema. Due to the importance of the Reinke's space in speech, it is important that minimally invasive techniques be perfected that minimize the risk of complications. The CO2 laser has been successfully incorporated into the surgical technique, however, there are several other lasers being investigated for use in Reinke's edema. These include photoangiolytic lasers[19] and potassium titanyl phosphate lasers.[20] ## See also[edit] * List of voice disorders * Histology of the Vocal Folds ## References[edit] 1. ^ 'Oedema' is the standard form defined in the Concise Oxford English Dictionary (2011), with the precision that the spelling in the United States is 'edema'. 2. ^ a b c d e f g h i j Rubin, John (2014). Diagnosis and Treatment of Voice Disorders. Plural Publishing. p. 104. ISBN 978-1-59756-644-5. 3. ^ F. B. Reinke. Untersuchungen über das menschliche Stimmband. Fortschritte der Medizin, München, 1895, 13: 469-478. 4. ^ a b c d e f g h i j Goswami, Saileswar (2003). "A Clinico-pathological Study of Reinke's Oedema". Indian Journal of Otolaryngology and Head & Neck Surgery. 55 (3): 160–5. doi:10.1007/BF02991943 (inactive 2021-01-16). PMC 3451126. PMID 23119968.CS1 maint: DOI inactive as of January 2021 (link) 5. ^ Hirano, M (1976). "An improvement in surgical treatment for polypoid vocal cord: sucking technique". Otologia (Fukuoka). 22 (5): 583–9. 6. ^ a b c Altman MD, PhD, Ken W. (2002). "The Center for Voice @ Northwestern". Benign Vocal Lesions - Nodules, Polyps, Cysts. Archived from the original on 2007-08-17. Retrieved 24 October 2015. 7. ^ a b c d e f g h i j k l m n o p q Rosen, Clark (2009). Operative Techniques in Laryngology. Springer-Verlag Berlin Heidelberg. p. 113. ISBN 978-3-540-25806-3. 8. ^ Hajek, M. (1891). "Anatomische Untersuchungen über das Larynxödem". Langenbecks Arch Chir. 9. ^ Tillmann, B. (1995). "Morphological studies on the pathogenesis of Reinke's edema". Eur Arch Otorhinolaryngol. 252 (8): 469–74. doi:10.1007/BF02114753. PMID 8719588. S2CID 10032256. 10. ^ a b c d e f g h i Zeitels, Steven (2002). "Management of common voice problems: Committee report". Otolaryngology–Head and Neck Surgery. 126 (4): 333–348. doi:10.1067/mhn.2002.123546. PMID 11997771. S2CID 26308857. 11. ^ a b c Verdolini, Katherine (2014). Classification Manual for Voice Disorders-I. Psychology Press. p. 55. ISBN 978-0-8058-5631-6. 12. ^ a b Martins, Regina Helena Garcia (2009). "Is Reinke's Edema a Precancerous Lesion? Histological and Electron Microscopic Aspects". Journal of Voice. 23 (6): 721–725. doi:10.1016/j.jvoice.2008.03.001. PMID 18619781. 13. ^ Jovanovic, Milan (2007). "Contact Telescopy Reveals Blood Vessel Alterations of Vocal Fold Mucosa in Reinke's Edema". Journal of Voice. 21 (3): 355–360. doi:10.1016/j.jvoice.2006.01.004. PMID 16564676. 14. ^ a b "The Voice Foundation". Diagnosis. Elsevier Health Science. 2015. Retrieved 17 October 2015. 15. ^ Krausert, Christopher R (2011). "Mucosal Wave Measurement and Visualization Techniques". J Voice. 25 (4): 395–405. doi:10.1016/j.jvoice.2010.02.001. PMC 2976773. PMID 20471798. 16. ^ Diaz-Flores, Lucio (2014). "CD34-Positive Fibroblasts in Reinke's Edema". Laryngoscope. 124 (3): E73–E80. doi:10.1002/lary.24407. PMID 24115077. S2CID 206201456. 17. ^ Branski, Ryan C. (2011). "The Effects of Cigarette Smoke Condensate on Vocal Fold Transepithelial Resistance and Inflammatory Signaling in Vocal Fold Fibroblasts". Laryngoscope. 121 (3): 601–605. doi:10.1002/lary.21388. PMC 3132796. PMID 21298639. 18. ^ Hanshew, Alissa S. (2014). "Characterization and comparison of bacterial communities in benign vocal fold lesions". Microbiome. 2: 43. doi:10.1186/2049-2618-2-43. PMC 4323261. PMID 25671105. 19. ^ Koszewski, IJ (2015). "Office-Based Photoangiolytic Laser Treatment of Reinke's Edema: Safety and Voice Outcomes". Otolaryngol Head Neck Surg. 152 (6): 1075–81. doi:10.1177/0194599815577104. PMID 25820581. S2CID 20506230. 20. ^ Young, VN (2015). "Analysis of Potassium Titanyl Phosphate Laser Settings and Voice Outcomes in the Treatment of Reinke's Edema". Ann Otol Rhinol Laryngol. 13 (3): 972–7. doi:10.1177/0003489414549155. PMID 5169585. S2CID 10895483. Notes * "Benign Vocal Lesions - Nodules, Polyps, Cysts". The Center for Voice at Northwestern University. Archived from the original on August 17, 2007. Retrieved July 24, 2007. ## External links[edit] Classification D * ICD-10: J38.4 * ICD-9-CM: 478.6 * DiseasesDB: 32572 Wikimedia Commons has media related to Reinke's edema. * "Illustration of Reinke's Edema". The Center for Voice at Northwestern University. Archived from the original on August 17, 2007. Retrieved July 24, 2007. * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis 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Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	Reinke's edema	c0472519	30,156	wikipedia	https://en.wikipedia.org/wiki/Reinke%27s_edema	2021-01-18T18:39:45	{"icd-9": ["478.6"], "icd-10": ["J38.4"], "wikidata": ["Q786896"]}
A rare, genetic, non-syndromic, developmental defect during embryogenesis malformation syndrome characterized by a congenital, non-progressive, occipitofrontal head circumference that is 2 or more standard deviations below the mean for age, gender and ethnicity which is associated with normal brain architecture and uncomplicated by other abnormalities. Borderline to moderate intellectual disability, as well as early psychomotor delay, may or may not 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	Autosomal dominant primary microcephaly	c0220693	30,157	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2514	2021-01-23T17:04:25	{"gard": ["3605"], "mesh": ["C537323"], "omim": ["156580", "616311"], "umls": ["C0220693"], "icd-10": ["Q02"]}
Water mold disease Crayfish plague Mycelial filaments from Aphanomyces astaci on membranes of Pacifastacus leniusculus Scientific classification Clade: SAR Phylum: Oomycota Order: Saprolegniales Family: Leptolegniaceae Genus: Aphanomyces Species: A. astaci Binomial name Aphanomyces astaci Schikora, 1906 [1] Crayfish plague (Aphanomyces astaci) is a water mold that infects crayfish, most notably the European Astacus which dies within a few weeks of being infected. When experimentally tested, species from Australia, New Guinea and Japan were also found to be susceptible to the infection.[2] ## Contents * 1 History * 2 Transmission * 3 Signs * 4 References * 5 External links ## History[edit] Crayfish plague first arrived in Europe in Italy in 1859, either with imported crayfish from North America,[3] or in ballast water discharge.[4] After its original introduction in Italy in 1860, it spread quickly through Europe and was discovered in Sweden in 1907, in Spain in 1972, in Norway in 1971, in Great Britain in 1981, in Turkey in 1984 and in Ireland in 1987. In 1959, to bolster dwindling stocks of native crayfish, the signal crayfish was introduced to Sweden.[3] The signal crayfish was known to be resistant, and it was not recognised at that time that it was a carrier of the disease.[3] After 150 years of contact, no resistance has been discovered in native European crayfish.[5] This species was studied and named by the German Mycologist Friedrich Schikora (1859–1932), from a type specimen in Germany in 1906. ## Transmission[edit] Signal crayfish, rear view, from Grand Union Canal near its inflow/overflow with the River Nene. Implantations of the signal crayfish were the reason for the spread of the disease to United Kingdom and Ireland. Transport of signal crayfish, red swamp crayfish and infected native European freshwater crayfish between waters is the main cause for contamination. Transmission of the disease through items that has been in contact with contaminated water, such as a fishing tool or footwear, is also possible.[6] The spores are also sensitive to high or low temperatures. Most authorities have local rules and regulations that the amount of water moved between different waters (in for example a boat) is minimised. It is usually also recommended to only use fishing bait from the same lake when fishing, alternatively freeze it to at least −10 °C (14 °F) for one day before use, if risk for contamination exists. The spores of crayfish plague disappear from an infected water system (connected lakes and rivers) in a few weeks after the last infected crayfish is gone.[6] Reintroduction is then possible, as long as no infected waters are in contact with the lake. ## Signs[edit] Infection with Aphanomyces astaci is accompanied by few signs in its early stages, and the first indication of infection may be mortality.[7] In the later stages, the muscles of the tail may appear whitened, or brownish-red where blood cells have encapsulated the hyphae. The effects of the neurotoxins in the oomycete can include appearing in daytime (crayfish are typically nocturnal) and a lack of coordination.[7] ## References[edit] 1. ^ Paul Kirk (2010). "Aphanomyces astaci Schikora, 1906". World Register of Marine Species. Retrieved June 29, 2011. 2. ^ Susan M. Bower (June 28, 2006). "Crayfish plague (fungus disease)". Synopsis of Infectious Diseases and Parasites of Commercially Exploited Shellfish. Fisheries and Oceans Canada. Archived from the original on December 12, 2008. Retrieved June 29, 2011. 3. ^ a b c Christian Nellemann & Emily Corcoran, ed. (2010). "Restoration of a depleted crayfish fishery in Europe – lessons learnt". Dead Planet, Living Planet: Biodiversity and Ecosystem Restoration for Sustainable Development (PDF). UNEP / Earthprint. pp. 90–91. ISBN 978-82-7701-083-0. 4. ^ Kei Westman (2002). "Alien crayfish in Europe: negative and positive impacts and interactions with native crayfish". In Erkki Leppäkoski, Stephan Gollasch & Sergej Olenin (ed.). Invasive Aquatic Species of Europe: Distribution, Impacts, and Management. Springer. pp. 76–95. ISBN 978-1-4020-0837-5. 5. ^ David Alderman (December 18, 2006). "Aphanomyces astaci" (PDF). Delivering Alien Invasive Species Inventories for Europe. Archived from the original (PDF) on September 24, 2015. Retrieved June 29, 2011. 6. ^ a b "Crayfish plague". Environment Agency. June 2, 2011. Archived from the original on September 21, 2008. Retrieved June 29, 2011. 7. ^ a b Nicky Buller (September 2008). "Crayfish Plague" (PDF). Australia and New Zealand Standard Diagnostic Procedure. Sub-Committee on Animal Health Laboratory Standards. Archived from the original (PDF) on 2015-03-11. Retrieved 2015-06-26. ## External links[edit] * "Crayfish plague". Environment Agency. June 2, 2011. * Global Invasive Species Database * Canadian Fisheries and Oceans Crayfish Plague information * Trade Environment Database Case Study on Crayfish Plague * v * t * e Diseases of crustaceans * Bitter crab disease * Crayfish plague * Gaffkaemia * Infectious hypodermal and haematopoietic necrosis * Necrotising hepatopancreatitis * Paragonimiasis * Taura syndrome * White spot syndrome * Yellowhead disease Taxon identifiers * Wikidata: Q2858203 * Wikispecies: Aphanomyces astaci * EoL: 133454 * EPPO: APHAAS * Fungorum: 118727 * GBIF: 3202936 * GISD: 107 * iNaturalist: 209110 * IRMNG: 11247906 * ISC: 93177 * ITIS: 13861 * NBN: BMSSYS0000001544 * NCBI: 112090 * WoRMS: 394837 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Crayfish plague	None	30,158	wikipedia	https://en.wikipedia.org/wiki/Crayfish_plague	2021-01-18T19:09:35	{"wikidata": ["Q602370"]}
## Description Chiari malformation type II (CM2), also known as the Arnold-Chiari malformation, consists of elongation and descent of the inferior cerebellar vermis, cerebellar hemispheres, pons, medulla, and fourth ventricle through the foramen magnum into the spinal canal. CM2 is uniquely associated with myelomeningocele (open spina bifida; see 182940) and is found only in this population (Stevenson, 2004). It is believed to be a disorder of neuroectodermal origin (Schijman, 2004). For a general phenotypic description of the different forms of Chiari malformations, see Chiari malformation type I (CM1; 118420). Clinical Features Lindenberg and Walker (1971) described the Arnold-Chiari malformation in 2 successively born daughters of nonconsanguineous parents. Both children had associated hydrocephalus and lumbar meningomyelocele. In a review, Stevenson (2004) noted that CM2 is associated with polygyria, partial or complete agenesis of the corpus callosum, subnormal intelligence, ventricular abnormalities, and hydrocephalus. Symptoms in infants include inspiratory stridor, prolonged expiratory apnea with cyanosis, neurogenic dysphagia, and feeding difficulties. Other features include hypotonia, opisthotonus, nystagmus, and weak cry. Older children may experience upper extremity weakness, spasticity, ataxia, and occipital headache. Syringomyelia (186700) may also be present. History The term 'Chiari malformation' is used in recognition of the work of Hans van Chiari, a Viennese pathologist who practiced medicine in Vienna, Prague, and Strasbourg in the late 19th century. Chiari (1891) described a 17-year-old woman with elongation of the cerebellar tonsils and medulla into the spinal cord, what is now referred to as the Chiari type II malformation. However, the Chiari II malformation was probably first described by Cleland (1883) in a child with spina bifida, hydrocephalus, and anatomic alterations of the cerebellum and brainstem (Stevenson, 2004). Arnold (1894) described a single patient with myelomeningocele and herniation of the cerebellum into the cervical canal. Animal Model Using Cre-recombinase-activated markers in transgenic mice, Matsuoka et al. (2005) mapped a cryptic neural crest-mesoderm boundary inside the neck and shoulder girdle skeleton in which cellular distributions of neural crest and mesoderm correspond precisely to muscle attachment scaffolds to the shoulder girdle. The study challenged the 'ossification model' and corroborated the 'scaffold model' of vertebrate neck and shoulder evolution. The skeleton that Matsuoka et al. (2005) identified as neural crest-derived is specifically affected in human Klippel-Feil syndrome (118100), Sprengel deformity (184400), and Arnold-Chiari malformation. Loss or dysplasia of post-otic neural crest (PONC)-derived basicranial (clivus) bone attachments for the internal pharynx and larynx constrictors and ensuing widening of the foramen magnum are the primary mechanical cause of the Arnold-Chiari malformation. In this case PONC respecification from endochondral attachment bone to connective tissue is the likely cause of cryptic basicranial instability and early death. INHERITANCE \- Multifactorial HEAD & NECK Eyes \- Nystagmus RESPIRATORY \- Inspiratory stridor \- Expiratory apnea with cyanosis ABDOMEN Gastrointestinal \- Dysphagia \- Choking \- Poor feeding NEUROLOGIC Central Nervous System \- Herniation and elongation of the cerebellar tonsils, cerebellar vermis, brainstem, and fourth ventricle through the foramen magnum \- Small, thin cerebellum \- Absent cisterna magna \- Polygyria \- Ventricular anomalies \- Partial or total agenesis of the corpus callosum (33%) \- Hypotonia \- Opisthotonos \- Bulbar signs \- Heterotopias \- Cervical myelopathy \- Upper limb weakness \- Spasticity \- Ataxia \- Headache, occipital \- Subnormal intelligence (62%) \- Hydrocephalus \- Open spina bifida (myelomeningocele, 182940 ) \- Associated with syringomyelia ( 186700 ) MISCELLANEOUS \- Symptom onset at birth or infancy Arnold-Chiari type II is uniquely associated with myelomeningocele ( 182940 ) ▲ 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	CHIARI MALFORMATION TYPE II	c0003803	30,159	omim	https://www.omim.org/entry/207950	2019-09-22T16:30:51	{"mesh": ["D001139"], "omim": ["207950"], "icd-10": ["Q07.0"], "orphanet": ["1136"], "synonyms": ["Alternative titles", "CM2", "ARNOLD-CHIARI MALFORMATION"]}
Koilonychia Other namesSpoon nails Koilonychia SpecialtyDermatology Koilonychia, also known as spoon nails,[1]:782 is a nail disease that can be a sign of hypochromic anemia, especially iron-deficiency anemia.[2]:656[3] It refers to abnormally thin nails (usually of the hand) which have lost their convexity, becoming flat or even concave in shape. In a sense, koilonychia is the opposite of nail clubbing. In early stages nails may be brittle and chip or break easily. Koilonychia is associated with Plummer–Vinson syndrome and iron deficiency anemia. It has also been associated with lichen planus, syphilis, and rheumatic fever. The term is from the Greek: κοῖλος, koilos, "hollow", ὄνυξ, onyx, "nail". Even though Koilonychia has been associated with iron deficiency in case reports, it is more likely seen as an occupational change in nails and may be idiopathic; ruling out iron deficiency anemia in these patients is the only work-up necessary in this condition.[4] ## See also[edit] * Kyrle disease * 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. 2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 3. ^ Kumar, Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005. Saunders. 4. ^ Rich P. Stratman E, Corona R (eds.). "Overview of nail disorders". UpToDate. Waltham MA. Retrieved April 27, 2020. ## External links[edit] Classification D * ICD-10: L60.3, Q84.6 * ICD-9-CM: 703.8, 757.5 * DiseasesDB: 7207 External resources * MedlinePlus: 003247 * DermAtlas 1726262099 * v * t * e Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia * v * t * e Congenital malformations and deformations of skin appendages Nail disease * Anonychia * Leukonychia * Pachyonychia congenita/Onychauxis * Koilonychia Hair disease * hypotrichosis/abnormalities: keratin disease * Monilethrix * IBIDS syndrome * Sabinas brittle hair syndrome * Pili annulati * Pili torti * Uncombable hair syndrome * Björnstad syndrome * Giant axonal neuropathy with curly hair * hypertrichosis: Zimmermann–Laband syndrome 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	Koilonychia	c0221261	30,160	wikipedia	https://en.wikipedia.org/wiki/Koilonychia	2021-01-18T18:54:46	{"umls": ["C0221261", "C3840868"], "icd-9": ["757.5", "703.8"], "icd-10": ["L60.3", "Q84.6"], "wikidata": ["Q968206"]}
## Description Macrostomia is a congenital defect resulting from persistent lateral facial clefts, caused by failure of the maxillary and mandibular portions of the first branchial arch to unite normally. Macrostomia is a rare anomaly, with an estimated incidence of 1 in 150,000 to 300,000 births and is most often associated with other anomalies. Unilateral macrostomia is more common than bilateral (summary by Hawkins et al., 1973). Clinical Features Hawkins et al. (1973) reported a 9-month-old girl with isolated bilateral macrostomia who underwent successful repair at 5 months of age. There was no history of medication, illness, or nutritional deficiency during early pregnancy, and no family history of congenital anomalies. Gleizal et al. (2007) reviewed 90 reported cases of congenital macrostomia over the previous 50 years. Unilateral macrostomia was seen in 70 (80%) of the cases, and 62 (89%) of those were associated with other facial deformities such as ear anomalies, preauricular tags, and mandibular dysplasia. Analysis of the 20 reported cases of bilateral macrostomia, 14 of which had been previously published (see, e.g., McCarthy and West, 1977 and 200110), revealed that 12 (60%) were isolated and 4 (20%) were associated with bilateral microsomia. Only 3 cases presented with ear deformities and preauricular skin tags. Gleizal et al. (2007) concluded that bilateral macrostomia represents a distinct entity from unilateral macrostomia and provided details of surgical repair techniques. Mapping Fan et al. (2009) performed linkage analysis in a large 4-generation Han Chinese family segregating autosomal dominant macrostomia and obtained a maximum lod score of 4.18 (theta = 0.0) at marker D1S2797. Haplotype analysis identified an interval between markers D1S193 and D1S2652 on chromosome 1p34-p32. Molecular Genetics In 6 affected and 2 unaffected members of a large 4-generation Han Chinese family segregating autosomal dominant macrostomia mapping to chromosome 1p34-p32, Fan et al. (2009) identified heterozygosity for a 1423G-A transition in exon 11 of the PTCH2 gene (603673), resulting in a val471-to-ile (V471I) substitution in the fourth transmembrane domain. The mutation was not found in 520 unrelated controls. Functional studies in mouse mesenchymal stem cells demonstrated that wildtype but not mutant PTCH2 inhibited SMO-induced luciferase activity, and overexpression of wildtype PTCH2 significantly inhibited cell proliferation, but overexpression of the V471I mutant did not appear to have a major effect on cell growth rate. Fan et al. (2009) suggested that the PTCH2 V471I mutation may be associated with macrostomia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	MACROSTOMIA, ISOLATED	c0024433	30,161	omim	https://www.omim.org/entry/613545	2019-09-22T15:58:20	{"mesh": ["D008265"], "omim": ["613545"], "orphanet": ["141276"], "synonyms": ["Alternative titles", "LATERAL CLEFT, ISOLATED", "COMMISSURAL CLEFT, ISOLATED", "TRANSVERSE CLEFT, ISOLATED"]}
Adenocarcinoma, NOS Micrograph of an adenocarcinoma showing mucin containing vacuoles. Pap test. SpecialtyOncology, pathology Adenocarcinoma[1] (/ˌædɪnoʊkɑːrsɪˈnoʊmə/; plural adenocarcinomas or adenocarcinomata /ˌædɪnoʊkɑːrsɪˈnoʊmɪtə/) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them. In the most specific usage (narrowest sense), the glandular origin or traits are exocrine; endocrine gland tumors, such as a VIPoma, an insulinoma, or a pheochromocytoma, are typically not referred to as adenocarcinomas but rather are often called neuroendocrine tumors. Epithelial tissue sometimes includes, but is not limited to, the surface layer of skin, glands, and a variety of other tissue that lines the cavities and organs of the body. Epithelial tissue can be derived embryologically from any of the germ layers (ectoderm, endoderm, or mesoderm). To be classified as adenocarcinoma, the cells do not necessarily need to be part of a gland, as long as they have secretory properties. Adenocarcinoma is the malignant counterpart to adenoma, which is the benign form of such tumors. Sometimes adenomas transform into adenocarcinomas, but most do not. Well differentiated adenocarcinomas tend to resemble the glandular tissue that they are derived from, while poorly differentiated adenocarcinomas may not. By staining the cells from a biopsy, a pathologist can determine whether the tumor is an adenocarcinoma or some other type of cancer. Adenocarcinomas can arise in many tissues of the body owing to the ubiquitous nature of glands within the body, and, more fundamentally, to the potency of epithelial cells. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma. ## Contents * 1 Histopathology * 1.1 Breast * 1.2 Colon * 1.3 Lung * 1.4 Other * 2 Etymology * 3 See also * 4 References * 5 External links ## Histopathology[edit] Many seborrheic keratoses on back of person with Leser–Trélat sign due to colon cancer. Examples of cancers where adenocarcinomas are a common form: * esophageal cancer; most cases in the developed world are adenocarcinomas.[2] * pancreas; over 80% of pancreatic cancers are ductal adenocarcinomas.[3] * prostate cancer is nearly always adenocarcinoma * cervical cancer: most is squamous cell cancer, but 10–15% of cervical cancers are adenocarcinomas[4] * stomach cancer: is almost always an adenocarcinoma but in rare cases are extranodal marginal zone B-cell lymphomas (also termed MALT lymphomas).[5] ### Breast[edit] Most breast cancers start in the ducts or lobules, and are adenocarcinomas. The three most common histopathological types collectively represent approximately three-quarters of breast cancers: * Invasive ductal carcinoma: 55% of breast cancers[6] * Ductal carcinoma in situ: 13%[6] * Invasive lobular carcinoma: 5%[6] ### Colon[edit] Gross appearance of an opened colectomy specimen containing two adenomatous polyps (the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly-shaped tumor located above the label). Histopathologic image of colonic carcinoid stained by hematoxylin and eosin. The vast majority of colorectal cancers are adenocarcinomas. This is because the colon has numerous glands within the tissue. Normal colonic glands tend to be simple and tubular in appearance with a mixture of mucus-secreting goblet cells and water-absorbing cells. These glands are called glands because they secrete a substance into the lumen of the colon, this substance being mucus. The purpose of these glands is twofold. The first is to absorb water from the feces back into the blood. The second purpose is to secrete mucus into the colon lumen to lubricate the now dehydrated feces. This is crucial as a failure to lubricate the feces can result in colonic damage by the feces as it passes towards the rectum.[7] When these glands undergo a number of changes at the genetic level, they proceed in a predictable manner as they move from benign to an invasive, malignant colon cancer. In their research paper "Lessons from Hereditary Colorectal Cancer", Vogelstein, et al., suggested that colon cells lose the APC tumor suppressor gene and become a small polyp. Next, they suggested that k-Ras becomes activated and the polyp becomes a small, benign adenoma. The adenoma, lacking the "carcinoma" attached to the end of it, suggests that it is a benign version of the malignant adenocarcinoma. The gastroenterologist uses a colonoscopy to find and remove these adenomas and polyps to prevent them from continuing to acquire genetic changes that will lead to an invasive adenocarcinoma. Vogelstein et al. went on to suggest that loss of the DCC gene and of p53 result in a malignant adenocarcinoma.[8] There will be a mass of a different color to the surrounding tissue. Bleeding from the tumor is often apparent as the tumor tends to grow blood vessels into it in a haphazard manner via secretion of a number of angiogenesis promoting factors such as VEGF. Histologically, tumours resembling the original structures are classified as well differentiated. Tumour cells that have lost any resemblance to original tissue, both in appearance and structure form, are denoted as poorly differentiated tumour cells. Regardless of the grade, malignant tumors tend to have a large nucleus with prominent nucleoli. There will also be a noticeable increase in the incidence of mitosis, or cell divisions. ### Lung[edit] Main article: Adenocarcinoma of the lung Pie chart showing incidence of adenocarcinoma of the lung (shown in yellow) as compared to other lung cancer types, with fractions of non-smokers versus smokers shown for each type.[9] Nearly 40% of lung cancers are adenocarcinomas, which usually originates in peripheral lung tissue.[10] Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"),[11] adenocarcinoma is the most common form of lung cancer.[12] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have a better long-term survival.[13] This cancer usually is seen peripherally in the lungs, as opposed to small cell lung cancer and squamous cell lung cancer, which both tend to be more centrally located.[14][15] ### Other[edit] * Cholangiocarcinoma, or bile duct cancer * Vaginal cancer * Cancer of the urachus * Stomach cancer * Prostate cancer ## Etymology[edit] The term adenocarcinoma is derived from adeno-, meaning "pertaining to a gland", and carcinoma, which describes a cancer that has developed in the epithelial cells. ## See also[edit] * Clear-cell adenocarcinoma * Fetal adenocarcinoma ## References[edit] 1. ^ From adeno-, "gland" and karkin(o)-, "cancerous" and -oma, "tumor". 2. ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.3. ISBN 978-92-832-0429-9. 3. ^ Bond-Smith, G; Banga, N; Hammond, TM; Imber, CJ (May 16, 2012). "Pancreatic adenocarcinoma". BMJ (Clinical Research Ed.). 344: e2476. doi:10.1136/bmj.e2476. PMID 22592847. 4. ^ World Cancer Report 2014. World Health Organization. 2014. pp. 473–474. ISBN 978-92-832-0429-9. 5. ^ Burkitt MD, Duckworth CA, Williams JM, Pritchard DM (February 2017). "Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models". Disease Models & Mechanisms. 10 (2): 89–104. doi:10.1242/dmm.027649. PMC 5312008. PMID 28151409. 6. ^ a b c Percentage values are from United States statistics 2004. Subtype specific incidences are taken from Table 6 (invasive) and Table 3 (in situ) from Eheman CR, Shaw KM, Ryerson AB, Miller JW, Ajani UA, White MC (June 2009). "The changing incidence of in situ and invasive ductal and lobular breast carcinomas: United States, 1999–2004". Cancer Epidemiol. Biomarkers Prev. 18 (6): 1763–9. doi:10.1158/1055-9965.EPI-08-1082. PMID 19454615.. These are divided by total breast cancer incidence (211,300 invasive and 55,700 in situ cases) as reported from Breast Cancer Facts & Figures 2003–2004 "Archived copy". Archived from the original on 2009-04-15. Retrieved 2010-06-15.CS1 maint: archived copy as title (link) 7. ^ Heath JE, Young B, Wheater PR, Lowe JN, Stevens A (2006). Wheater's Functional histology: a text and colour atlas (5th ed.). Edinburgh: Churchill Livingstone Elsevier. p. 283. ISBN 978-0-443-06850-8. 8. ^ Kinzler KW, Vogelstein B (October 1996). "Lessons from hereditary colorectal cancer". Cell. 87 (2): 159–70. doi:10.1016/S0092-8674(00)81333-1. PMID 8861899. 9. ^ Smokers defined as current or former smoker of more than 1 year of duration. See image page in Commons for percentages in numbers. Reference: * Table 2 in: Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (2008). "Comparison of aspects of smoking among the four histological types of lung cancer". Tob Control. 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC 3044470. PMID 18390646. 10. ^ Lu, C; Onn A, Vaporciyan AA; et al. (2010). "78: Cancer of the Lung". Holland-Frei Cancer Medicine (8th ed.). People's Medical Publishing House. ISBN 978-1-60795-014-1. 11. ^ Horn, L; Pao W; Johnson DH (2012). "Chapter 89". In Longo, DL; Kasper, DL; Jameson, JL; Fauci, AS; Hauser, SL; Loscalzo, J (eds.). Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill. ISBN 978-0-07-174889-6. 12. ^ Subramanian, J; Govindan R (February 2007). "Lung cancer in never smokers: a review". Journal of Clinical Oncology. 25 (5): 561–570. doi:10.1200/JCO.2006.06.8015. PMID 17290066. 13. ^ Raz, DJ; He B; Rosell R; Jablons DM (March 2006). "Bronchioloalveolar carcinoma: a review". Clinical Lung Cancer. 7 (5): 313–322. doi:10.3816/CLC.2006.n.012. PMID 16640802. 14. ^ Chapter 13, box on morphology of adenocarcinoma in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition. 15. ^ Travis WD, Travis LB, Devesa SS (January 1995). "Lung cancer". Cancer. 75 (1 Suppl): 191–202. doi:10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y. PMID 8000996. ## External links[edit] Classification D * ICD-9-CM: 151.0, 182.0 * ICD-O: M8140/3 * MeSH: D000230 * SNOMED CT: 35917007 * Media related to Adenocarcinomas at Wikimedia Commons * "Adenocarcinoma"—NCI Dictionary of Cancer Terms * Surgical Videos, Images and Case Studies of Adenocarcinoma of the Sinuses * 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 Cancer involving the respiratory tract Upper RT Nasal cavity Esthesioneuroblastoma Nasopharynx Nasopharyngeal carcinoma Nasopharyngeal angiofibroma Larynx Laryngeal cancer Laryngeal papillomatosis Lower RT Trachea * Tracheal tumor Lung Non-small-cell lung carcinoma * Squamous-cell carcinoma * Adenocarcinoma (Mucinous cystadenocarcinoma) * Large-cell lung carcinoma * Rhabdoid carcinoma * Sarcomatoid carcinoma * Carcinoid * Salivary gland–like carcinoma * Adenosquamous carcinoma * Papillary adenocarcinoma * Giant-cell carcinoma Small-cell carcinoma * Combined small-cell carcinoma Non-carcinoma * Sarcoma * Lymphoma * Immature teratoma * Melanoma By location * Pancoast tumor * Solitary pulmonary nodule * Central lung * Peripheral lung * Bronchial leiomyoma Pleura * Mesothelioma * Malignant solitary fibrous tumor * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma * v * t * e * Tumors of the male urogenital system Testicles Sex cord– gonadal stromal * Sertoli–Leydig cell tumour * Sertoli cell tumour * Leydig cell tumour Germ cell G * Seminoma * Spermatocytic tumor * Germ cell neoplasia in situ NG * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma * Choriocarcinoma * Embryoma Prostate * Adenocarcinoma * High-grade prostatic intraepithelial neoplasia * HGPIN * Small-cell carcinoma * Transitional cell carcinoma Penis * Carcinoma * Extramammary Paget's disease * Bowen's disease * Bowenoid papulosis * Erythroplasia of Queyrat * Hirsuties coronae glandis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Adenocarcinoma	c0001418	30,162	wikipedia	https://en.wikipedia.org/wiki/Adenocarcinoma	2021-01-18T19:09:59	{"mesh": ["D000230"], "umls": ["C0001418"], "wikidata": ["Q356033"]}
Deoxyguanosine kinase deficiency is an inherited disorder that can cause liver disease and neurological problems. Researchers have described two forms of this disorder. The majority of affected individuals have the more severe form, which is called hepatocerebral because of the serious problems it causes in the liver and brain. Newborns with the hepatocerebral form of deoxyguanosine kinase deficiency may have a buildup of lactic acid in the body (lactic acidosis) within the first few days after birth. They may also have weakness, behavior changes such as poor feeding and decreased activity, and vomiting. Affected newborns sometimes have low blood sugar (hypoglycemia) as a result of liver dysfunction. During the first few weeks of life they begin showing other signs of liver disease which may result in liver failure. They also develop progressive neurological problems including very weak muscle tone (severe hypotonia), abnormal eye movements (nystagmus) and the loss of skills they had previously acquired (developmental regression). Children with this form of the disorder usually do not survive past the age of 2 years. Some individuals with deoxyguanosine kinase deficiency have a milder form of the disorder without severe neurological problems. Liver disease is the primary symptom of this form of the disorder, generally becoming evident during infancy or childhood. Occasionally it first appears after an illness such as a viral infection. Affected individuals may also develop kidney problems. Mild hypotonia is the only neurological effect associated with this form of the disorder. ## Frequency The prevalence of deoxyguanosine kinase deficiency is unknown. Approximately 100 affected individuals have been identified. ## Causes The DGUOK gene provides instructions for making the enzyme deoxyguanosine kinase. This enzyme plays a critical role in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the building blocks of mitochondrial DNA. Mutations in the DGUOK gene reduce or eliminate the activity of the deoxyguanosine kinase enzyme. Reduced enzyme activity leads to problems with the production and maintenance of mitochondrial DNA. A reduction in the amount of mitochondrial DNA (known as mitochondrial DNA depletion) impairs mitochondrial function in many of the body's cells and tissues. These problems lead to the neurological and liver dysfunction associated with deoxyguanosine kinase deficiency. ### Learn more about the gene associated with Deoxyguanosine kinase deficiency * DGUOK ## Inheritance Pattern Deoxyguanosine kinase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In most cases, the parents of an individual with this condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	Deoxyguanosine kinase deficiency	c3151513	30,163	medlineplus	https://medlineplus.gov/genetics/condition/deoxyguanosine-kinase-deficiency/	2021-01-27T08:25:12	{"gard": ["3972"], "omim": ["251880"], "synonyms": []}
A rare, highly aggressive uterine cancer, macroscopically appearing as an irregular, slow-growing, non-friable, polypoid mass on the uterine cervix and histologically showing a pseudoglandular or cribriform growth pattern. It presents with vaginal bleeding and discharge and abdominal or pelvic pain. The tumor is highly infiltrative, often associated with vascular, lymphatic and perineural invasion, with subsequent haematogenous spread and early recurrence. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Adenoid cystic carcinoma of the cervix uteri	c1332911	30,164	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=213823	2021-01-23T18:21:37	{"icd-10": ["C53.0", "C53.1", "C53.8"], "synonyms": ["Cervical adenoid cystic carcinoma"]}
A number sign (#) is used with this entry because of evidence that trichothiodystrophy-6 (TTD6) is caused by homozygous mutation in the GTF2E2 gene (189964) on chromosome 8p12. For a discussion of genetic heterogeneity of trichothiodystrophy, see 601675. Clinical Features Kuschal et al. (2016) reported a 10-year-old Asian boy and a 16-year-old Moroccan girl who both presented with short stature, microcephaly, brittle hair with 'tiger tail' banding on polarized microscopy, dry ichthyotic skin, and developmental delay with a happy personality. Laboratory studies showed low red blood cell mean corpuscular volume and elevated hemoglobin A2. Cells from both patients had normal post-UV DNA repair, with normal recruitment and efficiency of nucleotide excision repair (NER) proteins. Molecular Genetics In a 10-year-old Asian boy with nonphotosensitive trichothiodystrophy (TTD), who was negative for mutation in the MPLKIP gene (609188), Kuschal et al. (2016) performed whole-exome sequencing and identified homozygosity for a missense mutation in the GTF2E2 gene (A150P; 189964.0001). His unaffected parents were heterozygous for the mutation, and his healthy brother did not carry the variant. By targeted Sanger sequencing of both TFIIE subunits, GTF2E1 (189962) and GTF2E2, in a 16-year-old Moroccan girl with nonphotosensitive TTD, the authors identified homozygosity for a different missense mutation in GTF2E2 (D187Y; 189964.0002) that segregated with disease in her family. Sanger sequencing of GTF2E1 and GTF2E2 in 41 additional patients with clinically suspected TTD, who were negative for NER defects or mutation in MPLKIP, did not reveal any mutations, suggesting further genetic heterogeneity. Kuschal et al. (2016) noted that in their combined cohort of 125 TTD patients, mutations in GTF2E2 accounted for approximately 2% of cases. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Low weight HEAD & NECK Head \- Microcephaly \- Triangular head consistent with craniosynostosis (in one patient) Ears \- Sensorineural hearing loss, mild Eyes \- Microcornea (in one patient) \- Nystagmus (in one patient) \- Strabismus (in one patient) SKELETAL \- Delayed bone age (in one patient) Skull \- Coronal craniosynostosis (in one patient) Pelvis \- Coxa valga, bilateral (in one patient) Feet \- Pes cavus, bilateral (in one patient) SKIN, NAILS, & HAIR Skin \- Dry skin \- Ichthyosiform scaling \- Lamellar ichthyosis No sun sensitivity Hair \- Short, brittle hair \- 'Tiger tail' banding on polarized microscopy NEUROLOGIC Central Nervous System \- Mental retardation, moderate \- Motor delay \- Speech articulation disorder \- Positive Babinski sign (in one patient) \- Deep tendon reflexes slightly decreased (in one patient) \- Beats of clonus at ankles (in one patient) \- Wide-based gait (in one patient) \- Spastic-ataxic gait (in one patient) Behavioral Psychiatric Manifestations \- Happy personality HEMATOLOGY \- Low RBC mean corpuscular volume \- Elevated hemoglobin A2 MISCELLANEOUS \- Based on report of 2 unrelated patients (last curated May 2016) MOLECULAR BASIS \- Caused by mutation in the general transcription factor IIE polypeptide-2 gene (GTF2E2, 189964.0001 ) ▲ 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	TRICHOTHIODYSTROPHY 6, NONPHOTOSENSITIVE	c1955934	30,165	omim	https://www.omim.org/entry/616943	2019-09-22T15:47:25	{"mesh": ["D054463"], "omim": ["616943"], "orphanet": ["33364"]}
## Summary ### Clinical characteristics. BCL11A-related intellectual disability (BCL11A-ID) is characterized by developmental delay / intellectual disability of variable degree, neonatal hypotonia, microcephaly, distinctive but variable facial characteristics, behavior problems, and asymptomatic persistence of fetal hemoglobin. Growth delay, seizures, and autism spectrum disorder have also been reported in some affected individuals. ### Diagnosis/testing. The diagnosis of BCL11A-ID is established in a proband with suggestive clinical and laboratory findings and a heterozygous pathogenic variant in BCL11A identified by molecular genetic testing. ### Management. Treatment of manifestations: Treatment is primarily supportive and dictated by symptoms. Standard antiepileptic medication for seizure disorder; standard treatment for abnormal vision and/or strabismus, sleep disturbance, scoliosis, joint laxity, gastroesophageal reflux disease (GERD), constipation, and developmental issues. Surveillance: Assessment of growth parameters, feeding difficulties, GERD, constipation, scoliosis, developmental progress, and behavior at each visit. Monitor seizures as clinically indicated. Assessment of vision and eye alignment as needed. ### Genetic counseling. BCL11A-ID is inherited in an autosomal dominant manner; however, most affected individuals have the disorder as the result of a de novo BCL11A pathogenic variant. Once the BCL11A pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible. ## Diagnosis Formal clinical diagnostic criteria for BCL11A-related intellectual disability (BCL11A-ID) have not been established. ### Suggestive Findings BCL11A-ID should be considered in individuals presenting with the following clinical, laboratory, and neuroimaging findings. Clinical findings * Mild-to-severe developmental delay or intellectual disability; AND * Any of the following features presenting in infancy or childhood: * Microcephaly * Craniofacial features including flat midface, small nares, thin vermilion of the upper lip and everted vermilion of the lower lip [Dias et al 2016] (see Figure 1) * External ear anomalies * Strabismus * Blue sclerae in infancy * Generalized hypotonia of infancy * Infant feeding difficulties * Language delay and/or dyspraxia * Joint laxity * Behavioral concerns (repetitive behavior, autism spectrum disorder) * Sleep disturbance * Seizures Laboratory findings. Persistence of fetal hemoglobin detected by standardized laboratory methods, such as hemoglobin HPLC (high-performance liquid chromatography) or hemoglobin electrophoresis Nonspecific brain MRI findings. Hypoplasia of the corpus callosum, hypoplasia of the cerebellar vermis, or white matter abnormalities ### Establishing the Diagnosis The diagnosis of BCL11A-ID is established in a proband with suggestive findings by identification of a heterozygous pathogenic variant in BCL11A on molecular genetic testing (see Table 1). Molecular genetic testing in a child with developmental delay or an older individual with intellectual disability typically begins with chromosomal microarray analysis (CMA). If CMA is not diagnostic, the next step is typically either a multigene panel or exome sequencing. Note: Single-gene testing (sequence analysis of BCL11A, followed by gene-targeted deletion/duplication analysis) may be considered in individuals with nonfamilial persistence of fetal hemoglobin identified by hematologic assays. CMA uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including BCL11A) that cannot be detected by sequence analysis. See Genetically Related Disorders for discussion of individuals who have larger deletions or duplications of the 2p15-p16.1 region, which includes BCL11A and surrounding genes. An intellectual disability (ID) multigene panel that includes BCL11A and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition in a person with a nondiagnostic CMA at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. Of note, given the rarity of BCL11A-ID, some panels for ID may not include this gene. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Exome sequencing, which does not require the clinician to determine which gene is likely involved, yields results similar to an ID multigene panel but has the advantage that all rare genes recently identified as causing ID are represented, while some newly identified ID genes may not be included on a multigene panel. 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 BCL11A-Related Intellectual Disability View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method BCL11ASequence analysis 321/27 4 Gene-targeted deletion/duplication analysis 5Unknown 6 CMA 7, 86/27 9 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\. Firth et al [2009], De Rubeis et al [2014], Iossifov et al [2014], Dias el al [2016], Cai et al [2017], Landrum et al [2018], Peron et al [2018], Soblet et al [2018], Yoshida et al [2018] 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\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 7\. Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including BCL11A) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 2p15-p16.1 region. CMA designs in current clinical use target the 2p15-p16.2 region. 8\. Includes partial or whole-gene deletions of BCL11A without disrupting other protein-coding genes (excludes contiguous gene deletion syndromes, namely 2p15-16.1 microdeletion syndrome). 9\. Firth et al [2009], Peter et al [2014], Balci et al [2015], Peron et al [2018] ## Clinical Characteristics ### Clinical Description BCL11A-related intellectual disability (BCL11A-ID) is characterized by developmental delay / intellectual disability of variable degree (from mild to severe, but most frequently in the moderate range), neonatal hypotonia, microcephaly, distinctive but variable facial characteristics, behavior problems, and asymptomatic persistence of fetal hemoglobin (HbF). Growth delay, seizures, and autism spectrum disorder have also been reported in some affected individuals. To date, 27 individuals have been reported with a pathogenic (or likely pathogenic) variant in BCL11A [Firth et al 2009, De Rubeis et al 2014, Iossifov et al 2014, Peter et al 2014, Balci et al 2015, Deciphering Developmental Disorders Study Group 2015, Dias et al 2016, Cai et al 2017, Landrum et al 2018, Peron et al 2018, Soblet et al 2018, Yoshida et al 2018]; the authors are aware of additional affected individuals. The following description of the phenotypic features associated with this condition is based on the reported cases and the authors' experience. Developmental delay (DD) and intellectual disability (ID). All individuals with BCL11A-ID present with DD. Speech delay is always present, and gross and fine motor delays are usually seen as well. All affected individuals have ID, with variable levels ranging from mild to severe. Other neurodevelopmental features: * Neonatal hypotonia is seen in the majority of affected individuals, and may result in delayed acquisition of motor milestones (average age at walking: ~30 months). Hypotonia may resolve in childhood, though in some it persists into adolescence. * Infant feeding difficulties are occasionally present and thought to be associated with central hypotonia as opposed to primary dysphagia. * Ataxia and/or broad-based gait has been reported in three affected individuals. Epilepsy has been reported in 5/25 affected individuals [Cai et al 2017, Peron et al 2018, Yoshida et al 2018]. * Various types of seizures have been described (including myoclonic, tonic, and atonic seizures; absence seizures; and spasms) without a common electroclinical pattern. * Age at seizure onset among individuals reported in the literature varied from two months to three years. * Seizures are usually controlled with single or combined (2) antiepileptic medication(s). Three reported individuals had seizures that were drug resistant [Peron et al 2018, Yoshida et al 2018] (see also Genetically Related Disorders). Behavior problems. Most individuals reported have presented with behavior problems [Dias et al 2016]. * Autism spectrum disorder has been described in a subset of affected individuals [De Rubeis et al 2014, Iossifov et al 2014, Dias et al 2016, Cai et al 2017]. * Others exhibit autistic-like traits, such as repetitive behaviors. * Other behavior problems: * Attention deficit and self-injurious behaviors have been reported in one person each. * Sleep disturbances have been reported in three people. Hematologic. A key manifestation of BCL11A-ID is the persistence of fetal hemoglobin (HbF) in affected individuals. In individuals from the general population, HbF is high in the second and third trimester of gestation and in the neonatal period, physiologically decreasing after birth and within the first 12 months of life (with a transition to adult hemoglobin). Therefore, age-specific reference values for hemoglobin variants should be used up to age 24 months. * Elevated HbF (% of total hemoglobin) has been identified in all affected individuals who have been tested [Dias et al 2016, Cai et al 2017, Peron et al 2018, Soblet et al 2018, Yoshida et al 2018]. * Persistence of HbF is not known to cause symptoms, and no affected individuals with hematologic problems have been reported thus far. Growth. Intrauterine growth restriction (IUGR) and postnatal growth delay are occasionally present [Dias et al 2016, Cai et al 2017, Yoshida et al 2018], but more than half of the affected individuals have normal growth parameters. Microcephaly (-2 to -3.5 SD) is seen in approximately half of affected individuals [Dias et al 2016, Cai et al 2017, Soblet et al 2018, Yoshida et al 2018]. Eyes. Strabismus has been reported in 10/21 affected individuals [Dias et al 2016, Cai et al 2017, Peron et al 2018] but no other vision or hearing impairments have been documented. Some affected children with pathogenic loss-of-function variants exhibit blue sclerae in infancy (see Genotype-Phenotype Correlations) [Dias et al 2016]. Neuroimaging. Brain MRI is normal in only a minority of affected individuals; however, most abnormal brain MRI findings are mild and/or nonspecific. * Structural anomalies of the central nervous system can be present, including hypoplasia of the corpus callosum and/or cerebellar vermis [Dias et al 2016, Peron et al 2018]. * White matter abnormalities, including reduced white matter volume, have been reported [Dias et al 2016]. Other associated features * Musculoskeletal features * Joint hypermobility is a common finding (>80%) in individuals with BCL11A-ID. * Scoliosis has occasionally been reported [Dias et al 2016, Cai et al 2017]. * Gastrointestinal problems. Infantile feeding problems with poor weight gain, gastroesophageal reflux disease (GERD), and constipation have occasionally been reported [Dias et al 2016]. * Craniofacial features. No specific dysmorphic features have been observed. If present, dysmorphic features are nonspecific. * Affected individuals frequently have flat midface, full cheeks, small nares, thin vermilion of the upper lip, and full or everted vermilion of the lower lip [Dias et al 2016, Peron et al 2018]. * A subset of individuals have external ear anomalies, including overfolded helix, everted ears, and small earlobe [Liang et al 2009, Dias et al 2016, Soblet et al 2018]. Prognosis. BCL11A-ID is a congenital disorder without known regression of skills. Life span and typical cause of death are unknown due to the limited number of individuals reported to date and ascertainment bias toward diagnosis in childhood. However, the lack of life-limiting congenital anomalies in affected individuals suggests a favorable long-term prognosis with appropriate support. The authors are aware of two affected individuals who are alive and well at 19 and 23 years, respectively [Authors, personal observation], demonstrating that survival into adulthood is possible. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported. ### Genotype-Phenotype Correlations With the limited number of affected individuals reported to date, no statistically significant genotype-phenotype correlations can be made. However, certain features described to date have been seen only in individuals with loss-of-function (nonsense and frameshift) variants [Dias et al 2016, Yoshida et al 2018]: * Blue sclerae in infancy * Epicanthal folds * Micrognathia or retrognathia * Short stature (mild) ### Prevalence The prevalence of BCL11A-ID is unknown. To date, 27 affected individuals have been reported in the literature. ## Differential Diagnosis Table 2 describes specific conditions that may have features that overlap with BCL11A-related intellectual disability (BCL11A-ID). Note: The phenotypic features associated with BCL11A-ID are generally not sufficient to diagnose this condition. All disorders with intellectual disability (ID) without other distinctive findings should be considered in the differential diagnosis. To date more than 180 such disorders with ID have been identified. See OMIM Phenotypic Series: Autosomal dominant ID, Autosomal recessive ID, Nonsyndromic X-linked ID, and Syndromic X-linked ID. ### Table 2. Selected Disorders to Consider in the Differential Diagnosis of BCL11A-Related Intellectual Disability View in own window DisorderGene(s)MOIKey Clinical Features of Differential Diagnosis Disorder Overlapping w/BCL11A-IDDistinguishing from BCL11A-ID KANSL1-related intellectual disability syndromeKANSL1ADID, infant hypotonia, joint hypermobility, everted lower lip, strabismus * Facial features incl blepharophimosis & bulbous or tubular nose * More frequent congenital anomalies (renal & urogenital anomalies, heart defects) Alpha-thalassemia X-linked intellectual disability syndrome (ATRX)ATRXXL * ID, hypotonia, small head circumference, everted lower lip, short nose, short stature * Facial gestalt in a subset of individuals w/BCL11A-ID resembles that of ATRX. 1 * Craniofacial features (telecanthus, tented vermilion of upper lip, progressive coarsening of facial features), genital abnormalities, & skeletal abnormalities * ID is typically severe to profound in boys (heterozygous females w/craniofacial features, ID, & growth restriction have been described). 2 * Alpha-thalassemia (in ~85% of individuals) AD = autosomal dominant; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked 1\. Peron et al [2018] 2\. Badens et al [2006] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with BCL11A-ID, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with BCL11A-Related Intellectual Disability View in own window System/ConcernEvaluationComment NeurologicAssessment for hypotonia & signs/symptoms of seizures * EEG if seizures suspected * Consider brain MRI to detect brain abnormalities. Psychiatric/ BehavioralNeuropsychiatric evaluationFor individuals age >18 mos: screen for behavior problems incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD. ConstitutionalWeight, length/height, & head circumferenceAssess for evidence of short stature, failure to thrive, microcephaly. EyesOphthalmologic evaluationAssess for strabismus, visual acuity. MusculoskeletalClinical evaluation for scoliosisConsider radiographic scoliosis survey based on clinical suspicion & referral to orthopedic surgeon as appropriate. Clinical evaluation for joint laxityConsider referral to rehabilitation specialist & occupational therapist. Gastrointestinal/ FeedingAssessment of feeding problems in infancy & for GERD at any ageReferral to feeding therapist if feeding problems identified HematologicHemoglobin HPLC or hemoglobin electrophoresisExpect elevated HbF. Miscellaneous/ OtherDevelopmental assessment * Incl evaluation of motor, speech/language, general cognitive, & vocational skills * Refer to speech & rehabilitation therapy, PT, & OT as appropriate. Consultation w/clinical geneticist &/or genetic counselor ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; GERD = gastroesophageal reflux disorder; HbF = fetal hemoglobin; HPLC = high-performance liquid chromatography; OT = occupational therapy; PT = physical therapy ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with BCL11A-Related Intellectual Disability View in own window Manifestation/ConcernTreatmentConsiderations/Other SeizuresStandardized treatment w/AEDs by experienced neurologist 1Many different AEDs may be effective, & no one AED has been demonstrated effective specifically for this disorder. Sleep disturbancesStandard management.Consider melatonin. Abnormal vision &/or strabismusStandard treatment(s) as recommended by ophthalmologist. ScoliosisStandard management as recommended by orthopedist Joint laxityPT &/or OT GERD &/or constipationReferral to (pediatric) gastroenterologistSymptomatic management to enhance nutritional intake & hydration AED = antiepileptic drug; GERD = gastroesophageal reflux disorder; OT = occupational therapy; PT = physical therapy 1\. Education of parents regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed. Ages 5-21 years * In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21. * Discussion about transition plans including financial, vocation/employment, guardianship, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life. Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. In the US: * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Motor Dysfunction Gross motor dysfunction * Physical therapy is recommended to maximize mobility. * Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers). Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing. Oral motor dysfunction. Assuming that the individual is safe to eat by mouth, feeding therapy, typically from an occupational or speech therapist, is recommended for affected individuals who have difficulty feeding due to poor oral motor control. Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. #### Social/Behavioral Concerns Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one-on-one with a board-certified behavior analyst. Consultation with a developmental pediatrician and/or a psychiatrist may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder (ADHD), when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance ### Table 5. Recommended Surveillance for Individuals with BCL11A-Related Intellectual Disability View in own window System/ConcernEvaluationFrequency NeurologicMonitor those w/seizures as clinically indicated.As clinically indicated PsychiatricBehavioral assessment for anxiety, attention, & aggressive or self-injurious behaviorMonitor clinically at each visit; refer for evaluation as indicated. ConstitutionalWeight, length/height, & head circumference measurements plotted on standard growth chartAt each visit EyesOphthalmologic evaluationAs clinically indicated MusculoskeletalMonitor for scoliosis. Orthopedic evaluation as indicated.Monitor clinically at each visit. GastrointestinalAssessment of feeding difficulties, GERD, constipationAt each visit (particularly in infancy) Miscellaneous/ OtherMonitor developmental progress & educational needs.At each visit GERD = gastroesophageal reflux disorder ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	BCL11A-Related Intellectual Disability	c4310833	30,166	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK547048/	2021-01-18T21:40:29	{"synonyms": ["Dias-Logan Syndrome", "Intellectual Developmental Disorder with Persistence of Fetal Hemoglobin"]}
This article is about the consequences of topical steroids. For other uses, see Burn and Sunburn. Topical steroid withdrawal Other namesTopical steroid addiction, steroid dermatitis, red burning skin syndrome, red skin syndrome, iatrogenic exfoliative dermatitis (idiopathic erythroderma)[1] Red burning skin syndrome from topical steroids. Face pattern with nose sign and spared palms (soles spared too) SpecialtyDermatology SymptomsRed skin, burning sensation, itchiness[2] CausesStopping topical steroids after frequent long term use[2] PreventionUsing steroid creams for less than two weeks[2][3] FrequencyRare[2] Topical steroid withdrawal, also known as red burning skin and steroid dermatitis, has been reported in long-term users of topical steroids after they stop the use.[4][5][2][1] Symptoms include redness of the skin, a burning sensation, and itchiness.[2] This may then be followed by skin peeling.[2] It generally requires the application of a topical steroid at least daily for more than a year. It appears to be a specific adverse effect of topical corticosteroid use.[6] People with atopic dermatitis are most at risk.[7] Treatment involves discontinuing the use of topical steroids.[2] These can either be stopped gradually or suddenly.[2] Counselling and cold compresses may also help.[2] The condition is rare.[2] Cases have been reported in adults with a few possible cases in children.[2][1] It was first described in 1979.[3] ## Contents * 1 Signs and symptoms * 1.1 Duration * 2 Cause * 3 Mechanism of action * 4 Diagnosis * 5 Prevention * 6 Treatment * 7 Epidemiology * 8 History * 9 References * 10 External links ## Signs and symptoms[edit] Red burning skin syndrome from topical steroids. Typical pattern on lower arms and hands Topical steroid addiction (TSA) is characterised by uncontrollable, spreading dermatitis and worsening skin inflammation which requires a stronger topical steroid to get the same result as the first prescription. This cycle is known as steroid addiction syndrome.[8] When topical steroid medication is stopped, the skin experiences redness, burning, itching, hot skin, swelling, and/or oozing for a length of time. This is also called 'red skin syndrome' or 'topical steroid withdrawal' (TSW). After the withdrawal period is over the atopic dermatitis can cease or is less severe than it was before.[9] Topical steroid addiction has also been reported in the male scrotum area.[10] ### Duration[edit] The duration of acute topical corticosteroid withdrawal is variable, it can take months to years to return to the skin's original condition.[2] The duration of steroid use may influence the recovery factor time, with the patients who used steroids for the longest reporting the slowest recovery. ## Cause[edit] It generally requires the application of a topical steroid at least daily for more than a year.[2] It does not occur with normal use.[2] Cases have, however, been reported to occur after as short as 2 months of use.[11][1] ## Mechanism of action[edit] Historically, it was believed that cortisol was only produced by the adrenal glands. Recent research has shown that keratinocytes in human skin also produce cortisol.[12] Prolonged TS application changes the glucocorticoid receptor (GR) expression pattern on the surface of lymphocytes; patients experiencing resistance to TSs have a low ratio of GR-α to GR-β. In addition, the erythema characteristic of ‘‘red skin syndrome’’ is due to a release of stored endothelial nitric oxide (NO) and subsequent vasodilation of dermal vessels.[1] ## Diagnosis[edit] Diagnosis is based on a rash occurring within weeks of stopping long term topical steroids.[2] Headlight sign - redness of the lower part of the face but not the nose and around the mouth. Red sleeve - rebound eruption stopping suddenly at lower arms and hand. Elephant wrinkles - reduced skin elasticity.[7] Differentiating from the skin condition the steroids were used to treat can be difficult.[2] Red burning skin may be misdiagnosed.[9] ## Prevention[edit] Prevention is by not using moderate or high strength steroid creams for periods of time longer than two weeks.[2][3] ## Treatment[edit] Treatment involves not using topical steroids.[2] These can either be stopped gradually or suddenly.[2] Counselling and cold compresses may also help.[2] Antihistamines may help for itchiness.[3] Immunosuppressants and light therapy may also help some people.[3] Psychological support is often recommended.[2][7][11] ## Epidemiology[edit] The condition is rare.[2] Cases have been reported in adults with a few possible cases in children.[2][1] One survey estimated that maybe up to 12% of people with atopic dermatitis have steroid addiction.[9] ## History[edit] The first description of the condition occurred in 1979.[3] ## References[edit] 1. ^ a b c d e f Juhász, MLW; Curley, RA; Rasmussen, A; Malakouti, M; Silverberg, N; Jacob, E (September–October 2017). "Systematic review of the topical steroid addiction and topical steroid withdrawal phenomenon in children diagnosed with atopic dermatitis and treated with topical corticosteroids". Journal of the Dermatology Nurses' Association. 9 (5): 233–240. doi:10.1097/JDN.0000000000000331. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x "Topical corticosteroid withdrawal". DermNet NZ. Retrieved 19 July 2016. 3. ^ a b c d e f Sheary, B (June 2016). "Topical corticosteroid addiction and withdrawal - An overview for GPs". Australian Family Physician. 45 (6): 386–8. PMID 27622228. 4. ^ Nnoruka, Edith; Daramola, Olaniyi; Ike, Samuel (2007). "Misuse and abuse of topical steroids: implications". Expert Review of Dermatology. 2 (1): 31–40. doi:10.1586/17469872.2.1.31. Retrieved 2014-12-18. 5. ^ Sanjay, Rathi; D'Souza, Paschal (2012). "Rational and ethical use of topical corticosteroids based on safety and efficacy". Indian Journal of Dermatology. 57 (4): 251–259. doi:10.4103/0019-5154.97655. PMC 3401837. PMID 22837556. 6. ^ Hajar, T; Leshem, YA; Hanifin, JM; Nedorost, ST; Lio, PA; Paller, AS; Block, J; Simpson, EL; (the National Eczema Association Task, Force). (March 2015). "A systematic review of topical corticosteroid withdrawal ("steroid addiction") in patients with atopic dermatitis and other dermatoses". Journal of the American Academy of Dermatology. 72 (3): 541–549.e2. doi:10.1016/j.jaad.2014.11.024. PMID 25592622. 7. ^ a b c Sheary, BMed, FRACGP, General Practitioner, Belinda. "Topical corticosteroid addiction and withdrawal – An overview for GPs". The Royal Australian College of General Practitioners Ltd. Australian Family Physician.CS1 maint: multiple names: authors list (link) 8. ^ Smith, M. C.; Nedorost, S.; Tackett, B. (2007). "Facing up to withdrawal from topical steroids". Nursing. 37 (9): 60–1. doi:10.1097/01.NURSE.0000287732.08659.83. PMID 17728660. 9. ^ a b c Fukaya, M; Sato, K; Sato, M; Kimata, H; Fujisawa, S; Dozono, H; Yoshizawa, J; Minaguchi, S (2014). "Topical steroid addiction in atopic dermatitis". Drug, Healthcare and Patient Safety. 6: 131–8. doi:10.2147/dhps.s69201. PMC 4207549. PMID 25378953. 10. ^ "Corticosteroid-dependent scrotum". Journal of the American Academy of Dermatology. 52 (3): P47. 2005-03-01. doi:10.1016/j.jaad.2004.10.202. ISSN 0190-9622. 11. ^ a b Ghosh, Aparajita; Sengupta, Sujata; Coondoo, Arijit; Jana, Amlankusum (2014). "Topical corticosteroid addiction and phobia". Indian Journal of Dermatology. 59 (5): 465–8. doi:10.4103/0019-5154.139876. PMC 4171914. PMID 25284851. 12. ^ Cirillo, N; Prime, S (2011). "Keratinocytes synthesize and activate cortisol". Journal of Cellular Biochemistry. 112 (6): 1499–505. doi:10.1002/jcb.23081. PMID 21344493. ## External links[edit] Classification D * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Topical steroid withdrawal	None	30,167	wikipedia	https://en.wikipedia.org/wiki/Topical_steroid_withdrawal	2021-01-18T19:06:16	{"wikidata": ["Q25323840"]}
Lopes et al. (1994) described a Brazilian family in which members of 4 generations showed absence of the lower eyelashes associated with thin and short upper tarsus, normal upper eyelashes, and hypoplastic lower eyelids with short and small tarsus. There were a few short, thin, and light-colored lower eyelashes visible only on biomicroscopy. Lopes et al. (1994) suggested the designation short tarsus--absence of lower eyelashes (STALE) and raised the question of similarity to the findings in a father and son reported by Traquair (1912). Autosomal dominant inheritance seemed quite clear from the presence of 5 instances of male-to-male transmission. Eyes \- Thin and short upper tarsus \- Absent lower eyelashes \- Normal upper eyelashes \- Hypoplastic lower eyelids \- Short and small lower tarsus 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	SHORT TARSUS WITH ABSENCE OF LOWER EYELASHES	c1838328	30,168	omim	https://www.omim.org/entry/600269	2019-09-22T16:16:29	{"mesh": ["C537036"], "omim": ["600269"], "orphanet": ["2832"]}
A number sign (#) is used with this entry because 3-methylglutaconic aciduria type I (MCGA1) can be caused by homozygous or compound heterozygous mutation in the AUH gene (600529), which encodes 3-methylglutaconyl-CoA hydratase, on chromosome 9q22. Description Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). ### Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA (MGCA2), also known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene (TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (MGCA3; 258501), caused by mutation in the OPA3 gene (606580) on chromosome 19q13, involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (MGCA4; 250951) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (MGCA5; 610198), caused by mutation in the DNAJC19 gene (608977) on chromosome 3q26, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Type VI MGCA (MGCA6; 614739), caused by mutation in the SERAC1 gene (614725) on chromosome 6q25, includes deafness, encephalopathy, and a Leigh-like syndrome. Type VII MGCA (MGCA7; 616271), caused by mutation in the CLPB gene (616254) on chromosome 11q13, includes cataracts, neurologic involvement, and neutropenia. Type VIII MCGA (MGCA8; 617248) is caused by mutation in the HTRA2 gene (606441) on chromosome 2p13. Type IX MCGA (MGCA9; 617698) is caused by mutation in the TIMM50 gene (607381) on chromosome 19q13. Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003. Wortmann et al. (2013) proposed a pathomechanism-based classification for 'inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.' Clinical Features Greter et al. (1978) described brother and sister with choreoathetosis, spastic paraparesis, dementia, optic atrophy, and, in the urine, increased amounts of 3-methylglutaric and 3-methylglutaconic acids. The excretion was increased by leucine loading. 3-Methylglutaconic acid is known to be an intermediate in the catabolism of leucine. 3-Methylglutaconyl-CoA hydratase was postulated to be the deficient enzyme. Robinson et al. (1976) gave a brief report of a case of 3-methylglutaconic aciduria. The clinical picture was somewhat different and the amounts of the 2 organic acids in the urine were about 5 times greater. The hydratase mentioned above was about 30% of normal in skeletal muscle. The authors were not convinced that the primary enzyme defect was in 3-methylglutaconyl-CoA hydratase. In fibroblasts from 2 brothers with 3-methylglutaconic aciduria reported by Duran et al. (1982), Narisawa et al. (1986) demonstrated deficiency (2 to 3% of normal) of 3-methylglutaconyl-CoA hydratase (EC 4.2.1.18). The phenotype in these brothers was different from that in the cases reported by Greter et al. (1978) and others, with a progressive degenerative neurologic disorder and lesser amounts of 3-methylglutaconic acid in the urine. In patients of the latter type, Narisawa et al. (1986) found normal activity of 3-MG-CoA-hydratase. In the sibs with deficiency, the clinical picture was similar. Both had retardation of speech development and in 1 this was the only abnormality. Motor development was also delayed in the older brother, who walked first at 2 years of age and had a short attention span. He had had an unexplained episode of unconsciousness lasting nearly a day. He responded to an 18-hour fast with symptomatic hypoglycemia and metabolic acidosis. Fasting did not produce hypoglycemia in the younger brother. Fibroblasts of the parents, who were not known to be related, were not available for study. Fibroblasts from patients with the neurologic degenerative form of 3-methylglutaconic aciduria had normal levels of the enzyme 3-MG-CoA-hydratase. Defects in all 8 enzymes involved in leucine degradation have been reported; see Figure 1 of Narisawa et al. (1986). Gibson et al. (1991) emphasized phenotypic heterogeneity of this metabolic disorder. Zeharia et al. (1992) described a seemingly 'new' variant in 2 sibs with normal enzyme activity who had choreoathetoid movements, optic atrophy, and mild developmental delay. The boy demonstrated developmental improvement in his second year of life and his sister developed well, with normal school performance. Kuhara et al. (1992) reported 3-methylglutaconic aciduria discovered during pregnancy in 2 women who were generally healthy. Gibson et al. (1998) described 3 patients with this disorder, bringing the total number of patients identified with 3-MG-CoA hydratase deficiency to 8 (7 families). The phenotypic presentation has varied from mild, including delayed development of language and hyperchloremic acidosis associated with gastroesophageal reflux, to a much more severe phenotype, including seizures, cerebellar findings, and atrophy of the basal ganglia. Shoji et al. (1999) reported a 9-month-old Japanese boy with type I MGCA, who was born of consanguineous parents. He showed progressive neurologic impairment with quadriplegia, athetoid movements, and severe psychomotor retardation from age 4 months. Wiley et al. (1999) reported a boy, born of first-cousin parents of Lebanese extraction, who was found on newborn screening to have 3-methylglutaconic aciduria type I. In this patient and younger asymptomatic sib, Nga Ly et al. (2003) identified a homozygous mutation in the AUH gene (600529.0003). At 2.5 years of age, the boy was healthy, with entirely normal growth and development. Wortmann et al. (2010) provided follow-up of the Lebanese sibs reported by Nga Ly et al. (2003). At ages 9 and 6.5 years, both had normal development and unremarkable physical examinations. Brain imaging was not performed. Illsinger et al. (2004) reported a German boy with type I MGCA who had normal psychomotor development, but repeated febrile seizures. He carried a homozygous mutation (600529.0005) in the AUH gene. Wortmann et al. (2010) reported follow-up of the German patient reported by Illsinger et al. (2004). At age 10 years, he showed normal development and attended regular school but had attention-deficit/hyperactivity disorder. Brain MRI showed mild signal abnormalities in the deep frontal white matter with sparing of the U-fibers. The authors suggested that these changes may represent the earliest stages of a slowly progressive neurodegenerative disorder. Eriguchi et al. (2006) reported a 55-year-old woman who presented with progressive forgetfulness, unsteady gait, hyperreflexia, cerebellar ataxia, dysarthria, and urinary incontinence. Brain MRI showed leukoencephalopathy with hyperintensities in the cerebral white matter extending into the subcortical U-fibers and in the middle cerebellar peduncles. Urine amino acid analysis showed a pattern consistent with type I MGCA. She was born of first-cousin parents and had normal development. Genetic analysis identified a homozygous mutation (600529.0002) in the AUH gene. Wortmann et al. (2010) reported 2 unrelated patients with genetically confirmed type I MGCA who first developed symptoms as adults. A Dutch woman presented with progressive visual loss with optic atrophy at age 35, and developed dysarthria, limb ataxia, and gait ataxia over the following 16 years. A British man presented with mild cerebellar ataxia at age 30, which progressed to spastic paraparesis, nystagmus, and dementia over the next 29 years. Brain MRI at ages 61 and 50 years, respectively, showed extensive confluent white matter abnormalities in both patients. Lesions were restricted to the supratentorial region with involvement of the deep and subcortical white matter, but sparing of the cerebellum and corpus callosum. Genetic analysis identified compound heterozygous (600529.0006 and 600529.0007) and homozygous (600529.0008) mutations in the AUH gene, respectively. Wortmann et al. (2010) noted that patients with adult-onset show a distinct clinical pattern of progressive ataxia and spasticity associated with brain white matter lesions. Molecular Genetics By mutation analysis of the AUH gene in 2 patients with 3-methylglutaconyl aciduria type I, Ijlst et al. (2002) identified a nonsense mutation (600529.0001) and a splice site mutation (600529.0002). In the patient reported by Shoji et al. (1999), Matsumori et al. (2005) identified homozygosity for a splice site mutation (600529.0004). INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Eyes \- Optic atrophy GENITOURINARY Bladder \- Urinary incontinence (adult) NEUROLOGIC Central Nervous System \- Psychomotor retardation (in some patients) \- Delayed motor development \- Spastic quadriplegia \- Dystonia \- Athetosis \- Cerebellar ataxia \- Cognitive impairment \- Hyperreflexia \- Delayed speech development \- Short attention span \- Febrile seizures (reported in 1 patient) \- Dysarthria \- Cerebral atrophy, progressive \- Basal ganglia atrophy, progressive \- Leukoencephalopathy METABOLIC FEATURES \- Metabolic acidosis LABORATORY ABNORMALITIES \- Increased urinary 3-methylglutaconic acid \- Increased urinary hydroxyisovaleric acid \- Decreased activity of 3-methylglutaconyl-CoA hydratase MISCELLANEOUS \- Highly variable phenotype \- Some patients have no clinical symptoms and are detected by routine newborn screening \- Onset in infancy \- Adult onset of symptoms has been reported MOLECULAR BASIS \- Caused by mutation in the AU-specific RNA-binding protein gene (AUH, 600529.0001 ) ▲ 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	3-METHYLGLUTACONIC ACIDURIA, TYPE I	c0342727	30,169	omim	https://www.omim.org/entry/250950	2019-09-22T16:25:14	{"doid": ["0110002"], "mesh": ["C562801"], "omim": ["250950"], "orphanet": ["67046"], "synonyms": ["Alternative titles", "MGA, TYPE I", "3-METHYLGLUTACONYL-CoA HYDRATASE DEFICIENCY", "3-MG-CoA-HYDRATASE DEFICIENCY"]}
A recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma. ## Epidemiology Naxos was first described in families originating from the Greek island of Naxos. Moreover, affected families have been identified in other Aegean islands, Turkey, Israel and Saudi Arabia. A syndrome with the same cutaneous phenotype and predominantly left ventricular involvement has been described in families from India and Ecuador (Carvajal syndrome, see this term). ## Clinical description Woolly hair appears from birth, palmoplantar keratoderma develop during the first year of life and cardiomyopathy is clinically manifested by adolescence with 100% penetrance. Patients present with syncope, sustained ventricular tachycardia or sudden death. Symptoms of right heart failure appear during the end stages of the disease. In the Carvajal variant the cardiomyopathy is clinically manifested during childhood leading more frequently to heart failure. ## Etiology Mutations in the genes encoding the desmosomal proteins plakoglobin and desmoplakin have been identified as the cause of Naxos disease. Defects in the linking sites of these proteins can interrupt the contiguous chain of cell adhesion, particularly under conditions of increased mechanical stress or stretch, leading to cell death, progressive loss of myocardium and fibro-fatty replacement. ## Genetic counseling The disease is transmitted autosomal recessively. ## Management and treatment Implantation of an automatic cardioverter defibrillator is indicated for prevention of sudden cardiac death. Antiarrhythmic drugs are used for preventing recurrences of episodes of sustained ventricular tachycardia and classical pharmacological treatment for congestive heart failure, while heart transplantation is considered at the end stages. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Naxos disease	c1832600	30,170	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=34217	2021-01-23T18:34:28	{"gard": ["9795"], "mesh": ["C538346"], "omim": ["601214"], "umls": ["C1832600"], "icd-10": ["Q87.8"], "synonyms": ["KWWH type I", "Keratoderma with woolly hair type I", "Keratosis palmoplantaris with arrythmogenic cardiomyopathy", "Palmoplantar hyperkeratosis with arrythmogenic cardiomyopathy", "Palmoplantar keratoderma with arrythmogenic cardiomyopathy"]}
Weaver syndrome (WVS) is a rare, multisystem disorder characterized by tall stature, a typical facial appearance (hypertelorism, retrognathia) and variable intellectual disability. Additional features may include camptodactyly, soft doughy skin, umbilical hernia, and a low hoarse cry. ## Epidemiology Around 50 cases of Weaver syndrome have been reported to date. Precise prevalence and incidence rates are not available. ## Clinical description WVS is an overgrowth disorder that covers a very wide clinical spectrum: some affected individuals have only tall stature while others have a classic Weaver clinical picture. Tall stature (≥ two standard deviations above the mean) is found in 90% of mutation-positive individuals and most affected patients have higher than normal birth weight and length. The subtle but characteristic facial appearance is most easily recognized in early childhood when there is ocular hypertelorism, large fleshy ears and retrognathia with the appearance of a ''stuck-on'' chin with associated horizontal skin crease. About 80% of patients have mild intellectual disability. A smaller number have moderate intellectual disability with a greater impact on autonomy, while severe deficits are rare. Other variable features include macrocephaly, joint laxity, mild to severe scoliosis, pectus excavatum, hypo- and/or hypertonia, poor coordination, soft skin, clinodactyly, camptodactyly of the fingers and/or toes, umbilical hernia, and a hoarse low cry in infancy. A slightly higher risk of neuroblastoma is suspected. There is currently no data to support an increased risk of other malignancies. ## Etiology WVS is caused by mutations in the EZH2 gene (7q35-q36), a histone methyltransferase involved in transcription control. Currently there are no other known causes of WVS although there has been a single case report of an individual in whom there was a clinical suspicion of WVS and a mutation within EED, which complexes with EZH2. ## Diagnostic methods The clinical suspicion of WVS is confirmed through molecular genetic testing and the identification of a heterozygous germline mutation in EZH2. Given the subtle phenotype associated with WVS, if a germline EZH2 mutation is not identified, alternative diagnoses should be sought. ## Differential diagnosis The main differential diagnosis is Sotos syndrome (see this term) which has considerable overlap with WVS. Other disorders to consider include Beckwith-Wiedemann, Simpson-Golabi-Behmel, Malan overgrowth, tall stature-intellectual disability-facial dysmorphism and Marfan syndromes (see these terms). ## Antenatal diagnosis Prenatal diagnosis in at-risk pregnancies is possible. ## Genetic counseling WVS follows an autosomal dominant pattern of inheritance although the majority of cases to date have arisen de novo. Genetic counseling should be provided to affected families. ## Management and treatment There is no specific treatment for WVS although individual symptom management may be indicated. No specific tumor surveillance is currently recommended but clinical vigilance and early investigation for possible tumor (particularly neuroblastoma)-related symptoms are recommended. ## Prognosis With suitable treatment and support, patients with WVS have a normal 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	Weaver syndrome	c0265210	30,171	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3447	2021-01-23T18:56:32	{"gard": ["7878"], "mesh": ["C536687"], "omim": ["277590"], "umls": ["C0265210"], "icd-10": ["Q87.3"], "synonyms": ["Camptodactyly-overgrowth-unusual facies syndrome"]}
Oncogenic osteomalacia Other namesTumor-induced osteomalacia Oncogenic osteomalacia also known as oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathogenesis * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 6 Popular culture * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] Adult patients have worsening myalgias, bone pains and fatigue which are followed by recurrent fractures. Children present with difficulty in walking, stunted growth and deformities of the skeleton (features of rickets).[1] ## Cause[edit] Tumor-induced osteomalacia is usually referred to as a paraneoplastic phenomenon, however, the tumors are usually benign and the symptomatology is due to osteomalacia or rickets.[2] A benign mesenchymal or mixed connective tissue tumor (usually phosphaturic mesenchymal tumor [3] and hemangiopericytoma) are the most common associated tumors.[4] Association with mesenchymal malignant tumors, such as osteosarcoma and fibrosarcoma, has also been reported.[4] Locating the tumor can prove to be difficult and may require whole body MRI. Some of the tumors express somatostatin receptors and may be located by octreotide scanning. A phosphaturic mesenchymal tumor is an extremely rare benign neoplasm of soft tissue and bone that inappropriately produces fibroblast growth factor 23\. This tumor may cause tumor-induced osteomalacia, a paraneoplastic syndrome, by the secretion of FGF23, which has phosphaturic activity (by inhibition of renal tubular reabsorption of phosphate and renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D). The paraneoplastic effects can be debilitating and are only reversed on discovery and surgical resection of the tumor.[4] ## Pathogenesis[edit] FGF23 (fibroblast growth factor 23) inhibits phosphate transport in the renal tubule and reduces calcitriol production by the kidney. Tumor production of FGF23,[5] Secreted frizzled-related protein 4 [6] and matrix extracellular phosphoglycoprotein (MEPE)[7] have all been identified as possible causative agents for the hypophosphatemia. ## Diagnosis[edit] Biochemical studies reveal hypophosphatemia (low blood phosphate), elevated alkaline phosphatase and low serum 1, 25 dihydroxyvitamin D levels. Routine laboratory tests do not include serum phosphate levels and this can result in considerable delay in diagnosis. Even when low phosphate is measured, its significance is often overlooked. The next most appropriate test is measurement of urine phosphate levels. If there is inappropriately high urine phosphate (phosphaturia) in the setting of low serum phosphate (hypophosphatemia), there should be a high suspicion for tumor-induced osteomalacia. FGF23 (see below) can be measured to confirm the diagnosis but this test is not widely available. Once hypophosphatemia and phosphaturia have been identified, a search for the causative tumor should begin. These are small and difficult to define. Gallium-68 DOTA-Octreotate (DOTA-TATE) positron emission tomography (PET) scanning is the best way to locate these tumors.[8] If this scan is not available, other options include Indium-111 Octreotide (Octreoscan) SPECT/CT, whole body CT or MRI imaging. ### Differential diagnosis[edit] Serum chemistries are identical in tumor-induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopepetidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF-23 gene will identify patients with ADHR. ## Treatment[edit] Resection of the tumor is the ideal treatment and results in correction of hypophosphatemia (and low calcitriol levels) within hours of resection. Resolution of skeletal abnormalities may take many months. If the tumor cannot be located, treatment with calcitriol (1-3 µg/day) and phosphorus (1-4 g/day in divided doses) is instituted. Tumors which secrete somatostatin receptors may respond to treatment with octreotide. If hypophosphatemia persists despite calcitriol and phosphate supplementation, administration of cinacalcet has been shown to be useful.[9] ## Popular culture[edit] In season 2 of the USA Network series Royal Pains, Reshma Shetty (as Divya Katdare) diagnoses a storm chaser (Jamie Ray Newman) with recurring fractures to have tumor-induced osteomalacia. ## References[edit] 1. ^ Jan de Beur, SM (Sep 2005). "Tumor-induced osteomalacia". JAMA. 294 (10): 1260–7. doi:10.1001/jama.294.10.1260. PMID 16160135. 2. ^ Carpenter, TO (April 2003). "Oncogenic osteomalacia—a complex dance of factors". N Engl J Med. 348 (17): 175–8. doi:10.1056/NEJMe030037. PMID 12711747. 3. ^ Wasserman, JK; Purgina, B; Lai, CK; Gravel, D; Mahaffey, A; Bell, D; Chiosea, SI (12 January 2016). "Phosphaturic Mesenchymal Tumor Involving the Head and Neck: A Report of Five Cases with FGFR1 Fluorescence In Situ Hybridization Analysis". Head and Neck Pathology. 10 (3): 279–85. doi:10.1007/s12105-015-0678-1. PMC 4972751. PMID 26759148. 4. ^ a b c Zadik Y, Nitzan DW (October 2011). "Tumor induced osteomalacia: A forgotten paraneoplastic syndrome?". Oral Oncol. 48 (2): e9–10. doi:10.1016/j.oraloncology.2011.09.011. PMID 21985764. 5. ^ Shimada, T; Mizutani, S; Muto, T; Yoneya, T; Hino, R; Takeda, S; Takeuchi, Y; Fujita, T; Fukumoto, S; Yamashita, T (May 2001). "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia". Proc Natl Acad Sci U S A. 98 (11): 6500–5. Bibcode:2001PNAS...98.6500S. doi:10.1073/pnas.101545198. PMC 33497. PMID 11344269. 6. ^ Berndt, T; Craig, TA; Bowe, AE; Vassiliadis, J; Reczek, D; Finnegan, R; Jan De Beur, SM; Schiavi, SC; Kumar, R (Sep 2003). "Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent". J Clin Invest. 112 (5): 785–94. doi:10.1172/JCI18563. PMC 182208. PMID 12952927. 7. ^ Rowe, PS; de Zoysa, PA; Dong, R; Wang, HR; White, KE; Econs, MJ; Oudet, CL (Jul 2000). "MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia". Genomics. 67 (1): 54–68. doi:10.1006/geno.2000.6235. PMID 10945470. 8. ^ Clifton-Bligh, R. J.; Hofman, M. S.; Duncan, E.; Sim, I. -W.; Darnell, D.; Clarkson, A.; Wong, T.; Walsh, J. P.; Gill, A. J.; Ebeling, P. R.; Hicks, R. J. (2013). "Improving Diagnosis of Tumor-Induced Osteomalacia with Gallium-68 DOTATATE PET/CT". Journal of Clinical Endocrinology & Metabolism. 98 (2): 687–694. doi:10.1210/jc.2012-3642. PMID 23295468. 9. ^ Geller, J L; et al. (Jun 2007). "Cinacalcet in the management of tumor-induced osteomalacia". Journal of Bone and Mineral Research. 22 (6): 931–37. doi:10.1359/jbmr.070304. PMID 17352646. ## Further reading[edit] * Chong, WH; Molinolo, AA; Chen, CC; Collins, MT (Jun 2011). "Tumor-induced osteomalacia". Endocr Relat Cancer. 18 (3): R53–77. doi:10.1530/ERC-11-0006. PMC 3433741. PMID 21490240. * Wasserman, JK; Purgina, B; Lai, CK; Gravel, D; Mahaffey, A; Bell, D; Chiosea, SI (12 January 2016). "Phosphaturic Mesenchymal Tumor Involving the Head and Neck: A Report of Five Cases with FGFR1 Fluorescence In Situ Hybridization Analysis". Head and Neck Pathology. 10 (3): 279–85. doi:10.1007/s12105-015-0678-1. PMC 4972751. PMID 26759148. ## External links[edit] Classification D * ICD-10: M83.8 * MeSH: C537751 External resources * Orphanet: 352540 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * 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[SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Oncogenic osteomalacia	c1274103	30,172	wikipedia	https://en.wikipedia.org/wiki/Oncogenic_osteomalacia	2021-01-18T18:55:18	{"gard": ["9652"], "mesh": ["C537751"], "umls": ["C1274103"], "orphanet": ["352540"], "wikidata": ["Q7852667"]}
Plott (1964) described 3 brothers with permanent congenital laryngeal abductor paralysis and mental deficiency. A fourth male sib suspected of having been affected died perinatally. Dysgenesis of the nucleus ambiguus was considered likely. Watters and Fitch (1973) presented a pedigree which made X-linked recessive inheritance likely. Two brothers were affected together with a first cousin once removed connected through females. Opitz (1977) made the useful point that brain damage resulting from respiratory distress may dominate the picture so that X-linked mental retardation (see 309530) may be suspected. Opitz et al. (1978) published 2 pedigrees collected by Durkin (1974) which showed typical X-linked recessive inheritance. Resp \- Congenital laryngeal stridor Neuro \- Congenital laryngeal abductor paralysis \- Mental retardation Inheritance \- X-linked recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [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	LARYNGEAL ABDUCTOR PARALYSIS	c0396059	30,173	omim	https://www.omim.org/entry/308850	2019-09-22T16:17:56	{"mesh": ["C536354"], "omim": ["308850"], "orphanet": ["2375"], "synonyms": ["Alternative titles", "VOCAL CORD DYSFUNCTION, FAMILIAL", "PLOTT SYNDROME"]}
## Clinical Features Clunie and Mason (1962) described a seemingly distinct disorder in 3 brothers whose parents were first cousins. All had recurrent femoral and/or inguinal hernias and diverticula of the large and small bowel or urinary bladder. Two of the brothers had a marfanoid habitus. A sister had diverticula. Severe myopia, internal strabismus, and retinal detachment were present in the 3 brothers. De Silva et al. (1996) described a brother and sister, offspring of consanguineous Sri Lankan parents, with marfanoid features (see 154700), visceral diverticula, and diaphragmatic eventration. There was no evidence of lens dislocation and the aortic root measurement was normal. The brother had a large bladder diverticulum. The eventration of the left hemidiaphragm developed between ages 4 years and 8 years. The sister had mitral valve prolapse. Both had inguinal hernia. The sister had malrotation and volvulus of the bowel producing bowel obstruction and multiple colonic diverticula. Gangrenous diverticula required surgery. By the age of 11, left diaphragmatic hernia developed. Inheritance Affected sibs of consanguineous, unaffected parents suggests autosomal recessive inheritance of this disorder (de Silva et al., 1996). GU \- Bladder diverticula Inheritance \- Autosomal recessive Abdomen \- Inguinal hernia \- Femoral hernia GI \- Colon diverticula \- Small bowel diverticula Eyes \- Myopia \- Strabismus \- Retinal detachment ▲ 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	DIVERTICULOSIS OF BOWEL, HERNIA, AND RETINAL DETACHMENT	c1857227	30,174	omim	https://www.omim.org/entry/223330	2019-09-22T16:28:40	{"mesh": ["C565619"], "omim": ["223330"], "orphanet": ["2464"]}
## Description Torsade de pointes is characterized by an electrocardiographic (ECG) pattern of nonuniform but still-organized electrical activity with progressive changes in morphology, amplitude, and polarity of the QRS complexes, the peaks of which twist around the isoelectric baseline before ending spontaneously. In classic torsade de pointes, the coupling interval of the first beat is long (see LQT1, 192500), whereas in this short-coupled variant, the coupling interval of the first beat is very short (summary by Leenhardt et al., 1994). Clinical Features Leenhardt et al. (1994) described 14 patients, 7 men and 7 women (mean age, 34.6 years) without structural heart disease, who were referred for the evaluation and treatment of severe syncope; each had at least 1 documented episode of ventricular tachyarrhythmia showing the electrical characteristics of torsade de pointes. Syncope was provoked by emotion in 2 patients and by exercise in 1 patient. In 10 of the 14 patients, degeneration of torsade de pointes into ventricular fibrillation was documented, and the patients required resuscitation; 4 patients had a family history of sudden death. In all 14 patients, the coupling interval of the first beat of the torsade de pointes was very short (around 245 ms; range, 200 to 300 ms), in contrast to the long coupling interval of the first beat in classic torsade de pointes. The morphology of the first beat and of isolated ventricular premature beats were strikingly similar in 9 patients, with a left axis deviation and a left bundle branch block pattern. The morphology was different in the 5 other patients, with right axis and/or right bundle branch block, but the coupling interval was always short. Resting ECGs were normal in all but 1 patient, who had rate-dependent left bundle branch block. Electrophysiologic study of all 14 patients showed no abnormality of basic electrophysiologic parameters, including ventricular refractoriness. Over a mean follow-up period of 7 years, there were 6 deaths: 1 was due to stroke in a hypertensive patient, and the other 5 occurred suddenly, during sleep for 2 patients and in undefined circumstances for the other 3. Of the 8 living patients, 3 underwent placement of an implantable cardioverter-defibrillator (ICD) device. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	TORSADE DE POINTES, SHORT-COUPLED VARIANT	c3150851	30,175	omim	https://www.omim.org/entry/613600	2019-09-22T15:58:13	{"omim": ["613600"], "orphanet": ["51084"], "synonyms": []}
Combined immunodeficiency (CID) due to Ca2+ release activated Ca2+(CRAC) channel dysfunction is a form of CID characterized by recurrent infections, autoimmunity, congenital myopathy and ectodermal dysplasia. It comprises two sub-types that are due to mutations in the ORAI1 and STIM1 genes: CID due to ORAI1 deficiency and CID due to STIM1 deficiency. ## Epidemiology CID due to CRAC channel dysfunction has been reported in 10 patients from 5 families, 6 patients in 3 families with ORAI1 mutations and 4 patients in two families with STIM1 mutations. ## Clinical description CID due to CRAC channel dysfunction is characterized by recurrent viral, bacterial, mycobacterial and fungal infections from birth, chronic diarrhea, pneumonia, meningitis, enteritis, gastrointestinal candidiasis, sepsis and otitis media. In addition, patients present at birth with congenital myopathy, which is characterized by non-progressive generalized muscular dysplasia. For cases with ORAI1 mutations this presents as poor head control after birth, delayed ambulation and a positive Gower's sign, while patients with STIM1 mutations present with global muscular hypotonia and partial iris hypoplasia. All patients present with ectodermal dysplasia that is characterized by hypocalcified amelogenesis imperfecta (see this term) and leads to the loss of soft dental enamel. Patients with ORAI1 mutations also have anhydrosis, which is characterized by inability to sweat and recurrent fever episodes associated with impaired thermoregulation. Patients with STIM1 mutations also show signs of lymphoproliferative and autoimmune disease including lymphadenopathy, hepatosplenomegaly, autoimmune thrombocytopenia and autoimmune hemolytic anemia. ## Etiology CID due to CRAC channel dysfunction is caused by mutations in the ORAI1 and STIM1 genes (12q24 and 11p15.5). ## Diagnostic methods Diagnosis is based on clinical features and testing the function and proliferation of T cells. Patients have normal lymphocyte counts and serum immunoglobulin levels but severely compromised T cell activation. ## Differential diagnosis Differential diagnoses include combined immunodeficiency (CID) due to ZAP70 deficiency, CID due to CD3gamma deficiency, immunodeficiency due to CD25 deficiency, hypohidrotic ectodermal dysplasia with immunodeficiency and anhidrotic ectodermal dysplasia - immunodeficiency - osteopetrosis - lymphedema syndrome. ## Antenatal diagnosis Prenatal diagnosis can be performed where there is a family history and where the genetic mutation has been identified. ## Genetic counseling Transmission is autosomal recessive. ## Management and treatment Treatment with hematopoietic stem cell transplantation (HSCT) has been successful in some cases. ## Prognosis Without treatment, patients fail to thrive and die in their first year 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	Combined immunodeficiency due to CRAC channel dysfunction	c2748568	30,176	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169090	2021-01-23T18:03:48	{"mesh": ["C557826"], "omim": ["612782", "612783"], "icd-10": ["D81.8"], "synonyms": ["Immune dysfunction due to T-cell inactivation due to calcium entry defect"]}
## Clinical Features Shahidi (1967) described a 17-year-old girl with severe methemoglobinemia and hemolysis following ingestion of acetophenetidin. The activity of G6PD, 6PGD, diaphorase, and glutathione reductase was normal, as was the concentration of reduced glutathione. Hemoglobin was physically normal. Previously unknown metabolites of acetophenetidin were found in the urine. A 38-year-old sister showed the same abnormality. Inadequate deethylation was suggested with increased hydroxylation of acetophenetidin to hydroxyphenetidin which was thought to be responsible for methemoglobin production. Phenobarbital administration had adverse effects, possibly by stimulation of the hydroxylation process. The parents were not related. The family was of German extraction (Shahidi, 1967). Shahidi (1982) was not aware of additional reports of acetophenetidin toxicity. He noted that because of the toxicity, particularly nephrotoxicity, of acetophenetidin, N-acetyl-p-aminophenol (acetaminophen; e.g., Tylenol) had almost totally replaced it. Inheritance \- Autosomal recessive Miscellaneous \- Phenobarbital worsens Heme \- Acetophenetidin sensitivity \- Methemoglobinemia \- Hemolysis ▲ 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	ACETOPHENETIDIN SENSITIVITY	c1860214	30,177	omim	https://www.omim.org/entry/200300	2019-09-22T16:31:41	{"omim": ["200300"]}
A rare hereditary ataxia characterized by progressive truncal and limb ataxia resulting in gait instability. Dysarthria, dysphagia, nystagmus, spasticity of the lower limbs, mild peripheral sensory neuropathy, cognitive impairment and accelerated ageing have also been 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	Autosomal recessive cerebellar ataxia due to STUB1 deficiency	c4014261	30,178	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=412057	2021-01-23T17:28:04	{"omim": ["615768"], "icd-10": ["G11.1"], "synonyms": ["SCAR16", "Spinocerebellar ataxia autosomal recessive type 16"]}
A locus associated with susceptibility to basal cell carcinoma has been identified on chromosome 1p36 (BCC1). Description Cutaneous basal cell carcinoma (BCC) is the most common cancer among people of European ancestry (Stacey et al., 2009). The primary environmental risk factor for BCC is sun exposure, but genetics also has a substantial role. Some of the sequence variants that confer susceptibility seem to operate through their association with fair-pigmentation traits common among Europeans, resulting in reduced protection from the damaging effects of ultraviolet (UV) radiation. Other sequence variants have no obvious role in pigmentation or UV susceptibility but instead seem to operate in the contexts of growth and differentiation of the basal layers of the skin (Stacey et al., 2008; Epstein, 2008; Gudbjartsson et al., 2008; Rafnar et al., 2009). See ASIP (600201), TYR (606933), and SHEP5 (227240) for examples of basal cell carcinoma associated with fair skin or sensitivity to sun. Basal cell carcinoma occurs as a feature of multiple syndromes, including basal cell nevus syndrome (BCNS; 109400), Bazex syndrome (301845), Rombo syndrome (180730), Brooke-Spiegler syndrome (605041), Muir-Torre syndrome (158320), and xeroderma pigmentosum (see 278700). Abnormalities in the Hedgehog signaling pathway are found in basal cell carcinomas; see SHH (600725) and SMOH (601500). ### Genetic Heterogeneity of Susceptibility to Basal Cell Carcinoma Susceptibility to basal cell carcinoma is a genetically heterogeneous trait. The BCC1 locus maps to chromosome 1p36. Also see BCC2 (613058) on 1q42; BCC3 (613059) on 5p15; BCC4 (613061) on 12q13; BCC5 (613062)on 9p21; and BCC6 (613063)on 7q32. Variation in the 3-prime untranslated region of TP53 (191170) increases susceptibility to basal cell carcinoma (BCC7; 614740). Somatic mutation contributing to the formation of basal cell carcinoma has been identified in the RASA1 (139150), PTCH1 (601309), and PTCH2 (603673) genes. Clinical Management Basal cell carcinomas are usually managed surgically. Von Hoff et al. (2009) reported the results of a phase I clinical trial using GDC-0449, a small molecule inhibitor of SMO (601500), on metastatic or locally advanced basal cell carcinoma. Of 33 patients followed over a median period of 9.8 months, 18 had an objective response to GDC-0449, 2 with complete resolution and 16 with a partial response. Among the other 15 patients, disease was either stable (11 patients) or progressive (4 patients). Among 6 patients, there were 8 grade 3 adverse events that were deemed to be possibly related to the study drug, including fatigue, hyponatremia, muscle spasm, and atrial fibrillation. One patient withdrew from the study because of adverse events. In a Ptch1-Trp53 mouse model of BCC, Biehs et al. (2018) found that mice treated with the SMOH inhibitor vismodegib harbored quiescent residual tumors that regrew upon cessation of treatment. Profiling experiments revealed that residual BCCs initiate a transcriptional program that closely resembles that of stem cells of the interfollicular epidermis and isthmus, whereas untreated BCCs are more similar to the hair follicle bulge. This cell identity switch was enabled by a mostly permissive chromatin state accompanied by rapid Wnt (see 604663) pathway activation and reprogramming of superenhancers to drive activation of key transcription factors involved in cellular identity. Accordingly, treatment of BCC with both vismodegib and a Wnt pathway inhibitor reduced the residual tumor burden and enhanced differentiation. Biehs et al. (2018) concluded that their study identified a resistance mechanism in which tumor cells evade treatment by adopting an alternative identity that does not rely on the original oncogenic driver for survival. Sanchez-Danes et al. (2018) used 2 genetically engineered mouse models of BCC to investigate the mechanisms by which inhibition of SMOH mediates tumor regression, and found that vismodegib mediates BCC regression by inhibiting a hair follicle-like fate and promoting the differentiation of tumor cells. However, a small population of tumor cells persists and is responsible for tumor relapse following treatment discontinuation, mimicking the situation found in humans. In both mouse and human BCC, this persisting, slow-cycling tumor population expresses LGR5 (606667) and is characterized by active Wnt signaling. Combining Lgr5 lineage ablation or inhibition of Wnt signaling with vismodegib treatment leads to eradication of BCC. Sanchez-Danes et al. (2018) concluded that vismodegib induces tumor regression by promoting tumor differentiation, and demonstrated that the synergy between Wnt and Smoothened inhibitors is a clinically relevant strategy for overcoming tumor relapse in BCC. Inheritance Happle (2000) postulated that there is an autosomal dominant phenotype characterized by multiple superficial BCC without associated anomalies that is distinct from nevoid basal cell carcinoma syndrome (109400). The author cited 2 lines of evidence in favor of this hypothesis. First, there are several reports of multiple cases of BCC occurring in 2 generations of a family, including male-to-male transmission. Second, there are 3 reports of strictly unilateral manifestation of multiple superficial BCC, suggesting somatic mosaicism. This occurrence is difficult to explain without the assumption that nonsyndromic multiple superficial BCC may occur as a distinct mendelian trait. Pathogenesis Ramachandran et al. (2001) presented evidence suggesting that different mechanisms underlie the development of truncal and nontruncal BCC. They studied 100 patients who, at the time of initial presentation, had truncal BCC lesions and 493 patients who had lesions on the head and neck. The 493 patients with head and neck lesions included 36 patients who subsequently developed truncal BCCs and 457 patients who did not. The mean truncal tumor accrual after initial presentation in patients who presented with initial truncal BCC lesions was 0.13 BCC lesions per year compared with 0.03 BCC lesions per year in patients who presented with initial head and neck lesions (P less than 0.001). Patients with truncal lesions were significantly younger at the time of initial presentation and developed more clusters of BCC lesions (2 to 10 new tumors at any presentation) compared with patients who did not develop tumors on the trunk. Constitutive Hedgehog (see 600725) signaling underlies several human tumors, including BCC and basaloid follicular hamartoma in skin. Intriguingly, superficial BCCs arise as de novo epithelial buds resembling embryonic hair germs, collections of epidermal cells whose development is regulated by canonical Wnt (164820)/beta-catenin (116806) signaling. Yang et al. (2008) found that similar to embryonic hair germs, human BCC buds showed increased levels of cytoplasmic and nuclear beta-catenin and expressed early hair follicle lineage markers. Yang et al. (2008) also detected canonical Wnt/beta-catenin signaling in epithelial buds and hamartomas from mice expressing an oncogene, M2-SMO (601500.0001), leading to constitutive hedgehog signaling in skin. Conditional overexpression of the Wnt pathway antagonist Dkk1 (605189) in M2SMO-expressing mice potently inhibited epithelial bud and hamartoma development without affecting hedgehog signaling. Yang et al. (2008) concluded that their findings uncovered a hitherto unknown requirement for ligand-driven, canonical Wnt/beta-catenin signaling for hedgehog pathway-driven tumorigenesis, identified a new pharmacologic target for these neoplasms, and established the molecular basis for the well-known similarity between early superficial BCCs and embryonic hair germs. Mapping In a genomewide SNP association study of 930 Icelanders with BCC and 33,117 controls, Stacey et al. (2008) observed signals from loci at chromosomes 1p36 and 1q42 (BCC2; 613058). These associations were replicated in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, p = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, p = 5.9 x 10(-12)). Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Stacey et al. (2008) estimated that approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers. The 1p36 SNP rs7538876 is in intron 13 of the peptidylarginine deiminase-6 gene (PADI6; 610363). The A allele of rs7538876 was associated with a younger age at diagnosis of BCC in both Icelandic and Eastern European samples (P = 6.0 x 10(-4)). Molecular Genetics Friedman et al. (1993) analyzed 188 human tumor samples for mutations within the catalytic domain of the GAP gene and for mutations within its C-terminal SH2 region. Although no mutations could be demonstrated in the catalytic domain, 3 different nonsense mutations in the SH2 region were observed in basal cell carcinomas (e.g., 139150.0001). The region in which the mutations were clustered is A/T rich, raising the possibility that UV radiation is a contributing factor. Using single-strand conformation polymorphism (SSCP), Gailani et al. (1996) screened 37 sporadic BCCs for mutations in the PTCH1 gene and found mutations in 16 (e.g., 601309.0009). Variants in 4 of these 16 were also found in constitutional DNA, and each had been found in at least 12% of normal controls. Nine of the 12 tumor-specific alterations were in the remaining allele of tumors with loss of heterozygosity (LOH) for 9q22, and in 3 tumors without LOH a single variant was found. Of 26 sporadic BCC screened by Aszterbaum et al. (1998) for mutations in PTCH1, 3 had PTCH1 mutations (e.g., 601309.0010), each in a different exon of the gene. Each of these 3 had sustained deletion of the second allele. Aszterbaum et al. (1998) concluded that PTCH1 acts as a classic tumor suppressor gene, requiring 2 'hits' for tumorigenesis in at least some BCC. Using SSCP and heteroduplex analysis, Smyth et al. (1999) identified a nucleotide substitution in the splice donor site of exon 20 of the PTCH2 gene (603673.0002) in a basal 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	BASAL CELL CARCINOMA, SUSCEPTIBILITY TO, 1	c2751544	30,179	omim	https://www.omim.org/entry/605462	2019-09-22T16:11:24	{"omim": ["605462"]}
Jansen's metaphyseal chondrodysplasia (JMC) is a very rare autosomal dominant skeletal dysplasia characterized by short-limbed short stature (due to severe metaphyseal changes that are often discovered in childhood by imaging), waddling gait, bowed legs, contracture deformities of the joints, short hands with clubbed fingers, clinodactyly, prominent upper face and small mandible, as well as chronic parathyroid hormone-independent hypercalcemia, hypercalciuria, and mild hypophosphatemia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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, Jansen type	c0265295	30,180	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33067	2021-01-23T17:36:16	{"gard": ["79"], "mesh": ["C537564"], "omim": ["156400"], "umls": ["C0265295"], "icd-10": ["Q78.5"]}
A number sign (#) is used with this entry because Charcot-Marie-Tooth disease type 1A is caused by duplication of, or mutation in, the gene encoding peripheral myelin protein-22 (PMP22; 601097). Deletion of the PMP22 gene characteristically results in hereditary neuropathy with liability to pressure palsies (HNPP; 162500). Point mutations have also been described in the PMP22 gene in patients thought to have hypertrophic neuropathy of Dejerine-Sottas (145900). Description For a general phenotypic description and a discussion of genetic heterogeneity of Charcot-Marie-Tooth disease type 1, see CMT1B (118200). CMT1A is the most common form of CMT. The average age of onset of clinical symptoms is 12.2 +/- 7.3 years. Slow nerve conduction velocity (NCV) less than 38 m/s is highly diagnostic and is a 100% penetrant phenotype independent of age (Lupski et al. (1991, 1992)). Clinical Features Bird et al. (1983) and Dyck et al. (1983) reported families of typical CMT1 except that linkage to the Duffy blood group locus (Fy) on chromosome 1, where CMT1B maps, was excluded. Whereas Dyck et al. (1983) could discern no phenotypic differences between the linked and unlinked forms, Bird et al. (1983) suggested that slowing of nerve conduction is less marked and onion bulb formation on sural nerve biopsy less conspicuous in the Duffy-unlinked form. Berciano et al. (1994) observed that clinically normal adult CMT1A patients are rare, but do exist. They referred to 1 duplication-positive woman who had normal neurologic examinations at least up to the age of 31 even though her motor nerve conduction velocities were 30 meters per second in the median nerve. This patient had a clinically affected 4-year-old son. Berciano et al. (1994) stressed the importance of doing not only neurologic examinations but also electrophysiologic studies or DNA studies to exclude the diagnosis of CMT1A. Hoogendijk et al. (1994) reviewed the clinical and neurographic features of 44 affected individuals, aged 8 to 68 years (mean 34 years), from 6 families with chromosome 17p duplication. Motor nerve conduction velocity and, to a lesser extent, compound muscle action potential amplitude were inversely related to clinical severity. Neither clinical severity nor NCV was significantly related to age. They interpreted the findings as suggesting that the primary pathologic process is not active, or only slightly active, after childhood. Garcia et al. (1995) found remarkable concordance of nerve conduction velocities in each of 2 pairs of male homozygotic twins with a type 1A duplication. There was also congruity between the left and right side of each twin as well as between twin brothers. However, there was marked dissimilarity in the clinical severity in each of the twin pairs, as well as asymmetric clinical involvement of each affected individual. Palpable nerve enlargement was greater in the less affected twins than in their more severely affected brothers. The marked discrepancy between nerve conduction velocities and clinical weakness suggested that other factors must be responsible. Lupski et al. (1993) studied 2 unrelated patients with both CMT1 and neurofibromatosis type I (NF1; 162200). Since both of these disorders map to the pericentric region of chromosome 17, they investigated whether this might be a contiguous gene syndrome. In both patients, however, the CMT1A was inherited from the father, who did not have NF1. Furthermore, molecular analysis showed that the CMT1A duplication was stable in the 2 patients. One patient transmitted both disorders to her daughter. Thus, this was a chance concurrence of 2 common disorders. Bosch et al. (1981) had also reported the concurrence of these 2 conditions. Pyramidal dysfunction due to compression of the cervical spinal cord by hypertrophied nerve roots, resembling radicular neurofibromas, had been reported in several individuals with type 1 Charcot-Marie-Tooth disease by Rosen et al. (1989). Butefisch et al. (1999) reported an individual with compression of the cervical spine and the cauda equina, similar to the cases described by Rosen et al. (1989). By demonstrating a duplication of the PMP22 gene, they confirmed that this individual had CMT1A. Liehr et al. (1996) identified mosaicism for the CMT1A duplication by 3 different and independent techniques. Mosaicism was supported by the clinical features of the patient. The 25-year-old woman reported painful sensations in the shoulders, which increased after exercise. She had markedly reduced motor and sensory nerve conduction velocities and showed bilateral pes cavus. She showed a mild distally pronounced muscular weakness of the arms and legs. Muscle stretch reflexes were absent. Sensory disturbances of the limbs were located distal to the elbow and knees. Vibration sense was reduced at the malleolus internus. Sural nerve biopsy showed a marked reduction of myelinated fibers with signs of demyelination and onion bulb formation. Four different tissues were investigated successfully, yielding different patterns of mosaicism. Dematteis et al. (2001) diagnosed sleep apnea (107650) and CMT1A in 1 family member and prospectively investigated 13 further members not previously suspected of having neuropathy or sleep apnea. Eleven of the 14 family members had the autosomal dominant demyelinating form of CMT with PMP22 gene duplication. In addition, all 11 individuals had sleep apnea syndrome with a mean apnea-hypopnea index of 46.6 per hour (28.5) of sleep (normal value less than 15 per hour). The remaining 3 family members were free from neuropathy and sleep apnea syndrome. Sleep apnea and neuropathy severity were highly correlated; the compound muscle action potential amplitude of the median nerve was inversely correlated with the apnea-hypopnea index. The severity of neuropathy and of sleep apnea was higher in male CMT individuals and correlated with age and body mass index. No wake or sleep diaphragmatic dysfunction was shown. Dematteis et al. (2001) concluded that sleep apnea syndrome is related to a pharyngeal neuropathy. Patients with CMT disease are particularly susceptible to vincristine neurotoxicity (Weiden and Wright, 1972; Griffiths et al., 1985). Naumann et al. (2001) reported a 31-year-old woman with recurrent Hodgkin lymphoma (236000) and unrecognized HMSN I who developed severe motor neuropathy 3 weeks after the first cycle of treatment including 2 mg of vincristine. After the fact, the patient was found to have bilateral pes cavus deformity since early childhood, contractions of ankle joints, and shortened Achilles tendons. Her brother and mother had areflexia and moderate foot deformity. The diagnosis of HMSN IA was confirmed by molecular analysis. Swan et al. (2007) found no differences in disability, as measured by a CMT neuropathy score, between 44 previously pregnant women with CMT1A compared to both 47 affected men or 15 affected women who had never been pregnant. Statistical analysis revealed no difference in severity between men and woman overall. Approximately 50% of women who had been pregnant noted a worsening of symptoms during pregnancy, mainly weakness, changes in balance, and alterations in sensation. Nine of these women reported a permanent worsening, and 13 felt it was temporary, lasting about 2.5 months after giving birth. However, symptom scores between these 2 groups were not significant. Swan et al. (2007) concluded that men and women are equally disabled by CMT1A and that neither gender, pregnancy, nor plasma progesterone levels significantly contribute to the severity of neuropathy in women with CMT1A. Diagnosis Matise et al. (1994) referred to the tandem duplication underlying CMT1A as resulting in segmental trisomy. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within the duplication. Matise et al. (1994) demonstrated that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. They devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. Schiavon et al. (1994) devised a rapid, informative, economical, and easily interpretable nonradioactive test for detection of the CMT1A duplication based on a microsatellite polymorphism. They found the CMT1A duplication in 76% of 56 unrelated patients. King et al. (1998) described a patient with CMT1A caused by duplication of the PMP22 gene through an unusual mechanism: unbalanced translocation of 17p to the X chromosome. This finding further supported the hypothesis of gene dosage as the basis of CMT1A. The case highlighted the importance of fluorescence in situ hybridization as an alternative molecular technique in the diagnosis of CMT1A. The duplication would not have been detected by standard commercial methods based on identification of a novel junction fragment by pulsed field gel electrophoresis. Aarskog and Vedeler (2000) described a quantitative PCR method for detecting both duplication and deletion of the PMP22 gene in CMT1A and HNPP, respectively. Their method of real-time quantitative PCR is a sensitive, specific, and reproducible method allowing 13 patients to be diagnosed in 2 hours. It involves no radioisotopes and requires no post-PCR handling. Saporta et al. (2011) were able to find a molecular basis for 527 (67%) of 787 patients with a clinical diagnosis of CMT. The most common CMT subtypes were CMT1A in 55%, CMT1X (302800) in 15.2%, HNPP (162500) in 9.1%, CMT1B (118200) in 8.5%, and CMT2A2 (609260) in 4.0%. All other subtypes accounted for less than 1% each. Eleven patients had more than 1 genetically identified subtype of CMT. Patients with genetically identified CMT were separable into specific groups based on age of onset and the degree of slowing of motor nerve conduction velocities. Saporta et al. (2011) concluded that combining features of the phenotype and physiology allowed for identification of patients with specific subtypes of CMT, and proposed a strategy of focused genetic testing for CMT. Clinical Management In a double-blind, randomized, placebo-controlled pilot study, Sahenk et al. (2005) found that subcutaneous administration of the nerve growth factor neurotrophin-3 (NT3; 162660) promoted peripheral nerve regeneration and sensory improvement in 4 patients with CMT1A compared to 4 untreated patients. Similar results were observed for 2 mouse models of CMT: 1 with the common PMP22 duplication and 1 with a PMP22 point mutation. Sahenk et al. (2005) concluded that NT3 improved mutant Schwann cell survival and differentiation, resulting in increases in the available Schwann cell pool, which in turn increased the number of myelinated fibers. Selles et al. (2006) reported that the Rotterdam Intrinsic Hand Myometer (RIHM) demonstrated excellent reliability in the measurement of intrinsic hand muscle strength in patients with CMT. Shy et al. (2008) reported use of the 'CMT Neuropathy Score' (CMTNS) and the 'Neuropathy Impairment Score' (NIS) to determine the rate of disease progression in patients with CMT1A over time. The scoring systems could be used to monitor disease progression and standardize the efficacy of certain treatments. Videler et al. (2008) presented evidence that loss of motor axons is the major cause of hand dysfunction in patients with CMT1A. Evaluation of fine motor skills of the hand in 48 patients with CMT1A showed a correlation between decreased pinch strength, clawing of the fingers, and decreased manual dexterity, and motor axon loss as measured by compound muscle action potentials and motor unit number estimation. There was no significant correlation between motor and sensory impairment. Mapping Middleton-Price et al. (1989, 1990), Nicholson et al. (1989), and Vance et al. (1989) presented evidence that one form of Charcot-Marie-Tooth disease is determined by a mutation on chromosome 17. In all 3 reports, high lod scores were obtained for linkage to D17S58 and D17S71. The disorder mapping to chromosome 17 was referred to as Charcot-Marie-Tooth disease type 1A or hereditary motor and sensory neuropathy type I (HMSN I). In studies of 7 families, Chance et al. (1989, 1990) found a high probability of linkage to chromosome 17 markers in 5. Of the other 2, linkage to the Duffy blood group was suggested in 1 and excluded in the other. In the 2 families that did not show linkage to chromosome 17, the disease was more severe than in the chromosome 17 families. In a multigenerational family in Belgium, Raeymaekers et al. (1989) excluded chromosome 1 as the site of the mutation and demonstrated linkage to D17S58 and D17S71. By further linkage studies in this family, Timmerman et al. (1990) demonstrated that the CMT1A gene is located in the chromosomal region 17p12-p11.2 between marker D17S71 and the gene for myosin heavy chain polypeptide-2 of adult skeletal muscle (MYH2; 160740). In a large French-Acadian kindred, Patel et al. (1990) confirmed the localization of CMT1A to the pericentromeric region of chromosome 17. McAlpine et al. (1990) provided linkage data on 5 Caucasian families which excluded linkage of CMT1A to the Fy area of chromosome 1 and demonstrated close linkage to D17S58, located at 17p11.2-p11.1; maximum lod = 10.828 at theta = 0.0. The CMT1A locus appeared to be proximal to MYH2, which maps to 17p13. By differential Alu-PCR of a rodent-human hybrid cell containing only chromosome 17 and a rodent-human cell containing only chromosome 17 with a deletion of the p11.2 band, Patel et al. (1990) isolated a marker that showed linkage to CMT1A with a peak lod score of 3.41 at a recombination fraction of 0.12. By multipoint linkage analysis, Vance et al. (1991) localized the CMT1A gene to 17p11.2 and identified flanking DNA markers. Lebo et al. (1992) studied the order of markers in the region of the CMT1A gene by means of multicolor in situ hybridization which they showed could resolve loci within 0.5 Mb on early-metaphase chromosomes. Molecular Genetics ### Common 1.5-Mb Duplication on Chromosome 17p12-p11 See 601097.0001 for discussion of the work of Lupski et al. (1991) and others indicating that a DNA duplication on chromosome 17 in the p12-p11.2 region is frequently the basis of CMT1A. Hoogendijk et al. (1992) found that 9 of 10 sporadic patients had the duplication in chromosome 17 as a de novo change. Hertz et al. (1994) also demonstrated that a sporadic case of CMT1A was due to de novo duplication of the 17p12-p11.2 region. In all 12 de novo CMT1A duplications reported to that time, the duplication was of paternal origin. Sorour et al. (1995) described a case of CMT1A with molecular duplication of 17p12-p11.2 and inheritance of the duplication from a mosaic father. Whereas the patient had typical clinical features, the father had minimal findings of CMT1A. To investigate the frequency of de novo CMT1A duplications, Blair et al. (1996) examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. They estimated that 10% or more of autosomal dominant CMT1 families are due to de novo duplications. Using polymorphic markers from within the duplicated region, they showed that 7 of the duplications were of paternal and 1 of maternal origin. This was the first report of a de novo duplication of maternal origin. Bort et al. (1997) reported that the prevalence of de novo mutation in duplication-positive CMTA1 families was 18.3%. They reported that the ratio of maternal to paternal origin of the duplication was 1:8 in their study. Weterman et al. (2010) identified a heterozygous 186-kb deletion on chromosome 17p12 with breakpoints within the common 1.5-Mb duplication but not involving the PMP22 gene in 6 probands with CMT1A. The duplication segregated with the disorder in 2 families and was absent in more than 2,000 control chromosomes. Haplotype analysis of 2 families suggested a founder effect. The junction breakpoints were located in a repeat-rich region, located 90-kb from the proximal CMT repeat region on 1 side and 3-kb upstream of PMP22 between PMP22 and TEKT3 (612683) on the other side. The junctions created by this duplication were located outside of any known genes or open reading frames, and there was no indication for the involvement of genes located within the duplication. Weterman et al. (2010) postulated that this duplication affects PMP22 expression levels through an as yet unidentified mechanism. Weterman et al. (2010) noted that the 186-kb duplication would not be detected in most diagnostic assays. ### Point Mutations in the PMP22 Gene In a Dutch kindred with CMT1A, Valentijn et al. (1992) identified a point mutation in the PMP22 gene (601097.0002). Thus, either duplication or point mutation in the PMP22 gene can result in CMT1A. Fabrizi et al. (1999) reported a family in which 4 individuals over 4 generations had severe CMT1A with focal myelin thickenings with a regular fusiform contour (tomacula) or a coarsely granular appearance. Ultrastructural examination disclosed uncompacted myelin and redundant irregular myelin loops. All affected patients had a heterozygous mutation in the PMP22 gene (601097.0016). Fabrizi et al. (2000) noted that myelin outfoldings have been described in other autosomal dominant CMT patients with mutations in MPZ (159440.0023), EGR2 (129010.0004), and PMP22, and that the finding is not restricted to CMT4B (see CMT4B1; 601382). Kleopa et al. (2004) reported a family from Cyprus in which 4 affected individuals had features of HNPP and/or CMT1A. One patient presented with typical HNPP, which later progressed to severe CMT1, 2 patients had HNPP with features of CMT1, and 1 patient had a chronic asymptomatic CMT1 phenotype. All 4 patients had the same heterozygous point mutation in the PMP22 gene (601457.0019). Kleopa et al. (2004) emphasized the broad phenotypic spectrum resulting from mutations in the PMP22 gene, as well as the phenotypic overlap of HNPP and CMT1A. Genotype/Phenotype Correlations Suter and Patel (1994) reviewed and discussed the curious finding that gene dosage and point mutations affecting the same gene can lead to a similar phenotype. They pointed to a possibly identical situation with Pelizaeus-Merzbacher disease (312080) in which either deletion of the entire locus encoding proteolipid protein (PLP1) (Raskind et al., 1991), as described in 300401.0006, or duplication of the PLP1 locus (Cremers et al., 1987) can cause Pelizaeus-Merzbacher disease. Gabreels-Festen et al. (1995) compared the histology of peripheral nerve in patients with duplication of the PMP22 gene to those with point mutations. In the duplication cases, onion bulbs developed gradually in the first years of life, and the ratio of the axon diameter versus the fiber diameter was significantly lower than normal. In contrast, in patients with point mutations in PMP22, nearly all myelinated fibers had a high ratio of axon diameter versus fiber diameter, and onion bulbs were abundant from an early age. Pellegrino et al. (1996) illustrated how it is possible in some instances to determine the genetic basis of clinical features in chromosomal rearrangements. They reported a child with monosomy 10q and dup(17p) resulting from an apparently balanced maternal translocation t(10;17)(q26.3;p11.2). Manifestations of both the duplication and the monosomy were present; however, the overall development was better than that previously reported in either syndrome. The patient's motor development was significantly more impaired than cognitive development, and signs of a peripheral neuropathy were found and attributed to duplication of 17p. Indeed, the patient was found to be trisomic for the PMP22 gene resulting in demyelinating neuropathy. An elevated serum alpha-fetoprotein had been detected at 16 weeks of gestation. The infant showed bilateral inguinal hernias and hydroceles at birth, and echocardiogram demonstrated ventriculoseptal defect (VSD) and bicuspid aortic valve. There was gastroesophageal reflux requiring Nissen fundoplication with gastrostomy tube. The VSD closed spontaneously. Hypoplastic corpus callosum was demonstrated by MRI. Terminal deletions of 10q had been reported in 26 patients, resulting in a definite phenotype (Wulfsberg et al., 1989). The manifestations included postnatal growth retardation, microcephaly, downslanting palpebral fissures, clinodactyly, syndactyly, congenital heart disease, and urogenital anomalies, all of which were present in the patient reported by Pellegrino et al. (1996). Gouvea et al. (2010) reported an unusual case of a father and daughter with CMT who had 2 mutations in the PMP22 gene: the common 1.4-Mb duplication and S72L (601097.0007). Restriction analysis indicated that the S72L mutation was only present in 1 of the 3 PMP22 genes for both father and daughter. Both patients had a relatively mild form of the disease, manifest mainly as generalized pain without significant motor or sensory defects. The findings suggested that presence of 2 mutations in the PMP22 gene results in an attenuated form of the disease rather than a more severe form. Gouvea et al. (2010) hypothesized that the increased dosage resulting from the 1.4-Mb duplication offset the toxic gain-of-function effects of the S72L mutation on intracellular trafficking. In 2 unrelated patients with a severe form of CMT1A, Liu et al. (2014) identified a 1.4-Mb triplication of the PMP22 gene (601097.0022). Each individual was part of a family with autosomal dominant CMT1A in which the other affected family members had the common 1.4-Mb duplication and a more typical CMT1A phenotype that was less severe. In both families, molecular analysis of the triplication indicated that it occurred on the chromosome with the duplication and arose from the duplication during meiosis in the affected mother. Haplotype analysis indicated 2 different mechanisms: in 1 family, the triplication arose via intrachromosomal nonallelic homologous recombination (NAHR), whereas in the other family it arose from intrachromosomal NAHR followed by a gene-conversion event that most likely exchanged alleles between the maternal homologous chromosomes. A review of a database for CMT1A duplication testing identified 13% with duplication and 0.024% with a duplication-to-triplication event. These findings suggested that the rate of duplication to triplication is higher than that of de novo duplication. Liu et al. (2014) proposed that individuals with duplications are predisposed to acquiring triplications and that the population prevalence of triplication may be underestimated. The inheritance pattern in this scenario resembles genetic anticipation and has implications for genetic counseling. Pathogenesis Katona et al. (2009) found highly variable levels of PMP22 protein, ranging from below normal to above normal, in skin biopsies from 20 patients with CMT1A due to the common 1.4-Mb duplication in the PMP22 gene. The findings were somewhat surprising, since an overall increase in PMP22 gene expression and protein was expected. In addition, there was no correlation between PMP22 mRNA or protein levels and phenotypic severity in CMT1A. In contrast, 6 individuals with HNPP (162500) due to the reciprocal PMP22 deletion had similarly decreased PMP22 levels. Katona et al. (2009) noted that PMP22 levels are tightly coordinated in the normal state, and that about 90% of translated PMP22 is rapidly degraded and never inserted into myelin (Pareek et al., 1997). Katona et al. (2009) hypothesized that dysregulation and variability of PMP22 expression may cause CMT1A, but noted that the disorder cannot result simply from a loss of normal function, since the phenotypes of CMT1A and HNPP are so different. The findings indicated that phenotypic variability in CMT1A cannot be explained by PMP22 levels in myelin. Population Genetics Lupski et al. (1992) stated that CMT in all of its forms is the most common inherited peripheral neuropathy in humans, with a total prevalence rate of 1 in 2,500. In a series of 172 index cases of Italian families in which there was at least 1 subject with CMT1, Mostacciuolo et al. (2001) found that among 170 informative unrelated patients, the frequency of the chromosome 17 duplication was 57.6%. A difference was observed between the duplication frequency in familial (71.6%) as opposed to nonfamilial cases (36.8%). Among the patients without the duplication, 2 had mutations in the PMP22 gene, 12 in the GJB1 gene (304040), 4 in the MPZ gene (159440), and none in the EGR2 gene (129010). Among 153 unrelated patients with CMT, Boerkoel et al. (2002) found that 79 had a PMP22 duplication. The 1.5-Mb duplication of PMP22 is the predominant cause of autosomal dominant CMT1, accounting for approximately 70% of all cases (Reilly, 2005). Among 227 Japanese patients with demyelinating CMT, Abe et al. (2011) found that 53 (23.3%) carried PMP22 duplications and 10 (4.4%) carried PMP22 mutations. These were the most common genetic causes of demyelinating CMT, but the frequency of duplications was less than that observed in Caucasian populations. A molecular basis for demyelinating CMT could not be identified in 111 Japanese patients. Animal Model In a review of hereditary motor and sensory neuropathies, Vance (1991) pointed to the autosomal dominant 'Trembler' mutation (Tr) in the mouse as a possibly homologous condition. A hypomyelin neuropathy with onion bulb formation develops in older animals. Because of the extensive homology of synteny between mouse 11 and human 17 (Green, 1989), it is particularly attractive to think that these may be fundamentally the same disorder. In 2 allelic forms of the Trembler mouse, Suter et al. (1992, 1992) demonstrated point mutations in 2 distinct putative membrane-associated domains of a potentially growth-regulated 22-kD protein, peripheral myelin protein-22 (Pmp22). PMP22 is expressed by Schwann cells and is localized mainly in compact peripheral nervous system myelin. Baechner et al. (1995) demonstrated widespread distribution of PMP22 RNA in several mesodermal and ectodermal tissues of developing mice, as well as in the villi of the adult gut, suggesting to them a broader biologic significance for Pmp22 in cell proliferation or differentiation. Huxley et al. (1996) constructed a mouse model for CMT1A by pronuclear injection of a YAC containing the human PMP22 gene and a large proportion of the region duplicated in CMT1A. They noted that CMT1A represents a unique case in which partial trisomy of a major gene leads to the pathology. Yeast artificial chromosomes are ideal for creating animal models of overexpression of genes since they contain very large stretches of DNA within which not only the structural gene but the long range controlling elements that confer full levels of tissue-specific expression may be present. In 1 transgenic line, about 8 copies of the human DNA was integrated into a mouse chromosome. This mouse developed a peripheral neuropathy closely similar to that seen in human CMT1A, with progressive weakness of the hind legs, severe demyelination in the peripheral nervous system, and the presence of onion bulb formations. Perea et al. (2001) generated a transgenic mouse model for CMT in which mouse Pmp22 overexpression occurs specifically in Schwann cells of the peripheral nerve and is switched off when the mice are fed tetracycline. Overexpression of Pmp22 throughout life (in the absence of tetracycline) causes demyelination. In contrast, myelination is nearly normal when Pmp22 overexpression is switched off throughout life by feeding the mice tetracycline. When overexpression of Pmp22 is switched off in adult mice, correction begins within 1 week and myelination is well advanced by 3 months, suggesting that the Schwann cells are poised to start myelination. Upregulation of the gene in adult mice (which had previously had normal Pmp22 expression) is followed by active demyelination within 1 week. The authors hypothesized that even adult mice are sensitive to the level of expression of Pmp22 with respect to homeostasis of the myelin sheath. The steroid hormone progesterone has been shown to stimulate Pmp22 gene expression both in cultured Schwann cells and in adult mice (Melcangi et al., 1999). Using a rat model of CMT1A with extra copies of the Pmp22 gene, Sereda et al. (2003) demonstrated that the progesterone antagonist onapristone reduced overexpression of Pmp22 and improved the CMT phenotype in male mice, as indicated by maintenance of large axons and improved motor performance. Pmp22 mRNA was decreased by 15% in onapristone-treated animals. Sereda et al. (2003) suggested that a reduction in Pmp22 transcription may have a beneficial effect on the disease course. In mutant mice overexpressing Pmp22, Passage et al. (2004) found that treatment with ascorbic acid resulted in amelioration of the CMT1A phenotype, as measured by improved motor function and increased survival. The treated mice also showed a 10-fold decrease in Pmp22 RNA in sciatic nerves. Passage et al. (2004) noted that ascorbic acid is a promoter of myelination, and proposed a mechanism of Pmp22 suppression via inhibition of cAMP. In HeLa cell studies, Khajavi et al. (2007) observed that Tr and TrJ mutant human PMP22 proteins accumulated within the endoplasmic reticulum (ER) and induced apoptosis. Treatment of these cells with curcumin, a chemical compound derived from turmeric, decreased apoptosis, similar to that observed in a previous study of mutant MPZ (Khajavi et al., 2005). Oral curcumin treatment of TrJ newborn mice resulted in dose-dependent improved motor performance that correlated pathologically with decreased Schwann cell apoptosis, increased axonal caliber, and increased myelin thickness compared to untreated mice. Bioavailability studies showed low serum levels of curcumin with accumulation in sciatic nerves and brain of treated animals. Treated mice exhibited no side effects. Khajavi et al. (2007) concluded that curcumin reduced the toxic effects of mutant aggregation-induced apoptosis, possibly by enabling a more efficient protein-trafficking process in the ER. Meyer zu Horste et al. (2007) found that long-term treatment with subcutaneous onapristone in 5-week-old rats with a duplication of the Pmp22 gene resulted in significantly increased muscle strength and muscle mass at 26 weeks. Detailed studies of peripheral nerves indicated that treatment reduced progressive axonal loss but did not alter the visible myelination pathology, suggesting that axonal support and myelin assembly are distinct physiologic functions of Schwann cells, both of which are interrupted in CMT. Pmp22 levels in cutaneous nerve at 9 weeks correlated with hind-limb grip strength at 26 weeks. INHERITANCE \- Autosomal dominant SKELETAL Spine \- Kyphoscoliosis may occur Hands \- Claw hand deformities (in severe cases) Feet \- Pes cavus \- Hammer toes \- Foot deformities NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- 'Steppage' gait \- Foot drop \- Cold-induced muscle cramps \- Distal sensory impairment \- Hyporeflexia \- Areflexia \- Decreased motor nerve conduction velocity (NCV) (less than 38 m/s) \- Hypertrophic nerve changes \- 'Onion bulb' formations on nerve biopsy \- Segmental demyelination/remyelination on nerve biopsy \- Decreased number of myelinated fibers \- Myelin outfoldings may occur in a subset of patients MISCELLANEOUS \- Onset in first or second decade \- Usually begins in feet and legs (peroneal distribution) \- Upper limb involvement usually occurs later \- Slowly progressive \- Insidious onset \- Variable severity \- Genetic heterogeneity (see CMT1B, 118200 ) \- Allelic disorders with overlapping phenotypes include Dejerine-Sottas syndrome (DSS, 145900 ), hereditary neuropathy with liability to pressure palsies (HNPP, 162500 ), and CMT with deafness ( 118300 ) MOLECULAR BASIS \- Caused by mutations in the peripheral myelin protein-22 gene (PMP22, 601097.0001 ) ▲ 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, DEMYELINATING, TYPE 1A	c0270911	30,181	omim	https://www.omim.org/entry/118220	2019-09-22T16:43:24	{"doid": ["0110148"], "mesh": ["D002607"], "omim": ["118220"], "orphanet": ["101081"], "synonyms": ["Alternative titles", "HEREDITARY MOTOR AND SENSORY NEUROPATHY IA", "HMSN1A", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1A", "CHARCOT-MARIE-TOOTH DISEASE, AUTOSOMAL DOMINANT, WITH FOCALLY FOLDED MYELIN SHEATHS, TYPE 1A"]}
Moloney leukemia virus, a retrovirus lacking a transforming (onc) gene, induces thymic lymphomas in rats and mice. In rat and mouse thymomas, proviral integration occurs nonrandomly in at least 9 DNA regions. Anagnou et al. (1989) cloned the human homolog of one of these integration sites, called MLVI2. As an initial step in the investigation of its possible role in the induction and progression of human neoplasms, they studied its map location by use of a panel of human/rodent somatic cell hybrids and in situ hybridization to metaphase chromosomes. They showed that MLVI2 maps to 5p14. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	MOLONEY LEUKEMIA VIRUS INTEGRATION SITE 2, MOUSE, HOMOLOG OF	c1417195	30,182	omim	https://www.omim.org/entry/157960	2019-09-22T16:38:05	{"omim": ["157960"]}
A number sign (#) is used with this entry because of evidence that the Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is caused by heterozygous mutation in the keratin-14 gene (KRT14; 148066) on chromosome 17q21. A closely related disorder, dermatopathia pigmentosa reticularis (DPR; 125595), is also caused by heterozygous mutation in the KRT14 gene. Clinical Features Naegeli (1927) described the syndrome in a father and 2 daughters. In a restudy of the original family, Franceschetti and Jadassohn (1954) documented autosomal dominant inheritance. The disorder was earlier confused with incontinentia pigmenti (IP; see 308300). Differences from IP include (1) equal frequency in males and females; (2) plantar and palmar hypohidrosis and hyperkeratosis; and (3) uncommon blistering and inflammatory phenomena. The cardinal features are reticular cutaneous pigmentation (starting at about the age of 2 years without a preceding inflammatory stage), discomfort provoked by heat with diminished sweat gland function, poor teeth, and moderate hyperkeratosis of the palms and soles. Males and females are equally affected. Sparrow et al. (1976) described 7 affected persons in 1 family, with male-to-male transmission. Hypoplasia of the dermatoglyphics was present. Itin et al. (1993) reexamined the original family with NFJS 65 years after the first description (Naegeli, 1927). The pedigree included 62 members with 14 affected patients; Itin et al. (1993) examined the 10 living patients. They found that the reticulate pigmentation faded after puberty and sometimes disappeared completely in old age. Hypohidrosis, the main problem for the patients, remained constant. Teeth were always severely affected, leading to early total loss. All patients lacked dermatoglyphics. (Adermatoglyphia is a feature of several ectodermal dysplasias (Freire-Maia and Pinheiro, 1984).) Diffuse palmoplantar keratoderma may coexist with punctate keratoses that are sometimes accentuated in the creases or exhibit a linear pattern. Four patients had congenital malalignment of the great toenails, a feature not previously described. See 246500 for a similar condition possibly inherited as a recessive. NFJS and dermatopathia pigmentosa reticularis (DPR; 125595) are closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. Mapping Whittock et al. (2000) studied a multigeneration NFJS family of Anglo-Saxon British descent using microsatellite markers. Significant genetic linkage to chromosome 17q was observed using marker D17S1787, with a maximum 2-point lod score of 4.166 at a recombination fraction of theta = 0. Recombination events in the family place the gene in a 26.97-cM interval between markers D17S798 and D17S957, a region known to contain the type I keratin (see 601077) gene cluster and other genes expressed in epithelia. Keratins K15 (148030), K19 (148020), and K20 (608218), plakoglobin (JUP; 173325), and MEOX1 (600147) were excluded as candidates by direct sequencing of genomic PCR products. Sprecher et al. (2002) studied the large Swiss family with NFJS originally described by Naegeli (1927) and assessed linkage to chromosome 17q, which was proposed to harbor the NFJ syndrome gene. Their results narrowed the NFJS locus region to 6 cM flanked by D17S933 and D17S934 with a maximum multipoint lod score of 2.7 at marker locus D17S800. The critical interval spanned approximately 5.4 Mb and contained a minimum of 45 distinct genes. Sprecher et al. (2002) scrutinized 13 new candidate genes in addition to 5 genes previously examined, established the genomic organization of 10 of these genes, and excluded all of them by mutation analysis. They identified a novel keratin protein (KRT24; 607742) that bears high similarity to the type I keratins and displays a unique expression profile. Lugassy et al. (2006) studied 4 families with NFJS, including the family originally reported by Naegeli (1927), as well as a family with a closely related disorder, dermatopathia pigmentosa reticularis (DPR; 125595). They confirmed the previously demonstrated linkage of NFJS/DPR to 17q11.2-q21. Combined multipoint analysis generated a maximal lod score of 8.3 at marker D17S800 at a recombination fraction of 0.0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Molecular Genetics In 4 families with NFJS, including the family originally reported by Naegeli (1927), as well as in a family with DPR, Lugassy et al. (2006) identified heterozygous nonsense or frameshift mutations in the KRT14 gene that segregated with the disease trait in all 5 families (148066.0015, 148066.0016, and 148066.0019). In contrast with KRT14 mutations affecting the central alpha-helical rod domain of keratin-14, which cause epidermolysis bullosa simplex of several clinical types, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and were predicted to result in very early termination of translation. The data suggested that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules confers protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR. History Family 1 in the study of NFJS by Lugassy et al. (2006) was the large multigenerational Swiss family in which the disorder was originally described by Naegeli in 1927 and had been followed since that time in a number of reports over a period of 80 years (Franceschetti and Jadassohn, 1954; Itin et al., 1993). INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Premature tooth loss \- Carious teeth \- Yellow discoloration SKIN, NAILS, & HAIR Skin \- Reticulate hyperpigmentation (periocular, perioral, chest, neck, abdomen) \- Hypohidrosis \- Absent fingerprints \- Palmoplantar keratoderma \- Multiple, small punctate keratoses (palms and soles) Nails \- Brittle nails \- Congenital malalignment of great toenails MISCELLANEOUS \- Heat intolerance \- Onset of hyperpigmentation in early childhood (3 months-6 years) that fades after puberty MOLECULAR BASIS \- Caused by mutation in the keratin-14 gene (KRT14, 148066.0015 ) ▲ 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	NAEGELI-FRANCESCHETTI-JADASSOHN SYNDROME	c0343111	30,183	omim	https://www.omim.org/entry/161000	2019-09-22T16:37:40	{"mesh": ["C538331"], "omim": ["161000"], "orphanet": ["69087"], "synonyms": ["Alternative titles", "NAEGELI SYNDROME", "NFJ SYNDROME"]}
A number sign (#) is used with this entry because of evidence that familial hypertrophic cardiomyopathy-9 (CMH9) is caused by heterozygous mutation in the TTN gene (188840) on chromosome 2q31. For a phenotypic description and a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy (CMH), see CMH1 (192600). Molecular Genetics In 1 of 82 patients with hypertrophic cardiomyopathy who had no mutation in known disease genes, Satoh et al. (1999) identified a mutation in the TTN gene (188840.0001) that was not found in more than 500 normal chromosomes and increased the binding affinity of titin to alpha-actinin (see 102575) in the yeast 2-hybrid assay. Herman et al. (2012) used next-generation sequencing to analyze the TTN gene in 203 individuals with dilated cardiomyopathy (CMD; see CMD1G, 604145), 231 with CMH, and 249 controls. The frequency of TTN mutations was significantly higher among individuals with CMD (27%) than among those with CMH (1%) or controls (3%). In the 3 patients with CMH in whom TTN truncating or splicing mutations were identified, concurrent analyses revealed a pathogenic mutation in the known CMH genes MYH7 (160760) or MYBPC3 (600958). Herman et al. (2012) suggested that TTN truncations rarely, if ever, cause hypertrophic cardiomyopathy. Lopes et al. (2013) analyzed the coding, intronic, and regulatory regions of 41 cardiovascular genes in 223 unrelated patients with CMH using high-throughput sequencing technology. They found 219 rare variants in 142 (63.6%) of the patients: 30 patients (13%) had titin candidate variants in isolation, 22 (10%) had titin variants only in association with desmosomal gene candidate variants or ion channel disease-associated variants, and 171 (77%) carried a TTN candidate variant in association with sarcomere, Z-disc, or calcium-handling gene variants. Lopes et al. (2013) noted that titin has been difficult to sequence and study due to its size, large number of isoforms, and unsolved tertiary structure. All of the individual variants present in this cohort occurred with a frequency of less than 0.5% in the 1000 Genomes Project, suggesting that a proportion of them might be, at the very least, modulators of the phenotype. However, the overall frequency of variants in the CMH cohort was actually lower than that seen in the control exome population. Lopes et al. (2013) concluded that further work on understanding the role of titin in CMH was necessary. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy MISCELLANEOUS \- Based on report of 1 patient MOLECULAR BASIS \- Caused by mutation in the titin gene (TTN, 188840.0001 ) ▲ 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	CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 9	c1861065	30,184	omim	https://www.omim.org/entry/613765	2019-09-22T15:57:34	{"mesh": ["C566044"], "omim": ["613765"]}
Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) is a condition that can affect the muscles, bones, and brain. The first symptom of IBMPFD is often muscle weakness (myopathy), which typically appears in mid-adulthood. Weakness first occurs in muscles of the hips and shoulders, making it difficult to climb stairs and raise the arms above the shoulders. As the disorder progresses, weakness develops in other muscles in the arms and legs. Muscle weakness can also affect respiratory and heart (cardiac) muscles, leading to life-threatening breathing difficulties and heart failure. About half of all adults with IBMPFD develop a disorder called Paget disease of bone. This disorder most often affects bones of the hips, spine, and skull, and the long bones of the arms and legs. Bone pain, particularly in the hips and spine, is usually the major symptom of Paget disease. Rarely, this condition can weaken bones so much that they break (fracture). In about one-third of people with IBMPFD, the disorder also affects the brain. IBMPFD is associated with a brain condition called frontotemporal dementia, which becomes noticeable in a person's forties or fifties. People with frontotemporal dementia initially may have trouble speaking, remembering words and names (dysnomia), and using numbers (dyscalculia). Over time, the condition damages parts of the brain that control reasoning, personality, social skills, speech, and language. Personality changes, a loss of judgment, and inappropriate social behavior are also hallmarks of the disease. As the dementia worsens, affected people ultimately become unable to speak, read, or care for themselves. People with IBMPFD usually live into their fifties or sixties. ## Frequency Although the prevalence of IBMPFD is unknown, this condition is rare. It has been diagnosed in several hundred people worldwide. ## Causes Mutations in the VCP gene cause IBMPFD. The VCP gene provides instructions for making an enzyme called valosin-containing protein, which has a wide variety of functions within cells. One of its most critical jobs is to help break down (degrade) proteins that are abnormal or no longer needed. Mutations in the VCP gene alter the structure of valosin-containing protein, impairing its ability to break down other proteins. As a result, excess and abnormal proteins build up in muscle, bone, and brain cells. The proteins form clumps that interfere with the normal functions of these cells. It remains unclear how damage to muscle, bone, and brain cells leads to the specific features of IBMPFD. ### Learn more about the gene associated with Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia * VCP ## 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. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia	c4551951	30,185	medlineplus	https://medlineplus.gov/genetics/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia/	2021-01-27T08:25:31	{"gard": ["10899"], "omim": ["167320"], "synonyms": []}
Epilepsy syndrome that is characterised by generalised seizures with no apparent cause Generalized epilepsy Other namesPrimary generalized epilepsy, idiopathic epilepsy Generalized 3 Hz spike-and-wave discharges on an electroencephalogram SpecialtyNeurology Generalized epilepsy is a form of epilepsy characterised by generalised seizures with no apparent cause.[1] Generalized seizures, as opposed to focal seizures, are a type of seizure that impairs consciousness and distorts the electrical activity of the whole or a larger portion of the brain (which can be seen, for example, on electroencephalography, EEG).[2] Generalized epilepsy is primary because the epilepsy is the originally diagnosed condition itself, as opposed to secondary epilepsy, which occurs as a symptom of a diagnosed condition.[3] ## Contents * 1 Manifestation * 2 Prognosis * 3 Treatment * 4 References * 5 External links ## Manifestation[edit] Generalized seizures can be either absence seizures, myoclonic seizures, clonic seizures, tonic-clonic seizures or atonic seizures. Generalized seizures occur in various seizure syndromes, including myoclonic epilepsy, familial neonatal convulsions, childhood absence epilepsy, absence epilepsy, infantile spasms (West's syndrome), Juvenile Myoclonic Epilepsy, Lennox-Gastaut syndrome and Generalized epilepsy with occipital semiology.[4] ## Prognosis[edit] Most generalized epilepsy starts during childhood. While some patients outgrow their epilepsy during adolescence and no longer need medication, in others, the condition remains for life, thereby requiring lifelong medication and monitoring. ## Treatment[edit] Seven anti-epileptic drugs are approved[where?][when?] for use in cases of suspected primary generalized epilepsy: * Brand Name: Felbatol Generic Name: Felbamate [5] * Levetiracetam * Zonisamide * Topiramate * Valproate * Lamotrigine * Perampanel Valproate, a relatively old drug, is often considered the first-line treatment. It is highly effective, but its association with fetal malformations when taken in pregnancy limits its use in young women.[6] All anti-epileptic drugs (including the above) can be used in cases of partial seizures. ## References[edit] 1. ^ "Comprehensive Epilepsy Center \| NYU Langone Medical Center". Med.nyu.edu. Retrieved 2016-12-16. 2. ^ "Primary Generalized Epilepsy". Nervous-system-diseases.com. 2013-09-09. Retrieved 2016-12-16. 3. ^ "Seizures or epilepsy". Pediatricservices.com. 2013-01-26. Retrieved 2016-12-16. 4. ^ Gómez-Porro, Pablo; Serrano, Angel Aledo; Toledano, Rafael; García-Morales, Irene; Gil-Nagel, Antonio (October 2018). "Genetic (idiopathic) generalized epilepsy with occipital semiology". Epileptic Disorders. 20 (5): 434–439. doi:10.1684/epd.2018.0994. ISSN 1294-9361. 5. ^ Personal Use 6. ^ Vajda, FJ; O'brien, TJ; Hitchcock, A; Graham, J; Cook, M; Lander, C; Eadie, MJ (November 2004). "Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy". Journal of Clinical Neuroscience. 11 (8): 854–8. doi:10.1016/j.jocn.2004.05.003. PMID 15519862. ## External links[edit] Classification D * ICD-10: G40.3 * ICD-9-CM: 345.0-345.1 * MeSH: D004829 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis * v * t * e Seizures and epilepsy Basics * Seizure types * Aura (warning sign) * Postictal state * Epileptogenesis * Neonatal seizure * Epilepsy in children Management * Anticonvulsants * Investigations * Electroencephalography * Epileptologist Personal issues * Epilepsy and driving * Epilepsy and employment Seizure types Focal Seizures Simple partial Complex partial Gelastic seizure Epilepsy Temporal lobe epilepsy Frontal lobe epilepsy Rolandic epilepsy Nocturnal epilepsy Panayiotopoulos syndrome Vertiginous epilepsy Generalised * Tonic–clonic * Absence seizure * Atonic seizure * Automatism * Benign familial neonatal seizures * Lennox–Gastaut syndrome * Myoclonic astatic epilepsy * Epileptic spasms Status epilepticus * Epilepsia partialis continua * Complex partial status epilepticus Myoclonic epilepsy * Progressive myoclonus epilepsy * Dentatorubral–pallidoluysian atrophy * Unverricht–Lundborg disease * MERRF syndrome * Lafora disease * Juvenile myoclonic epilepsy Non-epileptic seizure * Febrile seizure * Psychogenic non-epileptic seizure Related disorders * Sudden unexpected death in epilepsy * Todd's paresis * Landau–Kleffner syndrome * Epilepsy in animals Organizations * Citizens United for Research in Epilepsy (US) * Epilepsy Action (UK) * Epilepsy Action Australia * Epilepsy Foundation (US) * Epilepsy Outlook (UK) * Epilepsy Research UK * Epilepsy Society (UK) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer 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Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Generalized epilepsy	c0014548	30,186	wikipedia	https://en.wikipedia.org/wiki/Generalized_epilepsy	2021-01-18T18:55:50	{"mesh": ["D004829"], "umls": ["C0014548"], "icd-9": ["345.1", "345.0"], "icd-10": ["G40.4"], "wikidata": ["Q5532415"]}
Darier's disease Other namesDarier disease, Darier–White disease,[1] Dyskeratosis follicularis,[1] and Keratosis follicularis[2]:523[3]:567 Linear Darier's disease SpecialtyMedical genetics Darier's disease (DAR) is an autosomal dominant disorder discovered by French dermatologist Ferdinand-Jean Darier. Darier's is characterized by dark crusty patches on the skin that are mildly greasy and that emit a strong odor. These patches, also known as keratotic papules, keratosis follicularis, or dyskeratosis follicularis, most often appear on the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear.[4][5] Mild forms of the disease are the most common, consisting solely of skin rashes that flare up under certain conditions such as high humidity, high stress, or tight-fitting clothes. Short stature, when combined with poorly-formed fingernails that contain vertical striations, is diagnostic even for mild forms of DAR. Symptoms will usually appear in late childhood or early adulthood between the ages of 15 to 30 years and will vary over the course of one’s life. ## Contents * 1 Genetics * 2 Epidemiology * 3 Symptoms and diagnosis * 4 Treatment * 5 History * 6 See also * 7 References ## Genetics[edit] Mutations in a single gene, ATP2A2, are responsible for the development of Darier’s disease. ATP2A2 encodes the SERCA2 protein, which is a calcium pump localized to the membranes of the endoplasmic reticulum (ER) in nearly all cells and the sarcoplasmic reticulum (SR) in muscle cells. The ER is where protein processing and transport begins for proteins targeted for secretion. The SR is a specialized form of ER found in muscle cells that sequesters calcium, the regulated efflux of which into the cytosol stimulates muscle fiber contraction. Calcium acts as a second messenger in many cellular signal transduction pathways. SERCA2 is required for Ca2+ signaling in cells by removing nearly all Ca2+ ions from the cytoplasm and storing them in the ER/SR compartments.[6][7][8][9] Darier's disease has an autosomal dominant pattern of inheritance. A large number of mutant alleles of ATP2A2 have been identified in association with Darier’s Disease. One study of 19 families and 6 sporadic cases found 24 specific, novel mutations associated with DAR symptoms. This study reported a loose, imperfect correlation between the severity of ATP2A2 mutations with the severity of the condition. Significant variability in disease severity between members of the same family carrying the same mutation was also reported by this study, suggesting that genetic modifiers contribute to the phenotypic penetrance of certain mutations.[10] The mutation is inherited in an autosomal dominant pattern. This means that only one allele needs to be mutated in order to express the trait. This also means that someone who is born to one parent with DAR has a 50% chance of inheriting the mutant allele and having the disease. Loss-of-function mutations typically display recessive inheritance while the gain-of-function or hyperactive function of proteins is characteristic of dominant mutations. The observation that only one mutated allele of the SERCA2 is sufficient to produce clinical symptoms suggests that proper “gene dosage” is necessary for maintaining Ca2+ homeostasis in cells.[7] This means that two wild type copies of ATP2A2 are needed for proper cell function, which provides a logical basis for dominant phenotypes arising from loss-of-function alleles. Most ATP2A2 mutations are haploinsufficiency mutations, which means that only having only one functional copy of the functional gene results in a reduced level of protein expression that is not sufficient for wild type function for making enough of the coded protein for the cell to function properly. However, there is significant variability in disease severity in how the mutations are expressed even within families that have the same mutation. It is currently unclear in the current research why a reduction in SERCA2 expression/activity causes clinical symptoms restricted to the epidermis. One hypothesis that some researchers have given is that other cell types express additional “back-up” Ca2+ pumps that can compensate for the reduced function or expression of the SERCA2 protein, while skin cells rely exclusively on the SERCA2 gene for calcium sequestration, meaning only they are affected by its reduction in expression.[8] As mentioned above, some cases of DAR result from somatic mutations to ATP2A2 in epidermal stem cells. These cases are referred to as instances of “linear” Darier’s disease. Such individuals display phenotypic mosaicism, where the Darier’s phenotype only affects the subset of epidermal tissue arising from the mutated progenitor cell. Somatic mutations are not inherited by the offspring of such individuals.[11] ## Epidemiology[edit] Worldwide prevalence is estimated as between 1:30,000 and 1:100,000. Case studies have shown estimated prevalence by country to be 3.8:100,000 in Slovenia,[12] 1:36,000 in north-east England,[13] 1:30,000 in Scotland,[14] and 1:100,000 in Denmark.[15] ## Symptoms and diagnosis[edit] Diagnosis of Darier disease is often made by the appearance of the skin, family history, or genetic testing for the mutation in the ATP2A2 gene. However, many individuals affected by this disorder are never diagnosed, due to the mildness of symptoms in most cases. Mild cases present clinically are minor rashes (without odor) that can become exacerbated by heat, humidity, stress, and sunlight. The symptoms of the disease are thought to be caused by an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion.[8][16] [16] Rash associated with Darier's disease Malformed, weak nails with V-shaped chips, a common sign of Darier's disease[16] Darier's disease is an incommunicable disorder that is seen in males and females equally. Symptoms typically arise between the ages of 15 and 30. One study of 100 British individuals diagnosed with Darier's disease reported that affected individuals display elevated frequencies of neuropsychiatric conditions. There were high lifetime rates for mood disorders (50%), including depression (30%), bipolar disorder (4%), suicidal thoughts (31%), and suicide attempts (13%), suggesting a possible common genetic link.[17] Several case studies have suggested affected populations display elevated frequencies of learning disorders, but this has yet to be confirmed. * Clinical symptoms that are often used in the diagnosis of the disease: * Seborrhoeic areas * This is defined as areas where excess oil and sebum is released. * Overall greasy or scaly skin either in the central chest and back or in the folds of the skin. * Fragile or poorly formed fingernails * Nail disease leading to V-shaped nicks at the edge of the nail. * Rash that covers many areas of the body * The rash is often associated with a strong unpleasant odor * The rash can be aggravated by heat, humidity, and exposure to sunlight. * Mucosal manifestation * White cobblestone pattern of small papules * Overgrowth of gums * Usually affects the mouth, esophagus, rectum, vulva, vagina * Oral symptoms can be diagnosed by a routine dental examination * Other symptoms and their overall prevalence in the affected population:[18] * In 80-90% of patients * Acrokeratosis Verruciformis[16] * Acrokeratosis is characterized by several small wart-like and flat-topped bumps that line the skin on typically the hand and feet.[19] * Hypermelanotic macule * Patches on the skin that contain excess pigment, they often appear as dark patches in the skin. * Pruritus * Itching * Subungual hyperkeratotic fragments * Thickened skin that is often discolored, under nails, on either hands or feet. * Palmar pits * Usually red in color, they are pits or depressions in the palms or soles of the hands and feet. * In 30-79% of patients * Abnormal hair morphology * Acne Conglobata * Typically described as cystic acne ## Treatment[edit] Treatment of Darier disease depends on the severity of the presented clinical symptoms. In most minor cases, the disorder can be managed using sunscreen, moisturizing lotions, avoidance of non-breathable clothing, and excessive perspiration. In more severe cases of Darier's disease, affected individuals may display frequent relapse and remit patterns. In less severe cases, signs and symptoms may clear up completely through hygienic interventions. Most patients with Darier's disease live normal, healthy lives. Rapid resolution of rash symptoms can be complicated due to the increased vulnerability of affected skin surfaces by secondary bacterial or viral infections. Epidermal Staphylococcus aureus, human papillomavirus (HPV) and herpes simplex virus (HSV) infections have been reported. In these cases, topical and/or oral antibiotic/antiviral medications may need to be prescribed.[20] Typical recommendations are: * Application of antiseptics * Soak in astringents * Antibiotics * Benzoyl peroxide[21] * Topical diclofenac sodium[22][23] If Darier's is more localized, common treatments include: * Topical retinoids: used to help in the reduction of hyperkeratosis, retinoids work by causing the skin cells in the top layers to die and be shed off. The common retinoids used for this disorder are: * Adapalene * Tazarotene gel * Tretinoin * Dermabrasion * Removal of the top layer of skin to help smooth and stimulate new growth of the skin.[24] * Electrosurgery * Used to help stop bleeding and remove abnormal skin growths. * Topical corticosteroids If symptoms are severe, oral retinoids be prescribed and have been proven to be 90% effective. However, there can be many adverse side-effects associated with prolonged use.[25] Common oral retinoids are: * Acitretin * Isotretinoin * Cyclosporine Some patients are able to prevent flares with use of topical sunscreens and oral vitamin C.[26] Further information on and advocacy work for Darier's disease are provided by the FIRST Skin Foundation.[27] ## History[edit] Darier’s disease was first described in a paper from 1917 by the dermatologist Ferdinand-Jean Darier in the French dermatological journal Annales de dermatologie et de syphilographie. Darier was a well-regarded dermatologist of the time who was the head of the medical department at the Hôpital Saint-Louis. Darier was an early proponent of histopathology, or the examination of samples of diseased flesh under a microscope to determine the cause of illnesses. Using this technique, he was able to uncover the origins of Darier’s disease and a host of others that also bear his name.[28] James Clark White, a dermatologist at Harvard Medical School, independently characterized and published his observations on this dermatological disorder in the same year as Darier (1889), which is why Darier's disease is also referred to as Darier-White disease. ## See also[edit] * Linear Darier disease * List of cutaneous conditions * Darier's sign ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis, MO: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. ISBN 0-7216-2921-0. 4. ^ National Organization for Rare Disorders (2002). NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. ISBN 0-7817-3063-5. 5. ^ Sehgal, V. N.; Srivastava, G. (2005). "Darier's (Darier-White) disease/keratosis follicularis". International Journal of Dermatology. 44 (3): 184–192. doi:10.1111/j.1365-4632.2004.02408.x. PMID 15807723. S2CID 45303870. 6. ^ Monk, Sarah; Sakuntabhai, Anavaj; Carter, Simon A.; Bryce, Steven D.; Cox, Roger; Harrington, Louise; Levy, Elaine; Ruiz-Perez, Victor L.; Katsantoni, Eleni; Kodvawala, Ahmer; Munro, Colin S. (April 1998). "Refined Genetic Mapping of the Darier Locus to a <1-cM Region of Chromosome 12q24.1, and Construction of a Complete, High-Resolution P1 Artificial Chromosome/Bacterial Artificial Chromosome Contig of the Critical Region". The American Journal of Human Genetics. 62 (4): 890–903. doi:10.1086/301794. ISSN 0002-9297. PMC 1377034. PMID 9529352. 7. ^ a b Foggia, Lucie; Hovnanian, Alain (2004). "Calcium pump disorders of the skin". American Journal of Medical Genetics Part C: Seminars in Medical Genetics (in French). 131C (1): 20–31. doi:10.1002/ajmg.c.30031. ISSN 1552-4876. PMID 15468148. S2CID 675895. 8. ^ a b c Reference, Genetics Home. "Darier disease". Genetics Home Reference. Retrieved 2020-05-08. 9. ^ Sakuntabhai, Anavaj; Ruiz-Perez, Victor; Carter, Simon; Jacobsen, Nick; Burge, Susan; Monk, Sarah; Smith, Melanie; Munro, Colin S.; O'Donovan, Michael; Craddock, Nick; Kucherlapati, Raju (March 1999). "Mutations in ATP2A2, encoding a Ca 2+ pump, cause Darier disease". Nature Genetics. 21 (3): 271–277. doi:10.1038/6784. ISSN 1546-1718. PMID 10080178. S2CID 38684482. 10. ^ Ruiz-Perez, Victor L.; Carter, Simon A.; Healy, Eugene; Todd, Carole; Rees, Jonathan L.; Steijlen, Peter M.; Carmichael, Andrew J.; Lewis, Helen M.; Hohl, D.; Itin, Peter; Vahlquist, Anders (1999-09-01). "ATP2A2 Mutations in Darier's Disease: Variant Cutaneous Phenotypes Are Associated with Missense Mutations, But Neuropsychiatry Features Are Independent of Mutation Class". Human Molecular Genetics. 8 (9): 1621–1630. doi:10.1093/hmg/8.9.1621. ISSN 0964-6906. PMID 10441324. 11. ^ Sakuntabhai, Anavaj; Dhitavat, Jittima; Hovnanian, Alain; Burge, Susan (December 2000). "Mosaicism for ATP2A2 Mutations Causes Segmental Darier's Disease". Journal of Investigative Dermatology. 115 (6): 1144–1147. doi:10.1046/j.1523-1747.2000.00182.x. ISSN 0022-202X. PMID 11121153. 12. ^ Godic A, Miljkovic J, Kansky A, Vidmar G (June 2005). "Epidemiology of Darier's Disease in Slovenia". Acta Dermatovenerol Alp Pannonica Adriat. 14 (2): 43–8. PMID 16001099. 13. ^ Munro CS (August 1992). "The phenotype of Darier's disease: penetrance and expressivity in adults and children". Br. J. Dermatol. 127 (2): 126–30. doi:10.1111/j.1365-2133.1992.tb08044.x. PMID 1390140. S2CID 2911858. 14. ^ Tavadia S, Mortimer E, Munro CS (January 2002). "Genetic epidemiology of Darier's disease: a population study in the west of Scotland". Br. J. Dermatol. 146 (1): 107–9. doi:10.1046/j.1365-2133.2002.04559.x. PMID 11841374. S2CID 42621572. 15. ^ Burge SM, Wilkinson JD (July 1992). "Darier-White disease: a review of the clinical features in 163 patients". J. Am. Acad. Dermatol. 27 (1): 40–50. doi:10.1016/0190-9622(92)70154-8. PMID 1619075. 16. ^ a b c d "Darier disease NZ". DermNet. Retrieved 2020-05-07. 17. ^ Gordon-Smith K, Jones LA, Burge SM, Munro CS, Tavadia S, Craddock N (September 2010). "The neuropsychiatric phenotype in Darier disease". Br. J. Dermatol. 163 (3): 515–22. doi:10.1111/j.1365-2133.2010.09834.x. PMID 20456342. S2CID 22856369. 18. ^ "Darier disease \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-05-08. 19. ^ "Acrokeratosis Verruciformis of Hopf: Background, Pathophysiology, Etiology". 2020-03-26. Cite journal requires `\|journal=` (help) 20. ^ Hohl, D. Hand, J. Darier disease. (2017) Corona, R. (Ed) Uptodate. 21. ^ Lippincott's Illustrated Reviews: Biochemistry (Champe, Harvey & Ferrier, ISBN 0-7817-2265-9, 3rd ed., Lippincott Williams & Wilkins 2005) 22. ^ Kamijo M, Nishiyama C, Takagi A, Nakano N, Hara M, Ikeda S, Okumura K, Ogawa H (May 2012). "Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes: possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease". Br. J. Dermatol. 166 (5): 1017–22. doi:10.1111/j.1365-2133.2011.10789.x. PMID 22413864. S2CID 42918432. 23. ^ Millán-Parrilla F, Rodrigo-Nicolás B, Molés-Poveda P, Armengot-Carbó M, Quecedo-Estébanez E, Gimeno-Carpio E (April 2014). "Improvement of Darier disease with diclofenac sodium 3% gel". J. Am. Acad. Dermatol. 70 (4): e89–e90. doi:10.1016/j.jaad.2013.11.033. PMID 24629373. 24. ^ "Dermabrasion: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2020-05-08. 25. ^ "How do retinol creams work, anyway?". Sundaily. Retrieved 2020-05-08. 26. ^ Andrew's Diseases of the Skin (James, Berger, Elston, 10th ed., Saunders Elsevier, 2006) 27. ^ FIRST Skin Foundation 28. ^ Cadogan, Dr Mike (2019-03-01). "Ferdinand-Jean Darier • LITFL". Life in the Fast Lane • LITFL • Medical Blog. Retrieved 2020-05-08. Cardoso CL, Freitas P, Taveira LAA, Consolaro A. Darier disease: case report with oral manifestations. Med Oral Patol Oral Cir Bucal 2006;11:E404-6 Classification D * ICD-10: Q82.8 (ILDS Q82.868) * ICD-9-CM: 757.39 * OMIM: 124200 * MeSH: D007644 * DiseasesDB: 3467 External resources * eMedicine: derm/209 * 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 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 Genetic disorder, membrane: ATPase disorders ATP1 * ATP1A2 (Alternating hemiplegia of childhood) ATP2 * ATP2A1 (Brody myopathy) * ATP2A2 (Darier's disease, Acrokeratosis verruciformis) * ATP2C1 (Hailey–Hailey disease) ATP7 * ATP7A (Menkes disease) * ATP7B (Wilson's disease) ATP13 * ATP13A2 (Kufor–Rakeb syndrome) Other * Osteopetrosis B1 see also ATPase * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Darier's disease	c0022595	30,187	wikipedia	https://en.wikipedia.org/wiki/Darier%27s_disease	2021-01-18T18:35:43	{"gard": ["6243"], "mesh": ["D007644"], "umls": ["C0022595"], "icd-9": ["757.39"], "orphanet": ["218"], "wikidata": ["Q580506"]}
A rare syndromic disorder with strabismus characterized by congenital non-progressive ophthalmoplegia affecting the oculomotor and/or trochlear nucleus/nerve and their innervated muscles. Patients present with abnormal resting position of the eyes (in most cases infraducted and exotropic), limitation of vertical and horizontal gaze, impaired binocular vision, amblyopia, unilateral or bilateral blepharoptosis, and compensatory abnormal head posture. Extraocular manifestations include intellectual disability, peripheral neuropathy, and skeletal abnormalities, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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 fibrosis of extraocular muscles	c1302995	30,188	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=45358	2021-01-23T18:32:05	{"gard": ["12590"], "mesh": ["C580012"], "omim": ["135700", "600638", "602078", "609384", "609428", "609612"], "umls": ["C1302995"], "icd-10": ["H49.8"], "synonyms": ["FEOM"]}
For a general phenotypic description and a discussion of loci that may affect fetal hemoglobin levels, see HBFQTL1 (141749). Mapping In the same large Indian kindred in which Thein et al. (1994) and Craig et al. (1996) mapped a gene modifying hemoglobin F and F-cell (FC) production to chromosome 6q23 (see 142470), Garner et al. (2002) identified a quantitative trait locus (QTL) on 8q that interacts with the common sequence variant at position -158 upstream of the HBG2 gene, termed the 'XmnI-G-gamma polymorphism' (142250.0028). Using a 2-locus model, in which the second locus was the QTL at the XmnI-G-gamma site, Garner et al. (2002) showed suggestive linkage to 8q. A maximum single-point lod score of 4.33 and a multipoint lod score of 4.75 were found in a 15- to 20-cM region of 8q. The results indicated that an interaction between the XmnI-G-gamma site and a QTL on 8q influence the production of fetal hemoglobin. Garner et al. (2004) reported replication of linkage to 8q in a sample of European twin pairs, providing strong evidence that a quantitative trait locus exists on chromosome 8q that influences the developmental switch from fetal to adult hemoglobin. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 4	c1969842	30,189	omim	https://www.omim.org/entry/606789	2019-09-22T16:10:02	{"omim": ["606789"]}
HIV/AIDS in Japan has been recognized as a serious health issue in recent years.[1] However, overall awareness amongst the general population of Japan regarding sexually transmitted infections, including HIV/AIDS, remains low.[2] Human Immunodeficiency Virus (HIV) first came to attention in the 1980s in the United States, followed by global interest in the years that followed. Among the many countries affected, Japan's population of affected people remains low in comparison to other developed countries such as the United States and theEuropean countries. The number of cases continues to rise. Official reports indicate that 6 homosexual men were diagnosed in 1985, which grew to 100 people infected by 1990. The primary group affected in the 1980s was hemophiliacs, but that shifted to sexual transmission in the late 1980s and early 1990s. Due to poor media coverage and the lack of momentum from activist groups, large misconceptions about the disease, homosexuals, and foreigners spread about the general population. Today, Japan remains one of the top providers of funds for global efforts such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria and World Health Organization for HIV/AIDS prevention and treatment. ## Contents * 1 Epidemiology * 1.1 HIV-tainted blood scandal * 1.2 Foreigner and homosexual discrimination * 2 Funding * 3 References ## Epidemiology[edit] In April 2016, sexual contact was the primary mode of HIV/AIDS transmission. In homosexuals, it accounted for 57.3% of all HIV cases and 38.7% of AIDS cases. Heterosexual transmission is responsible for 27.2% of HIV infections and 35.7% of AIDS infections.[3] The age distribution is mostly people in their twenties and thirties and are more likely to be in an urban setting than a rural one, and infected people are mostly male (15,567 males; 2,342 females diagnosed with HIV from 1985-2015).[4] One study found a positive correlation between population density and the number of HIV/AIDS cases in the given area.[5] They proposed that the increased number of people in an area of space increases the chance of possible encounters with an infected person as well as increased the general mobility of the disease. People were reluctant to get help during the offset of the disease due to the country's conservatism in dealing with issues surrounding sexual orientation. This delay and apprehension to get treatment lead to a greater population being diagnosed with AIDS. In 2015, 30% of the HIV/AIDS diagnoses were made once the virus had already progressed to AIDS.[4] Initially, the disease was seen in hemophiliacs receiving it from tainted blood supply in the early 1980s, however, in the mid 80s to the present, there was increasing prevalence in homosexual and then heterosexual demographics. About 1,500 HIV/AIDS cases arise each year, of this group, homosexual men dominate this group, followed by heterosexual men, heterosexual women, intravenous drug use, and maternal transmission.[4] ### HIV-tainted blood scandal[edit] Japan started HIV/AIDS surveillance in 1984 and the following year, the first homosexual infection was observed. However, in 1982-1985, the disease primarily infected hemophiliacs. About 40% of hemophiliacs were infected by the means of contaminated blood supply. In 1989, HIV-infected hemophiliacs filed lawsuits against Japan's Ministry of Health, Labour, and Welfare and five pharmaceutical companies. The companies were accused of importing blood products from the United States without heating them with the knowledge that doing so has serious repercussions and risks. This became known as the HIV-tainted blood scandal. ### Foreigner and homosexual discrimination[edit] The first official report of HIV/AIDS was a male artist who lived in America for years and then returned to Japan. The continued trend of homosexual infection and the portrayal in the media of AIDS as a "foreign" disease gave the illusion that native Japanese heterosexuals were at low risk.[6] Owing to the lower number of cases relative to the rest of the world, the HIV/AIDS crisis seemed distant and unimportant. In a poll conducted in 1987, 68% of Americans deemed HIV/AIDS to be the most urgent health problem facing the country, 39% of the French thought the same, but only 13% of Japanese people thought this to be true. When the severity of the disease increased, much of it was attributed to foreigners due to lack of general information.[6] Foreigners were fired from their jobs, prevented from entering certain public facilities, and some removed from their apartments.[6] In 2015, non-Japanese people accounted for 108 (88 male; 20 female) out of 1,006 cases. This indicates that the population of infected people in Japan has shifted since the first emergence of the disease in the country.[4] Homosexual men remain the most affected demographic of people. ## Funding[edit] Japan does not rely on global funds to finance their AIDS research and treatment. AIDS spending is a domestic cost. In 2011, they issued US$67.91 million for domestic HIV/AIDS expenditure.[7] In contributing to HIV/AIDS as a global crisis, Japan has a role in the funding. Japan was a founding country contributing to the Global Fund. In 2016, Japan pledged US$313 million to help the cause. Since its founding, the Global Fund has saved the lives of 20 million people.[8] In 2019, Japan continued to make significant contributions to the Global Fund.[9][10] ## References[edit] 1. ^ "New HIV Infections Hit High in Japan". The Nation. 7 February 2007. Retrieved 18 December 2012. 2. ^ "Everybody's talking sex in Japan, but nobody's hearing AIDS". Mainichi Daily News. 24 February 2004. Retrieved 18 December 2012.[permanent dead link] 3. ^ "HIV/AIDS Trends in Japan April 2016" (PDF). UNAIDS. 4. ^ a b c d "HIV/AIDS in Japan, 2015". National Institute of Infectious Diseases. 37: 167–168. September 2016. 5. ^ Hiroshi, Yoshikura (2016). "Geo-Demography of HIV/AIDS in Japan from 1985 to 2011: Incidence and Transmission Mode under Influence of Population Size/Density". Japan Journal of Infectious Disease. 6. ^ a b c Kim, Young Soo (2015). "Japan Addresses the Global HIV/AIDS Crisis: The Roles of Media and Civil Society in Shaping Perceptions and Aid". Asian Perspective. 39 (3): 483–511. doi:10.1353/apr.2015.0021. ProQuest 1704715108. 7. ^ "HIV/AIDS Country Profiles: Japan". Evidence to Action. 8. ^ Jaureguizar, Ibon Villelabeitia (March 27, 2017). "Japan Secures US$313 Million Contribution to the Global Fund". The Global Fund. Retrieved December 13, 2017. 9. ^ Japan Makes Significant Contribution to Global Fund 10. ^ Global Fund Welcomes Japan’s Commitment to Save One Million Lives * v * t * e HIV/AIDS in Asia Sovereign states * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor (Timor-Leste) * Egypt * Georgia * India * Indonesia * Iran * Iraq * Israel * Japan * Jordan * Kazakhstan * North Korea * South Korea * Kuwait * Kyrgyzstan * Laos * Lebanon * Malaysia * Maldives * Mongolia * Myanmar * Nepal * Oman * Pakistan * Philippines * Qatar * Russia * Saudi Arabia * Singapore * Sri Lanka * Syria * Tajikistan * Thailand * Turkey * Turkmenistan * United Arab Emirates * Uzbekistan * Vietnam * Yemen States with limited recognition * Abkhazia * Artsakh * Northern Cyprus * Palestine * South Ossetia * Taiwan Dependencies and other territories * British Indian Ocean Territory * Christmas Island * Cocos (Keeling) Islands * Hong Kong * Macau * Book * Category * Asia portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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 in Japan	None	30,190	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Japan	2021-01-18T18:28:41	{"wikidata": ["Q5629855"]}
Larsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with dislocations of the hips, knees, or elbows. Foot abnormalities, such as inward- and upward-turning feet (clubfeet), are also common. Affected individuals generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate). Characteristic facial features in people with Larsen syndrome include a prominent forehead (frontal bossing), flattening of the bridge of the nose and middle of the face (midface hypoplasia), and wide-set eyes (ocular hypertelorism). Many people with Larsen syndrome have an opening in the roof of the mouth (a cleft palate). Affected individuals may also have hearing loss caused by malformations in tiny bones in the ears (ossicles). Short stature is a common feature of Larsen syndrome. In addition, people with the condition may have an unusually large range of joint movement (hypermobility) or joint deformities (contractures) that restrict movement. People with Larsen syndrome can also have abnormal curvature of the spine (kyphosis or scoliosis) that can impair breathing or compress the spinal cord and lead to weakness of the limbs. Some affected individuals experience respiratory problems, such as partial closing of the airways, short pauses in breathing (apnea), and frequent respiratory infections. Heart and kidney problems can also occur in people with Larsen syndrome. People with this condition can survive into adulthood. Their intellectual function is usually unaffected. ## Frequency Larsen syndrome occurs in approximately 1 in 100,000 newborns. However, some doctors think the condition is more common and is misdiagnosed as other conditions with similar features. ## Causes Mutations in the FLNB gene cause Larsen syndrome. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development. Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation), for maturation (differentiation) of chondrocytes, and for the ossification of cartilage. FLNB gene mutations that cause Larsen syndrome change single protein building blocks (amino acids) in the filamin B protein or delete a small section of the protein sequence, resulting in an abnormal protein. This abnormal protein appears to have a new, atypical function that interferes with the proliferation or differentiation of chondrocytes, impairing ossification and leading to the signs and symptoms of Larsen syndrome. ### Learn more about the gene associated with Larsen syndrome * FLNB ## 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 some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Autosomal recessive inheritance of Larsen syndrome has been reported in a small number of families. Autosomal recessive means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In some of these cases, the appearance of autosomal recessive inheritance may actually result from multiple siblings in a family each inheriting a single altered gene from an unaffected parent who has an FLNB mutation only in some or all of their sperm or egg cells. When a mutation is present only in reproductive cells, it is known as germline mosaicism. A few rarer conditions with overlapping signs and symptoms and autosomal recessive inheritance have sometimes been diagnosed as Larsen syndrome, but they are now generally considered to be different disorders because they are typically more severe and are not caused by FLNB gene mutations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Larsen syndrome	c0175778	30,191	medlineplus	https://medlineplus.gov/genetics/condition/larsen-syndrome/	2021-01-27T08:25:08	{"gard": ["6860"], "mesh": ["C580241"], "omim": ["150250", "245600"], "synonyms": []}
Osteomalacia is a disease that is characterized by a weakening of the bone, often due to a deficiency of vitamin D. This vitamin supports the development of the bones of the body, so when there are low levels of vitamin D, the bones are not strong enough. Symptoms of osteomalacia can include muscle weakness, bone pain, and walking with a waddling gait. Pain is especially likely to occur in the lower back, hips, and legs. The weakening of the bones may also cause them to easily fracture. Osetomalacia can be caused by having a low level of vitamin D in the diet or lack of sun exposure. The condition may also be the result of an underlying disease such as celiac disease, or kidney or liver disorders. Diagnosis of osteomalacia is possible through blood or urine tests to check for vitamin D levels or a bone biopsy. Treatment options include supplementing the diet with more vitamin D or calcium. Any underlying condition will also need to be treated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Osteomalacia	c0029442	30,192	gard	https://rarediseases.info.nih.gov/diseases/7285/osteomalacia	2021-01-18T17:58:32	{"umls": ["C0029442"], "synonyms": []}
"Alcoholic" redirects here. For alcoholic beverages, see alcoholic drink. For the song by Starsailor, see Alcoholic (song). Problematic alcohol consumption Alcoholism Other namesAlcohol addiction, alcohol dependence syndrome, alcohol use disorder (AUD)[1] "King Alcohol and His Prime Minister" c. 1820 SpecialtyPsychiatry, clinical psychology, toxicology, addiction medicine SymptomsDrinking large amounts of alcohol over a long period, difficulty cutting down, acquiring and drinking alcohol taking up a lot of time, usage resulting in problems, withdrawal occurring when stopping[2] ComplicationsMental illness, delirium, Wernicke–Korsakoff syndrome, irregular heartbeat, cirrhosis of the liver, cancer, fetal alcohol spectrum disorder, suicide[3][4][5][6] DurationLong term[2] CausesEnvironmental and genetic factors[4] Risk factorsStress, anxiety, inexpensive, easy access[4][7] Diagnostic methodQuestionnaires, blood tests[4] TreatmentAlcohol detoxification typically with benzodiazepines, counselling, acamprosate, disulfiram, naltrexone[8][9][10] Frequency380 million / 5.1% adults (2016)[11][12] Deaths3.3 million / 5.9%[13] Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems.[14] Alcoholism is not a recognized diagnostic entity. Predominant diagostic classifications are alcohol use disorder[2] (DSM-5)[4] or alcohol dependence (ICD-11).[15] Excessive alcohol use can damage all organ systems, but it particularly affects the brain, heart, liver, pancreas and immune system.[4][5] Alcoholism can result in mental illness, delirium tremens, Wernicke–Korsakoff syndrome, irregular heartbeat, an impaired immune response, liver cirrhosis and increased cancer risk.[4][5][16] Drinking during pregnancy can result in fetal alcohol spectrum disorders.[3] Women are generally more sensitive than men to the harmful effects of alcohol, primarily due to their smaller body weight, lower capacity to metabolize alcohol, and higher proportion of body fat.[11] In a small number of individuals, prolonged, severe alcohol abuse ultimately leads to frank dementia. Environmental factors and genetics are two factors affecting risk for alcoholism, with about half the risk attributed to each.[4] Someone with a parent or sibling with alcoholism is three to four times more likely to become an alcoholic themselves, but only a minority of them do.[4] Environmental factors include social, cultural and behavioral influences.[17] High stress levels and anxiety, as well as alcohol's inexpensive cost and easy accessibility, increase the risk.[4][7] People may continue to drink partly to prevent or improve symptoms of withdrawal.[4] After a person stops drinking alcohol, they may experience a low level of withdrawal lasting for months.[4] Medically, alcoholism is considered both a physical and mental illness.[18][19] Questionnaires are usually used to detect possible alcoholism.[4][20] Further information is then collected to confirm the diagnosis.[4] Prevention of alcoholism may be attempted by regulating and limiting the sale of alcohol (particularly to minors), taxing alcohol to increase its cost, and providing education and inexpensive treatment. Prohibition did not work.[21] Treatment of alcoholism may take several forms.[9] Due to medical problems that can occur during withdrawal, alcohol detoxification should be carefully controlled.[9] One common method involves the use of benzodiazepine medications, such as diazepam.[9] These can be either given while admitted to a health care institution or occasionally while a person remains in the community with close supervision.[9] Mental illness or other addictions may complicate treatment.[22] After detoxification, various forms of individual or group therapy or support groups can help keep a person from returning to drinking.[8][23] One commonly used form of support is the group Alcoholics Anonymous.[24] The medications acamprosate, disulfiram or naltrexone may also be used to help prevent further drinking.[10] The World Health Organization has estimated that as of 2016, there were 380 million people with alcoholism worldwide (5.1% of the population over 15 years of age).[11][12] As of 2015 in the United States, about 17 million (7%) of adults and 0.7 million (2.8%) of those age 12 to 17 years of age are affected.[13] Alcoholism is most common among males and young adults.[4] Geographically, it is least common in Africa (1.1% of the population) and has the highest rates in Eastern Europe (11%).[4] Alcoholism directly resulted in 139,000 deaths in 2013, up from 112,000 deaths in 1990.[25] A total of 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol.[13] Alcoholism reduces a person's life expectancy by approximately ten years.[26] Many terms, some insulting and others informal, have been used to refer to people affected by alcoholism; the expressions include tippler, drunkard, dipsomaniac and souse.[27] In 1979, the World Health Organization discouraged the use of "alcoholism" due to its inexact meaning, preferring "alcohol dependence syndrome".[28] ## Contents * 1 Signs and symptoms * 1.1 Long-term misuse * 2 Alcohol abuse * 2.1 Warning signs * 2.1.1 Physical * 2.1.1.1 Short-term effects * 2.1.1.2 Long-term effects * 2.1.2 Psychiatric * 2.1.3 Social effects * 2.2 Alcohol withdrawal * 3 Causes * 3.1 Availability * 3.2 Gender difference * 3.3 Genetic variation * 4 Diagnosis * 4.1 Definition * 4.1.1 Alcoholism * 4.1.2 DSM and ICD * 4.2 Social barriers * 4.3 Screening * 4.4 Urine and blood tests * 5 Prevention * 6 Management * 6.1 Detoxification * 6.2 Psychological * 6.3 Moderate drinking * 6.4 Medications * 7 Disulfiram-like drug * 7.1 Dual addictions and dependences * 8 Epidemiology * 9 Prognosis * 10 History * 11 Society and culture * 12 See also * 13 References * 14 External links ## Signs and symptoms Play media Effects of alcohol on the body The risk of alcohol dependence begins at low levels of drinking and increases directly with both the volume of alcohol consumed and a pattern of drinking larger amounts on an occasion, to the point of intoxication, which is sometimes called "binge drinking". ### Long-term misuse ## Alcohol abuse Some of the possible long-term effects of ethanol an individual may develop. Additionally, in pregnant women, alcohol can cause fetal alcohol syndrome. Alcoholism is characterised by an increased tolerance to alcohol – which means that an individual can consume more alcohol – and physical dependence on alcohol, which makes it hard for an individual to control their consumption. The physical dependency caused by alcohol can lead to an affected individual having a very strong urge to drink alcohol. These characteristics play a role in decreasing an alcoholic's ability to stop drinking.[29] Alcoholism can have adverse effects on mental health, contributing to psychiatric disorders and increasing the risk of suicide. A depressed mood is a common symptom of heavy alcohol drinkers.[30][31] ### Warning signs Warning signs of alcoholism include the consumption of increasing amounts of alcohol and frequent intoxication, preoccupation with drinking to the exclusion of other activities, promises to quit drinking and failure to keep those promises, the inability to remember what was said or done while drinking (colloquially known as "blackouts"), personality changes associated with drinking, denial or the making of excuses for drinking, the refusal to admit excessive drinking, dysfunction or other problems at work or school, the loss of interest in personal appearance or hygiene, marital and economic problems, and the complaint of poor health, with loss of appetite, respiratory infections, or increased anxiety.[32] #### Physical ##### Short-term effects Main article: Short-term effects of alcohol consumption Drinking enough to cause a blood alcohol concentration (BAC) of 0.03–0.12% typically causes an overall improvement in mood and possible euphoria (a "happy" feeling), increased self-confidence and sociability, decreased anxiety, a flushed, red appearance in the face and impaired judgment and fine muscle coordination. A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC of 0.18% to 0.30% causes profound confusion, impaired speech (e.g. slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting (death may occur due to inhalation of vomit (pulmonary aspiration) while unconscious) and respiratory depression (potentially life-threatening). A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning. With all alcoholic beverages, drinking while driving, operating an aircraft or heavy machinery increases the risk of an accident; many countries have penalties for drunk driving. ##### Long-term effects See also: Long-term effects of alcohol consumption Having more than one drink a day for women or two drinks for men increases the risk of heart disease, high blood pressure, atrial fibrillation, and stroke.[33] Risk is greater with binge drinking, which may also result in violence or accidents. About 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol each year.[13] Alcoholism reduces a person's life expectancy by around ten years[26] and alcohol use is the third leading cause of early death in the United States.[33] No professional medical association recommends that people who are nondrinkers should start drinking.[33][34] Long-term alcohol abuse can cause a number of physical symptoms, including cirrhosis of the liver, pancreatitis, epilepsy, polyneuropathy, alcoholic dementia, heart disease, nutritional deficiencies, peptic ulcers[35] and sexual dysfunction, and can eventually be fatal. Other physical effects include an increased risk of developing cardiovascular disease, malabsorption, alcoholic liver disease, and several cancers. Damage to the central nervous system and peripheral nervous system can occur from sustained alcohol consumption.[36][37] A wide range of immunologic defects can result and there may be a generalized skeletal fragility, in addition to a recognized tendency to accidental injury, resulting a propensity to bone fractures.[38] Women develop long-term complications of alcohol dependence more rapidly than do men. Additionally, women have a higher mortality rate from alcoholism than men.[39] Examples of long-term complications include brain, heart, and liver damage[40] and an increased risk of breast cancer. Additionally, heavy drinking over time has been found to have a negative effect on reproductive functioning in women. This results in reproductive dysfunction such as anovulation, decreased ovarian mass, problems or irregularity of the menstrual cycle, and early menopause.[39] Alcoholic ketoacidosis can occur in individuals who chronically abuse alcohol and have a recent history of binge drinking.[41][42] The amount of alcohol that can be biologically processed and its effects differ between sexes. Equal dosages of alcohol consumed by men and women generally result in women having higher blood alcohol concentrations (BACs), since women generally have a lower weight and higher percentage of body fat and therefore a lower volume of distribution for alcohol than men.[43] #### Psychiatric Long-term misuse of alcohol can cause a wide range of mental health problems. Severe cognitive problems are common; approximately 10 percent of all dementia cases are related to alcohol consumption, making it the second leading cause of dementia.[44] Excessive alcohol use causes damage to brain function, and psychological health can be increasingly affected over time.[45] Social skills are significantly impaired in people suffering from alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The social skills that are impaired by alcohol abuse include impairments in perceiving facial emotions, prosody perception problems and theory of mind deficits; the ability to understand humour is also impaired in alcohol abusers.[46] Psychiatric disorders are common in alcoholics, with as many as 25 percent suffering severe psychiatric disturbances. The most prevalent psychiatric symptoms are anxiety and depression disorders. Psychiatric symptoms usually initially worsen during alcohol withdrawal, but typically improve or disappear with continued abstinence.[47] Psychosis, confusion, and organic brain syndrome may be caused by alcohol misuse, which can lead to a misdiagnosis such as schizophrenia.[48] Panic disorder can develop or worsen as a direct result of long-term alcohol misuse.[49][50] The co-occurrence of major depressive disorder and alcoholism is well documented.[51][52][53] Among those with comorbid occurrences, a distinction is commonly made between depressive episodes that remit with alcohol abstinence ("substance-induced"), and depressive episodes that are primary and do not remit with abstinence ("independent" episodes).[54][55][56] Additional use of other drugs may increase the risk of depression.[57] Psychiatric disorders differ depending on gender. Women who have alcohol-use disorders often have a co-occurring psychiatric diagnosis such as major depression, anxiety, panic disorder, bulimia, post-traumatic stress disorder (PTSD), or borderline personality disorder. Men with alcohol-use disorders more often have a co-occurring diagnosis of narcissistic or antisocial personality disorder, bipolar disorder, schizophrenia, impulse disorders or attention deficit/hyperactivity disorder (ADHD).[58] Women with alcoholism are more likely to experience physical or sexual assault, abuse and domestic violence than women in the general population,[58] which can lead to higher instances of psychiatric disorders and greater dependence on alcohol. #### Social effects See also: Drug-related crime Serious social problems arise from alcoholism; these dilemmas are caused by the pathological changes in the brain and the intoxicating effects of alcohol.[44][59] Alcohol abuse is associated with an increased risk of committing criminal offences, including child abuse, domestic violence, rape, burglary and assault.[60] Alcoholism is associated with loss of employment,[61] which can lead to financial problems. Drinking at inappropriate times and behavior caused by reduced judgment can lead to legal consequences, such as criminal charges for drunk driving[62] or public disorder, or civil penalties for tortious behavior. An alcoholic's behavior and mental impairment while drunk can profoundly affect those surrounding him and lead to isolation from family and friends. This isolation can lead to marital conflict and divorce, or contribute to domestic violence. Alcoholism can also lead to child neglect, with subsequent lasting damage to the emotional development of the alcoholic's children.[63] For this reason, children of alcoholic parents can develop a number of emotional problems. For example, they can become afraid of their parents, because of their unstable mood behaviors. In addition, they can develop considerable amount of shame over their inadequacy to liberate their parents from alcoholism. As a result of this failure, they develop wretched self-images, which can lead to depression.[64] ### Alcohol withdrawal Main article: Alcohol withdrawal syndrome See also: Kindling (sedative-hypnotic withdrawal) A French temperance poster from the Union des Françaises contre l'Alcool (this translates as "Union of French Women Against Alcohol"). The poster states "Ah! Quand supprimera-t'on l'alcool?", which translates as "Ah! When will we [the nation] abolish alcohol?" As with similar substances with a sedative-hypnotic mechanism, such as barbiturates and benzodiazepines, withdrawal from alcohol dependence can be fatal if it is not properly managed.[59][65] Alcohol's primary effect is the increase in stimulation of the GABAA receptor, promoting central nervous system depression. With repeated heavy consumption of alcohol, these receptors are desensitized and reduced in number, resulting in tolerance and physical dependence. When alcohol consumption is stopped too abruptly, the person's nervous system suffers from uncontrolled synapse firing. This can result in symptoms that include anxiety, life-threatening seizures, delirium tremens, hallucinations, shakes and possible heart failure.[66][67] Other neurotransmitter systems are also involved, especially dopamine, NMDA and glutamate.[29][68] Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1-week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In the period of 3–6 weeks following cessation, anxiety, depression, fatigue, and sleep disturbance are common.[69] Similar post-acute withdrawal symptoms have also been observed in animal models of alcohol dependence and withdrawal.[70] A kindling effect also occurs in alcoholics whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol-dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression.[71] Kindling also results in the intensification of psychological symptoms of alcohol withdrawal.[69] There are decision tools and questionnaires that help guide physicians in evaluating alcohol withdrawal. For example, the CIWA-Ar objectifies alcohol withdrawal symptoms in order to guide therapy decisions which allows for an efficient interview while at the same time retaining clinical usefulness, validity, and reliability, ensuring proper care for withdrawal patients, who can be in danger of death.[72] ## Causes William Hogarth's Gin Lane, 1751 A complex combination of genetic and environmental factors influences the risk of the development of alcoholism. Drinking excessive alcohol during childhood or adolescence, is a risk factor, or to have low autoestime, thus to be someone with antisocial, addictive or wrathful behaviour, so as also minimize or naturalize so much alcohol abuse, alcohol dependence and the long-term effects of alcohol or also the short-term effects of alcohol consumption in the human body, is very known that some people depending of their life perspective or outlook can have more or less probabilities of to have drinking problems [73] Genes that influence the metabolism of alcohol also influence the risk of alcoholism, as can a family history of alcoholism.[74] There is compelling evidence that alcohol use at an early age may influence the expression of genes which increase the risk of alcohol dependence. These genetic and epigenetic results are regarded as consistent with large longitudinal population studies finding that the younger the age of drinking onset, the greater the prevalence of lifetime alcohol dependence.[75][76] Severe childhood trauma is also associated with a general increase in the risk of drug dependency.[73] Lack of peer and family support is associated with an increased risk of alcoholism developing.[73] Genetics and adolescence are associated with an increased sensitivity to the neurotoxic effects of chronic alcohol abuse. Cortical degeneration due to the neurotoxic effects increases impulsive behaviour, which may contribute to the development, persistence and severity of alcohol use disorders. There is evidence that with abstinence, there is a reversal of at least some of the alcohol induced central nervous system damage.[77] The use of cannabis was associated with later problems with alcohol use.[78] Alcohol use was associated with an increased probability of later use of tobacco and illegal drugs such as cannabis.[79] ### Availability Alcohol is the most available, distributed, imported, exported, sold, labeled, most legal, most socially accepted, widely used widely consumed, widely misused and widely abused psychoactive drug, just Beer alone is in the world's on of most widely consumed drinks in world only after of coffee and tea[80] alcoholic beverage; it is the third-most popular drink overall, after coffee and tea.[81] It is thought by some to be the oldest fermented beverage.[82][83][84][85] ### Gender difference Based on combined data in the US from SAMHSA's 2004–2005 National Surveys on Drug Use & Health, the rate of past-year alcohol dependence or abuse among persons aged 12 or older varied by level of alcohol use: 44.7% of past month heavy drinkers, 18.5% binge drinkers, 3.8% past month non-binge drinkers, and 1.3% of those who did not drink alcohol in the past month met the criteria for alcohol dependence or abuse in the past year. Males had higher rates than females for all measures of drinking in the past month: any alcohol use (57.5% vs. 45%), binge drinking (30.8% vs. 15.1%), and heavy alcohol use (10.5% vs. 3.3%), and males were twice as likely as females to have met the criteria for alcohol dependence or abuse in the past year (10.5% vs. 5.1%).[86] ### Genetic variation See also: Addiction § Genetic factors There are genetic variations that affect the risk for alcoholism.[74][73][87][88] Some of these variations are more common in individuals with ancestry from certain areas, for example Africa, East Asia, the Middle East and Europe. The variants with strongest effect are in genes that encode the main enzymes of alcohol metabolism, ADH1B and ALDH2.[74][87][88] These genetic factors influence the rate at which alcohol and its initial metabolic product, acetaldehyde, are metabolized.[74] They are found at different frequencies in people from different parts of the world.[89][74][90] The alcohol dehydrogenase allele ADH1B2 causes a more rapid metabolism of alcohol to acetaldehyde, and reduces risk for alcoholism;[74] it is most common in individuals from East Asia and the Middle East. The alcohol dehydrogenase allele ADH1B3 also causes a more rapid metabolism of alcohol. The allele ADH1B3 is only found in some individuals of African descent and certain Native American tribes. African Americans and Native Americans with this allele have a reduced risk of developing alcoholism.[74][90][91] Native Americans, however, have a significantly higher rate of alcoholism than average; risk factors such as cultural environmental effects e.g. trauma have been proposed to explain the higher rates.[92][93] The aldehyde dehydrogenase allele ALDH22 greatly reduces the rate at which acetaldehyde, the initial product of alcohol metabolism, is removed by conversion to acetate; it greatly reduces the risk for alcoholism.[74][89] A genome-wide association study of more than 100,000 human individuals identified variants of the gene KLB, which encodes the transmembrane protein β-Klotho, as highly associated with alcohol consumption. The protein β-Klotho is an essential element in cell surface receptors for hormones involved in modulation of appetites for simple sugars and alcohol.[94] A GWAS has found differences in the genetics of alcohol consumption and alcohol dependence, although the two are to some degree related.[87][88] ## Diagnosis ### Definition A man drinking from a bottle of liquor while sitting on a boardwalk, ca. 1905–1914. Picture by Austrian photographer Emil Mayer. Misuse, problem use, abuse, and heavy use of alcohol refer to improper use of alcohol, which may cause physical, social, or moral harm to the drinker.[95] The Dietary Guidelines for Americans defines "moderate use" as no more than two alcoholic beverages a day for men and no more than one alcoholic beverage a day for women.[96] The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as the amount of alcohol leading to a blood alcohol content (BAC) of 0.08, which, for most adults, would be reached by consuming five drinks for men or four for women over a two-hour period. According to the NIAAA, men may be at risk for alcohol-related problems if their alcohol consumption exceeds 14 standard drinks per week or 4 drinks per day, and women may be at risk if they have more than 7 standard drinks per week or 3 drinks per day. It defines a standard drink as one 12-ounce bottle of beer, one 5-ounce glass of wine, or 1.5 ounces of distilled spirits.[97] Despite this risk, a 2014 report in the National Survey on Drug Use and Health found that only 10% of either "heavy drinkers" or "binge drinkers" defined according to the above criteria also met the criteria for alcohol dependence, while only 1.3% of non-binge drinkers met the criteria. An inference drawn from this study is that evidence-based policy strategies and clinical preventive services may effectively reduce binge drinking without requiring addiction treatment in most cases.[98] #### Alcoholism The term alcoholism is commonly used amongst laypeople, but the word is poorly defined. Despite the imprecision inherent in the term, there have been attempts to define how the word alcoholism should be interpreted when encountered. In 1992, it was defined by the National Council on Alcoholism and Drug Dependence (NCADD) and ASAM as "a primary, chronic disease characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking."[99] MeSH has had an entry for "alcoholism" since 1999, and references the 1992 definition.[100] The WHO calls alcoholism "a term of long-standing use and variable meaning", and use of the term was disfavored by a 1979 WHO expert committee. In professional and research contexts, the term "alcoholism" is not currently favored, but rather alcohol abuse, alcohol dependence, or alcohol use disorder are used.[4][2] Talbot (1989) observes that alcoholism in the classical disease model follows a progressive course: if a person continues to drink, their condition will worsen. This will lead to harmful consequences in their life, physically, mentally, emotionally and socially.[101] Johnson (1980) explores the emotional progression of the addict's response to alcohol. He looks at this in four phases. The first two are considered "normal" drinking and the last two are viewed as "typical" alcoholic drinking.[101] Johnson's four phases consist of: 1. Learning the mood swing. A person is introduced to alcohol (in some cultures this can happen at a relatively young age), and the person enjoys the happy feeling it produces. At this stage, there is no emotional cost. 2. Seeking the mood swing. A person will drink to regain that feeling of euphoria experienced in phase 1; the drinking will increase as more intoxication is required to achieve the same effect. Again at this stage, there are no significant consequences. 3. At the third stage there are physical and social consequences, i.e., hangovers, family problems, work problems, etc. A person will continue to drink excessively, disregarding the problems. 4. The fourth stage can be detrimental, as Johnson cites it as a risk for premature death. As a person now drinks to feel normal, they block out the feelings of overwhelming guilt, remorse, anxiety, and shame they experience when sober.[101] 1. #### DSM and ICD In the United States, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the most common diagnostic guide for substance use disorders, whereas most countries use the International Classification of Diseases (ICD) for diagnostic (and other) purposes. The two manuals use similar but not identical nomenclature to classify alcohol problems. Manual Nomenclature Definition DSM-IV Alcohol abuse, Binge drinking or Alcohol dependence * Alcohol abuse - repeated use despite recurrent adverse consequences.[102] * Alcohol dependence - alcohol abuse combined with tolerance, withdrawal, and an uncontrollable drive to drink.[102] The term "alcoholism" was split into "alcohol abuse" and "alcohol dependence" in 1980's DSM-III, and in 1987's DSM-III-R behavioral symptoms were moved from "abuse" to "dependence".[103] Some scholars suggested that DSM-5 merge alcohol abuse and alcohol dependence into a single new entry,[104] named "alcohol-use disorder".[105] DSM-5 Alcohol use disorder and Alcohol addiction "A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by [two or more symptoms out of a total of 12], occurring within a 12-month period ...."[106] ICD-10 Alcohol harmful use, or Alcohol dependence syndrome Definitions are similar to that of the DSM-IV. The World Health Organization uses the term "alcohol dependence syndrome" rather than alcoholism.[28] The concept of "harmful use" (as opposed to "abuse") was introduced in 1992's ICD-10 to minimize underreporting of damage in the absence of dependence.[103] The term "alcoholism" was removed from ICD between ICD-8/ICDA-8 and ICD-9.[107] ICD-11 Episode of harmful use of alcohol, Dipsomania, Harmful pattern of use of alcohol, or Alcohol dependence * Episode of harmful use of alcohol \- "A single episode of use of alcohol that has caused damage to a person’s physical or mental health or has resulted in behaviour leading to harm to the health of others ...."[108] * Harmful pattern of use of alcohol \- "A pattern of alcohol use that has caused damage to a person’s physical or mental health or has resulted in behaviour leading to harm to the health of others ...."[109] * Alcohol dependence \- "Alcohol dependence is a disorder of regulation of alcohol use arising from repeated or continuous use of alcohol. The characteristic feature is a strong internal drive to use alcohol ... The features of dependence are usually evident over a period of at least 12 months but the diagnosis may be made if alcohol use is continuous (daily or almost daily) for at least 1 month."[110] ### Social barriers Attitudes and social stereotypes can create barriers to the detection and treatment of alcohol abuse. This is more of a barrier for women than men. Fear of stigmatization may lead women to deny that they are suffering from a medical condition, to hide their drinking, and to drink alone. This pattern, in turn, leads family, physicians, and others to be less likely to suspect that a woman they know is an alcoholic.[39] In contrast, reduced fear of stigma may lead men to admit that they are suffering from a medical condition, to display their drinking publicly, and to drink in groups. This pattern, in turn, leads family, physicians, and others to be more likely to suspect that a man they know is an alcoholic.[58] ### Screening Screening is recommended among those over the age of 18.[111] Several tools may be used to detect a loss of control of alcohol use. These tools are mostly self-reports in questionnaire form. Another common theme is a score or tally that sums up the general severity of alcohol use.[112] The CAGE questionnaire, named for its four questions, is one such example that may be used to screen patients quickly in a doctor's office. > Two "yes" responses indicate that the respondent should be investigated further. > > The questionnaire asks the following questions: > > 1. Have you ever felt you needed to Cut down on your drinking? > 2. Have people Annoyed you by criticizing your drinking? > 3. Have you ever felt Guilty about drinking? > 4. Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?[113][114] > The CAGE questionnaire has demonstrated a high effectiveness in detecting alcohol-related problems; however, it has limitations in people with less severe alcohol-related problems, white women and college students.[115] Other tests are sometimes used for the detection of alcohol dependence, such as the Alcohol Dependence Data Questionnaire, which is a more sensitive diagnostic test than the CAGE questionnaire. It helps distinguish a diagnosis of alcohol dependence from one of heavy alcohol use.[116] The Michigan Alcohol Screening Test (MAST) is a screening tool for alcoholism widely used by courts to determine the appropriate sentencing for people convicted of alcohol-related offenses,[117] driving under the influence being the most common. The Alcohol Use Disorders Identification Test (AUDIT), a screening questionnaire developed by the World Health Organization, is unique in that it has been validated in six countries and is used internationally. Like the CAGE questionnaire, it uses a simple set of questions – a high score earning a deeper investigation.[118] The Paddington Alcohol Test (PAT) was designed to screen for alcohol-related problems amongst those attending Accident and Emergency departments. It concords well with the AUDIT questionnaire but is administered in a fifth of the time.[119] ### Urine and blood tests There are reliable tests for the actual use of alcohol, one common test being that of blood alcohol content (BAC).[120] These tests do not differentiate alcoholics from non-alcoholics; however, long-term heavy drinking does have a few recognizable effects on the body, including:[121] * Macrocytosis (enlarged MCV) * Elevated GGT * Moderate elevation of AST and ALT and an AST: ALT ratio of 2:1 * High carbohydrate deficient transferrin (CDT) With regard to alcoholism, BAC is useful to judge alcohol tolerance, which in turn is a sign of alcoholism.[4] Electrolyte and acid-base abnormalities including hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia, metabolic acidosis, and respiratory alkalosis are common in alcoholics.[5] However, none of these blood tests for biological markers is as sensitive as screening questionnaires. ## Prevention Further information: Alcohol education The World Health Organization, the European Union and other regional bodies, national governments and parliaments have formed alcohol policies in order to reduce the harm of alcoholism.[122][123] Increasing the age at which licit drugs of abuse such as alcohol can be purchased, and banning or restricting alcohol beverage advertising are common methods to reduce alcohol use among adolescents and young adults in particular. Credible, evidence-based educational campaigns in the mass media about the consequences of alcohol abuse have been recommended. Guidelines for parents to prevent alcohol abuse amongst adolescents, and for helping young people with mental health problems have also been suggested.[124] ## Management Treatments are varied because there are multiple perspectives of alcoholism. Those who approach alcoholism as a medical condition or disease recommend differing treatments from, for instance, those who approach the condition as one of social choice. Most treatments focus on helping people discontinue their alcohol intake, followed up with life training and/or social support to help them resist a return to alcohol use. Since alcoholism involves multiple factors which encourage a person to continue drinking, they must all be addressed to successfully prevent a relapse. An example of this kind of treatment is detoxification followed by a combination of supportive therapy, attendance at self-help groups, and ongoing development of coping mechanisms. Much of the treatment community for alcoholism supports an abstinence-based zero tolerance approach; however, some prefer a harm-reduction approach.[125] ### Detoxification Main article: Alcohol detoxification Alcohol detoxification or 'detox' for alcoholics is an abrupt stop of alcohol drinking coupled with the substitution of drugs, such as benzodiazepines, that have similar effects to prevent alcohol withdrawal. Individuals who are only at risk of mild to moderate withdrawal symptoms can be detoxified as outpatients. Individuals at risk of a severe withdrawal syndrome as well as those who have significant or acute comorbid conditions are generally treated as inpatients. Detoxification does not actually treat alcoholism, and it is necessary to follow up detoxification with an appropriate treatment program for alcohol dependence or abuse to reduce the risk of relapse.[9] Some symptoms of alcohol withdrawal such as depressed mood and anxiety typically take weeks or months to abate while other symptoms persist longer due to persisting neuroadaptations.[69] Alcoholism has serious adverse effects on brain function; on average it takes one year of abstinence to recover from the cognitive deficits incurred by chronic alcohol abuse.[126] ### Psychological A regional service center for Alcoholics Anonymous. Various forms of group therapy or psychotherapy can be used to deal with underlying psychological issues that are related to alcohol addiction, as well as provide relapse prevention skills. The mutual-help group-counseling approach is one of the most common ways of helping alcoholics maintain sobriety.[8] Alcoholics Anonymous was one of the first organizations formed to provide mutual, nonprofessional counseling, and it is still the largest. Others include LifeRing Secular Recovery, SMART Recovery, Women for Sobriety, and Secular Organizations for Sobriety.[127] Alcoholics Anonymous and twelve-step programs appear more effective than cognitive behavioral therapy or abstinence.[128] ### Moderate drinking Rationing and moderation programs such as Moderation Management and DrinkWise do not mandate complete abstinence. While most alcoholics are unable to limit their drinking in this way, some return to moderate drinking. A 2002 US study by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) showed that 17.7 percent of individuals diagnosed as alcohol dependent more than one year prior returned to low-risk drinking. This group, however, showed fewer initial symptoms of dependency.[129] A follow-up study, using the same subjects that were judged to be in remission in 2001–2002, examined the rates of return to problem drinking in 2004–2005. The study found abstinence from alcohol was the most stable form of remission for recovering alcoholics.[130] There was also a 1973 study showing chronic alcoholics drinking moderately again,[131] but a 1982 follow-up showed that 95% of subjects were not able to moderately drink over the long term.[132][133] Another study was a long-term (60 year) follow-up of two groups of alcoholic men which concluded that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence."[134] Internet based measures appear to be useful at least in the short term.[135] ### Medications ## Disulfiram-like drug In the United States there are four approved medications for alcoholism: acamprosate, two methods of using naltrexone and disulfiram.[136] * Acamprosate may stabilise the brain chemistry that is altered due to alcohol dependence via antagonising the actions of glutamate, a neurotransmitter which is hyperactive in the post-withdrawal phase.[137] By reducing excessive NMDA activity which occurs at the onset of alcohol withdrawal, acamprosate can reduce or prevent alcohol withdrawal related neurotoxicity.[138] Acamprosate reduces the risk of relapse amongst alcohol-dependent persons.[139][140] * Naltrexone is a competitive antagonist for opioid receptors, effectively blocking the effects of endorphins and opioids. Naltrexone is used to decrease cravings for alcohol and encourage abstinence. Alcohol causes the body to release endorphins, which in turn release dopamine and activate the reward pathways; hence in the body reduces the pleasurable effects from consuming alcohol.[141] Evidence supports a reduced risk of relapse among alcohol-dependent persons and a decrease in excessive drinking.[140] Nalmefene also appears effective and works in a similar manner.[140] * The Sinclair method is another approach to using naltrexone or other opioid antagonists to treat alcoholism by having the person take the medication about an hour before they drink alcohol and only then.[142][143] The medication blocks the positive reinforcement effects of ethanol and hypothetically allows the person to stop drinking or drink less.[143] * Disulfiram prevents the elimination of acetaldehyde, a chemical the body produces when breaking down ethanol. Acetaldehyde itself is the cause of many hangover symptoms from alcohol use. The overall effect is discomfort when alcohol is ingested: an extremely fast-acting and long-lasting, uncomfortable hangover. Several other drugs are also used and many are under investigation. * Benzodiazepines, while useful in the management of acute alcohol withdrawal, if used long-term can cause a worse outcome in alcoholism. Alcoholics on chronic benzodiazepines have a lower rate of achieving abstinence from alcohol than those not taking benzodiazepines. This class of drugs is commonly prescribed to alcoholics for insomnia or anxiety management.[144] Initiating prescriptions of benzodiazepines or sedative-hypnotics in individuals in recovery has a high rate of relapse with one author reporting more than a quarter of people relapsed after being prescribed sedative-hypnotics. Those who are long-term users of benzodiazepines should not be withdrawn rapidly, as severe anxiety and panic may develop, which are known risk factors for relapse into alcohol abuse. Taper regimes of 6–12 months have been found to be the most successful, with reduced intensity of withdrawal.[145][146] * Calcium carbimide works in the same way as disulfiram; it has an advantage in that the occasional adverse effects of disulfiram, hepatotoxicity and drowsiness, do not occur with calcium carbimide.[147] * Ondansetron and topiramate are supported by tentative evidence in people with certain genetics.[148][149] Evidence for ondansetron is more in those who have just begun having problems with alcohol.[148] Topiramate is a derivative of the naturally occurring sugar monosaccharide D-fructose. Review articles characterize topiramate as showing "encouraging",[148] "promising",[148] "efficacious",[150] and "insufficient"[151] evidence in the treatment of alcohol use disorders. Evidence does not support the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antipsychotics, or gabapentin.[140] ### Dual addictions and dependences Alcoholics may also require treatment for other psychotropic drug addictions and drug dependences. The most common dual dependence syndrome with alcohol dependence is benzodiazepine dependence, with studies showing 10–20 percent of alcohol-dependent individuals had problems of dependence and/or misuse problems of benzodiazepine drugs such as diazepam or clonazepam. These drugs are, like alcohol, depressants. Benzodiazepines may be used legally, if they are prescribed by doctors for anxiety problems or other mood disorders, or they may be purchased as illegal drugs. Benzodiazepine use increases cravings for alcohol and the volume of alcohol consumed by problem drinkers.[152] Benzodiazepine dependency requires careful reduction in dosage to avoid benzodiazepine withdrawal syndrome and other health consequences. Dependence on other sedative-hypnotics such as zolpidem and zopiclone as well as opiates and illegal drugs is common in alcoholics. Alcohol itself is a sedative-hypnotic and is cross-tolerant with other sedative-hypnotics such as barbiturates, benzodiazepines and nonbenzodiazepines. Dependence upon and withdrawal from sedative-hypnotics can be medically severe and, as with alcohol withdrawal, there is a risk of psychosis or seizures if not properly managed.[153] ## Epidemiology Disability-adjusted life year for alcohol use disorders per million inhabitants in 2012. 234–806 814–1,501 1,551–2,585 2,838 2,898–3,935 3,953-5,069 5,168 5,173–5,802 5,861–8,838 9,122–25,165 Alcohol consumption per person 2016.[154] The World Health Organization estimates that as of 2016 there are 380 million people with alcoholism worldwide, (5.1% of the population over 15 years of age upon 65 years old) and in 2012 is estimated that aproximally more of 3.000.000 people died from problems related with heavy drinking.[11][12] Substance use disorders are a major public health problem facing many countries. "The most common substance of abuse/dependence in patients presenting for treatment is alcohol."[125] In the United Kingdom, the number of 'dependent drinkers' was calculated as over 2.8 million in 2001.[155] About 12% of American adults have had an alcohol dependence problem at some time in their life.[156] In the United States and Western Europe, 10 to 20 percent of men and 5 to 10 percent of women at some point in their lives will meet criteria for alcoholism.[157] Estonia and Russia had the highest death rate from alcohol in Europe in 2015 at 8.8 per 100,000 population.[158] In the United States, 30% of people admitted to hospital have a problem related to alcohol.[159] Within the medical and scientific communities, there is a broad consensus regarding alcoholism as a disease state. For example, the American Medical Association considers alcohol a drug and states that "drug addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite often devastating consequences. It results from a complex interplay of biological vulnerability, environmental exposure, and developmental factors (e.g., stage of brain maturity)."[160] Alcoholism has a higher prevalence among men, though, in recent decades, the proportion of female alcoholics has increased.[40] Current evidence indicates that in both men and women, alcoholism is 50–60 percent genetically determined, leaving 40–50 percent for environmental influences.[161] Most alcoholics develop alcoholism during adolescence or young adulthood.[73] ## Prognosis Alcohol use disorders deaths per million persons in 2012 0–0 1–3 4–6 7–13 14–20 21–37 38–52 53–255 Alcoholism often reduces a person's life expectancy by around ten years.[26] The most common cause of death in alcoholics is from cardiovascular complications.[162] There is a high rate of suicide in chronic alcoholics, which increases the longer a person drinks. Approximately 3–15 percent of alcoholics commit suicide,[163] and research has found that over 50 percent of all suicides are associated with alcohol or drug dependence. This is believed to be due to alcohol causing physiological distortion of brain chemistry, as well as social isolation. Suicide is also very common in adolescent alcohol abusers, with 25 percent of suicides in adolescents being related to alcohol abuse.[164] Among those with alcohol dependence after one year, some met the criteria for low-risk drinking, even though only 25.5 percent of the group received any treatment, with the breakdown as follows: 25 percent were found to be still dependent, 27.3 percent were in partial remission (some symptoms persist), 11.8 percent asymptomatic drinkers (consumption increases chances of relapse) and 35.9 percent were fully recovered – made up of 17.7 percent low-risk drinkers plus 18.2 percent abstainers.[165] In contrast, however, the results of a long-term (60-year) follow-up of two groups of alcoholic men indicated that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence."[134] There was also "return-to-controlled drinking, as reported in short-term studies, is often a mirage." ## History Adriaen Brouwer, Inn with Drunken Peasants, 1620s 1904 advertisement describing alcoholism as a disease. Historically the name "dipsomania" was coined by German physician C.W. Hufeland in 1819 before it was superseded by "alcoholism".[166][167] That term now has a more specific meaning.[168] The term "alcoholism" was first used in 1849 by the Swedish physician Magnus Huss to describe the systematic adverse effects of alcohol.[169] Alcohol has a long history of use and misuse throughout recorded history. Biblical, Egyptian and Babylonian sources record the history of abuse and dependence on alcohol. In some ancient cultures alcohol was worshiped and in others, its abuse was condemned. Excessive alcohol misuse and drunkenness were recognized as causing social problems even thousands of years ago. However, the defining of habitual drunkenness as it was then known as and its adverse consequences were not well established medically until the 18th century. In 1647 a Greek monk named Agapios was the first to document that chronic alcohol misuse was associated with toxicity to the nervous system and body which resulted in a range of medical disorders such as seizures, paralysis, and internal bleeding. In the 1910s and 1920s, the effects of alcohol abuse and chronic drunkenness boosted membership of the temperance movement and led to the prohibition of alcohol in many Western countries, nationwide bans on the production, importation, transportation, and sale of alcoholic beverages that generally remained in place until the late 1920s or early 1930s; these policies resulted in the decline of death rates from cirrhosis and alcoholism.[170] In 2005 alcohol dependence and abuse was estimated to cost the US economy approximately 220 billion dollars per year, more than cancer and obesity.[171] ## Society and culture See also: List of deaths through alcohol The various health problems associated with long-term alcohol consumption are generally perceived as detrimental to society, for example, money due to lost labor-hours, medical costs due to injuries due to drunkenness and organ damage from long-term use, and secondary treatment costs, such as the costs of rehabilitation facilities and detoxification centers. Alcohol use is a major contributing factor for head injuries, motor vehicle injuriess (27%), interpersonal violence (18%), suicides (18%), and epilepsy (13%).[172] Beyond the financial costs that alcohol consumption imposes, there are also significant social costs to both the alcoholic and their family and friends.[59] For instance, alcohol consumption by a pregnant woman can lead to an incurable and damaging condition known as fetal alcohol syndrome, which often results in cognitive deficits, mental health problems, an inability to live independently and an increased risk of criminal behaviour, all of which can cause emotional stress for parents and caregivers.[173][174] Estimates of the economic costs of alcohol abuse, collected by the World Health Organization, vary from one to six percent of a country's GDP.[175] One Australian estimate pegged alcohol's social costs at 24% of all drug abuse costs; a similar Canadian study concluded alcohol's share was 41%.[176] One study quantified the cost to the UK of all forms of alcohol misuse in 2001 as £18.5–20 billion.[155][177] All economic costs in the United States in 2006 have been estimated at $223.5 billion.[178] The idea of hitting rock bottom refers to an experience of stress that is attributed to alcohol misuse. There is no single definition for this idea, and people may identify their own lowest points in terms of lost jobs, lost relationships, health problems, legal problems, or other consequences of alcohol misuse.[179] The concept is promoted by 12-step recovery groups and researchers using the transtheoretical model of motivation for behavior change.[179] The first use of this slang phrase in the formal medical literature appeared in a 1965 review in the British Medical Journal,[179] which said that some men refused treatment until they "hit rock bottom", but that treatment was generally more successful for "the alcohol addict who has friends and family to support him" than for impoverished and homeless addicts.[180] Stereotypes of alcoholics are often found in fiction and popular culture. The "town drunk" is a stock character in Western popular culture. Stereotypes of drunkenness may be based on racism or xenophobia, as in the fictional depiction of the Irish as heavy drinkers.[181] Studies by social psychologists Stivers and Greeley attempt to document the perceived prevalence of high alcohol consumption amongst the Irish in America.[182] Alcohol consumption is relatively similar between many European cultures, the United States, and Australia. In Asian countries that have a high gross domestic product, there is heightened drinking compared to other Asian countries, but it is nowhere near as high as it is in other countries like the United States. It is also inversely seen, with countries that have very low gross domestic product showing high alcohol consumption.[183] In a study done on Korean immigrants in Canada, they reported alcohol was even an integral part of their meal, and is the only time solo drinking should occur. They also believe alcohol is necessary at any social event as it helps conversations start.[184] Caucasians have a much lower abstinence rate (11.8%) and much higher tolerance to symptoms (3.4±2.45 drinks) of alcohol than Chinese (33.4% and 2.2±1.78 drinks respectively). Also, the more acculturation there is between cultures, the more influenced the culture is to adopt Caucasians drinking practices.[185] Peyote, a psychoactive agent, has even shown promise in treating alcoholism. 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S2CID 143549807. ## External links Classification D * ICD-10: F10.2 * ICD-9-CM: 303 * OMIM: 103780 * MeSH: D000437 External resources * MedlinePlus: 000944 * eMedicine: article/285913 Alcoholismat Wikipedia's sister projects * Definitions from Wiktionary * Media from Wikimedia Commons * Quotations from Wikiquote * Alcohol at Curlie * v * t * e Reinforcement disorders: Addiction and Dependence Addiction Drug * Alcohol * Amphetamine * Cocaine * Methamphetamine * Methylphenidate * Nicotine * Opioid Behavioral * Financial * Gambling * Shopping * Palatable food * Sex-related * Intercourse * Pornography * Internet-related * Internet addiction disorder * Internet sex addiction * Video game addiction * Digital media addictions Cellular mechanisms * Transcriptional * ΔFosB * c-Fos * Cdk5 * CREB * GluR2 * NF-κB * Epigenetic * G9a * G9a-like protein * HDAC1 * HDAC2 * HDAC3 * HDAC4 * HDAC5 * HDAC9 * HDAC10 * SIRT1 * SIRT2 * ... 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(2012) * Category Authority control * BNF: cb11964742x (data) * GND: 4001220-7 * HDS: 016558 * LCCN: sh85003292 * NARA: 10640440 * NDL: 00560352 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Alcoholism	c0001973	30,193	wikipedia	https://en.wikipedia.org/wiki/Alcoholism	2021-01-18T18:54:50	{"mesh": ["D000437"], "icd-9": ["303"], "icd-10": ["F10"], "wikidata": ["Q15326"]}
A number sign (#) is used with this entry because of evidence that Joubert syndrome-23 (JBTS23) is caused by homozygous or compound heterozygous mutation in the KIAA0586 gene (610178) on chromosome 14q23. Description Joubert syndrome-23 is an autosomal recessive neurodevelopmental disorder characterized by delayed development, abnormal eye movements, and abnormal breathing pattern associated with a characteristic hindbrain malformation apparent on brain imaging and known as the 'molar tooth sign.' Compared to other forms of Joubert syndrome, the phenotype is relatively mild, and other organ systems are generally not affected (summary by Bachmann-Gagescu et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300. Clinical Features Bachmann-Gagescu et al. (2015) reported 9 patients with Joubert syndrome-23. The phenotype was relatively homogeneous, consisting mainly of neurologic features, such as delayed development, abnormal eye movements, and the molar tooth sign on brain imaging. Two individuals had brainstem heterotopia, 1 had dysplasia of the cerebellar hemispheres, and 1 had a thick and dysplastic corpus callosum. Many patients had abnormal breathing patterns. Only 1 patient had polydactyly, and another had coloboma; none had retinal, renal, or liver involvement. Bachmann-Gagescu et al. (2015) concluded that the phenotype was at the mild end of the disease spectrum observed in Joubert syndrome. Inheritance The transmission pattern of JBTS23 in the families reported by Bachmann-Gagescu et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In affected individuals from 9 unrelated families with JBTS23, Bachmann-Gagescu et al. (2015) identified homozygous or compound heterozygous mutations in the KIAA0586 gene (see, e.g., 610178.0001-610178.0005). Mutations in the first patient were found by whole-exome sequencing; biallelic mutations in 8 additional families were found by sequencing the exons of the KIAA0586 gene in a cohort of 366 additional families with the disorder. Overall, biallelic mutations were found in 9 (2.5%) of 366 families. Seven additional patients had heterozygous mutations in the KIAA0586 gene. One recurrent truncating mutation (610178.0001) was found in 7 of the 9 families. Functional studies of the variants were not performed. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Abnormal eye movements \- Coloboma (1 patient) RESPIRATORY \- Apnea \- Tachypnea SKELETAL Hands \- Polydactyly (1 patient) NEUROLOGIC Central Nervous System \- Delayed development \- Molar tooth sign on brain imaging \- Cerebellar dysplasia (1 patient) \- Brainstem heterotopia (2 patients) \- Dysplastic corpus callosum (1 patient) MISCELLANEOUS \- Nine patients have been reported (last curated July 2015) \- Relatively mild phenotype MOLECULAR BASIS \- Caused by mutation in the KIAA0586 gene (KIAA0586, 610178.0001 ) ▲ 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	JOUBERT SYNDROME 23	c4551568	30,194	omim	https://www.omim.org/entry/616490	2019-09-22T15:48:41	{"doid": ["0110992"], "mesh": ["C536293"], "omim": ["213300", "616490"], "orphanet": ["475"], "synonyms": ["CPD IV", "Cerebelloparenchymal disorder IV", "Classic Joubert syndrome", "Joubert syndrome type A", "Joubert-Boltshauser syndrome", "Pure Joubert syndrome"], "genereviews": ["NBK1325"]}
Delta-beta-thalassemia is a form of beta-thalassemia (see this term) characterized by decreased or absent synthesis of the delta- and beta-globin chains with a compensatory increase in expression of fetal gamma-chain synthesis. ## Epidemiology Prevalence of this form is not known. The condition is found in many ethnic groups but is most common in Greece and Italy. ## Clinical description The heterozygous form of the condition is clinically asymptomatic with mild microcytosis and no elevation of HbA2 whereas the few homozygous patients have a mild clinical presentation. When inherited with heterozygous classical beta-thalassemia, patients usually have the thalassemia intermedia phenotype, but the thalassemia major phenotype has been described in some cases. ## Etiology Delta-beta-thalassemia is commonly caused by deletions of the entire delta and beta gene sequences with production of only gamma-globin and formation of HbF. Rarely, non-deletional forms have been reported. ## Diagnostic methods Diagnosis is based on hypochromic microcytic red cell indices with significant elevation of HbF, ranging from 5-15% in heterozygotes. HbF is heterogeneously distributed among the erythrocytes. The alpha/beta-globin synthesis ratio is >1. ## Differential diagnosis Hereditary persistence of fetal Hb and beta-thalassemia (see this term) is the main differential diagnosis. The distinction between these two conditions cannot always be made from routine hematologic analyses and alpha-beta-globin chain synthesis ratio and DNA analysis may be necessary. ## Genetic counseling Transmission is autosomal recessive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Delta-beta-thalassemia	c0271985	30,195	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231237	2021-01-23T18:51:48	{"mesh": ["C562716"], "omim": ["141749"], "umls": ["C0271985"], "icd-10": ["D56.2"]}
Curling's ulcer Other namesCurling ulcer SpecialtyGeneral surgery, Gastroenterology Curling's ulcer is an acute gastric erosion resulting as a complication from severe burns when reduced plasma volume leads to ischemia and cell necrosis (sloughing) of the gastric mucosa. The condition was first described in 1823 and named for a doctor, Thomas Blizard Curling, who observed ten such patients in 1842.[1][2] These stress ulcers (actually shallow multiple erosions) were once a common complication of serious burns, presenting in over 10% of cases,[1] and especially common in child burn victims.[3] They result in perforation and hemorrhage more often than other forms of intestinal ulceration[4] and had correspondingly high mortality rates (at least 80%).[1][5] A similar condition involving elevated intracranial pressure is known as Cushing's ulcer. ## Contents * 1 Treatment * 2 See also * 3 References * 4 External links ## Treatment[edit] While emergency surgery was once the only treatment, combination therapies including enteral feeding with powerful antacids such as H2-receptor antagonists or, more recently, proton pump inhibitors such as omeprazole have made Curling's ulcer a rare complication.[6] ## See also[edit] * Cushing ulcer ## References[edit] 1. ^ a b c Pruitt, Basil A. Jr.; F.D. Foley & John A. Moncrief (October 1970). "Curling's ulcer: a clinical-pathology study of 323 cases". Annals of Surgery. 172 (4): 523–39. doi:10.1097/00000658-197010000-00001. PMC 1397279. PMID 5311720. 2. ^ Curling, T. B. (1842). "On acute ulceration of the duodenum, in cases of burn". Medico-Chirurgical Transactions. 25: 260–281. 3. ^ Bruck, H.M.; Basil A. Pruitt Jr. (June 1972). "Curling's ulcer in children: a 12-year review of 63 cases". Journal of Trauma. 12 (6): 490–6. doi:10.1097/00005373-197206000-00006. PMID 5033495. 4. ^ Lev R.; Klein, Martin S.; Ennis, Frank; Sherlock, Paul; Winawer, Sidney J. (December 1973). "Letter: Stress erosions". Am J Dig Dis. 18 (12): 1099–100. doi:10.1007/BF01076530. PMID 4543410. 5. ^ Pedro-Pons, Agustín (1968). Patología y Clínica Médicas (in Spanish). 6 (3rd ed.). Barcelona: Salvat. p. 1198. ISBN 84-345-1106-1. 6. ^ Moran KT, O'Reilly T, Munster AM (October 1987). "A combined regimen for the prophylaxis of Curling's ulcer". Am Surg. 53 (10): 575–6. PMID 2890321. ## External links[edit] Classification D * MeSH: D004381 * DiseasesDB: 3237 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Curling's ulcer	c0010474	30,196	wikipedia	https://en.wikipedia.org/wiki/Curling%27s_ulcer	2021-01-18T19:06:30	{"mesh": ["D004381"], "umls": ["C0010474"], "wikidata": ["Q5194855"]}
A number sign (#) is used with this entry because of evidence that isolated question mark ears (QME) are caused by heterozygous mutation in the EDN1 gene (131240) on chromosome 6p24. Homozygous mutation in EDN1 causes auriculocondylar syndrome-3 (ARCND3; 615706). Description Question mark ear is an auricular abnormality characterized by a cleft between the lobule and the lower part of the helix, sometimes accompanied by a prominent or deficient upper part of the helix, shallow skin dimple on the posterior surface of the ear, or transposition of the ear lobe/antitragus. It is more prevalent among boys than girls (2:1), usually sporadic, and can be unilateral or bilateral (Shkalim et al., 2008). Clinical Features Cosman et al. (1970) described 2 unrelated patients with question mark ears. The first was a 38-year-old Puerto Rican man who had a unilateral deformity of the left ear, with prominence and protrusion of the upper third of the ear, an apparent absence of the helix and distal scapha in the middle third, and disjunction of the otherwise normal lobule from the rest of the ear in the lower third. There was no family history of ear abnormalities. The other patient was a 5-year-old black boy who had the same defect of the ears bilaterally, with a shallow 2-mm skin dimple posteriorly bilaterally and a skin tag on the left. His eardrums and hearing were normal. The boy had an apparently identical twin brother with completely normal ears. Cosman (1984) provided follow-up on the 2 patients described by Cosman et al. (1970), both of whom underwent repair of their ears with good cosmetic results. Cosman (1984) stated that 8 or 9 cases of question mark ears had been reported, some of which were associated with other anomalies (see, e.g., auriculocondylar syndrome, 602483). The author published photographs of the single case reported by Fumiiri and Hyakusoku (1983), with a unilateral ear defect that exhibited near identity to the previously depicted cases. Al-Qattan (1998) reported 2 unrelated girls with question mark ears. The first was a 5-year-old girl of Sudanese origin with a left ear deformity and a shallow 2-mm skin dimple on the posterior surface of the ear, who had a normal-appearing eardrum and normal hearing. The second was a 5-year-old Saudi girl with bilateral question mark ears, who also had another area of helical deficiency just superior to the Darwinian tubercle on the right ear, but no skin dimples; her hearing was normal. There was no family history of ear abnormalities in either case. Al-Qattan (1998) suggested that this anomaly be designated Cosman deformity of the auricle. Shkalim et al. (2008) reported a 3-generation family segregating question mark ears in an autosomal dominant pattern; the proband and her paternal grandfather were bilaterally affected, whereas her father had only a right-sided deformity. Affected members of this family were later found to have auriculocondylar syndrome-2 (ARCND2; 614669). Gordon et al. (2013) studied 2 families with isolated question mark ears. In a family from Armenia ('case 11'), the mother presented with a significant notch in the border of the helix, at the lobe-helix junction, bilaterally. Her daughter displayed bilateral clefting between the lobe and helix. No overt signs of mandibular hypoplasia were evident. X-rays of the mandible of the daughter at 2 years of age did not reveal any obvious anomalies. In a family of African origin ('case 12'), the mother displayed a notch at the lobe-helix junction, and her son and daughter each had protruding helices and clefting, or constriction, between the lobe and helix. The daughter had been treated for acute lymphoblastic leukemia. The authors were not able to assess mandibular x-rays in this family, but there were no external signs of micrognathia. Molecular Genetics In 2 unrelated patients from families with isolated question mark ears that were previously studied by Gordon et al. (2013) and found to be negative for mutation in the coding regions of the GNAI3 (139370), PLCB4 (600810), GNAQ (600998), and GNA11 (139313) genes and the catalytic domain exons of the PLCB3 gene (600230), Gordon et al. (2013) performed whole-exome sequencing and identified heterozygosity for a missense (V64D; 131240.0004) and a nonsense (Y83X; 131240.0005) mutation in the EDN1 gene, respectively. The mutations segregated with disease in both families. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Question mark ears \- Prominence and protrusion of upper third of the ear \- Absence of the helix and distal scapha in middle third of the ear \- Disjunction of otherwise normal lobule from remainder of ear \- Shallow skin dimple on posterior surface of ear \- Normal hearing MOLECULAR BASIS \- Caused by mutation in the endothelin 1 gene (EDN1, 131240.0004 ) ▲ 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	QUESTION MARK EARS, ISOLATED	c1865295	30,197	omim	https://www.omim.org/entry/612798	2019-09-22T16:00:39	{"mesh": ["C538270"], "omim": ["612798"], "orphanet": ["137888"], "synonyms": ["Alternative titles", "EARS, PROMINENT AND CONSTRICTED", "COSMAN DEFORMITY OF THE AURICLE", "AURICULAR CLEFT, CONGENITAL"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) Morning pseudoneutropenia is a transient reduction in the measured neutrophil count from peripheral samples. This is noticed in some patients who are taking antipsychotic medication. Morning pseudoneutropenia is thought to be due to diurnal variation in the amount of circulating white blood cells and changes in the levels of hematopoietic cytokines and granulocyte colony stimulating factor (GCSF).[1] Antipsychotics may amplify the natural variation in these hematopoietic factors. Neutropenia is a hematological disorder characterized by an abnormally low number of neutrophils in the blood. Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections. There is some variability in the neutrophil counts depending upon when the sample is taken, where the blood sample is taken from, and the system used by the medical lab for measuring the blood cells, but any significant reduction in function or number below the appropriate range may predispose individuals to infections. Case reports of such incidents are reported with clozapine,[2][3] risperidone,[4] and aripiprazole.[5] These case reports suggest that the observed cases of the morning pseudoneutropenia did not proceed to become agranulocytosis which is a significant and dangerous side effect of some of antipsychotics. Hence it was suggested[6] that although the morning neutrophil count may appear low, if the antipsychotic medication were considered efficacious then white cell counts may be repeated in the afternoon prior to making a decision based only on the morning counts. ## References[edit] 1. ^ Jilma B, Hergovich N, Stohlawetz P, Eichler HG, Bauer P, Wagner OF (August 1999). "Circadian variation of granulocyte colony stimulating factor levels in man". British Journal of Haematology. 106 (2): 368–70. doi:10.1046/j.1365-2141.1999.01543.x. PMID 10460592. 2. ^ Ahokas A, Elonen E (June 1999). "Circadian rhythm of white blood cells during clozapine treatment". Psychopharmacology. 144 (3): 301–2. doi:10.1007/s002130051008. PMID 10435399. S2CID 29904594. 3. ^ Esposito D, Aouillé J, Rouillon F, Limosin F (October 2003). "Morning pseudoneutropenia during clozapine treatment". The World Journal of Biological Psychiatry. 4 (4): 192–4. doi:10.1080/15622970310029918. PMID 14608591. S2CID 21205778. 4. ^ Singh, G.; Kodela, S. (2009). "Morning pseudoneutropenia during risperidone treatment". Case Reports. 2009: bcr0620080288. doi:10.1136/bcr.06.2008.0288. PMC 3029895. PMID 21686871. 5. ^ Pinnaka S, Roberto AJ, Giordano A, Siller P, Lapidus K (September 2015). "Aripiprazole-Induced Transient Morning Pseudoneutropenia in an 11-Year-Old Male". Journal of Child and Adolescent Psychopharmacology. 26 (9): 858–859. doi:10.1089/cap.2015.0128. PMID 26397725.CS1 maint: uses authors parameter (link) 6. ^ Esposito D, Corruble E, Hardy P, Chouinard G (February 2005). "Risperidone-induced morning pseudoneutropenia". The American Journal of Psychiatry. 162 (2): 397. doi:10.1176/appi.ajp.162.2.397. PMID 15677612. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: 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	Morning pseudoneutropenia	None	30,198	wikipedia	https://en.wikipedia.org/wiki/Morning_pseudoneutropenia	2021-01-18T18:55:02	{"wikidata": ["Q6912932"]}
A number sign (#) is used with this entry because some cases of hypereosinophilic syndrome are caused by fusion between the FIP1-like-1 (FIP1L1; 607686) and platelet-derived growth factor receptor-alpha (PDGFRA; 173490) genes. Clinical Features The hypereosinophilic syndrome is a rare hematologic disorder with sustained overproduction of eosinophils in the bone marrow, eosinophilia, tissue infiltration, and organ damage (Cools et al., 2003). The syndrome is more common in men than women (ratio of 9 to 1) and occurs predominantly between the ages of 20 and 50 years. Total leukocyte counts are usually less than 25,000 per cubic millimeter, with 30 to 70% eosinophils. Diagnosis The diagnosis of hypereosinophilic syndrome is based on the following criteria (Chusid et al., 1975): sustained eosinophilia (more than 1,500 eosinophils per cubic millimeter) for more than 6 months; the absence of other causes of eosinophilia, including parasitic infections and allergies; and signs and symptoms of organ involvement, most frequently the heart, the central and peripheral nervous system, lungs, and skin. The clonality of hypereosinophilic syndrome has been demonstrated in some cases by clonal karyotypic abnormalities and X-inactivation assays (Luppi et al., 1994; Chang et al., 1999). Klion et al. (2003) concluded that elevated serum tryptase is a sensitive marker of a myeloproliferative variant of HES that is characterized by tissue fibrosis, poor prognosis, and imatinib responsiveness. Clinical Management Gleich et al. (2002) reported that 4 of 5 cases of hypereosinophilic syndrome responded to imatinib (Gleevec, Novartis), a tyrosine kinase inhibitor. Cools et al. (2003) treated 11 patients with idiopathic hypereosinophilic syndrome with imatinib and found that 9 had responses lasting more than 3 months in which the eosinophil count returned to normal. In patients with hypereosinophilic syndrome who have clonal T cells and polymorphous skin lesions, interleukin-5 (147850) seems to play a critical pathogenic role (Cogan et al., 1994; Simon et al., 1999). In 3 patients with a hypereosinophilic syndrome and dermatologic manifestations, Plotz et al. (2003) reported the effect of mepolizumab, a neutralizing anti-interleukin-5 antibody. A graph demonstrated eosinophil counts over 42 days and a clearing of the skin was pictured. Molecular Genetics Cools et al. (2003) found that a hypereosinophilic syndrome patient being treated with imatinib had a complex chromosomal abnormality; this led to the identification of fusion of the FIP1L1 gene to the PDGFRA gene, which was caused by an interstitial deletion on chromosome 4q12. The resulting FIP1L1-PDGFRA gene was found to be a constitutively activated tyrosine kinase that transforms hematopoietic cells and is inhibited by imatinib. The authors subsequently detected the FIP1L1-PDGFRA gene in 9 of 16 patients with idiopathic hypereosinophilic syndrome and in 5 of the 9 patients with responses to imatinib that lasted more than 3 months. Relapse in 1 patient correlated with the appearance of a thr674-to-ile mutation in the PDGFRA gene (T674I; 173490.0008) that conferred resistance to imatinib. Griffin et al. (2003) found the 4q12 deletion in patients with HES, resulting in the same fusion gene involving PDGFRA and FIP1L1. They suggested that FIP1L1 be referred to as RAG (rearranged in hypereosinophilia). They demonstrated that the fusion kinase is constitutively phosphorylated and supports IL-3-independent growth when expressed in BaF3 cells. Proliferation and viability of EOL-1 and BaF3 cells expressing the fusion protein were ablated by imatinib and 2 other inhibitors of PDGFRA. The FIP1L1 and PDGFRA genes are both located in 4q12; the FIP1L1-PDGFRA fusion results from an apparent interstitial deletion that links FIP1L1 to exon 12 of PDGFRA. INHERITANCE \- Somatic mutation \- Isolated cases CARDIOVASCULAR Heart \- Cardiac infiltration of eosinophils \- Endomyocardial fibrosis \- Restrictive cardiomyopathy Vascular \- Venous thrombosis RESPIRATORY Lung \- Pulmonary infiltrates ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKIN, NAILS, & HAIR Skin \- Pruritus MUSCLE, SOFT TISSUES \- Myalgia NEUROLOGIC Central Nervous System \- Paraspinal masses \- Cauda equina syndrome Peripheral Nervous System \- Peripheral nervous system involvement HEMATOLOGY \- Sustained eosinophilia (greater than 1,500/cubic mm) for greater than 6 months \- Total white blood cell count less than 25,000/cubic mm with 30-70% eosinophils \- Bone marrow biopsy shows increased eosinophils without myeloblasts IMMUNOLOGY \- No concurrent parasitic infection \- No concurrent allergies MISCELLANEOUS \- Occurs at age 20-50 years \- Considered a myeloproliferative disorder \- Usually fatal \- More common in men (9:1 male:female ratio) MOLECULAR BASIS \- Caused by fusion of the FIP1-like 1 gene (FIP1L1, 607686 ) and the platelet-derived growth factor receptor-alpha gene (PDGFRA, 173490 ) ▲ 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	HYPEREOSINOPHILIC SYNDROME, IDIOPATHIC	c0206141	30,199	omim	https://www.omim.org/entry/607685	2019-09-22T16:08:47	{"mesh": ["D017681"], "omim": ["607685"], "orphanet": ["3260"]}

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